NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|71043698|ref|NP_001020822|]
View 

synaptotagmin-like protein 1 isoform 2 [Rattus norvegicus]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 267-386 5.87e-69

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


The actual alignment was detected with superfamily member cd08393:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 125  Bit Score: 217.69  E-value: 5.87e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRR--RSDPYVKSYLLPDK--QNKRKTSVKKRNLNPIFNETLRHSVQQAD 342
Cdd:cd08393   1 QGSVQFALDYDPKLRELHVHVIQCQDLAAADPKkqRSDPYVKTYLLPDKsnRGKRKTSVKKKTLNPVFNETLRYKVEREE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 71043698 343 LPGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEA-TWLPLQ 386
Cdd:cd08393  81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQpTWYPLQ 125
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 399-517 1.56e-58

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


:

Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 191.77  E-value: 1.56e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYIPAGSEG---GGQPPSGELHFWIKEAQGLVPLRP-GSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFN 474
Cdd:cd04020   1 RGELKVALKYVPPESEGalkSKKPSTGELHVWVKEAKNLPALKSgGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 71043698 475 HTMVYDGFGPADLRQACAELSLWDHGALAS-RQLGGTRLSLGTG 517
Cdd:cd04020  81 HTFVYDGVSPEDLSQACLELTVWDHDKLSSnDFLGGVRLGLGTG 124
PHD_SF super family cl22851
PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) ...
 35-90 1.01e-04

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.


The actual alignment was detected with superfamily member pfam02318:

Pssm-ID: 473978  Cd Length: 118  Bit Score: 41.97  E-value: 1.01e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 71043698    35 SFLTEEEQEAISDVLKRDAHLRQLEEGRVSKLRASLADPWQLKILTGDWFQEARSQ 90
Cdd:pfam02318   1 SKLTDEEAEHVWEVVQRDFDLRKKEEERLGELKGKLDKESSKRELLGNQAHLGETH 56
 
Name Accession Description Interval E-value
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 267-386 5.87e-69

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 217.69  E-value: 5.87e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRR--RSDPYVKSYLLPDK--QNKRKTSVKKRNLNPIFNETLRHSVQQAD 342
Cdd:cd08393   1 QGSVQFALDYDPKLRELHVHVIQCQDLAAADPKkqRSDPYVKTYLLPDKsnRGKRKTSVKKKTLNPVFNETLRYKVEREE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 71043698 343 LPGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEA-TWLPLQ 386
Cdd:cd08393  81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQpTWYPLQ 125
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 399-517 1.56e-58

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 191.77  E-value: 1.56e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYIPAGSEG---GGQPPSGELHFWIKEAQGLVPLRP-GSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFN 474
Cdd:cd04020   1 RGELKVALKYVPPESEGalkSKKPSTGELHVWVKEAKNLPALKSgGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 71043698 475 HTMVYDGFGPADLRQACAELSLWDHGALAS-RQLGGTRLSLGTG 517
Cdd:cd04020  81 HTFVYDGVSPEDLSQACLELTVWDHDKLSSnDFLGGVRLGLGTG 124
C2 pfam00168
C2 domain;
281-385 2.85e-27

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 105.48  E-value: 2.85e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698   281 GELRVQVIQCQGLAAA-RRRRSDPYVKSYLLPDKQnKRKTSVKKRNLNPIFNETLRHSVQqaDLPGRVLSLSVWHRESLG 359
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKdGNGTSDPYVKVYLLDGKQ-KKKTKVVKNTLNPVWNETFTFSVP--DPENAVLEIEVYDYDRFG 77

                          90       100
                  ....*....|....*....|....*..
gi 71043698   360 RNIFLGEVEVPLDTW-NWDSEATWLPL 385
Cdd:pfam00168  78 RDDFIGEVRIPLSELdSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 283-373 3.71e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 91.01  E-value: 3.71e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698    283 LRVQVIQCQGLAAARR-RRSDPYVKSYLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQqaDLPGRVLSLSVWHRESLGRN 361
Cdd:smart00239   2 LTVKIISARNLPPKDKgGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVP--PPELAELEIEVYDKDRFGRD 79

                           90
                   ....*....|..
gi 71043698    362 IFLGEVEVPLDT 373
Cdd:smart00239  80 DFIGQVTIPLSD 91
C2 pfam00168
C2 domain;
422-525 1.06e-14

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 70.04  E-value: 1.06e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698   422 GELHFWIKEAQGLVPL-RPGSLDTYIQCSVLpddSRASRQRTRVVRRSLSPVFNHTMVYDGFgpaDLRQACAELSLWDHG 500
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKdGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVP---DPENAVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*.
gi 71043698   501 ALASRQ-LGGTRLSLGTGEQSRPLRG 525
Cdd:pfam00168  75 RFGRDDfIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 424-514 5.56e-09

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 53.65  E-value: 5.56e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698    424 LHFWIKEAQGLVPL-RPGSLDTYIQCSVLPDDSRasRQRTRVVRRSLSPVFNHTMVYDGFGPADlrqACAELSLWDHGAL 502
Cdd:smart00239   2 LTVKIISARNLPPKdKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDKDRF 76

                           90
                   ....*....|...
gi 71043698    503 -ASRQLGGTRLSL 514
Cdd:smart00239  77 gRDDFIGQVTIPL 89
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
276-373 2.41e-07

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 53.99  E-value: 2.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698  276 YEPgTGELRVQVIQCQGLAAARRR-RSDPYVKsYLLPDKQNkRKTSVKKRNLNPIFNETLRHSVQQADLpgRVLSLSVWH 354
Cdd:COG5038 1036 VEN-SGYLTIMLRSGENLPSSDENgYSDPFVK-LFLNEKSV-YKTKVVKKTLNPVWNEEFTIEVLNRVK--DVLTINVND 1110

                         90
                 ....*....|....*....
gi 71043698  355 RESLGRNIFLGEVEVPLDT 373
Cdd:COG5038 1111 WDSGEKNDLLGTAEIDLSK 1129
FYVE_2 pfam02318
FYVE-type zinc finger; This FYVE-type zinc finger is found at the N-terminus of effector ...
 35-90 1.01e-04

FYVE-type zinc finger; This FYVE-type zinc finger is found at the N-terminus of effector proteins including rabphilin-3A and regulating synaptic membrane exocytosis protein 2.


Pssm-ID: 426716  Cd Length: 118  Bit Score: 41.97  E-value: 1.01e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 71043698    35 SFLTEEEQEAISDVLKRDAHLRQLEEGRVSKLRASLADPWQLKILTGDWFQEARSQ 90
Cdd:pfam02318   1 SKLTDEEAEHVWEVVQRDFDLRKKEEERLGELKGKLDKESSKRELLGNQAHLGETH 56
 
Name Accession Description Interval E-value
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 267-386 5.87e-69

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 217.69  E-value: 5.87e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRR--RSDPYVKSYLLPDK--QNKRKTSVKKRNLNPIFNETLRHSVQQAD 342
Cdd:cd08393   1 QGSVQFALDYDPKLRELHVHVIQCQDLAAADPKkqRSDPYVKTYLLPDKsnRGKRKTSVKKKTLNPVFNETLRYKVEREE 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 71043698 343 LPGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEA-TWLPLQ 386
Cdd:cd08393  81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQpTWYPLQ 125
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 399-517 1.56e-58

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 191.77  E-value: 1.56e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYIPAGSEG---GGQPPSGELHFWIKEAQGLVPLRP-GSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFN 474
Cdd:cd04020   1 RGELKVALKYVPPESEGalkSKKPSTGELHVWVKEAKNLPALKSgGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 71043698 475 HTMVYDGFGPADLRQACAELSLWDHGALAS-RQLGGTRLSLGTG 517
Cdd:cd04020  81 HTFVYDGVSPEDLSQACLELTVWDHDKLSSnDFLGGVRLGLGTG 124
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 268-385 2.24e-53

