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Conserved domains on  [gi|167744832]
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Chain A, Calcium binding protein 2

Protein Classification

EF-hand domain-containing protein( domain architecture ID 11473824)

EF-hand (EFh) domain-containing protein may be involved in binding intracellular calcium and in calcium signal transduction

Gene Ontology:  GO:0005509
PubMed:  2479149

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
3-132 1.61e-21

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


:

Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 83.30  E-value: 1.61e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFvsskrpikNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEkvgLKILYK 82
Cdd:COG5126    8 DRRFDLLDADGDGVLERDDFEAL--------FRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPF---ARAAFD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 167744832  83 LMDADGDGKLTKEEVTTFFKKFGYEKVVDQIM--KADANGDGYITLEEFLAF 132
Cdd:COG5126   77 LLDTDGDGKISADEFRRLLTALGVSEEEADELfaRLDTDGDGKISFEEFVAA 128
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
3-132 1.61e-21

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 83.30  E-value: 1.61e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFvsskrpikNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEkvgLKILYK 82
Cdd:COG5126    8 DRRFDLLDADGDGVLERDDFEAL--------FRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPF---ARAAFD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 167744832  83 LMDADGDGKLTKEEVTTFFKKFGYEKVVDQIM--KADANGDGYITLEEFLAF 132
Cdd:COG5126   77 LLDTDGDGKISADEFRRLLTALGVSEEEADELfaRLDTDGDGKISFEEFVAA 128
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
3-131 1.62e-15

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 69.71  E-value: 1.62e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFVSSKRpiKNEQLLQL--IFKAIDIDGNGEIDLAEFTKFAA-------AVKEQDLSDE 73
Cdd:NF041410  30 KQLFAKLDSDGDGSVSQDELSSALSSKS--DDGSLIDLseLFSDLDSDGDGSLSSDELAAAAPppppppdQAPSTELADD 107

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 167744832  74 kvglkiLYKLMDADGDGKLTKEEVTTFFKKFGYEKVVDQIMKA-DANGDGYITLEEFLA 131
Cdd:NF041410 108 ------LLSALDTDGDGSISSDELSAGLTSAGSSADSSQLFSAlDSDGDGSVSSDELAA 160
PTZ00184 PTZ00184
calmodulin; Provisional
 6-129 6.23e-15

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 66.71  E-value: 6.23e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   6 FKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEF-TKFAAAVKEQDLSDEkvgLKILYKLM 84
Cdd:PTZ00184  17 FSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFlTLMARKMKDTDSEEE---IKEAFKVF 93

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 167744832  85 DADGDGKLTKEEV----TTFFKKFGYEKVVDQIMKADANGDGYITLEEF 129
Cdd:PTZ00184  94 DRDGNGFISAAELrhvmTNLGEKLTDEEVDEMIREADVDGDGQINYEEF 142
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
 5-130 2.93e-12

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 61.45  E-value: 2.93e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   5 LFKQLDANGDGSVSYEEVKAFVS--SKRPIKNEqlLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEKVGLKilYK 82
Cdd:cd16226   40 IVDKIDKNGDGFVTEEELKDWIKyvQKKYIRED--VDRQWKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHES--YK 115

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167744832  83 LM-----------DADGDGKLTKEEVTTFF--KKFGY--EKVVDQIM-KADANGDGYITLEEFL 130
Cdd:cd16226  116 KMirrderrwkaaDQDGDGKLTKEEFTAFLhpEEFPHmrDIVVQETLeDIDKNKDGFISLEEYI 179
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
2-59 1.47e-08

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 51.22  E-value: 1.47e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 167744832   2 AEALFKQLDANGDGSVSYEEVKAFVSSKRpiKNEQLLQLiFKAIDIDGNGEIDLAEFT 59
Cdd:NF041410 105 ADDLLSALDTDGDGSISSDELSAGLTSAG--SSADSSQL-FSALDSDGDGSVSSDELA 159
EF-hand_7 pfam13499
EF-hand domain pair;
5-62 9.81e-08

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 46.09  E-value: 9.81e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832    5 LFKQLDANGDGSVSYEEVKAFVSSKRPIKN--EQLLQLIFKAIDIDGNGEIDLAEFTKFA 62
Cdd:pfam13499   7 AFKLLDSDGDGYLDVEELKKLLRKLEEGEPlsDEEVEELFKEFDLDKDGRISFEEFLELY 66
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
 3-58 2.43e-07

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 45.73  E-value: 2.43e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 167744832     3 EALFKQLDANGDGSVSYEEVKA-FVSSKRPIkneQLLQLIFKAIDIDGNGEIDLAEF 58
Cdd:smart00027  13 EQIFRSLDKNQDGTVTGAQAKPiLLKSGLPQ---TLLAKIWNLADIDNDGELDKDEF 66
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
3-132 1.61e-21

