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Conserved domains on  [gi|7303734|gb|AAF58783|]
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uncharacterized protein Dmel_CG17765 [Drosophila melanogaster]

Protein Classification

penta-EF hand family protein; EF hand domain-containing protein( domain architecture ID 11610863)

penta-EF hand (PEF) family protein; the family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also called programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin| EF hand domain-containing protein such as Dictyostelium Penta-EF hand domain-containing protein which is classified family of Ca(2+)-binding proteins that possess five EF-hand-like motifs.

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 34-198 1.01e-103

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


:

Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 295.71  E-value: 1.01e-103
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDS 113
Cdd:cd16184   1 EVQQWFQAVDRDRSGKISAKELQQALVNGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFDRDR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  114 SGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTV 193
Cdd:cd16184  81 SGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDFLTM 160


                ....*
gi 7303734  194 AIGCS 198
Cdd:cd16184 161 ALLNK 165
 
Name Accession Description Interval E-value
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 34-198 1.01e-103

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 295.71  E-value: 1.01e-103
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDS 113
Cdd:cd16184   1 EVQQWFQAVDRDRSGKISAKELQQALVNGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFDRDR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  114 SGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTV 193
Cdd:cd16184  81 SGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDFLTM 160


                ....*
gi 7303734  194 AIGCS 198
Cdd:cd16184 161 ALLNK 165
PTZ00184 PTZ00184
calmodulin; Provisional
 39-164 6.45e-11

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 57.85  E-value: 6.45e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734    39 FSMVDRDRSGKINASELqAALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLY-------NYINQWLQVFKTYDQ 111
Cdd:PTZ00184  17 FSLFDKDGDGTITTKEL-GTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMarkmkdtDSEEEIKEAFKVFDR 95

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 7303734   112 DSSGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQ 164
Cdd:PTZ00184  96 DGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMS 148
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
36-158 2.39e-10

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 56.34  E-value: 2.39e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   36 QQWFSMVDRDRSGKINASELQAALvngrgdhfsDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWL------QVFKTY 109
Cdd:COG5126   8 DRRFDLLDADGDGVLERDDFEALF---------RRLWATLFSEADTDGDGRISREEFVAGMESLFEATvepfarAAFDLL 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 7303734  110 DQDSSGHIEEQELTQAFTQMGfrFSPEFINFLVKKSDPQGHKEVSVDQF 158
Cdd:COG5126  79 DTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEF 125
EF-hand_7 pfam13499
EF-hand domain pair;
39-96 3.29e-09

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 51.10  E-value: 3.29e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 7303734     39 FSMVDRDRSGKINASELQAALVN-GRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLY 96
Cdd:pfam13499   8 FKLLDSDGDGYLDVEELKKLLRKlEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
26-95 4.33e-06

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 45.83  E-value: 4.33e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734    26 PQNAQVSPQAQQWFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMiSMFDNDASGTIDIYEFEKL 95
Cdd:NF041410  20 TSSARSQQFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELF-SDLDSDGDGSLSSDELAAA 88
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
39-130 1.54e-05

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 43.90  E-value: 1.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734    39 FSMVDRDRSGKINASELQAALVN--GRGDHF-SDNACKLMISMFDNDASGTIDIYEFEKLYNYI---NQWLQVFKTYDQD 112
Cdd:NF041410  69 FSDLDSDGDGSLSSDELAAAAPPppPPPDQApSTELADDLLSALDTDGDGSISSDELSAGLTSAgssADSSQLFSALDSD 148

                         90
                 ....*....|....*...
gi 7303734   113 SSGHIEEQELTQAFTQMG 130
Cdd:NF041410 149 GDGSVSSDELAAALQPPP 166
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 36-59 3.93e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 33.51  E-value: 3.93e-03
                           10        20
                   ....*....|....*....|....
gi 7303734      36 QQWFSMVDRDRSGKINASELQAAL 59
Cdd:smart00054   3 KEAFRLFDKDGDGKIDFEEFKDLL 26
 
Name Accession Description Interval E-value
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 34-198 1.01e-103

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 295.71  E-value: 1.01e-103
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDS 113
Cdd:cd16184   1 EVQQWFQAVDRDRSGKISAKELQQALVNGNWSHFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFDRDR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  114 SGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTV 193
Cdd:cd16184  81 SGSIDENELHQALSQMGYRLSPQFVQFLVSKYDPRARRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDFLTM 160


                ....*
gi 7303734  194 AIGCS 198
Cdd:cd16184 161 ALLNK 165
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 34-195 1.58e-70

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 211.62  E-value: 1.58e-70
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDS 113
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIETVRLMINMFDRDRSGTINFDEFVGLWKYIQDWRRLFRRFDRDR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  114 SGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTV 193
Cdd:cd16180  81 SGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEACVTLKRLTDAFRKYDTNRTGYATISYEDFLTM 160


                ..
gi 7303734  194 AI 195
Cdd:cd16180 161 VL 162
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
 37-195 1.13e-67

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 204.41  E-value: 1.13e-67
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   37 QWFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGH 116
Cdd:cd16183   4 NVFQRVDKDRSGQISATELQQALSNGTWTPFNPETVRLMIGMFDRDNSGTINFQEFAALWKYITDWQNCFRSFDRDNSGN 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7303734  117 IEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTVAI 195
Cdd:cd16183  84 IDKNELKQALTSFGYRLSDQFYDILVRKFDRQGRGTIAFDDFIQCCVVLQTLTDSFRRYDTDQDGWIQISYEQFLEMVF 162
EFh_PEF_Group_II_sorcin_like cd16181
Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The ...
 37-197 9.61e-47

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320056 [Multi-domain]  Cd Length: 165  Bit Score: 150.98  E-value: 9.61e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   37 QWFSMVdRDRSGKINASELQAAL----VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQD 112
Cdd:cd16181   4 GYFSAV-AGQDGQIDADELQRCLtqsgISGNYQPFSLETCRLMIAMLDRDHSGKMGFNEFKELWAALNQWKTTFMQYDRD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  113 SSGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGhkEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLT 192
Cdd:cd16181  83 RSGTVEPQELQQAIRSFGYNLSPQALNVIVKRYSKNG--RITFDDFVACAVRLRALTDRFRRRDTQQNGTATFQYDDFIQ 160