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 176.68  E-value: 2.24e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAAA--RRRRSDPYVKSYLLPDK--QNKRKTSVKKRNLNPIFNETLRHSVQQADL 343
Cdd:cd08521   1 GEIEFSLSYNYKTGSLEVHIKECRNLAYAdeKKKRSNPYVKVYLLPDKskQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 71043698 344 PGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEAT-WLPL 385
Cdd:cd08521  81 ETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSeWYPL 123
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 268-386 1.62e-46

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 158.76  E-value: 1.62e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAAA--RRRRSDPYVKSYLLPDK--QNKRKTSVKKRNLNPIFNETLRHSVQQADL 343
Cdd:cd04029   2 GEILFSLSYDYKTQSLNVHVKECRNLAYGdeAKKRSNPYVKTYLLPDKsrQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 71043698 344 PGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDS-EATWLPLQ 386
Cdd:cd04029  82 ETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSqHEECLPLH 125
C2A_SLP-3 cd08392
C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically ...
 268-385 4.81e-29

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176038 [Multi-domain]  Cd Length: 128  Bit Score: 111.46  E-value: 4.81e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLA--AARRRRSDPYVKSYLLPDK--QNKRKTSVKKRNLNPIFNETLRHSVQQADL 343
Cdd:cd08392   2 GEIEFALHYNFRTSCLEITIKACRNLAygDEKKKKCHPYVKVCLLPDKshNSKRKTAVKKGTVNPVFNETLKYVVEADLL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 71043698 344 PGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEAT----WLPL 385
Cdd:cd08392  82 SSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDTDSqrflWYPL 127
C2 pfam00168
C2 domain;
281-385 2.85e-27

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 105.48  E-value: 2.85e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698   281 GELRVQVIQCQGLAAA-RRRRSDPYVKSYLLPDKQnKRKTSVKKRNLNPIFNETLRHSVQqaDLPGRVLSLSVWHRESLG 359
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKdGNGTSDPYVKVYLLDGKQ-KKKTKVVKNTLNPVWNETFTFSVP--DPENAVLEIEVYDYDRFG 77

                          90       100
                  ....*....|....*....|....*..
gi 71043698   360 RNIFLGEVEVPLDTW-NWDSEATWLPL 385
Cdd:pfam00168  78 RDDFIGEVRIPLSELdSGEGLDGWYPL 104
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 268-385 3.69e-26

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 103.14  E-value: 3.69e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTgeLRVQVIQCQGLAAARRRRSDPYVKSYLLPD--KQNKRKTSVKKRNLNPIFNETLRHS-VQQADLP 344
Cdd:cd08381   2 GQVKLSISYKNGT--LFVMVMHAKNLPLLDGSDPDPYVKTYLLPDpqKTTKRKTKVVRKTRNPTFNEMLVYDgLPVEDLQ 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 71043698 345 GRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEAT-WLPL 385
Cdd:cd08381  80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEkWYPL 121
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 268-373 2.51e-24

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 98.42  E-value: 2.51e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAA-ARRRRSDPYVKSYLLPD--KQNKRKTSVKKRNLNPIFNETLRHSVQQADLP 344
Cdd:cd00276   1 GELLLSLSYLPTAERLTVVVLKARNLPPsDGKGLSDPYVKVSLLQGgkKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                        90       100
                ....*....|....*....|....*....
gi 71043698 345 GRVLSLSVWHRESLGRNIFLGEVEVPLDT 373
Cdd:cd00276  81 EVSLVITVVDKDSVGRNEVIGQVVLGPDS 109
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 266-373 3.49e-24

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 97.73  E-value: 3.49e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 266 VRGSVLFSLRYEPGTGELRVQVIQCQGLAAARRRR-SDPYVKSYLLPDKQ--NKRKTSVKKRNLNPIFNETLRHSVQQAD 342
Cdd:cd04030   1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDiPDPYVRLYLLPDKSksTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 71043698 343 LPGRVLSLSVWHRESL--GRNIFLGEVEVPLDT 373
Cdd:cd04030  81 LKRRTLDVAVKNSKSFlsREKKLLGQVLIDLSD 113
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 267-365 7.69e-24

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 97.78  E-value: 7.69e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPG------------TGELRVQVIQCQGLAAARRR-RSDPYVKSYLLPDKQ--NKRKTSVKKRNLNPIFN 331
Cdd:cd04020   1 RGELKVALKYVPPesegalkskkpsTGELHVWVKEAKNLPALKSGgTSDSFVKCYLLPDKSkkSKQKTPVVKKSVNPVWN 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 71043698 332 ETLRHS-VQQADLPGRVLSLSVWHRESLGRNIFLG 365
Cdd:cd04020  81 HTFVYDgVSPEDLSQACLELTVWDHDKLSSNDFLG 115
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 270-368 1.31e-23

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 96.26  E-value: 1.31e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 270 VLFSLRYEPGTGELRVQVIQCQGLAAARRRR-SDPYVKSYLLPDKQN--KRKTSVKKRNLNPIFNETLRHSVQQADLPGR 346
Cdd:cd08384   2 ILVSLMYNTQRRGLIVGIIRCVNLAAMDANGySDPFVKLYLKPDAGKksKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKK 81

                        90       100
                ....*....|....*....|...
gi 71043698 347 VLSLSVWHREsLGR-NIFLGEVE 368
Cdd:cd08384  82 TLEITVWDKD-IGKsNDYIGGLQ 103
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 267-387 1.58e-23

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 95.79  E-value: 1.58e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRR-RSDPYVKSYLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQQADLPG 345
Cdd:cd08385   2 LGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGgTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFKVPYSELGN 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 71043698 346 RVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEAT-WLPLQP 387
Cdd:cd08385  82 KTLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHVTEeWRDLES 124
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 283-385 2.26e-22

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 91.74  E-value: 2.26e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAA-RRRRSDPYVKSYLLPDKqnKRKTSVKKRNLNPIFNETlrHSVQQADLPGRVLSLSVWHRESLGRN 361
Cdd:cd00030   1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGGKQ--KFKTKVVKNTLNPVWNET--FEFPVLDPESDTLTVEVWDKDRFSKD 76

                        90       100
                ....*....|....*....|....*.
gi 71043698 362 IFLGEVEVPLDTWNWDSEAT--WLPL 385
Cdd:cd00030  77 DFLGEVEIPLSELLDSGKEGelWLPL 102
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 267-387 3.50e-22

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 92.01  E-value: 3.50e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAAR-RRRSDPYVKSYLLPDKQNKRKTSVKKRNLNPIFNETLR---HSVQQad 342
Cdd:cd08386   2 LGRIQFSVSYDFQESTLTLKILKAVELPAKDfSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLfegFPYEK-- 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 71043698 343 LPGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEAT-WLPLQP 387
Cdd:cd08386  80 LQQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQTfWKDLKP 125
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 283-373 3.71e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 91.01  E-value: 3.71e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698    283 LRVQVIQCQGLAAARR-RRSDPYVKSYLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQqaDLPGRVLSLSVWHRESLGRN 361
Cdd:smart00239   2 LTVKIISARNLPPKDKgGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVP--PPELAELEIEVYDKDRFGRD 79

                           90
                   ....*....|..
gi 71043698    362 IFLGEVEVPLDT 373
Cdd:smart00239  80 DFIGQVTIPLSD 91
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 273-386 1.46e-20

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 87.30  E-value: 1.46e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 273 SLRYEPGTGELRVQVIQCQGLAAARRRR-SDPYVKSYLLPDK--QNKRKTSVKKRNLNPIFNETLRHS-VQQADLPGRVL 348
Cdd:cd04031   8 QLWYDKVTSQLIVTVLQARDLPPRDDGSlRNPYVKVYLLPDRseKSKRRTKTVKKTLNPEWNQTFEYSnVRRETLKERTL 87