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 83.30  E-value: 1.61e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFvsskrpikNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEkvgLKILYK 82
Cdd:COG5126    8 DRRFDLLDADGDGVLERDDFEAL--------FRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPF---ARAAFD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 167744832  83 LMDADGDGKLTKEEVTTFFKKFGYEKVVDQIM--KADANGDGYITLEEFLAF 132
Cdd:COG5126   77 LLDTDGDGKISADEFRRLLTALGVSEEEADELfaRLDTDGDGKISFEEFVAA 128
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
1-106 2.90e-19

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 77.52  E-value: 2.90e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   1 MAEALFKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVkeqDLSDEKVglKIL 80
Cdd:COG5126   34 LWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTAL---GVSEEEA--DEL 108

                         90       100
                 ....*....|....*....|....*.
gi 167744832  81 YKLMDADGDGKLTKEEVTTFFKKFGY 106
Cdd:COG5126  109 FARLDTDGDGKISFEEFVAAVRDYYT 134
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
3-131 1.62e-15

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 69.71  E-value: 1.62e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFVSSKRpiKNEQLLQL--IFKAIDIDGNGEIDLAEFTKFAA-------AVKEQDLSDE 73
Cdd:NF041410  30 KQLFAKLDSDGDGSVSQDELSSALSSKS--DDGSLIDLseLFSDLDSDGDGSLSSDELAAAAPppppppdQAPSTELADD 107

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 167744832  74 kvglkiLYKLMDADGDGKLTKEEVTTFFKKFGYEKVVDQIMKA-DANGDGYITLEEFLA 131
Cdd:NF041410 108 ------LLSALDTDGDGSISSDELSAGLTSAGSSADSSQLFSAlDSDGDGSVSSDELAA 160
PTZ00184 PTZ00184
calmodulin; Provisional
 6-129 6.23e-15

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 66.71  E-value: 6.23e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   6 FKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEF-TKFAAAVKEQDLSDEkvgLKILYKLM 84
Cdd:PTZ00184  17 FSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFlTLMARKMKDTDSEEE---IKEAFKVF 93

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 167744832  85 DADGDGKLTKEEV----TTFFKKFGYEKVVDQIMKADANGDGYITLEEF 129
Cdd:PTZ00184  94 DRDGNGFISAAELrhvmTNLGEKLTDEEVDEMIREADVDGDGQINYEEF 142
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
 5-130 2.93e-12

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 61.45  E-value: 2.93e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   5 LFKQLDANGDGSVSYEEVKAFVS--SKRPIKNEqlLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEKVGLKilYK 82
Cdd:cd16226   40 IVDKIDKNGDGFVTEEELKDWIKyvQKKYIRED--VDRQWKEYDPNKDGKLSWEEYKKATYGFLDDEEEDDDLHES--YK 115

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167744832  83 LM-----------DADGDGKLTKEEVTTFF--KKFGY--EKVVDQIM-KADANGDGYITLEEFL 130
Cdd:cd16226  116 KMirrderrwkaaDQDGDGKLTKEEFTAFLhpEEFPHmrDIVVQETLeDIDKNKDGFISLEEYI 179
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 1-63 2.34e-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: 55.25  E-value: 2.34e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167744832   1 MAEALFKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFAA 63
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh_CREC_RCN3 cd16230
EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand ...
 12-131 3.80e-10

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal His-Asp-Glu-Leu (HDEL) tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320028 [Multi-domain]  Cd Length: 268  Bit Score: 55.75  E-value: 3.80e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  12 NGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEKVGLKILYKLM------- 84
Cdd:cd16230   49 DGDGWVSLAELRAWIAHTQQRHIRDSVSAAWQTYDTDRDGRVGWEELRNATYGHYEPGEEFHDVEDAETYKKMlarderr 128

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 167744832  85 ----DADGDGKLTKEEVTTFFKKFGYEK----VVDQIMK-ADANGDGYITLEEFLA 131
Cdd:cd16230  129 frvaDQDGDSMATREELTAFLHPEEFPHmrdiVVAETLEdLDKNKDGYVQVEEYIA 184
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
 3-131 7.90e-10

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 55.02  E-value: 7.90e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEKVGL----- 77
Cdd:cd16227   39 AVLAKKMDLNDDGFIDRKELKAWILRSFKMLDEEEANERFEEADEDGDGKVTWEEYLADSFGYDDEDNEEMIKDSteddl 118

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 167744832  78 ------KILYKLMDADGDGKLTKEEVTTFFKKFGYEK----VVDQIMKA-DANGDGYITLEEFLA 131
Cdd:cd16227  119 klleddKEMFEAADLNKDGKLDKTEFSAFQHPEEYPHmhpvLIEQTLRDkDKDNDGFISFQEFLG 183
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 82-132 2.18e-09

