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+.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  840 IFGRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNGLTEP 919
Cdd:cd04031    1 ITGRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 25150782  920 MLLQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDGEHSLMCI 963
Cdd:cd04031   81 TLKERTLEVTVWDYDRDGENDFLGEVVIDLADALLDDEPHWYPL 124

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782     11 SHLSAEEREIIENVFKRQKDEEAKEtqiSQKASEELSELDKQITERKETSKKLVGTQDDAI-CqiCQKTKFADGIGHKCF 89
Cdd:pfam02318    1 SKLTDEEAEHVWEVVQRDFDLRKKE---EERLGELKGKLDKESSKRELLGNQAHLGETHCIrC--LQPFGFLVNSKRQCL 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 25150782     90 YCQLRSCARCGgrAQSKNKAIWACSLCQKRQQILAKTGKWF 130
Cdd:pfam02318   76 DCRKNVCKKCG--VYNKPEQGWLCDPCSEARELKKGSLEWF 114

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+.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  840 IFGRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNGLTEP 919
Cdd:cd04031    1 ITGRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 25150782  920 MLLQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDGEHSLMCI 963
Cdd:cd04031   81 TLKERTLEVTVWDYDRDGENDFLGEVVIDLADALLDDEPHWYPL 124

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782     856 QLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRSEKsrRQSAVIAETLMPVWDEVFYYNgLTEPMLlqRVLELTVWDYDK 935
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFE-VPPPEL--AELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|...
gi 25150782     936 FGTNSFLGETLIDLASVPLDGEH 958
Cdd:smart00239   76 FGRDDFIGQVTIPLSDLLLGGRH 98

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782   1434 VEIIKAKNLVVKPGVKvCPAPYVKVYLMEGKQciaKAKTNAATKTTSPLFQQHLIFN-DSPKKKTLQVTVLgDYGRMERK 1512
Cdd:pfam00168    5 VTVIEAKNLPPKDGNG-TSDPYVKVYLLDGKQ---KKKTKVVKNTLNPVWNETFTFSvPDPENAVLEIEVY-DYDRFGRD 79

                           90       100
                   ....*....|....*....|....*.
gi 25150782   1513 VFMGISQIRLEDLELGsQPLIGWYKL 1538
Cdd:pfam00168   80 DFIGEVRIPLSELDSG-EGLDGWYPL 104

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782    1434 VEIIKAKNLVVKPGVKVCPaPYVKVYLmeGKQCIAKAKTNAATKTTSPLFQQHLIFN-DSPKKKTLQVTVLgDYGRMERK 1512
Cdd:smart00239    4 VKIISARNLPPKDKGGKSD-PYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY-DKDRFGRD 79

                            90
                    ....*....|....*.
gi 25150782    1513 VFMGISQIRLEDLELG 1528
Cdd:smart00239   80 DFIGQVTIPLSDLLLG 95

PDZ domain; PDZ domains are found in diverse signaling proteins.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782    655 NGDLGLKIVGGRrtDTGKLGAFITQVKPGSVADTIGrLRPGDEVVEWNGQSLQNATYEQV 714
Cdd:pfam00595    9 RGGLGFSLKGGS--DQGDPGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEA 65

FYVE-related domain found in rabphilin-3A and similar proteins; Rabphilin-3A, also termed exophilin-1, is an effector protein that binds to the GTP-bound form of Rab3A, which is one of the most abundant Rab proteins in neurons and predominantly localized to synaptic vesicles. Rabphilin-3A is homologous to alpha-Rab3-interacting molecules (RIMs). It is a multi-domain protein containing an N-terminal Rab3A effector domain, a proline-rich linker region, and two tandem C2 domains. The effector domain binds specifically to the activated GTP-bound state of Rab3A and harbors a conserved FYVE zinc finger. The C2 domains are responsible for the binding of phosphatidylinositol-4,5-bisphosphate (PIP2) , a key player in the neurotransmitter release process. Thus, Rabphilin-3A has also been implicated in vesicle trafficking. The FYVE domain of Rabphilin-3A resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 25150782   88 CFYCQLRSCARCGGRAQSKNKAIWACSLCQKRQQILAKTGKWF------QPEEQPQP 138
Cdd:cd15762   24 CEDCKKNVCTKCGVQTNNRPHSVWLCKICSEQREVWKRSGAWFfkglpkQVLPQPMP 80