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 71043698 349 SLSVWHRESLGRNIFLGEVEVPLDTWNWDSEATWLPLQ 386
Cdd:cd04031  88 EVTVWDYDRDGENDFLGEVVIDLADALLDDEPHWYPLQ 125
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 283-388 9.39e-20

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 85.50  E-value: 9.39e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAARRRRSDPYVK-SYLLPDKQNKRKTSVKKRNLNPIFNETL-------------RHSVQQADLPGRVL 348
Cdd:cd08675   1 LSVRVLECRDLALKSNGTCDPFARvTLNYSSKTDTKRTKVKKKTNNPRFDEAFyfeltigfsyekkSFKVEEEDLEKSEL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 71043698 349 SLSVWHRESLGRNIFLGEVEVPLDT-WNWDSEATWLPLQPR 388
Cdd:cd08675  81 RVELWHASMVSGDDFLGEVRIPLQGlQQAGSHQAWYFLQPR 121
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 268-387 1.27e-19

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 84.62  E-value: 1.27e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAA--ARRRRSDPYVKSYLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQQADLPG 345
Cdd:cd08390   1 GRLWFSVQYDLEEEQLTVSLIKARNLPPrtKDVAHCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQVSFKELQR 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 71043698 346 RVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEAT-WLPLQP 387
Cdd:cd08390  81 RTLRLSVYDVDRFSRHCIIGHVLFPLKDLDLVKGGVvWRDLEP 123
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 267-371 7.22e-19

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 82.72  E-value: 7.22e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAA-ARRRRSDPYVKSYLLP--DKQNKRKTSVKKRNLNPIFNETLR-HSVQQAD 342
Cdd:cd04035   1 LGTLEFTLLYDPANSALHCTIIRAKGLKAmDANGLSDPYVKLNLLPgaSKATKLRTKTVHKTRNPEFNETLTyYGITEED 80

                        90       100
                ....*....|....*....|....*....
gi 71043698 343 LPGRVLSLSVWHRESLGrNIFLGEVEVPL 371
Cdd:cd04035  81 IQRKTLRLLVLDEDRFG-NDFLGETRIPL 108
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 266-387 3.56e-18

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 80.53  E-value: 3.56e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 266 VRGSVLFSLRYEPGTGELRVQVIQCQGLAAarRRRS---DPYVKSYLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQQAD 342
Cdd:cd08387   1 TRGELHFSLEYDKDMGILNVKLIQARNLQP--RDFSgtaDPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVFEVPPQE 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 71043698 343 LPGRVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEAT-WLPLQP 387
Cdd:cd08387  79 LPKRTLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLDlWRKIQS 124
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 267-390 4.94e-18

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 80.54  E-value: 4.94e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAAR-RRRSDPYVKSYLL-PDKQ-NKRKTSVKKRNLNPIFNETLRHSVQQADL 343
Cdd:cd08405   1 RGELLLSLCYNPTANRITVNIIKARNLKAMDiNGTSDPYVKVWLMyKDKRvEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 71043698 344 PGRVLSLSVWHRESLGRN-----IFLGEVEVPLDTWNWDSEATwlplQPRIP 390
Cdd:cd08405  81 RETTLIITVMDKDRLSRNdligkIYLGWKSGGLELKHWKDMLS----KPRQP 128
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 422-525 1.04e-16

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 76.18  E-value: 1.04e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 422 GELHFWIKEAQGLVPLRPGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVYDGFGPADLRQACAELSLWDHGA 501
Cdd:cd08381  13 GTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQRVLQVSVWSHDS 92

                        90       100
                ....*....|....*....|....*
gi 71043698 502 LASR-QLGGTRLSLGTGEQSRPLRG 525
Cdd:cd08381  93 LVENeFLGGVCIPLKKLDLSQETEK 117
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 267-387 1.60e-16

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 75.85  E-value: 1.60e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRRR--SDPYVKSYLLPDKQNKRKTSVKKRNLNPIFNETLR-HSVQQADL 343
Cdd:cd08388   2 LGTLFFSLRYNSEKKALLVNIIECRDLPAMDEQSgtSDPYVKLQLLPEKEHKVKTRVLRKTRNPVYDETFTfYGIPYNQL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 71043698 344 PGRVLSLSVWHRESLGRNIFLGEVEVPL---DTWNWDSEATWLPLQP 387
Cdd:cd08388  82 QDLSLHFAVLSFDRYSRDDVIGEVVCPLagaDLLNEGELLVSREIQP 128
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 267-365 3.84e-16

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 74.99  E-value: 3.84e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEpgTGELRVQVIQCQ--------GLaaarrrrSDPYVKSYLLPD--KQNKRKTSVKKRNLNPIFNETLRH 336
Cdd:cd04026   1 RGRIYLKISVK--DNKLTVEVREAKnlipmdpnGL-------SDPYVKLKLIPDpkNETKQKTKTIKKTLNPVWNETFTF 71

                        90       100
                ....*....|....*....|....*....
gi 71043698 337 SVQQADLPGRvLSLSVWHRESLGRNIFLG 365
Cdd:cd04026  72 DLKPADKDRR-LSIEVWDWDRTTRNDFMG 99
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 268-367 7.01e-16

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 74.36  E-value: 7.01e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLaaarrRR------SDPYVKSYLLPD--KQNKRKTSVKKRNLNPIFNETLRHSVQ 339
Cdd:cd08402   2 GDICFSLRYVPTAGKLTVVILEAKNL-----KKmdvgglSDPYVKIHLMQNgkRLKKKKTTIKKRTLNPYYNESFSFEVP 76

                        90       100
                ....*....|....*....|....*...
gi 71043698 340 QADLPGRVLSLSVWHRESLGRNIFLGEV 367
Cdd:cd08402  77 FEQIQKVHLIVTVLDYDRIGKNDPIGKV 104
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 399-514 6.79e-15

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 71.16  E-value: 6.79e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYIPAGSEgggqppsgeLHFWIKEAQGLVPLRPGSL-DTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTM 477
Cdd:cd04035   1 LGTLEFTLLYDPANSA---------LHCTIIRAKGLKAMDANGLsDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETL 71

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 71043698 478 VYDGFGPADLRQACAELSLWDHGALASRQLGGTRLSL 514
Cdd:cd04035  72 TYYGITEEDIQRKTLRLLVLDEDRFGNDFLGETRIPL 108
C2 pfam00168
C2 domain;
422-525 1.06e-14

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 70.04  E-value: 1.06e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698   422 GELHFWIKEAQGLVPL-RPGSLDTYIQCSVLpddSRASRQRTRVVRRSLSPVFNHTMVYDGFgpaDLRQACAELSLWDHG 500
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKdGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVP---DPENAVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*.
gi 71043698   501 ALASRQ-LGGTRLSLGTGEQSRPLRG 525
Cdd:pfam00168  75 RFGRDDfIGEVRIPLSELDSGEGLDG 100
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 268-369 2.41e-14

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 69.84  E-value: 2.41e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAAAR-RRRSDPYVKSYLLPD--KQNKRKTSVKKRNLNPIFNETLRHSVQQADLP 344
Cdd:cd08403   1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDiTGFSDPYVKVSLMCEgrRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80

                        90       100
                ....*....|....*....|....*
gi 71043698 345 GRVLSLSVWHRESLGRNIFLGEVEV 369
Cdd:cd08403  81 NVSLIIAVVDYDRVGHNELIGVCRV 105
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 267-381 4.14e-14

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 69.38  E-value: 4.14e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRR-RSDPYVKSYLLPDKQN--KRKTSVKKRNLNPIFNETLRHSVQQADL 343
Cdd:cd08404   1 RGELLLSLCYQPTTNRLTVVVLKARHLPKMDVSgLADPYVKVNLYYGKKRisKKKTHVKKCTLNPVFNESFVFDIPSEEL 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 71043698 344 PGRVLSLSVWHRESLGRNIFLGEVEVpldtwNWDSEAT 381
Cdd:cd08404  81 EDISVEFLVLDSDRVTKNEVIGRLVL-----GPKASGS 113
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 283-407 1.56e-13