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: 50.24  E-value: 2.18e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 167744832  82 KLMDADGDGKLTKEEVTTFFKKFGY---EKVVDQIMK-ADANGDGYITLEEFLAF 132
Cdd:cd00051    7 RLFDKDGDGTISADELKAALKSLGEglsEEEIDEMIReVDKDGDGKIDFEEFLEL 61
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
2-59 1.47e-08

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 51.22  E-value: 1.47e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 167744832   2 AEALFKQLDANGDGSVSYEEVKAFVSSKRpiKNEQLLQLiFKAIDIDGNGEIDLAEFT 59
Cdd:NF041410 105 ADDLLSALDTDGDGSISSDELSAGLTSAG--SSADSSQL-FSALDSDGDGSVSSDELA 159
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
 4-131 2.09e-08

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 50.90  E-value: 2.09e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   4 ALFKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAE-----------FTKFAAAVKEQDLSD 72
Cdd:cd15899   39 VIVSKMDVDKDGFISAKELHSWILESFKRHAMEESKEQFRAVDPDEDGHVSWDEykndtygsvgdDEENVADNIKEDEEY 118

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 167744832  73 EKV--GLKILYKLMDADGDGKLTKEEVTTFF--KKFGYEK--VVDQIMKA-DANGDGYITLEEFLA 131
Cdd:cd15899  119 KKLllKDKKRFEAADQDGDLILTLEEFLAFLhpEESPYMLdfVIKETLEDlDKNGDGFISLEEFIS 184
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
 3-130 2.45e-08

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 50.52  E-value: 2.45e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFVSSKR-PIKNEQLLQLIFKAIDIDGNGEIDLAEFTK--FAAAVKEQDLSDEKVGLKI 79
Cdd:cd15899  126 KKRFEAADQDGDLILTLEEFLAFLHPEEsPYMLDFVIKETLEDLDKNGDGFISLEEFISdpYSADENEEEPEWVKVEKER 205

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 167744832  80 LYKLMDADGDGKLTKEEVTTFFKKFGYEKVVDQ----IMKADANGDGYITLEEFL 130
Cdd:cd15899  206 FVELRDKDKDGKLDGEELLSWVDPSNQEIALEEakhlIAESDENKDGKLSPEEIL 260
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 1-132 5.78e-08

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: 48.05  E-value: 5.78e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   1 MAEALFKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFAaavkeQDLSDEKVGLKIL 80
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELY-----KSLTERPELEPIF 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 167744832  81 YKLMDADGDGkLTKEEVTTFFKKFGYEKV----VDQIMK--ADANGDGYITLEEFLAF 132
Cdd:cd15898   76 KKYAGTNRDY-MTLEEFIRFLREEQGENVseeeCEELIEkyEPERENRQLSFEGFTNF 132
EF-hand_7 pfam13499
EF-hand domain pair;
5-62 9.81e-08

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 46.09  E-value: 9.81e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832    5 LFKQLDANGDGSVSYEEVKAFVSSKRPIKN--EQLLQLIFKAIDIDGNGEIDLAEFTKFA 62
Cdd:pfam13499   7 AFKLLDSDGDGYLDVEELKKLLRKLEEGEPlsDEEVEELFKEFDLDKDGRISFEEFLELY 66
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
 3-58 2.43e-07

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 45.73  E-value: 2.43e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 167744832     3 EALFKQLDANGDGSVSYEEVKA-FVSSKRPIkneQLLQLIFKAIDIDGNGEIDLAEF 58
Cdd:smart00027  13 EQIFRSLDKNQDGTVTGAQAKPiLLKSGLPQ---TLLAKIWNLADIDNDGELDKDEF 66
EF-hand_7 pfam13499
EF-hand domain pair;
77-132 3.40e-07

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 44.55  E-value: 3.40e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 167744832   77 LKILYKLMDADGDGKLTKEEVTTFFKKFGY-----EKVVDQIMK-ADANGDGYITLEEFLAF 132
Cdd:pfam13499   4 LKEAFKLLDSDGDGYLDVEELKKLLRKLEEgeplsDEEVEELFKeFDLDKDGRISFEEFLEL 65
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
 5-131 3.98e-07

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 47.31  E-value: 3.98e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   5 LFKQLDANGDGSVSYEEVKAFVSskrPIKNEQLLQLIFKAI----DIDGNGEIDLAEFtkFAAAVKEQDLSDEKVGLKIL 80
Cdd:cd16227  127 MFEAADLNKDGKLDKTEFSAFQH---PEEYPHMHPVLIEQTlrdkDKDNDGFISFQEF--LGDRAGHEDKEWLLVEKDRF 201

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 167744832  81 YKLMDADGDGKLTKEEVTTF----FKKFGYEKVVDQIMKADANGDGYITLEEFLA 131
Cdd:cd16227  202 DEDYDKDGDGKLDGEEILSWlvpdNEEIAEEEVDHLFASADDDHDDRLSFDEILD 256
PTZ00183 PTZ00183
centrin; Provisional
 6-130 1.04e-06