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+.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  840 IFGRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNGLTEP 919
Cdd:cd04031    1 ITGRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 25150782  920 MLLQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDGEHSLMCI 963
Cdd:cd04031   81 TLKERTLEVTVWDYDRDGENDFLGEVVIDLADALLDDEPHWYPL 124

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  842 GRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPR-NPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNgLTEPM 920
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKKKRsNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYH-ISKSQ 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 25150782  921 LLQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDGEHSLMCIL 964
Cdd:cd08521   80 LETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  842 GRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRseKSRRQSAVIAETLMPVWDEVFYYNGLTEPML 921
Cdd:cd08386    3 GRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDK--KHKLETKVKRKNLNPHWNETFLFEGFPYEKL 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 25150782  922 LQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDGE 957
Cdd:cd08386   81 QQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEE 116

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  842 GRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPR-NPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNgLTEPM 920
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPKKQRsDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYK-VEREE 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 25150782  921 LLQRVLELTVWDYDKFGTNSFLGETLIDLAS 951
Cdd:cd08393   81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGS 111

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  845 EVSFVYSHHDRQLSVALVRGFDLPPRsDGTPRNPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNGLTEPMLLQR 924
Cdd:cd08381    3 QVKLSISYKNGTLFVMVMHAKNLPLL-DGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQR 81

                         90       100       110
                 ....*....|....*....|....*....|...
gi 25150782  925 VLELTVWDYDKFGTNSFLGETLIDLASVPLDGE 957
Cdd:cd08381   82 VLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQE 114

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  842 GRIEVSFVYSHHDRQLSV------ALVRGFDLPPRSdgtprNPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNg 915
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVhvkecrNLAYGDEAKKRS-----NPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYS- 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 25150782  916 LTEPMLLQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDGEH 958
Cdd:cd04029   76 ISHSQLETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQH 118

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  857 LSVALVRGFDLPPRSDGTPRNPYVKIFLLPdrseKSRRQSAVIAETLMPVWDEVFYYNgLTEPMllQRVLELTVWDYDKF 936
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGG----KQKFKTKVVKNTLNPVWNETFEFP-VLDPE--SDTLTVEVWDKDRF 73

                         90       100
                 ....*....|....*....|.
gi 25150782  937 GTNSFLGETLIDLASVPLDGE 957
Cdd:cd00030   74 SKDDFLGEVEIPLSELLDSGK 94

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  841 FGRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNGLTEPM 920
Cdd:cd04035    1 LGTLEFTLLYDPANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEED 80

                         90       100
                 ....*....|....*....|....*....
gi 25150782  921 LLQRVLELTVWDYDKFGtNSFLGETLIDL 949
Cdd:cd04035   81 IQRKTLRLLVLDEDRFG-NDFLGETRIPL 108

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  841 FGRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRSEKSRRQSAVIAETLMPVWDEVFYYNgLTEPM 920
Cdd:cd04030    2 LGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEE 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 25150782  921 LLQRVLELTVWDYDKFGT--NSFLGETLIDLASVPL 954
Cdd:cd04030   81 LKRRTLDVAVKNSKSFLSreKKLLGQVLIDLSDLDL 116

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 25150782     656 GDLGLKIVGGRRTDTGklgAFITQVKPGSVADTIGrLRPGDEVVEWNGQSLQNATYEQVYDSIAASRydTSVELIVSR 733
Cdd:smart00228   12 GGLGFSLVGGKDEGGG---VVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAG--GKVTLTVLR 83

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782 1419 GEIQIALMAGRSGIDVEIIKAKNLVVKPGVkvCPAPYVKVYLMEGKQCIAKAKTNAATKTTSPLFQQHLIFNDSP----K 1494
Cdd:cd08381    2 GQVKLSISYKNGTLFVMVMHAKNLPLLDGS--DPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPvedlQ 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 25150782 1495 KKTLQVTVLGDyGRMERKVFMGISQIRLEDLELgSQPLIGWYKL 1538
Cdd:cd08381   80 QRVLQVSVWSH-DSLVENEFLGGVCIPLKKLDL-SQETEKWYPL 121

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782 1432 IDVEIIKAKNLVVKPGVKVcPAPYVKVYLMEGKqciaKAKTNAATKTTSPLFQQHLIFN-DSPKKKTLQVTVLgDYGRME 1510
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGK-SDPYVKVSLGGKQ----KFKTKVVKNTLNPVWNETFEFPvLDPESDTLTVEVW-DKDRFS 74

                         90       100
                 ....*....|....*....|....*...
gi 25150782 1511 RKVFMGISQIRLEDLELGSQPLIGWYKL 1538
Cdd:cd00030   75 KDDFLGEVEIPLSELLDSGKEGELWLPL 102

PDZ1 domain of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Gallus gallus uncharacterized syntaxin-binding protein 4 (STXBP4) isoform X1, and related domains. Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This STXBP4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  654 ANGdLGLKIVGGRRTDTGK-LGAFITQVKPGSVADTIGRLRPGDEVVEWNGQSLQNATYEQVYDSIAASRYDTSVELIVS 732
Cdd:cd06692    7 SKG-LGIKIIGGYRENTGEeFGIFIKRILPGGLAATDGRLKEGDLILEVNGESLQGVTNERAVSILRSASASNHMSLLIA 85

                 .
gi 25150782  733 R 733
Cdd:cd06692   86 R 86

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  842 GRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGTPRNPYVKIFLLPDRSekSRRQSAVIAETLMPVWDEVFYYnGLTEPML 921
Cdd:cd08387    3 GELHFSLEYDKDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRS--NTKQSKIHKKTLNPEFDESFVF-EVPPQEL 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 25150782  922 LQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDG 956
Cdd:cd08387   80 PKRTLEVLLYDFDQFSRDECIGVVELPLAEVDLSE 114

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  857 LSVALVRGFDLPPRSDGTPRNPYVKIFLlpdRSEKsrRQSAVIAETLMPVWDEVFYYNGLTEPMllqRVLELTVWDYDKF 936
Cdd:cd08376    2 VTIVLVEGKNLPPMDDNGLSDPYVKFRL---GNEK--YKSKVCSKTLNPQWLEQFDLHLFDDQS---QILEIEVWDKDTG 73

                         90       100
                 ....*....|....*....|....*...
gi 25150782  937 GTNSFLGETLIDLASVPLDGEHSLMCIL 964
Cdd:cd08376   74 KKDEFIGRCEIDLSALPREQTHSLELEL 101

PDZ domain 2 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2) and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This LNX family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  643 HMILHRTENSAangdLGLKIVggRRTDTGklGAFITQVKPGSVADTIGRLRPGDEVVEWNGQSLQNATYEQVYDSIAASr 722
Cdd:cd06678    2 HVTLNKRDGEQ----LGIKLV--RKKDEP--GVFILDLLEGGLAARDGRLKSDDRVLAINGQDLRHGTPEQAAQIIQAS- 72

                         90
                 ....*....|.
gi 25150782  723 yDTSVELIVSR 733
Cdd:cd06678   73 -GERVHFVVSR 82

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 25150782  658 LGLKIVGGRRTDTGKLGAFITQVKPGSVADTIGRLRPGDEVVEWNGQSLQNATYEQVYDSIAASRYDtsVELIVSRS 734
Cdd:cd06694   15 LGFTIVGGENSGSLDLGIFVKSIIPGGPADKDGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNAPDK--VELIISQP 89

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25150782  842 GRIEVSFVYSHHDRQLSVALVRGFDLPPRSDGT-PRNPYVKIFLLPDRSEKSRrqSAVIAETLMPVWDEVFYYNGLTEPM 920
Cdd:cd08388    3 GTLFFSLRYNSEKKALLVNIIECRDLPAMDEQSgTSDPYVKLQLLPEKEHKVK--TRVLRKTRNPVYDETFTFYGIPYNQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 25150782  921 LLQRVLELTVWDYDKFGTNSFLGETLIDLASVPLDGEHSLMC 962
Cdd:cd08388   81 LQDLSLHFAVLSFDRYSRDDVIGEVVCPLAGADLLNEGELLV 122