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 68.19  E-value: 1.56e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAaRRRRSDPYVKSYLL--PDKQNKRKTSVKKRNLNPIFNET--------LRHSVQQADLPG-----RV 347
Cdd:cd04010   2 LSVRVIECSDLAL-KNGTCDPYASVTLIysNKKQDTKRTKVKKKTNNPQFDEAfyfdvtidSSPEKKQFEMPEedaekLE 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71043698 348 LSLSVWHRESLGRNIFLGEVEVPLD--TWNWDSEATWLPLQPR--IPTSPDELPSR--GLLSLSLK 407
Cdd:cd04010  81 LRVDLWHASMGGGDVFLGEVRIPLRglDLQAGSHQAWYFLQPReeKSTPPGTRSSKdnSLGSLRLK 146
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 267-372 2.87e-13

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 66.88  E-value: 2.87e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRR-RSDPYVKSYLLPD----KQNKRKTSVKKRNLNPIFNETLRHSV--Q 339
Cdd:cd04009   2 YGVLTVKAYYRASEQSLRVEILNARNLLPLDSNgSSDPFVKVELLPRhlfpDVPTPKTQVKKKTLFPLFDESFEFNVppE 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 71043698 340 QADLPGRVLSLSVWHRESLGRNIFLGEVEVPLD 372
Cdd:cd04009  82 QCSVEGALLLFTVKDYDLLGSNDFEGEAFLPLN 114
C2B_Synaptotagmin-12 cd08406
C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking ...
 268-367 1.99e-12

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176051 [Multi-domain]  Cd Length: 136  Bit Score: 64.43  E-value: 1.99e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAAARRR-RSDPYVKSYLLPD--KQNKRKTSVKKRNLNPIFNETLRHSVQQADLP 344
Cdd:cd08406   2 GEILLSLSYLPTAERLTVVVVKARNLVWDNGKtTADPFVKVYLLQDgrKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                        90       100
                ....*....|....*....|...
gi 71043698 345 GRVLSLSVWHRESLGRNIFLGEV 367
Cdd:cd08406  82 DLSLRVTVAESTEDGKTPNVGHV 104
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 399-518 3.81e-12

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 63.43  E-value: 3.81e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYIpagsegggqppSGELHFWIKEAQGLVPLRPGSL-DTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTM 477
Cdd:cd04026   1 RGRIYLKISVK-----------DNKLTVEVREAKNLIPMDPNGLsDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETF 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 71043698 478 VYDgFGPADL-RQACAELSLWDhgaLASRQ--LGGtrLSLGTGE 518
Cdd:cd04026  70 TFD-LKPADKdRRLSIEVWDWD---RTTRNdfMGS--LSFGVSE 107
C2A_Synaptotagmin-14_16 cd08389
C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 268-387 7.66e-12

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176035 [Multi-domain]  Cd Length: 124  Bit Score: 62.64  E-value: 7.66e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAAARRRRSDPY-VKSYLLPDKQNKRKTSVKKRNlNPIFNETLRHS-VQQADLPG 345
Cdd:cd08389   3 GDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWqVHLVLLPSKKQRAKTKVQRGP-NPVFNETFTFSrVEPEELNN 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 71043698 346 RVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSE-ATWLPLQP 387
Cdd:cd08389  82 MALRFRLYGVERMRKERLIGEKVVPLSQLNLEGEtTVWLTLEP 124
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 431-498 7.62e-11

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 59.57  E-value: 7.62e-11
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71043698 431 AQGLVPLRPGSL-DTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVYDGFGPADLRQACAELSLWD 498
Cdd:cd04031  25 ARDLPPRDDGSLrNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRETLKERTLEVTVWD 93
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 268-367 9.44e-11

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 59.90  E-value: 9.44e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQC-QGLAAARRRRSDPYVKSYLLPDKQ--NKRKTSVKKRNLNPIFNETLRHSVQQADLP 344
Cdd:cd08410   1 GELLLSLNYLPSAGRLNVDIIRAkQLLQTDMSQGSDPFVKIQLVHGLKliKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80

                        90       100
                ....*....|....*....|...
gi 71043698 345 GRVLSLSVWHRESLGRNIFLGEV 367
Cdd:cd08410  81 NVSLVFTVYGHNVKSSNDFIGRI 103
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 283-371 4.44e-10

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 57.19  E-value: 4.44e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAARRR-RSDPYVKSYLlpdkQNKR--KTSVKKRNLNPIFNETLrhSVQQADLPGRVLSLSVWHRESLG 359
Cdd:cd04040   1 LTVDVISAENLPSADRNgKSDPFVKFYL----NGEKvfKTKTIKKTLNPVWNESF--EVPVPSRVRAVLKVEVYDWDRGG 74

                        90
                ....*....|..
gi 71043698 360 RNIFLGEVEVPL 371
Cdd:cd04040  75 KDDLLGSAYIDL 86
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 404-521 9.08e-10

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 56.97  E-value: 9.08e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 404 LSLKYIPAgsegggqppSGELHFWIKEAQGLVPL-RPGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVYDgF 482
Cdd:cd08384   4 VSLMYNTQ---------RRGLIVGIIRCVNLAAMdANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD-I 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 71043698 483 GPADLRQACAELSLWDHGALASRQ-LGGTRLSLGT-GEQSR 521
Cdd:cd08384  74 KHSDLAKKTLEITVWDKDIGKSNDyIGGLQLGINAkGERLR 114
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 281-371 4.57e-09

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 55.03  E-value: 4.57e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 281 GELRVQVIQCQGLAAARRRRSDPYVksyLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQQadlPGRVLSLSVWHRESLGR 360
Cdd:cd04038   2 GLLKVRVVRGTNLAVRDFTSSDPYV---VLTLGNQKVKTRVIKKNLNPVWNEELTLSVPN---PMAPLKLEVFDKDTFSK 75

                        90
                ....*....|.
gi 71043698 361 NIFLGEVEVPL 371
Cdd:cd04038  76 DDSMGEAEIDL 86
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 424-514 5.56e-09

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 53.65  E-value: 5.56e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698    424 LHFWIKEAQGLVPL-RPGSLDTYIQCSVLPDDSRasRQRTRVVRRSLSPVFNHTMVYDGFGPADlrqACAELSLWDHGAL 502
Cdd:smart00239   2 LTVKIISARNLPPKdKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDKDRF 76

                           90
                   ....*....|...
gi 71043698    503 -ASRQLGGTRLSL 514
Cdd:smart00239  77 gRDDFIGQVTIPL 89
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
 267-354 6.77e-09

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176054 [Multi-domain]  Cd Length: 137  Bit Score: 54.26  E-value: 6.77e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 267 RGSVLFSLRYEPGTGELRVQVIQCQGLAAARRRRSDPYVK-SYLLPDKQNKRK-TSVKKRNLNPIFNETLRHSVQQADLP 344
Cdd:cd08409   1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLDHAHTSVYVKvSLMIHNKVVKTKkTEVVDGAASPSFNESFSFKVTSRQLD 80

                        90
                ....*....|
gi 71043698 345 GRVLSLSVWH 354
Cdd:cd08409  81 TASLSLSVMQ 90
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 283-388 6.97e-09

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 54.27  E-value: 6.97e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAaarrRR-----SDPYVKSYLlpDKQnKRKTSVKKRNLNPIFNETLRHSVQQ-ADLPGRVLSLSVWHRE 356
Cdd:cd04022   2 LVVEVVDAQDLM----PKdgqgsSSAYVELDF--DGQ-KKRTRTKPKDLNPVWNEKLVFNVSDpSRLSNLVLEVYVYNDR 74

                        90       100       110
                ....*....|....*....|....*....|....*
gi 71043698 357 SLGR-NIFLGEVEVPLDTWNWDSEAT--WLPLQPR 388
Cdd:cd04022  75 RSGRrRSFLGRVRISGTSFVPPSEAVvqRYPLEKR 109
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 262-372 1.16e-08