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 45.07  E-value: 1.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   6 FKQLDANGDGSVSYEEVK-AFVSSKRPIKNEQLLQLIfKAIDIDGNGEIDLAEFtkFAAAVKEQDLSDEKVGLKILYKLM 84
Cdd:PTZ00183  23 FDLFDTDGSGTIDPKELKvAMRSLGFEPKKEEIKQMI-ADVDKDGSGKIDFEEF--LDIMTKKLGERDPREEILKAFRLF 99

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 167744832  85 DADGDGKLTKEEVTTFFKKFGY----EKVVDQIMKADANGDGYITLEEFL 130
Cdd:PTZ00183 100 DDDKTGKISLKNLKRVAKELGEtitdEELQEMIDEADRNGDGEISEEEFY 149
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
 6-132 1.05e-06

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.


Pssm-ID: 320023 [Multi-domain]  Cd Length: 278  Bit Score: 46.14  E-value: 1.05e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   6 FKQLDANGDGSVSYEEVKAFVSSK-----RPIKNEQllQLIFKAIDIDGNGEIDLAEF-TKFaaaVKEQDLSDEKVglki 79
Cdd:cd16225   40 FKKVDVNTDGFLSAEELEDWIMEKtqehfQEAVEEN--EQIFKAVDTDKDGNVSWEEYrVHF---LLSKGYSEEEA---- 110

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 167744832  80 lyKLMDADGDGKLTKEEVttffkKFGYEKVVDQIMKADANGDGYITLEEFLAF 132
Cdd:cd16225  111 --EEKIKNNEELKLDEDD-----KEVLDRYKDRWSQADEPEDGLLDVEEFLSF 156
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
 51-129 1.62e-06

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed calcium-binding protein ERC-55, or E6-binding protein (E6BP), or TCBP-49, is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. It is associated with tumorigenesis, in particular with transformation of cells of the cervix induced by human papillomavirus (HPV), through binding to human papillomavirus (HPV) E6 oncogenic protein. It specifically interacts with vitamin D receptor among nuclear receptors. RCN2 contains an N-terminal signal sequence followed by six copies of the EF-hand Ca2+-binding motif, and a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320022 [Multi-domain]  Cd Length: 268  Bit Score: 45.50  E-value: 1.62e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  51 GEIDLAEFTKFAAavkeqdlSDEKVGLKILYKLMDADGDGKLTKEEVTTF----FKKFGYEKVVDQIMKADANGDGYITL 126
Cdd:cd16224   19 GEEDADEFAKLSP-------EEQQKRLKSIIKKIDTDSDGFLTEEELSSWiqqsFRHYALEDAKQQFPEYDKDGDGAVTW 91


                 ...
gi 167744832 127 EEF 129
Cdd:cd16224   92 DEY 94
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 2-132 1.64e-06

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: 44.51  E-value: 1.64e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   2 AEALFKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFaaavkEQDLSDEKVGlkilY 81
Cdd:cd16185    2 LRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFAAL-----HQFLSNMQNG----F 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 167744832  82 KLMDADGDGKLTKEEVTTFFKKFGY---EKVVDQIMKA---DANG----DGYITLEEFLAF 132
Cdd:cd16185   73 EQRDTSRSGRLDANEVHEALAASGFqldPPAFQALFRKfdpDRGGslgfDDYIELCIFLAS 133
EFh_CREC_Calumenin cd16228
EF-hand, calcium binding motif, found in calumenin; Calumenin, also termed crocalbin, or IEF ...
 8-130 1.90e-06

EF-hand, calcium binding motif, found in calumenin; Calumenin, also termed crocalbin, or IEF SSP 9302, is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It is highly expressed in various brain regions. Thus it plays an important role in migration and differentiation of neurons, and/or in Ca2+ signaling between glial cells and neurons. Calumenin is involved in Ca2+ homeostasis through interacting with ryanodine receptor RyR2 and SERCA2. It acts as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. Calumenin also forms a Ca2+-dependent complex with thrombospondin-1, which is broadly involved in haemostasis and thrombosis. Moreover, calumenin is a molecular chaperone that endogenously regulates the vitamin K-dependent gamma-carboxylation of several proteins, including blood coagulation factors (such as FII, FVII, FIX, FX, and proteins C, S and Z), cell survival factors (Gas6) and bone metabolism proteins (such as matrix Gla protein or MGP, osteocalcin and periostin), through targeting the gamma-glutamyl carboxylase. It also functions as a charged F508del-cystic fibrosis transmembrane regulator (CFTR) folding modulator, as well as a G551D-CFTR associated protein. Furthermore, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. It binds to and stabilizes fibulin-1, and further inactivates extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling.