                ....*
gi 7303734  193 VAIGC 197
Cdd:cd16181 161 VTMSI 165
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 34-191 1.03e-42

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 140.81  E-value: 1.03e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAALVNGrGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDS 113
Cdd:cd16185   1 ELRQWFRAVDRDRSGSIDVNELQKALAGG-GLLFSLATAEKLIRMFDRDGNGTIDFEEFAALHQFLSNMQNGFEQRDTSR 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7303734  114 SGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFL 191
Cdd:cd16185  80 SGRLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIELCIFLASARNLFQAFDRQRTGRVTLDFNQFV 157
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 34-191 6.55e-40

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.


Pssm-ID: 320054 [Multi-domain]  Cd Length: 165  Bit Score: 133.71  E-value: 6.55e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVDRDrSGKINASELQAAL----VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTY 109
Cdd:cd15897   1 QLRNVFQAVAGD-DGEISATELQQALsnvgWTHFDLGFSLETCRSMIAMMDRDHSGKLNFSEFKGLWNYIKAWQEIFRTY 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  110 DQDSSGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDpQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFED 189
Cdd:cd15897  80 DTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYD-RGRGNIDFDDFIQCCVRLQRLTDAFRRYDKDQDGQIQVNYDE 158


                ..
gi 7303734  190 FL 191
Cdd:cd15897 159 FL 160
EFh_PEF_sorcin cd16187
Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2 ...
 48-191 2.14e-37

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.


Pssm-ID: 320062 [Multi-domain]  Cd Length: 165  Bit Score: 127.33  E-value: 2.14e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   48 GKINASELQAAL----VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQELT 123
Cdd:cd16187  14 GQIDADELQRCLtqsgIAGGYKPFNLETCRLMISMLDRDMSGTMGFNEFKELWAVLNGWRQHFISFDSDRSGTVDPQELQ 93

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7303734  124 QAFTQMGFRFSPEFINFLVKKSDPQGhkEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFL 191
Cdd:cd16187  94 KALTTMGFRLSPQAVNSIAKRYSTNG--KITFDDYIACCVKLRALTDSFRRRDTSQQGVVNFPYDDFI 159
EFh_PEF_grancalcin cd16186
Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic ...
 48-195 7.11e-36

Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It displays a Ca2+-dependent translocation to granules and plasma membrane upon neutrophil activation, suggesting roles in granule-membrane fusion and degranulation of neutrophils. It may also play a role in the regulation of vesicle/granule exocytosis through the reversible binding of secretory vesicles and plasma membranes upon the presence of calcium. Moreover, GCA is involved in inflammation, as well as in the process of adhesion of neutrophils to fibronectin. It plays a key role in leukocyte-specific functions that are responsible for host defense, and affects the function of integrin receptors on immune cells through binding to L-plastin in the absence of calcium. Furthermore, GCA can strongly interact with sorcin to form a heterodimer, and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320061 [Multi-domain]  Cd Length: 165  Bit Score: 123.44  E-value: 7.11e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   48 GKINASELQAAL----VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQELT 123
Cdd:cd16186  14 GEVDAEELQRCLtqsgINGTYTPFSLETCRIMIAMLDRDHTGKMGFNEFKELWAALNAWKQNFMTVDQDRSGTVEPHELR 93

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7303734  124 QAFTQMGFRFSPEFINFLVKKSDPQGhkEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFL--TVAI 195
Cdd:cd16186  94 QAIGAMGYRLSPQTLTTIVKRYSKNG--RIYFDDYVACCVKLRALTDFFRRRDHMQQGSVNFIYDDFLqcTMAI 165
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
 34-191 3.02e-27

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.


Pssm-ID: 320057 [Multi-domain]  Cd Length: 167  Bit Score: 101.15  E-value: 3.02e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVdRDRSGKINASELQAAL------VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFK 107
Cdd:cd16182   1 QVRELFEKL-AGEDEEIDAVELQKLLnasllkDMPKFDGFSLETCRSLIALMDTNGSGRLDLEEFKTLWSDLKKWQAIFK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  108 TYDQDSSGHIEEQELTQAFTQMGFRFSPEFINFLVKK-SDPQGHkeVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIG 186
Cdd:cd16182  80 KFDTDRSGTLSSYELRKALESAGFHLSNKVLQALVLRyADSTGR--ITFEDFVSCLVRLKTAFETFSALDKKNEGVIPLT 157


                ....*
gi 7303734  187 FEDFL 191
Cdd:cd16182 158 LEEWL 162
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
 46-195 1.38e-26

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.


Pssm-ID: 320071 [Multi-domain]  Cd Length: 167  Bit Score: 99.58  E-value: 1.38e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   46 RSGKINASELQAALVNG-----RGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQ 120
Cdd:cd16196  12 EDMEIDAYELQDILNTAfkkdfPFDGFSLDACRSMVAMMDVDRSGKLGFEEFKKLWEDLRSWKRVFKLFDTDGSGSFSSF 91

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7303734  121 ELTQAFTQMGFRFSPEFINFLVKK-SDPQGhkEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTVAI 195
Cdd:cd16196  92 ELRNALNSAGFRLSNATLNALVLRySNKDG--RISFDDFIMCAVKLKTMFEIFKEKDPRGGGRATFNLDEFLESTM 165
EFh_PEF_CPNS1_2 cd16188
Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit ...
 63-191 8.39e-20

Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit CAPNS1 and CAPNS2; CAPNS1, also termed calpain small subunit 1 (CSS1), or calcium-activated neutral proteinase small subunit (CANP small subunit), or calcium-dependent protease small subunit (CDPS), or calpain regulatory subunit, is a common 28-kDa regulatory calpain subunit encoded by the calpain small 1 (Capns1, also known as Capn4) gene. It acts as a binding partner to form a heterodimer with the 80 kDa calpain large catalytic subunit and is required in maintaining the activity of calpain. CAPNS1 plays a significant role in tumor progression of human cancer, and functions as a potential therapeutic target in human hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), glioma, and clear cell renal cell carcinoma (ccRCC). It may be involved in regulating migration and cell survival through binding to the SH3 domain of Ras GTPase-activating protein (RasGAP). It may also modulate Akt/FoxO3A signaling and apoptosis through PP2A. CAPNS1 contains an N-terminal glycine rich domain and a C-terminal PEF-hand domain. CAPNS2, also termed calpain small subunit 2 (CSS2), is a novel tissue-specific 30 kDa calpain small subunit that lacks two oligo-Gly stretches characteristic of the N-terminal Gly-rich domain of CAPNS1. CAPNS2 acts as a chaperone for the calpain large subunit, and appears to be the functional equivalent of CAPNS1. However, CAPNS2 binds the large subunit much more weakly than CAPNS1 and it does not undergo the autolytic conversion typical of CAPNS1.


Pssm-ID: 320063 [Multi-domain]  Cd Length: 169  Bit Score: 82.10  E-value: 8.39e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   63 RGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQELTQAFTQMGFRFSPEFINFLV 142
Cdd:cd16188  36 KTDGFGIDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQGIYKQFDTDRSGTIGSQELPGAFEAAGFHLNEQLYQMII 115

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 7303734  143 KK-SDPQGhkEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFL 191
Cdd:cd16188 116 RRySDEDG--NMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQEWL 163
EFh_PEF_CAPN3 cd16190
Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), ...
 49-191 8.31e-18

Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), or calpain L3, or calpain p94, or muscle-specific calcium-activated neutral protease 3, or new calpain 1 (nCL-1), is a calpain large subunit that is mainly expressed in skeletal muscle, or lens. The skeletal muscle-specific CAPN3 are pathologically associated with limb girdle muscular dystrophy type 2A (LGMD2A). Its autolytic activity can be positively regulated by calmodulin (CaM), a known transducer of the calcium signal. CAPN3 is also involved in human melanoma tumorigenesis and progression. It impairs cell proliferation and stimulates oxidative stress-mediated cell death in melanoma cells. Moreover, it plays an important role in sarcomere remodeling and mitochondrial protein turnover. Furthermore, the phosphorylated skeletal muscle-specific CAPN3 acts as a myofibril structural component and may participate in myofibril-based signaling pathways. In the eye, the lens-specific CAPN3, together with CAPN2, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. CAPN3 exists as a homodimer, rather than a heterodimer with the calpain small subunit. It may also form heterodimers with other calpain large subunits. CAPN3 contains a long N-terminal region, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. Ca2+ binding at EF5 of the CAPN3 PEF domain is a distinct feature not observed in other calpain isoforms.


Pssm-ID: 320065 [Multi-domain]  Cd Length: 169  Bit Score: 76.82  E-value: 8.31e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   49 KINASELQAALVNGRGDH-------FSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQE 121
Cdd:cd16190  15 EISADELRSVLNRVVKKHkdlktegFTLESCRSMIALMDTDGSGKLNLQEFRHLWNKIKQWQKIFKRYDTDKSGTINSYE 94

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  122 LTQAFTQMGFRFSPEFINFLVKKSDPQgHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFL 191
Cdd:cd16190  95 MRNAVNDAGFRLNNQLYDIITMRYADK-HMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVLEWL 163
EFh_PEF_CAPN1_like cd16189
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2) ...
 50-195 9.13e-18

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2), and similar proteins; The family includes mu-type calpain (CAPN1) and m-type calpain (CAPN2), both of which are ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine proteases that contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN1 or CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms a mu- or m-calpain heterodimer, respectively.


Pssm-ID: 320064 [Multi-domain]  Cd Length: 168  Bit Score: 76.62  E-value: 9.13e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   50 INASELQAAL-------VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQEL 122
Cdd:cd16189  16 ISAFELQTILnkvlskrKDIKTDGFSLETCRNMVNLLDKDGSGKLGLVEFQILWTKIQKYLKIYKKFDTDGSGTMSSYEM 95

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 7303734  123 TQAFTQMGFRFSPEFINFLVKKSDPQGHkEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTVAI 195
Cdd:cd16189  96 RLALEEAGFKLNNQLHQVLVARYADQEL-TIDFDNFVRCLVRLELLFKIFKQLDKDNTGTIELDLIQWLSFSL 167
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
 45-194 2.45e-17

Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and similar proteins; CAPN13, also termed calcium-activated neutral proteinase 13 (CANP 13), a 63.6 kDa calpain large subunit that exhibits a restricted tissue distribution with low levels of expression detected only in human testis and lung. In calpain family, CAPN13 is most closely related to calpain-14 (CAPN14). CAPN14, also termed calcium-activated neutral proteinase 14 (CANP 14), is a 76.7 kDa calpain large subunit that is most highly expressed in the oesophagus. Its expression and calpain activity can be induced by IL-13. Both CAPN13 and CAPN14 contain a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320070 [Multi-domain]  Cd Length: 168  Bit Score: 75.32  E-value: 2.45e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   45 DRSGKINASELQAAL-------VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHI 117
Cdd:cd16195  11 DQGGELDAEQLQKLLnenllkgLAGSGGGFSLDACRSMVALMDLSVNGRLSLEEFSRLWKKLRKYKDIFQKADVSKSGFL 90

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7303734  118 EEQELTQAFTQMGFRFSPEFINFLV-KKSDPQGHkeVSVDQFIVLCVQVQRFTEAFRQRdTQQNGTITIGFEDFLTVA 194
Cdd:cd16195  91 SLSELRNAIQAAGIRVSDDLLNLMAlRYGDSSGR--ISFESFICLMLRLECMAKIFRNL-SKDGGGIYLTESEWMQLT 165
EFh_PEF_CAPN1 cd16198
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed ...
 63-195 4.10e-17

Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed calpain-1 80-kDa catalytic subunit, or calpain-1 large subunit, or micromolar-calpain (muCANP), or calcium-activated neutral proteinase 1 (CANP 1), or cell proliferation-inducing gene 30 protein, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN1 in complex with a regulatory subunit encoded by CAPNS1 forms a mu-calpain heterodimer. CAPN1 plays a central role in postmortem proteolysis and meat tenderization processes, as well as in regulation of proliferation and survival of skeletal satellite cells. It also acts as a novel regulator in IgE-mediated mast cell activation and could serve as a potential therapeutic target for the management of allergic inflammation. Moreover, CAPN1 is involved in neutrophil motility and functions as a potential target for intervention in inflammatory disease. It also facilitates age-associated aortic wall calcification and fibrosis through the regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells, and thus plays a role in hypertension and atherosclerosis. The proteolytic cleavage of beta-amyloid precursor protein and tau protein by CAPN1 may be involved in plaque formation. Furthermore, CAPN1 is activated in the brains of individuals with Alzheimer's disease. It is involved in the maintenance of a proliferative neural stem cell pool. The activation and macrophage inflammation of CAPN1 in hypercholesterolemic nephropathy is promoted by nicotinic acetylcholine receptor alpha1 (nAChRalpha1). In addition, CAPN1 displays a functional role in hemostasis, as well as in sickle cell disease.


Pssm-ID: 320073 [Multi-domain]  Cd Length: 169  Bit Score: 74.84  E-value: 4.10e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   63 RGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQELTQAFTQMGFRFSPEFINFLV 142
Cdd:cd16198  36 RTDGFSLESCRSMVNLMDKDGNGKLGLVEFNILWNKIRNYLTIFRKFDLDKSGSMSAYEMRLALESAGFKLNNRLHQVIV 115

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 7303734  143 KK-SDPQghKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTVAI 195
Cdd:cd16198 116 ARyADPN--LAIDFDNFVCCLVRLETMFRFFKQLDTEETGTIEMDLFEWLQLTM 167
EFh_PEF_CAPN12 cd16194
Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed ...
 49-194 5.92e-17

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320069 [Multi-domain]  Cd Length: 169  Bit Score: 74.53  E-value: 5.92e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   49 KINASELQAALV-------NGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQE 121
Cdd:cd16194  15 EINASELQKILSialerahTSKPREFGLRTCRQLIQCFDHGQNGKLALEEFQQLWGYLLEWQAIFTKFDEDTSGTMDSYE 94

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7303734  122 LTQAFTQMGFRFSPEFINFLVKKSDPQGhKEVSVDQFiVLCvqVQRFTEAFRQ---RDTQQNGTITIGFEDFLTVA 194
Cdd:cd16194  95 LRLALNAAGFHLNNQLTETLTSRYRDSR-LRVDFESF-LSC--LAHLTCIFCQcsqHDDGGEGVICLTHRQWLELA 166
EFh_PEF_CAPN2 cd16199
Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2); CAPN2, also termed ...
 49-195 3.80e-16

Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2); CAPN2, also termed millimolar-calpain (m-calpain), or calpain-2 catalytic subunit, or calcium-activated neutral proteinase 2 (CANP 2), or calpain large polypeptide L2, or calpain-2 large subunit, is a ubiquitously expressed 80-kDa Ca2+-dependent intracellular cysteine protease that contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The catalytic subunit CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms an m-calpain heterodimer. CAPN2 acts as the key protease responsible for N-methyl-d-aspartic acid (NMDA)-induced cytoplasmic polyadenylation element-binding protein 3 (CPEB3) degradation in neurons. It cleaves several components of the focal adhesion complex, such as FAK and talin, triggering disassembly of the complex at the rear of the cell. The stimulation of CAPN2 activity is required for Golgi antiapoptotic proteins (GAAPs) to promote cleavage of FA kinase (FAK), cell spreading, and enhanced migration. calpain 2 is also involved in the onset of glial differentiation. It regulates proliferation, survival, migration, and tumorigenesis of breast cancer cells through a PP2A-Akt-FoxO-p27(Kip1) signaling cascade. Its expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer. Moreover, CAPN2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion. The activation of CAPN2 plays an essential role in hippocampal synaptic plasticity and in learning and memory. In the eye, CAPN2, together with a lens-specific variant of CAPN3, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation. Sometimes, CAPN2 compensates for loss of CAPN1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation. The main phosphorylation sites in m-calpain are Ser50 and Ser369/Thr370.


Pssm-ID: 320074 [Multi-domain]  Cd Length: 168  Bit Score: 72.24  E-value: 3.80e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   49 KINASELQAAL-------VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQE 121
Cdd:cd16199  15 EISAFELQTILrrvlakrEDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYILWTKIQKYQKIYREIDVDRSGTMNSYE 94

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 7303734  122 LTQAFTQMGFRFSPEFINFLVKK-SDPQghKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTVAI 195
Cdd:cd16199  95 MRKALEEAGFKLPCQLHQVIVARfADDD--LIIDFDNFVRCLVRLETLFKIFKQLDPENTGTIELDLISWLSFSV 167
EFh_PEF_CAPN11 cd16193
Penta-EF hand, calcium binding motifs, found in calpain-11 (CAPN11); CAPN11, also termed ...
 45-195 8.71e-15

Penta-EF hand, calcium binding motifs, found in calpain-11 (CAPN11); CAPN11, also termed calcium-activated neutral proteinase 11 (CANP 11), is a mammalian orthologue of micro/m calpain. It is one of the calpain large subunits that appears to be exclusively expressed in certain cells of the testis. It may be involved in regulating calcium-dependent signal transduction events during meiosis and sperm functional processes. CAPN11 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320068 [Multi-domain]  Cd Length: 169  Bit Score: 68.79  E-value: 8.71e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   45 DRSGKINASELQ-------AALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHI 117
Cdd:cd16193  11 NEDKEVDMYELQkllnrmaIKFKSFKTKGFSLDVCRRMINLMDKDGSGKLGLHEFKILWKKIKKWMEIFKECDQDRSGNL 90