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 53.93  E-value: 1.16e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 262 GPVQVRG-SVLFS-------LRYEPGTGELRVQVIQCQGLAAARRRR--SDPYVKSYLLPDKQ--NKRKTSVKKRNLNPI 329
Cdd:cd04028   2 GPGQLVGrQVLASpsmgdiqLGLYDKKGQLEVEVIRARGLVQKPGSKvlPAPYVKVYLLEGKKciAKKKTKIARKTLDPL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 71043698 330 FNETLRHSVQQAdlpGRVLSLSVW-HRESLGRNIFLGEVEVPLD 372
Cdd:cd04028  82 YQQQLVFDVSPT---GKTLQVIVWgDYGRMDKKVFMGVAQILLD 122
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 283-372 2.98e-08

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 52.16  E-value: 2.98e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGL---AAARRRRSDPYVKSYLL---PDKQNKRKTSVKKRN-LNPIFNETLRHSVQQADLPgrVLSLSVWHr 355
Cdd:cd00275   4 LTIKIISGQQLpkpKGDKGSIVDPYVEVEIHglpADDSAKFKTKVVKNNgFNPVWNETFEFDVTVPELA--FLRFVVYD- 80

                        90
                ....*....|....*..
gi 71043698 356 ESLGRNIFLGEVEVPLD 372
Cdd:cd00275  81 EDSGDDDFLGQACLPLD 97
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
 280-364 4.60e-08

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 51.69  E-value: 4.60e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 280 TGELRVQVIQCQGLAAARRRRSDPYVKSYLLPDKQNKR--KTSVKKRNLNPIFNETLRHSVQQADLPGRVLsLSVWHRES 357
Cdd:cd08685  11 NRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFrqKTSTVPDSANPLFHETFSFDVNERDYQKRLL-VTVWNKLS 89


                ....*..
gi 71043698 358 LGRNIFL 364
Cdd:cd08685  90 KSRDSGL 96
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 283-409 5.33e-08

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 51.58  E-value: 5.33e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAaarrRR-----SDPYVKSYLLPDKQNKRKTSV----KKRNLNPIFNETLRHSVQQADlpGRVLsLSVW 353
Cdd:cd04033   2 LRVKVLAGIDLA----KKdifgaSDPYVKISLYDPDGNGEIDSVqtktIKKTLNPKWNEEFFFRVNPRE--HRLL-FEVF 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71043698 354 HRESLGRNIFLGEVEVPL-------DTWNWDSEATWLPLQPRIPTSpdelPSRGLLSLSLKYI 409
Cdd:cd04033  75 DENRLTRDDFLGQVEVPLnnlptetPGNERRYTFKDYLLRPRSSKS----RVKGHLRLYMAYL 133
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 428-505 5.61e-08

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 51.50  E-value: 5.61e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71043698 428 IKEAQGLVPLRP-GSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQACAELSLWDHGALASR 505
Cdd:cd04030  22 VHKCRNLPPCDSsDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEELKRRTLDVAVKNSKSFLSR 99
C2_PKC_epsilon cd04014
C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...
 280-387 1.05e-07

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175981 [Multi-domain]  Cd Length: 132  Bit Score: 50.73  E-value: 1.05e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 280 TGELRVQVIQCQGL---AAARRRRS--------DPYVKSYLlpDKQNKRKTSVKKRNLNPIFNETLRHSVQQadlpGRVL 348
Cdd:cd04014   3 TGTLKIKICEAVDLkptDWSTRHAVpkkgsqllDPYVSIDV--DDTHIGKTSTKPKTNSPVWNEEFTTEVHN----GRNL 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 71043698 349 SLSVWHRESLGRNIFLGEVEVPL-DTWNWDSEAT--WLPLQP 387
Cdd:cd04014  77 ELTVFHDAAIGPDDFVANCTISFeDLIQRGSGSFdlWVDLEP 118
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 424-521 1.08e-07

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 50.14  E-value: 1.08e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 424 LHFWIKEAQGLVPL-RPGSLDTYIQCSVLPDdsraSRQRTRVVRRSLSPVFNHTMVydgFGPADLRQACAELSLWDHGAL 502
Cdd:cd00030   1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFE---FPVLDPESDTLTVEVWDKDRF 73

                        90       100
                ....*....|....*....|
gi 71043698 503 ASRQ-LGGTRLSLGTGEQSR 521
Cdd:cd00030  74 SKDDfLGEVEIPLSELLDSG 93
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 282-371 1.22e-07

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 50.31  E-value: 1.22e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 282 ELRVQVIQCQGLAAARR-RRSDPYVKSYLlpDKQNKRKTSV-KKRNLNPIFNETLRHSV--QQADLPGRVLSLSVWHRES 357
Cdd:cd04051   1 TLEITIISAEDLKNVNLfGKMKVYAVVWI--DPSHKQSTPVdRDGGTNPTWNETLRFPLdeRLLQQGRLALTIEVYCERP 78

                        90
                ....*....|....
gi 71043698 358 LGRNIFLGEVEVPL 371
Cdd:cd04051  79 SLGDKLIGEVRVPL 92
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 401-518 1.26e-07

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 50.66  E-value: 1.26e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 401 LLSLSlkYipagsegggQPPSGELHFWIKEAQGLVPL-RPGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVY 479
Cdd:cd00276   4 LLSLS--Y---------LPTAERLTVVVLKARNLPPSdGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSF 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 71043698 480 DgFGPADLRQACAELSLWDHGALAS-RQLGGTRLSLGTGE 518
Cdd:cd00276  73 D-VPAEQLEEVSLVITVVDKDSVGRnEVIGQVVLGPDSGG 111
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 284-366 1.29e-07

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 50.24  E-value: 1.29e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 284 RVQVIQCQGLAAARRR-RSDPYVKSYLLPDKQNKRKTSVKKrNLNPIFNETLRHSvqqADLPG-RVLSLSVWHRESLGRN 361
Cdd:cd04037   3 RVYVVRARNLQPKDPNgKSDPYLKIKLGKKKINDRDNYIPN-TLNPVFGKMFELE---ATLPGnSILKISVMDYDLLGSD 78


                ....*
gi 71043698 362 IFLGE 366
Cdd:cd04037  79 DLIGE 83
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 281-386 1.33e-07

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 50.37  E-value: 1.33e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 281 GELRVQVIQCQGLAAARRR-------RSDPYVKSYLLPdkqNKRKTSVKKRNLNPIFNETLRHSVQQAdlPGRVLSLSVW 353
Cdd:cd08391   1 GVLRIHVIEAQDLVAKDKFvgglvkgKSDPYVIVRVGA---QTFKSKVIKENLNPKWNEVYEAVVDEV--PGQELEIELF 75

                        90       100       110
                ....*....|....*....|....*....|....
gi 71043698 354 HrESLGRNIFLGEVEVPLDTWNWDSEA-TWLPLQ 386
Cdd:cd08391  76 D-EDPDKDDFLGRLSIDLGSVEKKGFIdEWLPLE 108
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 400-502 1.37e-07

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 50.33  E-value: 1.37e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 400 GLLSLSLKYipagsegggQPPSGELHFWIKEAQGLVPLRPG--SLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTM 477
Cdd:cd08521   1 GEIEFSLSY---------NYKTGSLEVHIKECRNLAYADEKkkRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETL 71

                        90       100
                ....*....|....*....|....*
gi 71043698 478 VYDgFGPADLRQACAELSLWDHGAL 502
Cdd:cd08521  72 KYH-ISKSQLETRTLQLSVWHHDRF 95
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
276-373 2.41e-07

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 53.99  E-value: 2.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698  276 YEPgTGELRVQVIQCQGLAAARRR-RSDPYVKsYLLPDKQNkRKTSVKKRNLNPIFNETLRHSVQQADLpgRVLSLSVWH 354
Cdd:COG5038 1036 VEN-SGYLTIMLRSGENLPSSDENgYSDPFVK-LFLNEKSV-YKTKVVKKTLNPVWNEEFTIEVLNRVK--DVLTINVND 1110