Pssm-ID: 320026 [Multi-domain]  Cd Length: 263  Bit Score: 45.32  E-value: 1.90e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   8 QLDANGDGSVSYEEVKAFV--SSKRPIKNEQLLQliFKAIDIDGNGEIDLAEF--TKFAAAVKEQDLSDEKVGLKIL--- 80
Cdd:cd16228   43 KIDEDKDGFVTEDELKAWIkfAQKRWIYEDVERQ--WKGHDLNEDGLVSWEEYknATYGYILDDPDPDDGFNYKQMMvrd 120

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 167744832  81 ---YKLMDADGDGKLTKEEVTTFF--KKFGYEK--VVDQIMK-ADANGDGYITLEEFL 130
Cdd:cd16228  121 errFKMADKDGDLRATKEEFTAFLhpEEYDYMKdiVVLETMEdIDKNGDGFIDLEEYI 178
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
 2-131 2.78e-06

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.


Pssm-ID: 320023 [Multi-domain]  Cd Length: 278  Bit Score: 44.98  E-value: 2.78e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   2 AEALFKQLDANGDGSVSYEEVKA-FVSSKrpikneqllqlifkaididGNGEIDLAEFTKFAAAVKEQDLSDEKVglkIL 80
Cdd:cd16225   75 NEQIFKAVDTDKDGNVSWEEYRVhFLLSK-------------------GYSEEEAEEKIKNNEELKLDEDDKEVL---DR 132

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  81 YKLM----DADGDGKLTKEEVTTFF----KKFGYEKVVDQIMKA-DANGDGYITLEEFLA 131
Cdd:cd16225  133 YKDRwsqaDEPEDGLLDVEEFLSFRhpehSRGMLKNMVKEILHDlDQDGDEKLTLDEFVS 192
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 5-132 9.40e-06

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain 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 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. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.


Pssm-ID: 320032 [Multi-domain]  Cd Length: 140  Bit Score: 42.21  E-value: 9.40e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   5 LFKQLDANGDGSVSYEEVKAFVS------SKRPIKneqllqLIFKAIDIDGNGEIDLAEFTKFAAAV-KEQDLSdekvgl 77
Cdd:cd16202    5 QFRKADKNGDGKLSFKECKKLLKklnvkvDKDYAK------KLFQEADTSGEDVLDEEEFVQFYNRLtKRPEIE------ 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167744832  78 kilyKLMD--ADGDGKLTKEEVTTFFKKFGYEKVVD-----QIMK-----ADANGDGYITLEEFLAF 132
Cdd:cd16202   73 ----ELFKkySGDDEALTVEELRRFLQEEQKVKDVTlewaeQLIEtyepsEDLKAQGLMSLDGFTLF 135
EFh_CREC_RCN1 cd16229
EF-hand, calcium binding motif, found in reticulocalbin-1 (RCN-1); RCN-1 is an endoplasmic ...
 8-131 1.06e-05

EF-hand, calcium binding motif, found in reticulocalbin-1 (RCN-1); RCN-1 is an endoplasmic reticulum resident low-affinity Ca2+-binding protein with six EF-hand motifs and a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It is expressed at the cell surface. RCN-1 acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signaling cascade. It also plays a key role in the development of doxorubicin-associated resistance.


Pssm-ID: 320027 [Multi-domain]  Cd Length: 267  Bit Score: 43.33  E-value: 1.06e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   8 QLDANGDGSVSYEEVKAFVS--SKRPIKNEqlLQLIFKAIDIDGNGEIDLAEFTK------FAAAVKEQDLSDEKVGLKI 79
Cdd:cd16229   43 RIDDDKDGFVTTEELKAWIKrvQKRYIYEN--VAKVWKDYDLNKDNKISWEEYKQatygyyLGNPEEFQDATDQFSFKKM 120

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167744832  80 L------YKLMDADGDGKLTKEEVTTFF--KKFGYEK---VVDQIMKADANGDGYITLEEFLA 131
Cdd:cd16229  121 LprderrFKAADLDGDLAATREEFTAFLhpEEFEHMKdivVLETLEDIDKNGDGFVDEDEYIA 183
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
 38-133 1.43e-05

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 42.96  E-value: 1.43e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  38 LQLIFKAIDIDGNGEIDLAEFTKFAAAVKEQDLSDEkvgLKILYKLMDADGDGKLTKEEvttfFKK--FGYEKVVDQIMK 115
Cdd:cd16226   37 LGIIVDKIDKNGDGFVTEEELKDWIKYVQKKYIRED---VDRQWKEYDPNKDGKLSWEE----YKKatYGFLDDEEEDDD 109

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 167744832 116 ------------------ADANGDGYITLEEFLAFN 133
Cdd:cd16226  110 lhesykkmirrderrwkaADQDGDGKLTKEEFTAFL 145
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
 6-130 2.47e-05

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.


Pssm-ID: 320023 [Multi-domain]  Cd Length: 278  Bit Score: 42.29  E-value: 2.47e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   6 FKQLDANGDGSVSYEEvkaFVSSKRPIKNEQLLQLIFKAI----DIDGNGEIDLAEFTKF-AAAVKEQDLSDEKVG---- 76
Cdd:cd16225  137 WSQADEPEDGLLDVEE---FLSFRHPEHSRGMLKNMVKEIlhdlDQDGDEKLTLDEFVSLpPGTVEEQQAEDDDEWkker 213

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 167744832  77 LKILYKLMDADGDGKLTKEEVTTFF----KKFGYEKVVDQIMKADANGDGYITLEEFL 130
Cdd:cd16225  214 KKEFEEVIDLNHDGKVTKEELEEYMdprnERHALNEAKQLIAVADENKDGKLSLEEIL 271
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
 38-132 3.31e-05

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 41.92  E-value: 3.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  38 LQLIFKAIDIDGNGEIDLAEFTKFAAAvKEQDLSDEKVglKILYKLMDADGDGKLTKEEVTTffKKFGYEKVVDQIMK-- 115
Cdd:cd16227   38 LAVLAKKMDLNDDGFIDRKELKAWILR-SFKMLDEEEA--NERFEEADEDGDGKVTWEEYLA--DSFGYDDEDNEEMIkd 112

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 167744832 116 ------------------ADANGDGYITLEEFLAF 132
Cdd:cd16227  113 steddlklleddkemfeaADLNKDGKLDKTEFSAF 147
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
 3-58 6.17e-05

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 38.74  E-value: 6.17e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 167744832   3 EALFKQLDANGDGSVSYEEVKA-FVSSKRPiknEQLLQLIFKAIDIDGNGEIDLAEF 58
Cdd:cd00052    2 DQIFRSLDPDGDGLISGDEARPfLGKSGLP---RSVLAQIWDLADTDKDGKLDKEEF 55
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
 2-132 9.06e-05

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: 39.90  E-value: 9.06e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   2 AEALFKQLdANGDGSVSYEEVKAFVSS---KRPIKNEQL-----LQLIFkAIDIDGNGEIDLAEFtkfaaavkeQDLSDE 73
Cdd:cd16182    2 VRELFEKL-AGEDEEIDAVELQKLLNAsllKDMPKFDGFsletcRSLIA-LMDTNGSGRLDLEEF---------KTLWSD 70

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 167744832  74 KVGLKILYKLMDADGDGKLTKEEVTTFFKKFGYE---KVVDQIMKADANGDGYITLEEFLAF 132
Cdd:cd16182   71 LKKWQAIFKKFDTDRSGTLSSYELRKALESAGFHlsnKVLQALVLRYADSTGRITFEDFVSC 132
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 5-131 9.71e-05

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: 39.72  E-value: 9.71e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   5 LFKQLDAnGDGSVSYEEVKAFVSS-----KRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEqdlsdekvgLKI 79
Cdd:cd15897    5 VFQAVAG-DDGEISATELQQALSNvgwthFDLGFSLETCRSMIAMMDRDHSGKLNFSEFKGLWNYIKA---------WQE 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 167744832  80 LYKLMDADGDGKLTKEEVTTFFKKFGY---EKVVDQIMKADANGDGYITLEEFLA 131
Cdd:cd15897   75 IFRTYDTDGSGTIDSNELRQALSGAGYrlsEQTYDIIIRRYDRGRGNIDFDDFIQ 129
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
 64-130 3.89e-04

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 38.72  E-value: 3.89e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167744832  64 AVKEQDLSDE--KVGLKILYKLMDADGDGKLTKEEVTTF----FKKFGYEKVVDQIMKADANGDGYITLEEFL 130
Cdd:cd16226   22 AKEFDQLTPEesKERLGIIVDKIDKNGDGFVTEEELKDWikyvQKKYIREDVDRQWKEYDPNKDGKLSWEEYK 94
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
 80-129 4.55e-04

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 36.43  E-value: 4.55e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 167744832  80 LYKLMDADGDGKLTKEEVTTFFKKFGYEKVV-DQIMK-ADANGDGYITLEEF 129
Cdd:cd00052    4 IFRSLDPDGDGLISGDEARPFLGKSGLPRSVlAQIWDlADTDKDGKLDKEEF 55
PTZ00183 PTZ00183
centrin; Provisional
 5-103 6.83e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 37.36  E-value: 6.83e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   5 LFKQLDANGDGSVSYEEVKAFVSSKRPIK-NEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKEqDLSDEKvgLKILYKL 83
Cdd:PTZ00183  58 MIADVDKDGSGKIDFEEFLDIMTKKLGERdPREEILKAFRLFDDDKTGKISLKNLKRVAKELGE-TITDEE--LQEMIDE 134

                         90       100
                 ....*....|....*....|
gi 167744832  84 MDADGDGKLTKEEVTTFFKK 103
Cdd:PTZ00183 135 ADRNGDGEISEEEFYRIMKK 154
EF-hand_8 pfam13833
EF-hand domain pair;
49-103 7.40e-04

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 35.37  E-value: 7.40e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 167744832   49 GNGEIDLAEFTKFAAAVKEQDLSDEKVglKILYKLMDADGDGKLTKEEVTTFFKK 103
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEV--DILFREFDTDGDGYISFDEFCVLLER 53
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
 38-132 7.90e-04

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 37.81  E-value: 7.90e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  38 LQLIFKAIDIDGNGEIDLAE---FTKFAAAVKEQDLSDEKvglkilYKLMDADGDGKLTKEE--VTTFFKKFGYEKVVD- 111
Cdd:cd15899   37 LGVIVSKMDVDKDGFISAKElhsWILESFKRHAMEESKEQ------FRAVDPDEDGHVSWDEykNDTYGSVGDDEENVAd 110

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 167744832 112 ---------QIM--------KADANGDGYITLEEFLAF 132
Cdd:cd15899  111 nikedeeykKLLlkdkkrfeAADQDGDLILTLEEFLAF 148
EFh_SPARC_EC cd00252
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 6-58 1.64e-03

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC)-like proteins; The SPARC protein family represents a diverse group of proteins that share a follistatin-like (FS) domain and an extracellular calcium-binding (EC) domain with two EF-hand motifs. It includes SPARC (for secreted protein acidic and rich in cysteine, also termed osteonectin/ON, or basement-membrane protein 40/BM-40), SPARC-like protein 1 (for secreted protein, acidic and rich in cysteines-like 1/ SPARCL1, also termed high endothelial venule protein/Hevi, or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2), testicans 1, 2, and 3 (also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycans, or SPOCK), secreted modular calcium-binding protein SMOC-1 (also termed SPARC-related modular calcium-binding protein 1) and SMOC-2 (also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2/SMAP-2), follistatin-related protein 1 (FRP-1, also termed follistatin-like protein 1/fstl-1, TSC-36/Flik, TGF-beta inducible protein). The SPARC proteins have been implicated in modulating cell interaction with the extracellular milieu, including regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways, as well as in development and disease.


Pssm-ID: 320009  Cd Length: 107  Bit Score: 35.81  E-value: 1.64e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 167744832   6 FKQLDANGDGSVSYEEVKAFVSSKRPIknEQLLQLIFKAIDIDGNGEIDLAEF 58
Cdd:cd00252   51 FDNLDNNKDGKLDKRELAPFRAPLMPL--EHCARGFFESCDLNKDKKISLQEW 101
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
 2-130 2.26e-03

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed calcium-binding protein ERC-55, or E6-binding protein (E6BP), or TCBP-49, is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. It is associated with tumorigenesis, in particular with transformation of cells of the cervix induced by human papillomavirus (HPV), through binding to human papillomavirus (HPV) E6 oncogenic protein. It specifically interacts with vitamin D receptor among nuclear receptors. RCN2 contains an N-terminal signal sequence followed by six copies of the EF-hand Ca2+-binding motif, and a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320022 [Multi-domain]  Cd Length: 268  Bit Score: 36.64  E-value: 2.26e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   2 AEALFKQLDANGDGSVSYEEVKafvsskrpikneqlLQLIFKAIDIDGNGEIDLAEFTKFaaavKEQDLSDEKvglkiLY 81
Cdd:cd16224   74 AKQQFPEYDKDGDGAVTWDEYN--------------MQMYDRVIDYDEDTVLDDEEEESF----RQLHLKDKK-----RF 130

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 167744832  82 KLMDADGDGKLTKEEVTTF--------FKKFGYEKVVDQImkaDANGDGYITLEEFL 130
Cdd:cd16224  131 DKANTDGGPGLNLTEFIAFehpeevdyMTEFVIQEALEEH---DKDGDGFISLEEFL 184
EFh_SPARC_EC cd00252
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 52-130 2.57e-03

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC)-like proteins; The SPARC protein family represents a diverse group of proteins that share a follistatin-like (FS) domain and an extracellular calcium-binding (EC) domain with two EF-hand motifs. It includes SPARC (for secreted protein acidic and rich in cysteine, also termed osteonectin/ON, or basement-membrane protein 40/BM-40), SPARC-like protein 1 (for secreted protein, acidic and rich in cysteines-like 1/ SPARCL1, also termed high endothelial venule protein/Hevi, or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2), testicans 1, 2, and 3 (also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycans, or SPOCK), secreted modular calcium-binding protein SMOC-1 (also termed SPARC-related modular calcium-binding protein 1) and SMOC-2 (also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2/SMAP-2), follistatin-related protein 1 (FRP-1, also termed follistatin-like protein 1/fstl-1, TSC-36/Flik, TGF-beta inducible protein). The SPARC proteins have been implicated in modulating cell interaction with the extracellular milieu, including regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways, as well as in development and disease.


Pssm-ID: 320009  Cd Length: 107  Bit Score: 35.04  E-value: 2.57e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  52 EIDLAEFTKFAAAVKEQDLS--DEKVGLKILYKLMDADGDGKLTKEEVTTF-FKKFGYEKVVDQ-IMKADANGDGYITLE 127
Cdd:cd00252   20 LKEQDENRSYDNNKRGHDLSgtMRKEIAQWEFDNLDNNKDGKLDKRELAPFrAPLMPLEHCARGfFESCDLNKDKKISLQ 99


                 ...
gi 167744832 128 EFL 130
Cdd:cd00252  100 EWL 102
calgranulins cd05030
Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 ...
 91-130 3.26e-03

Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 family of EF-hand calcium-modulated proteins, including S100A8, S100A9, and S100A12 . Note that the S-100 hierarchy, to which this Calgranulin group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. These proteins are expressed mainly in granulocytes, and are involved in inflammation, allergy, and neuritogenesis, as well as in host-parasite response. Calgranulins are modulated not only by calcium, but also by other metals such as zinc and copper. Structural data suggested that calgranulins may exist in multiple structural forms, homodimers, as well as hetero-oligomers. For example, the S100A8/S100A9 complex called calprotectin plays important roles in the regulation of inflammatory processes, wound repair, and regulating zinc-dependent enzymes as well as microbial growth.


Pssm-ID: 240156 [Multi-domain]  Cd Length: 88  Bit Score: 34.63  E-value: 3.26e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 167744832  91 KLTKEEVTTFFKKFGYEKVVDQIMKA-DANGDGYITLEEFL 130
Cdd:cd05030   34 QLVEKELPNFLKKEKNQKAIDKIFEDlDTNQDGQLSFEEFL 74
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 13-132 3.94e-03

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes 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 then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 320037 [Multi-domain]  Cd Length: 142  Bit Score: 35.30  E-value: 3.94e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832  13 GDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDIDGNGEIDLAEFTKFAAAVKE-QDlsdekvgLKILYKLMDADGDGK 91
Cdd:cd16207   15 GDERLDFEDVEKLCRRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKLLKRrKD-------IKAIFKQLTKPGSDG 87

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 167744832  92 LTKEEVTTFFKKFGYEKVVDQIM---------KADANGDGYITLEEFLAF 132
Cdd:cd16207   88 LTLEEFLKFLRDVQKEDVDRETWekifekfarRIDDSDSLTMTLEGFTSF 137
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 3-93 4.17e-03

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: 35.48  E-value: 4.17e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   3 EALFKQLDANGDGSVSYEEVKAFVSSKRPIKNEQLLQLIFKAIDiDGNGEIDLAEFTkfAAAVKEQDLSDekvglkiLYK 82
Cdd:cd15897   73 QEIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYD-RGRGNIDFDDFI--QCCVRLQRLTD-------AFR 142

                         90
                 ....*....|.
gi 167744832  83 LMDADGDGKLT 93
Cdd:cd15897  143 RYDKDQDGQIQ 153
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 4-132 5.10e-03

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 34.66  E-value: 5.10e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   4 ALFKQLDANGDGSVSYEEVkafvsskrpikneqlLQLIFKAididgngeidlaeftkfaaavkEQDLSDEKVglKILYKL 83
Cdd:cd16205    4 QTFEEADKNGDGLLSIGEI---------------LQLMHKL----------------------NVNLPRRKV--RQMFKE 44

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 167744832  84 MDAD-GDGKLTKEEVTTFFKKFGYEKVVDQIMKADANGDGYITLEEFLAF 132
Cdd:cd16205   45 ADTDdNQGTLDFEEFCAFYKMMSTRRELYLLLLSYSNKKDYLTLEDLARF 94
EFh_calglandulin_like cd16252
EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The ...
 6-59 6.08e-03

EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The family corresponds to a group of uncharacterized calglandulin-like proteins. Although their biological function remain unclear, they show high sequence similarity with human calglandulin-like protein GAGLP, which is an ortholog of calglandulin from the venom glands of Bothrops insularis snake. Both GAGLP and calglandulin are putative Ca2+-binding proteins with four EF-hand motifs. However, members in this family contain only three EF-hand motifs. In this point, they may belong to the parvalbumin-like EF-hand family, which is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix).


Pssm-ID: 319995 [Multi-domain]  Cd Length: 106  Bit Score: 34.04  E-value: 6.08e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167744832   6 FKQLDANGDGSVSYEEVKAFVSS------KRPIKNEQLlQLIFKAIDIDGNGEIDLAEFT 59
Cdd:cd16252   43 FQMLDKDKSGFIEWNEIKYILSTvpssmpVAPLSDEEA-EAMIQAADTDGDGRIDFQEFS 101
 
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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