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7303734  118 EEQELTQAFTQMGFRFSPEFINFLVKK-SDpqGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTVAI 195
Cdd:cd16193  91 NSYEMRLAIEKAGIKMNNRVTEVVVARyAD--DNMIVDFDSFINCFLRLKAMFAFFLSMDTKKTGSICLSINQWLQITM 167
EFh_PEF_CAPN8 cd16191
Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new ...
 49-195 1.08e-14

Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new calpain 2 (nCL-2), or stomach-specific M-type calpain, is a calpain large subunit predominantly expressed in the stomach. It appears to be involved in membrane trafficking in the gastric surface mucus cells (pit cells), via its location at the Golgi and interaction with the beta-subunit of coatomer complex (beta-COP) of vesicles derived from the Golgi. Moreover, CAPN8, together with CAPN9, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. CAPN8 exists as both a monomer and homo-oligomer, but not as a heterodimer with the conventional calpain regulatory subunit (30K). The monomer and homodimer forms predominate. CAPN8 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320066 [Multi-domain]  Cd Length: 168  Bit Score: 68.65  E-value: 1.08e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   49 KINASELQAAL-------VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQE 121
Cdd:cd16191  15 EVTANELQTILnrvlskrKDIKSDGFTINTCREMISLLDTDGTGTLGLVEFRILWMKIQKYLAIYKKVDSDRSGTIDAHE 94

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7303734  122 LTQAFTQMGFRFSPEFINFLVKK--SDPQGhkeVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFLTVAI 195
Cdd:cd16191  95 MRNALQEAGFTLNNKIQQSIVQRyaSNKLT---INFDGFIACMIRLETLFKMFQLLDKDKSGVVQLSLAEWLCCTL 167
EFh_PEF_CAPN9 cd16192
Penta-EF hand, calcium binding motifs, found in calpain-9 (CAPN9); CAPN9, also termed ...
 50-191 5.97e-14

Penta-EF hand, calcium binding motifs, found in calpain-9 (CAPN9); CAPN9, also termed digestive tract-specific calpain, or new calpain 4 (nCL-4), or protein CG36, is a calpain large subunit predominantly expressed in gastrointestinal tract. It plays a physiological role in the suppression of tumorigenesis. It acts as an important biomolecule link for the regression of colorectal cancer via intracellular calcium homeostasis. CAPN9 may also play a critical role in lumen formation. Moreover, CAPN9, together with CAPN8, forms an active protease complex, G-calpain, in which both proteins are essential for stability and activity. The G-Calpain has been implicated in gastric mucosal defense. Furthermore, down-regulation of calpain 9 has been linked to hypertensive heart and kidney disease in salt-sensitive Dahl rats. CAPN9 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320067 [Multi-domain]  Cd Length: 169  Bit Score: 66.74  E-value: 5.97e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   50 INASELQAALVNGRG-------DHFSDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIEEQEL 122
Cdd:cd16192  16 ISAEELQYVLNAVLArtkeikfKKLSLLSCKNIISLMDTSGNGKLGFSEFKVFWDKLKKWIGLFLKYDADRSGTMSSYEL 95

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7303734  123 TQAFTQMGFRFSPEFINFLVKKSdPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFL 191
Cdd:cd16192  96 RSALKAAGFQLNNQLLQLIVLRY-ADDYLQIDFDDFLNCLVRLENSFRVFQALDTKNTGEISLNMLEFI 163
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 39-92 4.31e-11

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 56.02  E-value: 4.31e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 7303734   39 FSMVDRDRSGKINASELQAALvNGRGDHFSDNACKLMISMFDNDASGTIDIYEF 92
Cdd:cd00051   6 FRLFDKDGDGTISADELKAAL-KSLGEGLSEEEIDEMIREVDKDGDGKIDFEEF 58
PTZ00184 PTZ00184
calmodulin; Provisional
 39-164 6.45e-11

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 57.85  E-value: 6.45e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734    39 FSMVDRDRSGKINASELqAALVNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLY-------NYINQWLQVFKTYDQ 111
Cdd:PTZ00184  17 FSLFDKDGDGTITTKEL-GTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTLMarkmkdtDSEEEIKEAFKVFDR 95

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 7303734   112 DSSGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQ 164
Cdd:PTZ00184  96 DGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGDGQINYEEFVKMMMS 148
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
36-158 2.39e-10

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 56.34  E-value: 2.39e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   36 QQWFSMVDRDRSGKINASELQAALvngrgdhfsDNACKLMISMFDNDASGTIDIYEFEKLYNYINQWL------QVFKTY 109
Cdd:COG5126   8 DRRFDLLDADGDGVLERDDFEALF---------RRLWATLFSEADTDGDGRISREEFVAGMESLFEATvepfarAAFDLL 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 7303734  110 DQDSSGHIEEQELTQAFTQMGfrFSPEFINFLVKKSDPQGHKEVSVDQF 158
Cdd:COG5126  79 DTDGDGKISADEFRRLLTALG--VSEEEADELFARLDTDGDGKISFEEF 125
PTZ00183 PTZ00183
centrin; Provisional
 39-159 9.97e-10

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 55.08  E-value: 9.97e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734    39 FSMVDRDRSGKINASELQAALvNGRGDHFSDNACKLMISMFDNDASGTIDIYEF-----EKLYNYIN--QWLQVFKTYDQ 111
Cdd:PTZ00183  23 FDLFDTDGSGTIDPKELKVAM-RSLGFEPKKEEIKQMIADVDKDGSGKIDFEEFldimtKKLGERDPreEILKAFRLFDD 101

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 7303734   112 DSSGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFI 159
Cdd:PTZ00183 102 DKTGKISLKNLKRVAKELGETITDEELQEMIDEADRNGDGEISEEEFY 149
EF-hand_7 pfam13499
EF-hand domain pair;
39-96 3.29e-09

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 51.10  E-value: 3.29e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 7303734     39 FSMVDRDRSGKINASELQAALVN-GRGDHFSDNACKLMISMFDNDASGTIDIYEFEKLY 96
Cdd:pfam13499   8 FKLLDSDGDGYLDVEELKKLLRKlEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
EFh_PEF_CalpC cd16197
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-C (CalpC) and ...
 41-191 4.89e-09

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-C (CalpC) and similar proteins; CalpC, also termed calcium-activated neutral proteinase homolog C (CANP C), is a catalytically inactive homolog of CalpA and CalpB found in Drosophila. It is strongly expressed in the salivary glands. In contrast with CalpA and CalpB, both of which are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. CalpC is a truncated calpain form missing domain I and about 20 residues from domain II. Moreover, due to all three mutated active site residues (Cys to Arg, His to Val and Asn to Ser), it may not have proteolytic activity.


Pssm-ID: 320072 [Multi-domain]  Cd Length: 166  Bit Score: 53.27  E-value: 4.89e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   41 MVDRDRSgkINASELQ----AALVNgrgDHFSDNA----CKLMISMFDNDASGTIDIYEFEKLYNYINQWLQVFKTYDQD 112
Cdd:cd16197   9 LADEHRT--VNAFELQelleACLPN---DYIKSCAnidvCRQVVLLMDNSGLGRLKFQDFKDFMCSLKWWQGVFKMHTKE 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 7303734  113 SSGHIEEQELTQAFTQMGFRFSPEFINFLVKKSdPQGHKEVSVDQFIVLCVQVQRFTEAFRQRDTQQNGTITIGFEDFL 191
Cdd:cd16197  84 KTGILRAERLRDALEDVGFQLNTDVLSILILRY-MRKDGTLRFGDFVSAVLHLTAAFGSFEKKDPLQNGFIKLSLTEWL 161
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
36-129 1.24e-08

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 51.33  E-value: 1.24e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   36 QQWFSMVDRDRSGKINASELQAALVNGRGDHFsDNACKLMISMFDNDASGTIDIYEFEKLYNYIN----QWLQVFKTYDQ 111
Cdd:COG5126  36 ATLFSEADTDGDGRISREEFVAGMESLFEATV-EPFARAAFDLLDTDGDGKISADEFRRLLTALGvseeEADELFARLDT 114

                        90
                ....*....|....*...
gi 7303734  112 DSSGHIEEQELTQAFTQM 129
Cdd:COG5126 115 DGDGKISFEEFVAAVRDY 132
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 34-124 3.61e-06

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 44.58  E-value: 3.61e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAALvngRGDHFSDNACKL--MISMFDNDASGTIDIYEFEKLYNYINQ---WLQVFKT 108
Cdd:cd15898   1 WLRRQWIKADKDGDGKLSLKEIKKLL---KRLNIRVSEKELkkLFKEVDTNGDGTLTFDEFEELYKSLTErpeLEPIFKK 77

                        90
                ....*....|....*.
gi 7303734  109 YDQDSSGHIEEQELTQ 124
Cdd:cd15898  78 YAGTNRDYMTLEEFIR 93
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
33-92 4.28e-06

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 44.40  E-value: 4.28e-06
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   33 PQAQQWFSMVDRDRSGKINASELQAALvngRGDHFSDNACKLMISMFDNDASGTIDIYEF 92
Cdd:COG5126  69 PFARAAFDLLDTDGDGKISADEFRRLL---TALGVSEEEADELFARLDTDGDGKISFEEF 125
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
26-95 4.33e-06

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 45.83  E-value: 4.33e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734    26 PQNAQVSPQAQQWFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMiSMFDNDASGTIDIYEFEKL 95
Cdd:NF041410  20 TSSARSQQFQKQLFAKLDSDGDGSVSQDELSSALSSKSDDGSLIDLSELF-SDLDSDGDGSLSSDELAAA 88
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
 39-190 8.50e-06

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 45.04  E-value: 8.50e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   39 FSMVDRDRSGKINASELQA---ALVNGRGDHFSDNAC-----KLMISMFDNDASGTIDIYEFEKLY----NYINQWL--- 103
Cdd:cd15902   5 WMHFDADGNGYIEGKELDSflrELLKALNGKDKTDDEvaekkKEFMEKYDENEDGKIEIRELANILpteeNFLLLFRreq 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734  104 ---------QVFKTYDQDSSGHIEEQEL----TQAFTQMGFRFSP----EFINFLVKKSDPQGHKEVSVDQFIVLC-VQv 165
Cdd:cd15902  85 plissvefmKIWRKYDTDGSGFIEAKELkgflKDLLLKNKKHVSPpkldEYTKLILKEFDANKDGKLELDEMAKLLpVQ- 163

                       170       180
                ....*....|....*....|....*
gi 7303734  166 qrftEAFRQRDTQQNGTITIGfEDF 190
Cdd:cd15902 164 ----ENFLLKFQILGAMDLTK-EDF 183
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 105-159 9.05e-06

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 41.76  E-value: 9.05e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 7303734  105 VFKTYDQDSSGHIEEQELTQAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFI 159
Cdd:cd00051   5 AFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFL 59
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
39-130 1.54e-05

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 43.90  E-value: 1.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734    39 FSMVDRDRSGKINASELQAALVN--GRGDHF-SDNACKLMISMFDNDASGTIDIYEFEKLYNYI---NQWLQVFKTYDQD 112
Cdd:NF041410  69 FSDLDSDGDGSLSSDELAAAAPPppPPPDQApSTELADDLLSALDTDGDGSISSDELSAGLTSAgssADSSQLFSALDSD 148

                         90
                 ....*....|....*...
gi 7303734   113 SSGHIEEQELTQAFTQMG 130
Cdd:NF041410 149 GDGSVSSDELAAALQPPP 166
EFh_parvalbumin_alpha cd16254
EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2 ...
 34-97 1.79e-05

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.


Pssm-ID: 319997 [Multi-domain]  Cd Length: 101  Bit Score: 42.12  E-value: 1.79e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAAL----VNGRgdHFSDNACKLMISMFDNDASGTIDIYEFEKLYN 97
Cdd:cd16254  35 DVKKVFHILDKDKSGFIEEDELKFVLkgfsPDGR--DLSDKETKALLAAGDKDGDGKIGIDEFATLVA 100
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 72-127 3.11e-05

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 40.22  E-value: 3.11e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 7303734   72 CKLMISMFDNDASGTIDIYEFEKLYNYIN------QWLQVFKTYDQDSSGHIEEQELTQAFT 127
Cdd:cd00051   2 LREAFRLFDKDGDGTISADELKAALKSLGeglseeEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
99-159 6.61e-05

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 39.54  E-value: 6.61e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 7303734     99 INQWLQVFKTYDQDSSGHIEEQELTQAFTQ--MGFRFSPEFINFLVKKSDPQGHKEVSVDQFI 159
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKleEGEPLSDEEVEELFKEFDLDKDGRISFEEFL 63
EFh_parvalbumin_like cd16251
EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes ...
 34-95 9.06e-05

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319994 [Multi-domain]  Cd Length: 101  Bit Score: 40.21  E-value: 9.06e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7303734   34 QAQQWFSMVDRDRSGKINASELQAAL--VNGRGDHFSDNACKLMISMFDNDASGTIDIYEFEKL 95
Cdd:cd16251  35 QIKKVFQILDKDKSGFIEEEELKYILkgFSIAGRDLTDEETKALLAAGDTDGDGKIGVEEFATL 98
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
 43-122 6.67e-04

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 39.26  E-value: 6.67e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   43 DRDRSGKINASELQA---ALVNGRGDHFSDNA----CKLMISMFDNDASGTIDIYEFEKLYNYINQWL------------ 103
Cdd:cd15902 100 DTDGSGFIEAKELKGflkDLLLKNKKHVSPPKldeyTKLILKEFDANKDGKLELDEMAKLLPVQENFLlkfqilgamdlt 179

                        90       100
                ....*....|....*....|....
gi 7303734  104 -----QVFKTYDQDSSGHIEEQEL 122
Cdd:cd15902 180 kedfeKVFEHYDKDNNGVIEGNEL 203
EFh_PEF_CPNS1_2 cd16188
Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit ...
 43-118 9.98e-04

Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit CAPNS1 and CAPNS2; CAPNS1, also termed calpain small subunit 1 (CSS1), or calcium-activated neutral proteinase small subunit (CANP small subunit), or calcium-dependent protease small subunit (CDPS), or calpain regulatory subunit, is a common 28-kDa regulatory calpain subunit encoded by the calpain small 1 (Capns1, also known as Capn4) gene. It acts as a binding partner to form a heterodimer with the 80 kDa calpain large catalytic subunit and is required in maintaining the activity of calpain. CAPNS1 plays a significant role in tumor progression of human cancer, and functions as a potential therapeutic target in human hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), glioma, and clear cell renal cell carcinoma (ccRCC). It may be involved in regulating migration and cell survival through binding to the SH3 domain of Ras GTPase-activating protein (RasGAP). It may also modulate Akt/FoxO3A signaling and apoptosis through PP2A. CAPNS1 contains an N-terminal glycine rich domain and a C-terminal PEF-hand domain. CAPNS2, also termed calpain small subunit 2 (CSS2), is a novel tissue-specific 30 kDa calpain small subunit that lacks two oligo-Gly stretches characteristic of the N-terminal Gly-rich domain of CAPNS1. CAPNS2 acts as a chaperone for the calpain large subunit, and appears to be the functional equivalent of CAPNS1. However, CAPNS2 binds the large subunit much more weakly than CAPNS1 and it does not undergo the autolytic conversion typical of CAPNS1.


Pssm-ID: 320063 [Multi-domain]  Cd Length: 169  Bit Score: 38.18  E-value: 9.98e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 7303734   43 DRDRSGKINASELQAALvNGRGDHFSDNACKLMISMFdNDASGTIDIYEFEKLYNYINQWLQVFKTYDQDSSGHIE 118
Cdd:cd16188  83 DTDRSGTIGSQELPGAF-EAAGFHLNEQLYQMIIRRY-SDEDGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQ 156
EFh_parvalbumin_alpha cd16254
EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2 ...
 104-164 1.07e-03

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.


Pssm-ID: 319997 [Multi-domain]  Cd Length: 101  Bit Score: 37.11  E-value: 1.07e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7303734  104 QVFKTYDQDSSGHIEEQELT---QAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQ 164
Cdd:cd16254  38 KVFHILDKDKSGFIEEDELKfvlKGFSPDGRDLSDKETKALLAAGDKDGDGKIGIDEFATLVAE 101
EF-hand_6 pfam13405
EF-hand domain;
101-130 1.15e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 35.23  E-value: 1.15e-03
                          10        20        30
                  ....*....|....*....|....*....|
gi 7303734    101 QWLQVFKTYDQDSSGHIEEQELTQAFTQMG 130
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
EFh_HEF_CB cd16176
EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or ...
 27-122 2.01e-03

EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or D-28K, or avian-type vitamin D-dependent calcium-binding protein, is a unique intracellular calcium binding protein that functions as both a calcium sensor and buffer in eukaryotic cells, which undergoes a conformational change upon calcium binding and protects cells against insults of high intracellular calcium concentration. CB is highly expressed in brain and sensory neurons. It plays essential roles in neural functioning, altering synaptic interactions in the hippocampus, modulating calcium channel activity, calcium transients, and intrinsic neuronal firing activity. It prevents a neuronal death, as well as maintains and controls calcium homeostasis. CB also modulates the activity of proteins participating in the development of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and bipolar disorder. Moreover, CB interacts with Ran-binding protein M, a protein known to involve in microtubule function. It also interacts with alkaline phosphatase and myo-inositol monophosphatase, as well as caspase 3, an enzyme that plays an important role in the regulation of apoptosis. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions with high affinity.


Pssm-ID: 320076 [Multi-domain]  Cd Length: 243  Bit Score: 37.90  E-value: 2.01e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   27 QNAQVSPQAQQWFSMVDRDRSGKINASELQA---ALVNGRGDHFSDNA----CKLMISMFDNDASGTIDIYEFEKLY--- 96
Cdd:cd16176  79 QQLKSSEEFMQTWRKYDADHSGFIEADELKSflkDLLKKANKPFDESKleeyTHTMLKMFDSNNDGKLGLTEMARLLpvq 158

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 7303734   97 -NYI----------NQWLQVFKTYDQDSSGHIEEQEL 122
Cdd:cd16176 159 eNFLlkfqgvkmcgKEFNKIFELYDQDGNGYIDENEL 195
EFh_parvalbumin_like cd16251
EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes ...
 104-164 3.66e-03

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319994 [Multi-domain]  Cd Length: 101  Bit Score: 35.59  E-value: 3.66e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 7303734  104 QVFKTYDQDSSGHIEEQELT---QAFTQMGFRFSPEFINFLVKKSDPQGHKEVSVDQFIVLCVQ 164
Cdd:cd16251  38 KVFQILDKDKSGFIEEEELKyilKGFSIAGRDLTDEETKALLAAGDTDGDGKIGVEEFATLVAG 101
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 36-59 3.93e-03

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 33.51  E-value: 3.93e-03
                           10        20
                   ....*....|....*....|....
gi 7303734      36 QQWFSMVDRDRSGKINASELQAAL 59
Cdd:smart00054   3 KEAFRLFDKDGDGKIDFEEFKDLL 26
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
 43-123 4.59e-03

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.


Pssm-ID: 320079 [Multi-domain]  Cd Length: 261  Bit Score: 37.00  E-value: 4.59e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   43 DRDRSGKINASELQA----ALVNG-RGDHFSDNacKL------MISMFDNDASGTIDIYEFEKLY----NYINQWL---- 103
Cdd:cd16179 105 DKDNSGYIEADELKNflkhLLKEAkRDNDVSED--KLieytdtILQLFDRNKDGKLQLSEMARLLpvkeNFLCRPIfkga 182

                        90       100
                ....*....|....*....|....*....
gi 7303734  104 ---------QVFKTYDQDSSGHIEEQELT 123
Cdd:cd16179 183 gkltredidRVFALYDRDNNGTIENEELT 211
EFh_HEF_CR cd16177
EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is ...
 43-122 5.41e-03

EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t specific neurons of the central and peripheral nervous system. It possibly functions as a calcium buffer, calcium sensor, and apoptosis regulator, which may be implicated in many biological processes, including cell proliferation, differentiation, and cell death. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. CR I-II consists of EF-hand motifs 1 and 2, and CR III-VI consists of EF-hand motifs 3-6. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. Thus, CR has two pairs of cooperative binding sites (I-II and III-IV), which display high affinity calcium-binding sites, and one independent calcium ion-binding site (V), which displays lower affinity binding.


Pssm-ID: 320077 [Multi-domain]  Cd Length: 248  Bit Score: 36.78  E-value: 5.41e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   43 DRDRSGKINASELQ---AALVNGRGDHFSDNA----CKLMISMFDNDASGTIDIYEFEKLY----NYI----------NQ 101
Cdd:cd16177 100 DTDRSGYIEANELKgflSDLLKKANRPYDEKKlqeyTQTILRMFDLNGDGKLGLSEMARLLpvqeNFLlkfqgmklssEE 179

                        90       100
                ....*....|....*....|.
gi 7303734  102 WLQVFKTYDQDSSGHIEEQEL 122
Cdd:cd16177 180 FNAIFAFYDKDGSGYIDENEL 200
EF-hand_5 pfam13202
EF hand;
36-57 7.43e-03

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 32.68  E-value: 7.43e-03
                          10        20
                  ....*....|....*....|..
gi 7303734     36 QQWFSMVDRDRSGKINASELQA 57
Cdd:pfam13202   2 KDTFRQIDLNGDGKISKEELRR 23
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
 38-141 7.63e-03

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4.


Pssm-ID: 320049 [Multi-domain]  Cd Length: 140  Bit Score: 35.21  E-value: 7.63e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   38 WFSMVDRDRSGKINASELQAALVNGRGDHFSDNACKLMiSMFDNDASGTIDIYEFEKLYNYINQ---WLQVFKTYDQDSs 114
Cdd:cd16219   5 WFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLF-QMADKSESGTLEGEEFVLFYKALTQredVLKIFQDFSADG- 82

                        90       100
                ....*....|....*....|....*..
gi 7303734  115 ghieeQELTQAftqmgfrfspEFINFL 141
Cdd:cd16219  83 -----QKLTLL----------EFVDFL 94
EFh_PEF_CAPN12 cd16194
Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed ...
 36-117 7.91e-03

Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed calcium-activated neutral proteinase 12 (CANP 12), is a calpain large subunit mainly expressed in the cortex of the hair follicle. It may affect apoptosis regulation. CAPN12 contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320069 [Multi-domain]  Cd Length: 169  Bit Score: 35.62  E-value: 7.91e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7303734   36 QQWFSMVDRDRSGKINASELQAALvNGRGDHFSDNACKLMISMFDNDASgTIDIYEFEKLYNYINQWLQVFKTYDQDSSG 115
Cdd:cd16194  76 QAIFTKFDEDTSGTMDSYELRLAL-NAAGFHLNNQLTETLTSRYRDSRL-RVDFESFLSCLAHLTCIFCQCSQHDDGGEG 153


                ..
gi 7303734  116 HI 117
Cdd:cd16194 154 VI 155
EF-hand_6 pfam13405
EF-hand domain;
34-59 9.77e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 32.53  E-value: 9.77e-03
                          10        20
                  ....*....|....*....|....*.
gi 7303734     34 QAQQWFSMVDRDRSGKINASELQAAL 59
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKAL 26
 
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.
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