                         90
                 ....*....|....*....
gi 71043698  355 RESLGRNIFLGEVEVPLDT 373
Cdd:COG5038 1111 WDSGEKNDLLGTAEIDLSK 1129
C2B_Synaptotagmin-14_16 cd08408
C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 270-382 3.01e-07

C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176053 [Multi-domain]  Cd Length: 138  Bit Score: 49.67  E-value: 3.01e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 270 VLFSLRYEPGTGELRVQVIQCQGLA-AARRRRSDPYVKSYLL-PDKQ--NKRKTSVKKRNLNPIFNETLRHSVQQADLPG 345
Cdd:cd08408   4 LLLGLEYNALTGRLSVEVIKGSNFKnLAMNKAPDTYVKLTLLnSDGQeiSKSKTSIRRGQPDPEFKETFVFQVALFQLSE 83

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 71043698 346 RVLSLSVWHRESLGRNIFLGEVEVPLDTWNWDSEATW 382
Cdd:cd08408  84 VTLMFSVYNKRKMKRKEMIGWFSLGLNSSGEEEEEHW 120
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 283-407 5.82e-07

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 48.64  E-value: 5.82e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAARRR-RSDPYVKSYLlpdKQNKRKTSVKKRNLNPIFNETLRHSVQQAdlPGRVLSLSVWHRESLGRN 361
Cdd:cd04025   2 LRCHVLEARDLAPKDRNgTSDPFVRVFY---NGQTLETSVVKKSCYPRWNEVFEFELMEG--ADSPLSVEVWDWDLVSKN 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 71043698 362 IFLGEVEVPLDTWNWD-SEATWLPLQPRIPTSPDELPSRGLLSLSLK 407
Cdd:cd04025  77 DFLGKVVFSIQTLQQAkQEEGWFRLLPDPRAEEESGGNLGSLRLKVR 123
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 298-419 8.35e-07

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 48.02  E-value: 8.35e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 298 RRRSDPYVKsylLPDKQNKRKTSVKKRNLNPIFNETLRHSVQQADLPGRVLSLSVWHRESLGRNIFLGEVEVpldtwnwd 377
Cdd:cd08373  12 KGKGDRIAK---VTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDPDESLEIVVKDYEKVGRNRLIGSATV-------- 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 71043698 378 seatwlPLQPRIPTSPDEL----------PSRGLLSLSLKYI-PAGSEGGGQP 419
Cdd:cd08373  81 ------SLQDLVSEGLLEVteplldsngrPTGATISLEVSYQpPDGAVGGWAD 127
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 400-516 8.46e-07

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 48.20  E-value: 8.46e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 400 GLLSLSLKYipagsegggQPPSGELHFWIKEAQGLV---PLRPGSlDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHT 476
Cdd:cd04029   2 GEILFSLSY---------DYKTQSLNVHVKECRNLAygdEAKKRS-NPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNET 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 71043698 477 MVYDgFGPADLRQACAELSLWDHGALASRQ-LGGTRLSLGT 516
Cdd:cd04029  72 LKYS-ISHSQLETRTLQLSVWHYDRFGRNTfLGEVEIPLDS 111
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 277-385 8.47e-07

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 48.91  E-value: 8.47e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 277 EPGTGELRVQVIQCQGLAAARRRR-SDPY---------------------------VKSYLLPDKQNKRkTSVKKRNLNP 328
Cdd:cd08676  24 EPPIFVLKVTVIEAKGLLAKDVNGfSDPYcmlgivpasrernsekskkrkshrkkaVLKDTVPAKSIKV-TEVKPQTLNP 102

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 71043698 329 IFNETLRHSVQqaDLPGRVLSLSVWHREslgrNIFLGEVEVPLDTWNWDSEATWLPL 385
Cdd:cd08676 103 VWNETFRFEVE--DVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSCGLDSWFKL 153
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 301-372 1.42e-06

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 47.20  E-value: 1.42e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71043698 301 SDPYVKsyLLPDKQNKRKTSVKKRNLNPIFNETLR---HSvqqadlPGRVLSLSVWHRESLGRNIFLGEVEVPLD 372
Cdd:cd04045  22 IDPYVR--VLVNGIVKGRTVTISNTLNPVWDEVLYvpvTS------PNQKITLEVMDYEKVGKDRSLGSVEINVS 88
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 281-386 1.67e-06

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 47.42  E-value: 1.67e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 281 GELRVQVIQCQGLAAARRRR---SDPYVksyLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQQAdlPGRVLSLSVWHRES 357
Cdd:cd04024   1 GVLRVHVVEAKDLAAKDRSGkgkSDPYA---ILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSA--QNQLLKLILWDKDR 75

                        90       100       110
                ....*....|....*....|....*....|...
gi 71043698 358 LGRNIFLGEVEVPLDTWNWDSEA----TWLPLQ 386
Cdd:cd04024  76 FAGKDYLGEFDIALEEVFADGKTgqsdKWITLK 108
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 428-487 1.73e-06

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 47.35  E-value: 1.73e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71043698 428 IKEAQGLVPLRP--GSLDTYIQCSVLPDdsRASRQRTRVVRRSLSPVFNHTMVYDGFGPADL 487
Cdd:cd08388  22 IIECRDLPAMDEqsGTSDPYVKLQLLPE--KEHKVKTRVLRKTRNPVYDETFTFYGIPYNQL 81
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 424-482 1.87e-06

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 46.94  E-value: 1.87e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71043698 424 LHFWIKEAQGLvPLR--PGSLDTYIQCSVLPDdsRASRQRTRVVRRSLSPVFNHTMVYDGF 482
Cdd:cd08386  18 LTLKILKAVEL-PAKdfSGTSDPFVKIYLLPD--KKHKLETKVKRKNLNPHWNETFLFEGF 75
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 284-373 5.10e-06

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 45.64  E-value: 5.10e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 284 RVQVIQCQGLAAARrrrSDPYVKSYLLPDKQnkrKTSVKKRNLNPIFNETLRHSVQ--QADLPGRVLSLSVWHRESLGRN 361
Cdd:cd04011   7 RVRVIEARQLVGGN---IDPVVKVEVGGQKK---YTSVKKGTNCPFYNEYFFFNFHesPDELFDKIIKISVYDSRSLRSD 80

                        90
                ....*....|..
gi 71043698 362 IFLGEVEVPLDT 373
Cdd:cd04011  81 TLIGSFKLDVGT 92
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 399-516 7.09e-06

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 45.87  E-value: 7.09e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYipagsegggQPPSGELHFWIKEAQGLVPLR-PGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTM 477
Cdd:cd08405   1 RGELLLSLCY---------NPTANRITVNIIKARNLKAMDiNGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESF 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 71043698 478 VYDgfGPAD-LRQACAELSLWDHGALASRQLGGtRLSLGT 516
Cdd:cd08405  72 IFN--IPLErLRETTLIITVMDKDRLSRNDLIG-KIYLGW 108
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 399-515 1.17e-05

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 45.11  E-value: 1.17e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYipagsegggQPPSGELHFWIKEAQGLvPLR--PGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHT 476
Cdd:cd08404   1 RGELLLSLCY---------QPTTNRLTVVVLKARHL-PKMdvSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNES 70

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 71043698 477 MVYDgfGPAD-LRQACAELSLWDHGALASRQLGGtRLSLG 515
Cdd:cd08404  71 FVFD--IPSEeLEDISVEFLVLDSDRVTKNEVIG-RLVLG 107
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 284-385 1.39e-05

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 44.75  E-value: 1.39e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 284 RVQVIQCQGL-AAARRRRSDPYVKSYLLPDKQnkrKTSVKKRNLNPIFNE--TLRHSVQQADLPGR-VLSLSVWHRESLG 359
Cdd:cd08682   2 QVTVLQARGLlCKGKSGTNDAYVIIQLGKEKY---STSVKEKTTSPVWKEecSFELPGLLSGNGNRaTLQLTVMHRNLLG 78

                        90       100
                ....*....|....*....|....*....
gi 71043698 360 RNIFLGEVEVPLDTWNWDSE---ATWLPL 385
Cdd:cd08682  79 LDKFLGQVSIPLNDLDEDKGrrrTRWFKL 107
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
 399-515 2.88e-05

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176054 [Multi-domain]  Cd Length: 137  Bit Score: 43.86  E-value: 2.88e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYIPAgsegggqppSGELHFWIKEAQGLVPLRPGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd08409   1 LGDIQISLTYNPT---------LNRLTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFS 71

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 71043698 479 YdGFGPADLRQACAELSLWDHGAL-ASRQLGgtRLSLG 515
Cdd:cd08409  72 F-KVTSRQLDTASLSLSVMQSGGVrKSKLLG--RVVLG 106
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
 428-480 5.90e-05

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 42.83  E-value: 5.90e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 71043698 428 IKEAQGLVPLRPGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVYD 480
Cdd:cd08685  18 VLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFD 70
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 398-514 6.62e-05

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 42.78  E-value: 6.62e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 398 SRGLLSLSLKYipagsegggQPPSGELHFWIKEAQGLVPLR-PGSLDTYIQCSVLPDDSRAsrQRTRVVRRSLSPVFNHT 476
Cdd:cd08387   1 TRGELHFSLEY---------DKDMGILNVKLIQARNLQPRDfSGTADPYCKVRLLPDRSNT--KQSKIHKKTLNPEFDES 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 71043698 477 MVYdGFGPADLRQACAELSLWDHGALaSRQ--LGGTRLSL 514
Cdd:cd08387  70 FVF-EVPPQELPKRTLEVLLYDFDQF-SRDecIGVVELPL 107
FYVE_2 pfam02318
FYVE-type zinc finger; This FYVE-type zinc finger is found at the N-terminus of effector ...
 35-90 1.01e-04

FYVE-type zinc finger; This FYVE-type zinc finger is found at the N-terminus of effector proteins including rabphilin-3A and regulating synaptic membrane exocytosis protein 2.


Pssm-ID: 426716  Cd Length: 118  Bit Score: 41.97  E-value: 1.01e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 71043698    35 SFLTEEEQEAISDVLKRDAHLRQLEEGRVSKLRASLADPWQLKILTGDWFQEARSQ 90
Cdd:pfam02318   1 SKLTDEEAEHVWEVVQRDFDLRKKEEERLGELKGKLDKESSKRELLGNQAHLGETH 56
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 400-524 1.22e-04

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 42.00  E-value: 1.22e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 400 GLLSLSLKYIPAgsegggqppSGELHFWIKEAQGLVPLRPGSL-DTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd08402   2 GDICFSLRYVPT---------AGKLTVVILEAKNLKKMDVGGLsDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFS 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 71043698 479 YDgFGPADLRQACAELSLWDHGALASRQLGGtRLSLGTGEQSRPLR 524
Cdd:cd08402  73 FE-VPFEQIQKVHLIVTVLDYDRIGKNDPIG-KVVLGCNATGAELR 116
C2A_SLP-3 cd08392
C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically ...
 445-535 1.68e-04

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176038 [Multi-domain]  Cd Length: 128  Bit Score: 41.74  E-value: 1.68e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 445 YIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQACAELSLWDHGALASRqlggtrlsLGTGEQSRPLR 524
Cdd:cd08392  40 YVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYV-VEADLLSSRQLQVSVWHSRTLKRR--------VFLGEVLIPLA 110

                        90
                ....*....|.
gi 71043698 525 GPKLGDTGSVG 535
Cdd:cd08392 111 DWDFEDTDSQR 121
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 283-387 2.09e-04

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 41.09  E-value: 2.09e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAARRRR-SDPYVKSYLlpdKQNKRKTSVKKRNLNPIFNEtlRHSVQQADLPGRVLSLSVWHRESLGRN 361
Cdd:cd08376   2 VTIVLVEGKNLPPMDDNGlSDPYVKFRL---GNEKYKSKVCSKTLNPQWLE--QFDLHLFDDQSQILEIEVWDKDTGKKD 76

                        90       100
                ....*....|....*....|....*....
gi 71043698 362 IFLGEVEVplDTWNWDSEAT---WLPLQP 387
Cdd:cd08376  77 EFIGRCEI--DLSALPREQThslELELED 103
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 283-371 2.79e-04

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 40.72  E-value: 2.79e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAARRRRSDPYVKsyLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQqadlPGRVLSLSVWHRESLGRNI 362
Cdd:cd04021   4 LQITVESAKLKSNSKSFKPDPYVE--VTVDGQPPKKTEVSKKTSNPKWNEHFTVLVT----PQSTLEFKVWSHHTLKADV 77


                ....*....
gi 71043698 363 FLGEVEVPL 371
Cdd:cd04021  78 LLGEASLDL 86
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 300-372 4.67e-04

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 39.86  E-value: 4.67e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 300 RSDPYVKSY-LLPDKQNK--RKTSVKKRNLNPIFNE-TLrhSVQQ---ADLpGRVLSLSVWHRESLGRNIFLGEVEVPLD 372
Cdd:cd04047  20 KSDPFLEISrQSEDGTWVlvYRTEVIKNTLNPVWKPfTI--PLQKlcnGDY-DRPIKIEVYDYDSSGKHDLIGEFETTLD 96
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 399-499 5.58e-04

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 39.94  E-value: 5.58e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 399 RGLLSLSLKYIPAgsegggqppSGELHFWIKEAQGLVPLR-PGSLDTYIQCSVLPDdsRASRQRTRVVRRSLSPVFNHTM 477
Cdd:cd08385   2 LGKLQFSLDYDFQ---------SNQLTVGIIQAADLPAMDmGGTSDPYVKVYLLPD--KKKKFETKVHRKTLNPVFNETF 70

                        90       100
                ....*....|....*....|..
gi 71043698 478 VYDgFGPADLRQACAELSLWDH 499
Cdd:cd08385  71 TFK-VPYSELGNKTLVFSVYDF 91
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 302-406 6.50e-04

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 39.95  E-value: 6.50e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 302 DPYVksyLLPDKQNKRKTSVKKRNLNPIFNEtlrhsvqQADL----PGRVLSLSVWHRESLGRNiFLGEVEVPLDTWNWD 377
Cdd:cd04046  25 DPYV---IIKCEGESVRSPVQKDTLSPEFDT-------QAIFyrkkPRSPIKIQVWNSNLLCDE-FLGQATLSADPNDSQ 93

                        90       100
                ....*....|....*....|....*....
gi 71043698 378 SEATwLPLQPRIPTSPDELPsrGLLSLSL 406
Cdd:cd04046  94 TLRT-LPLRKRGRDAAGEVP--GTISVKV 119
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 418-509 6.62e-04

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 39.91  E-value: 6.62e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 418 QPPSGELHFWIKEAQGLVPLRP-GSLDTYIQCSVLPDD--SRASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQ--ACA 492
Cdd:cd04009  12 RASEQSLRVEILNARNLLPLDSnGSSDPFVKVELLPRHlfPDVPTPKTQVKKKTLFPLFDESFEFN-VPPEQCSVegALL 90

                        90
                ....*....|....*..
gi 71043698 493 ELSLWDHGALASRQLGG 509
Cdd:cd04009  91 LFTVKDYDLLGSNDFEG 107
C2_Kibra cd08680
C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador ...
 270-371 6.73e-04

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176062  Cd Length: 124  Bit Score: 39.91  E-value: 6.73e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 270 VLFSLRYEPGTGELRVQVIQCQGLAA-ARRRRSDPYVKSYLLPDKQNKR---KTSVKKRNLNPIFNETLRHSVQQADLPG 345
Cdd:cd08680   3 VQIGLRYDSGDSSLVISVEQLRNLSAlSIPENSKVYVRVALLPCSSSTSclfRTKALEDQDKPVFNEVFRVPISSTKLYQ 82

                        90       100
                ....*....|....*....|....*.
gi 71043698 346 RVLSLSVWHRESLGRNIFLGEVEVPL 371
Cdd:cd08680  83 KTLQVDVCSVGPDQQEECLGGAQISL 108
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 400-509 1.03e-03

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 39.41  E-value: 1.03e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 400 GLLSLSLKYIPAgsegggqppSGELHFWIKEAQGLVPLR-PGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd08403   1 GELMFSLCYLPT---------AGRLTLTIIKARNLKAMDiTGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALV 71

                        90       100       110
                ....*....|....*....|....*....|.
gi 71043698 479 YDgFGPADLRQACAELSLWDHGALASRQLGG 509
Cdd:cd08403  72 FD-VPPENVDNVSLIIAVVDYDRVGHNELIG 101
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 283-385 1.13e-03

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 38.83  E-value: 1.13e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAARRRR--SDPYVKSYLLpdkQNKRKTSVKKRNLNPIFN-ETLRHSVQQADLPGRVLSLSVWHRESLG 359
Cdd:cd08688   1 LKVRVVAARDLPVMDRSSdlTDAFVEVKFG---STTYKTDVVKKSLNPVWNsEWFRFEVDDEELQDEPLQIRVMDHDTYS 77

                        90       100       110
                ....*....|....*....|....*....|
gi 71043698 360 RNIFLGEVEVPLDTWNWDSEAT----WLPL 385
Cdd:cd08688  78 ANDAIGKVYIDLNPLLLKDSVSqisgWFPI 107
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 283-410 1.21e-03

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 38.80  E-value: 1.21e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAarRRR---SDPYVKSyllpdKQNKR---KTSVKKRNLNPIFNETLRHSVQQADLPgrvLSLSVWHRE 356
Cdd:cd04042   2 LDIHLKEGRNLAA--RDRggtSDPYVKF-----KYGGKtvyKSKTIYKNLNPVWDEKFTLPIEDVTQP---LYIKVFDYD 71

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 71043698 357 SLGRNIFLGEVEVPLDTWNWDsEATWLPLQPRIPTSPDELpsrGLLSLSLKYIP 410
Cdd:cd04042  72 RGLTDDFMGSAFVDLSTLELN-KPTEVKLKLEDPNSDEDL---GYISLVVTLTP 121
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 279-371 1.49e-03

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 38.90  E-value: 1.49e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 279 GTGELRVQVIQCQGLAAARRR-RSDPYVKSYLLPDKQnkrKTSVKKRNLNPIFNETLRHSVQqaDLPGRVLSLSVWHRES 357
Cdd:cd08375  13 GIGRLMVVIVEGRDLKPCNSNgKSDPYCEVSMGSQEH---KTKVVSDTLNPKWNSSMQFFVK--DLEQDVLCITVFDRDF 87

                        90
                ....*....|....
gi 71043698 358 LGRNIFLGEVEVPL 371
Cdd:cd08375  88 FSPDDFLGRTEIRV 101
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
299-373 2.05e-03

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 41.28  E-value: 2.05e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71043698  299 RRSDPYVkSYLLPDKQnKRKTSVKKRNLNPIFNETLRHSVQQADLPgrvLSLSVWHRESLGRNIFLGEVEVPLDT 373
Cdd:COG5038  457 GTVDPYI-TVTFSDRV-IGKTRVKKNTLNPVWNETFYILLNSFTDP---LNLSLYDFNSFKSDKVVGSTQLDLAL 526
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 282-407 2.34e-03

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 38.06  E-value: 2.34e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 282 ELRVQVIQCQGLAaaRR---RRSDPYVKsyLLPDKQNKRKTSVKKRNLNPIFNETLRHSVQQADlpgrVLSLSVW----- 353
Cdd:cd08382   1 KVRLTVLCADGLA--KRdlfRLPDPFAV--ITVDGGQTHSTDVAKKTLDPKWNEHFDLTVGPSS----IITIQVFdqkkf 72

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 71043698 354 HRESLGrniFLGEVEVPLDTWN--WDSEATWLPLqpRIPTSPDELPSRGLLSLSLK 407
Cdd:cd08382  73 KKKDQG---FLGCVRIRANAVLplKDTGYQRLDL--RKLKKSDNLSVRGKIVVSLS 123
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 424-535 2.51e-03

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 38.51  E-value: 2.51e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 424 LHFWIKEAQGLVPLRPGSLDTYIQCSVLpDDSRASRQRTRVVRRSLSPVFNHTMVYDGFGPA------------DLRQAC 491
Cdd:cd08675   1 LSVRVLECRDLALKSNGTCDPFARVTLN-YSSKTDTKRTKVKKKTNNPRFDEAFYFELTIGFsyekksfkveeeDLEKSE 79

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 71043698 492 AELSLWdHGALASRQ--LGGTRLSLGTGEQS-----------RPLRGPKLGDTGSVG 535
Cdd:cd08675  80 LRVELW-HASMVSGDdfLGEVRIPLQGLQQAgshqawyflqpREAPGTRSSNDGSLG 135
C2B_Synaptotagmin-13 cd08407
C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking ...
 268-373 3.30e-03

C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176052 [Multi-domain]  Cd Length: 138  Bit Score: 38.04  E-value: 3.30e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 268 GSVLFSLRYEPGTGELRVQVIQCQGLAAARRRR---SDPYVKSYLLPD--KQNKRKTSVKKRNLNPIFNETLRHSVQQAD 342
Cdd:cd08407   2 GEVLLSISYLPAANRLLVVVIKAKNLHSDQLKLllgIDVSVKVTLKHQnaKLKKKQTKRAKHKINPVWNEMIMFELPSEL 81

                        90       100       110
                ....*....|....*....|....*....|.
gi 71043698 343 LPGRVLSLSVWHRESLGRNIFLGEVEVPLDT 373
Cdd:cd08407  82 LAASSVELEVLNQDSPGQSLPLGRCSLGLHT 112
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 283-388 5.16e-03

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 37.35  E-value: 5.16e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 283 LRVQVIQCQGLAAARRRrSDPYVkSYLLPDKQNKRKTSVKKRNLNPIFNETLRHsvqqaDLPGR--VLSLSVWHRESLGR 360
Cdd:cd08678   1 LLVKNIKANGLSEAAGS-SNPYC-VLEMDEPPQKYQSSTQKNTSNPFWDEHFLF-----ELSPNskELLFEVYDNGKKSD 73

                        90       100
                ....*....|....*....|....*....
gi 71043698 361 NIFLGEVEVPLDTWNWDSEATW-LPLQPR 388
Cdd:cd08678  74 SKFLGLAIVPFDELRKNPSGRQiFPLQGR 102
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 424-486 6.10e-03

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 37.38  E-value: 6.10e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71043698 424 LHFWIKEAQGLvPLRPGSLDTYIQCSVLPDDSRASRQRTRVVRRSLSPVFNHTMVYDGFGPAD 486
Cdd:cd04010   2 LSVRVIECSDL-ALKNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDSS 63
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 281-371 6.27e-03

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 36.89  E-value: 6.27e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043698 281 GELRVQVIQCQGLAAARRR-RSDPYVKSYLLPDKQnkrKTSVKKRNLNPIFNETLRHSVQqaDLPGrVLSLSVWHRESLG 359
Cdd:cd08377   1 GFLQVKVIRASGLAAADIGgKSDPFCVLELVNARL---QTHTIYKTLNPEWNKIFTFPIK--DIHD-VLEVTVYDEDKDK 74

                        90
                ....*....|..
gi 71043698 360 RNIFLGEVEVPL 371
Cdd:cd08377  75 KPEFLGKVAIPL 86
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH