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Conserved domains on  [gi|34098931|ref|NP_031612|]
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calretinin isoform 1 [Mus musculus]

Protein Classification

EF-hand domain-containing protein( domain architecture ID 11610853)

EF-hand (EFh) domain-containing protein may be involved in binding intracellular calcium and in calcium signal transduction; similar to Tetrahymena thermophila 23 kDa calcium-binding protein that may play a crucial role in calcium-dependent regulation of ciliary movement

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EFh_HEF_CR cd16177
EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is ...
 21-268 1.97e-173

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: 478.22  E-value: 1.97e-173
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  21 FLEIWKHFDADGNGYIEGKELENFFQELEKARKGSGMMSKSDNFGEKMKEFMQKYDKNSDGKIEMAELAQILPTEENFLL 100
Cdd:cd16177   1 FLEIWKHFDADGNGYIEGKELENFFRELERARRGAGVDSKSANFGEKMKEFMQKYDKNADGRIEMAELAQILPTEENFLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 101 CFRQHVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:cd16177  81 CFRQHVGSSSEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEKKLQEYTQTILRMFDLNGDGKLGLSEMARLL 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 181 PVQENFLLKFQGMKLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMNIQQLTTYRKSVMSLAEAGKLYRKD 260
Cdd:cd16177 161 PVQENFLLKFQGMKLSSEEFNAIFAFYDKDGSGYIDENELDALLKDLYEKNKKEMDIQQLTNYKKSIMSLSDGGKLYRKE 240


                ....*...
gi 34098931 261 LEIVLCSE 268
Cdd:cd16177 241 LEMVLCSE 248
 
Name Accession Description Interval E-value
EFh_HEF_CR cd16177
EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is ...
 21-268 1.97e-173

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: 478.22  E-value: 1.97e-173
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  21 FLEIWKHFDADGNGYIEGKELENFFQELEKARKGSGMMSKSDNFGEKMKEFMQKYDKNSDGKIEMAELAQILPTEENFLL 100
Cdd:cd16177   1 FLEIWKHFDADGNGYIEGKELENFFRELERARRGAGVDSKSANFGEKMKEFMQKYDKNADGRIEMAELAQILPTEENFLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 101 CFRQHVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:cd16177  81 CFRQHVGSSSEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEKKLQEYTQTILRMFDLNGDGKLGLSEMARLL 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 181 PVQENFLLKFQGMKLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMNIQQLTTYRKSVMSLAEAGKLYRKD 260
Cdd:cd16177 161 PVQENFLLKFQGMKLSSEEFNAIFAFYDKDGSGYIDENELDALLKDLYEKNKKEMDIQQLTNYKKSIMSLSDGGKLYRKE 240


                ....*...
gi 34098931 261 LEIVLCSE 268
Cdd:cd16177 241 LEMVLCSE 248
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
65-229 5.50e-15

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 69.82  E-value: 5.50e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  65 GEKMKEFMQKYDKNSDGKIEMAELAqilpteenfllcfrqhvgssAEFMEAWR----KYDTDRSGYIEANELKGFLSDLl 140
Cdd:COG5126   4 RRKLDRRFDLLDADGDGVLERDDFE--------------------ALFRRLWAtlfsEADTDGDGRISREEFVAGMESL- 62

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 141 kkaNRPYDEPKLQEytqtILRMFDLNGDGKLGLSEMSRLLpvqenfllkfQGMKLTSEEFNAIFTFYDKDGSGYIDENEL 220
Cdd:COG5126  63 ---FEATVEPFARA----AFDLLDTDGDGKISADEFRRLL----------TALGVSEEEADELFARLDTDGDGKISFEEF 125


                ....*....
gi 34098931 221 DALLKDLYE 229
Cdd:COG5126 126 VAAVRDYYT 134
PTZ00184 PTZ00184
calmodulin; Provisional
 13-180 3.67e-08

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 51.30  E-value: 3.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931   13 LAELTASQFLEIWKHFDADGNGYIEGKELenffqelekarkGSGMMSKSDNFGE-KMKEFMQKYDKNSDGKIEMAELAQI 91
Cdd:PTZ00184   5 LTEEQIAEFKEAFSLFDKDGDGTITTKEL------------GTVMRSLGQNPTEaELQDMINEVDADGNGTIDFPEFLTL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931   92 LPTEenfllcfRQHVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANrpydepklQEYTQTILRMFDLNGDGKL 171
Cdd:PTZ00184  73 MARK-------MKDTDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLT--------DEEVDEMIREADVDGDGQI 137


                 ....*....
gi 34098931  172 GLSEMSRLL 180
Cdd:PTZ00184 138 NYEEFVKMM 146
EF-hand_7 pfam13499
EF-hand domain pair;
113-180 6.98e-08

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 48.40  E-value: 6.98e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34098931   113 MEAWRKYDTDRSGYIEANELKGFLSDLLKkanrpyDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:pfam13499   5 KEAFKLLDSDGDGYLDVEELKKLLRKLEE------GEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
59-225 3.68e-06

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 46.98  E-value: 3.68e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931   59 SKSDNFGEKMkefMQKYDKNSDGKIEMAELAQILPTEENfllcfrqhVGSSAEFMEAWRKYDTDRSGYIEANELkgflSD 138
Cdd:NF041410  23 ARSQQFQKQL---FAKLDSDGDGSVSQDELSSALSSKSD--------DGSLIDLSELFSDLDSDGDGSLSSDEL----AA 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  139 LLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLLPVQENfllkfqgmkltSEEFNAIFTFYDKDGSGYIDEN 218
Cdd:NF041410  88 AAPPPPPPPDQAPSTELADDLLSALDTDGDGSISSDELSAGLTSAGS-----------SADSSQLFSALDSDGDGSVSSD 156


                 ....*..
gi 34098931  219 ELDALLK 225
Cdd:NF041410 157 ELAAALQ 163
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 111-139 5.64e-04

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: 36.59  E-value: 5.64e-04
                           10        20
                   ....*....|....*....|....*....
gi 34098931    111 EFMEAWRKYDTDRSGYIEANELKGFLSDL 139
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
EFh_HEF_CR cd16177
EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is ...
 21-268 1.97e-173

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: 478.22  E-value: 1.97e-173
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  21 FLEIWKHFDADGNGYIEGKELENFFQELEKARKGSGMMSKSDNFGEKMKEFMQKYDKNSDGKIEMAELAQILPTEENFLL 100
Cdd:cd16177   1 FLEIWKHFDADGNGYIEGKELENFFRELERARRGAGVDSKSANFGEKMKEFMQKYDKNADGRIEMAELAQILPTEENFLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 101 CFRQHVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:cd16177  81 CFRQHVGSSSEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEKKLQEYTQTILRMFDLNGDGKLGLSEMARLL 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 181 PVQENFLLKFQGMKLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMNIQQLTTYRKSVMSLAEAGKLYRKD 260
Cdd:cd16177 161 PVQENFLLKFQGMKLSSEEFNAIFAFYDKDGSGYIDENELDALLKDLYEKNKKEMDIQQLTNYKKSIMSLSDGGKLYRKE 240


                ....*...
gi 34098931 261 LEIVLCSE 268
Cdd:cd16177 241 LEMVLCSE 248
EFh_HEF_CB cd16176
EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or ...
 21-268 1.79e-126

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: 359.15  E-value: 1.79e-126
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  21 FLEIWKHFDADGNGYIEGKELENFFQELEKARKGSGMmsksdNFGEKMKEFMQKYDKNSDGKIEMAELAQILPTEENFLL 100
Cdd:cd16176   1 FLEIWHHYDNDGNGYIEGKELQSFIQELQQARKKAGL-----ELSDQMKAFVDQYGQSTDGKIGIVELAQILPTEENFLL 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 101 CFRQHVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:cd16176  76 FFRQQLKSSEEFMQTWRKYDADHSGFIEADELKSFLKDLLKKANKPFDESKLEEYTHTMLKMFDSNNDGKLGLTEMARLL 155

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 181 PVQENFLLKFQGMKLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMNIQQLTTYRKSVMSLAEAGKLYRKD 260
Cdd:cd16176 156 PVQENFLLKFQGVKMCGKEFNKIFELYDQDGNGYIDENELDALLKDLCEKNKKDLDINNISTYKKSIMALSDGGKLYRTE 235


                ....*...
gi 34098931 261 LEIVLCSE 268
Cdd:cd16176 236 LALILCAE 243
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
 21-268 7.25e-117

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: 335.48  E-value: 7.25e-117
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  21 FLEIWKHFDADGNGYIEGKELENFFQELEKARKGSGMmsKSDNFGEKMKEFMQKYDKNSDGKIEMAELAQILPTEENFLL 100
Cdd:cd15902   1 FMEVWMHFDADGNGYIEGKELDSFLRELLKALNGKDK--TDDEVAEKKKEFMEKYDENEDGKIEIRELANILPTEENFLL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 101 CFR--QHVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSR 178
Cdd:cd15902  79 LFRreQPLISSVEFMKIWRKYDTDGSGFIEAKELKGFLKDLLLKNKKHVSPPKLDEYTKLILKEFDANKDGKLELDEMAK 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 179 LLPVQENFLLKFQ---GMKLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMNIQQLTTYRKSVMSLAE--- 252
Cdd:cd15902 159 LLPVQENFLLKFQilgAMDLTKEDFEKVFEHYDKDNNGVIEGNELDALLKDLLEKNKADIDKPDLENFRDAILRACDknk 238

                       250
                ....*....|....*.
gi 34098931 253 AGKLYRKDLEIVLCSE 268
Cdd:cd15902 239 DGKIQKTELALFLSAK 254
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
 21-265 6.35e-80

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: 241.93  E-value: 6.35e-80
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  21 FLEIWKHFDADGNGYIEGKELENFFQELEKA----RKGSGMMSKSDnFGEKMKEFMQKYDKNSDGKIEMAELAQILPTEE 96
Cdd:cd16179   1 FMDVWNHYDTDGNGYIEGTELDGFLREFVSSvnpeDVGPEVVSETA-LEELKEEFMEAYDENQDGRIDIRELAQLLPTEE 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  97 NFLLCFRQH--VGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYD--EPKLQEYTQTILRMFDLNGDGKLG 172
Cdd:cd16179  80 NFLLLFRRDnpLDSSVEFMKVWREYDKDNSGYIEADELKNFLKHLLKEAKRDNDvsEDKLIEYTDTILQLFDRNKDGKLQ 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 173 LSEMSRLLPVQENFLLK--FQGM-KLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMNIQQLTTYRKSVMS 249
Cdd:cd16179 160 LSEMARLLPVKENFLCRpiFKGAgKLTREDIDRVFALYDRDNNGTIENEELTGFLKDLLELVQEDYDEQDLEEFKEIILR 239

                       250
                ....*....|....*....
gi 34098931 250 ---LAEAGKLYRKDLEIVL 265
Cdd:cd16179 240 gwdFNNDGKISRKELTMLL 258
EFh_HEF_SCGN cd16178
EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand ...
 21-265 3.72e-75

EF-hand, calcium binding motif, found in secretagogin (SCGN); 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 calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.


Pssm-ID: 320078 [Multi-domain]  Cd Length: 257  Bit Score: 229.60  E-value: 3.72e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  21 FLEIWKHFDADGNGYIEGKELENFFQELEKarkgsgMMSKSDNFGE----KMKE-FMQKYDKNSDGKIEMAELAQILPTE 95
Cdd:cd16178   1 FAEIWQHFDADESGYIEGKELDNFFKDLLK------KLGTKDTISAdevqDVKEcFMSAYDVTGDGRIQIQELANIILPD 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  96 ENFLLCFRQH---VGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLG 172
Cdd:cd16178  75 DENFLLFFRReepLDSSVEFMRIWRKYDADSSGYISAAELKNFLRDLFLQHKKVITEDKLDEYTDTMMKIFDKNKDGRLD 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 173 LSEMSRLLPVQENFLLKFQGMKLTSEE----FNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMNIQQLTTYRKSVM 248
Cdd:cd16178 155 LNDMARILALQENFLLQFKMDAMSEEErkrdFEKIFAHYDVSKTGALEGPEVDGFVKDMMELVKPSISGVQLDKFKEIIL 234

                       250       260
                ....*....|....*....|
gi 34098931 249 SLAEA---GKLYRKDLEIVL 265
Cdd:cd16178 235 NHCDVnkdGKIQKSELALCL 254
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
 20-180 4.32e-33

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: 121.36  E-value: 4.32e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  20 QFLEIWKHFDADGNGYIEGKELENFFQELEKARKgsgmmSKSDNFGEKMKEF----MQKYDKNSDGKIEMAELAQILPTE 95
Cdd:cd16179  96 EFMKVWREYDKDNSGYIEADELKNFLKHLLKEAK-----RDNDVSEDKLIEYtdtiLQLFDRNKDGKLQLSEMARLLPVK 170

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  96 ENFLL--CFRQ-HVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLG 172
Cdd:cd16179 171 ENFLCrpIFKGaGKLTREDIDRVFALYDRDNNGTIENEELTGFLKDLLELVQEDYDEQDLEEFKEIILRGWDFNNDGKIS 250


                ....*...
gi 34098931 173 LSEMSRLL 180
Cdd:cd16179 251 RKELTMLL 258
EFh_HEF_SCGN cd16178
EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand ...
 16-182 3.56e-28

EF-hand, calcium binding motif, found in secretagogin (SCGN); 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 calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.


Pssm-ID: 320078 [Multi-domain]  Cd Length: 257  Bit Score: 108.26  E-value: 3.56e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  16 LTAS-QFLEIWKHFDADGNGYIEGKELENFFQELEKARKGSGMMSKSDNFGEKMkefMQKYDKNSDGKIEMAELAQILPT 94
Cdd:cd16178  88 LDSSvEFMRIWRKYDADSSGYISAAELKNFLRDLFLQHKKVITEDKLDEYTDTM---MKIFDKNKDGRLDLNDMARILAL 164

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  95 EENFLLCFRQHVGSSAE----FMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGK 170
Cdd:cd16178 165 QENFLLQFKMDAMSEEErkrdFEKIFAHYDVSKTGALEGPEVDGFVKDMMELVKPSISGVQLDKFKEIILNHCDVNKDGK 244

                       170
                ....*....|..
gi 34098931 171 LGLSEMSRLLPV 182
Cdd:cd16178 245 IQKSELALCLGL 256
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
65-229 5.50e-15

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 69.82  E-value: 5.50e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  65 GEKMKEFMQKYDKNSDGKIEMAELAqilpteenfllcfrqhvgssAEFMEAWR----KYDTDRSGYIEANELKGFLSDLl 140
Cdd:COG5126   4 RRKLDRRFDLLDADGDGVLERDDFE--------------------ALFRRLWAtlfsEADTDGDGRISREEFVAGMESL- 62

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 141 kkaNRPYDEPKLQEytqtILRMFDLNGDGKLGLSEMSRLLpvqenfllkfQGMKLTSEEFNAIFTFYDKDGSGYIDENEL 220
Cdd:COG5126  63 ---FEATVEPFARA----AFDLLDTDGDGKISADEFRRLL----------TALGVSEEEADELFARLDTDGDGKISFEEF 125


                ....*....
gi 34098931 221 DALLKDLYE 229
Cdd:COG5126 126 VAAVRDYYT 134
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
15-180 1.07e-12

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 63.66  E-value: 1.07e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  15 ELTASQFLEIWKHFDADGNGYIEGKELENFFQELEKARKGsgmmsksdnfgekmkefmqKYDKNSDGKIEMAELAQILPT 94
Cdd:COG5126   1 DLQRRKLDRRFDLLDADGDGVLERDDFEALFRRLWATLFS-------------------EADTDGDGRISREEFVAGMES 61

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  95 EenfllcFRQHVGSSAEfmEAWRKYDTDRSGYIEANELKGFLSDLlkkanrPYDEPKLQEytqtILRMFDLNGDGKLGLS 174
Cdd:COG5126  62 L------FEATVEPFAR--AAFDLLDTDGDGKISADEFRRLLTAL------GVSEEEADE----LFARLDTDGDGKISFE 123


                ....*.
gi 34098931 175 EMSRLL 180
Cdd:COG5126 124 EFVAAV 129
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 111-180 5.26e-12

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: 59.87  E-value: 5.26e-12
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 111 EFMEAWRKYDTDRSGYIEANELKGFLSDLlkkanrpyDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSL--------GEGLSEEEIDEMIREVDKDGDGKIDFEEFLELM 62
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 113-219 5.04e-11

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: 59.92  E-value: 5.04e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 113 MEAW-RKYDTDRSGYIEANELKGFLSdllkKANRPYDEpklqEYTQTILRMFDLNGDGKLGLSEMSRLlpvqENFLLKFQ 191
Cdd:cd16185   2 LRQWfRAVDRDRSGSIDVNELQKALA----GGGLLFSL----ATAEKLIRMFDRDGNGTIDFEEFAAL----HQFLSNMQ 69

                        90       100
                ....*....|....*....|....*...
gi 34098931 192 gmkltseefnAIFTFYDKDGSGYIDENE 219
Cdd:cd16185  70 ----------NGFEQRDTSRSGRLDANE 87
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 111-227 9.04e-11

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: 59.08  E-value: 9.04e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 111 EFMEAWRKYDTDRSGYIEANELKGFLSDllkkanrpYDEPKLQEYT-QTILRMFDLNGDGKLGLSEMSRLLpvqeNFLLK 189
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKELQRALSN--------GDWTPFSIETvRLMINMFDRDRSGTINFDEFVGLW----KYIQD 68

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 34098931 190 FQGmkltseefnaIFTFYDKDGSGYIDENELDALLKDL 227
Cdd:cd16180  69 WRR----------LFRRFDRDRSGSIDFNELQNALSSF 96
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 111-226 4.01e-10

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: 57.44  E-value: 4.01e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 111 EFMEAWRKYDTDrSGYIEANELKGFLSdllKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLLpvqeNFLLKF 190
Cdd:cd15897   1 QLRNVFQAVAGD-DGEISATELQQALS---NVGWTHFDLGFSLETCRSMIAMMDRDHSGKLNFSEFKGLW----NYIKAW 72

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 34098931 191 QgmkltseefnAIFTFYDKDGSGYIDENELDALLKD 226
Cdd:cd15897  73 Q----------EIFRTYDTDGSGTIDSNELRQALSG 98
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 159-225 1.07e-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: 53.32  E-value: 1.07e-09
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34098931 159 ILRMFDLNGDGKLGLSEMSRLLPVQenfllkfqGMKLTSEEFNAIFTFYDKDGSGYIDENELDALLK 225
Cdd:cd00051   5 AFRLFDKDGDGTISADELKAALKSL--------GEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 20-92 2.01e-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: 52.55  E-value: 2.01e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34098931  20 QFLEIWKHFDADGNGYIEGKELENFFQELEkarkgsgmMSKSDnfgEKMKEFMQKYDKNSDGKIEMAELAQIL 92
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLG--------EGLSE---EEIDEMIREVDKDGDGKIDFEEFLELM 62
PTZ00184 PTZ00184
calmodulin; Provisional
 13-180 3.67e-08

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 51.30  E-value: 3.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931   13 LAELTASQFLEIWKHFDADGNGYIEGKELenffqelekarkGSGMMSKSDNFGE-KMKEFMQKYDKNSDGKIEMAELAQI 91
Cdd:PTZ00184   5 LTEEQIAEFKEAFSLFDKDGDGTITTKEL------------GTVMRSLGQNPTEaELQDMINEVDADGNGTIDFPEFLTL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931   92 LPTEenfllcfRQHVGSSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANrpydepklQEYTQTILRMFDLNGDGKL 171
Cdd:PTZ00184  73 MARK-------MKDTDSEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLT--------DEEVDEMIREADVDGDGQI 137


                 ....*....
gi 34098931  172 GLSEMSRLL 180
Cdd:PTZ00184 138 NYEEFVKMM 146
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 23-215 5.58e-08

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: 51.06  E-value: 5.58e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  23 EIWKHF---DADGNGYIEGKELENffqelekARKGSGMmsksdNFGEKMKE-FMQKYDKNSDGKIEMAELAQIlpteENF 98
Cdd:cd16185   1 ELRQWFravDRDRSGSIDVNELQK-------ALAGGGL-----LFSLATAEkLIRMFDRDGNGTIDFEEFAAL----HQF 64

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  99 LLCFRQhvgssaefmeAWRKYDTDRSGYIEANELKGFLSdllkKANRPYDEPKLqeytQTILRMFDLNGDGKLGLSEmsr 178
Cdd:cd16185  65 LSNMQN----------GFEQRDTSRSGRLDANEVHEALA----ASGFQLDPPAF----QALFRKFDPDRGGSLGFDD--- 123

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 34098931 179 llpvqenfllkFQGMKLTSEEFNAIFTFYDKDGSGYI 215
Cdd:cd16185 124 -----------YIELCIFLASARNLFQAFDRQRTGRV 149
EF-hand_7 pfam13499
EF-hand domain pair;
113-180 6.98e-08

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 48.40  E-value: 6.98e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34098931   113 MEAWRKYDTDRSGYIEANELKGFLSDLLKkanrpyDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:pfam13499   5 KEAFKLLDSDGDGYLDVEELKKLLRKLEE------GEPLSDEEVEELFKEFDLDKDGRISFEEFLELY 66
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
 15-92 8.48e-08

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: 51.97  E-value: 8.48e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34098931  15 ELTASQFLEIWKHFDADGNGYIEGKELENFFQELEKARKGSGMMSKSDNFgekMKEFMQKYDKNSDGKIEMAELAQIL 92
Cdd:cd15902 177 DLTKEDFEKVFEHYDKDNNGVIEGNELDALLKDLLEKNKADIDKPDLENF---RDAILRACDKNKDGKIQKTELALFL 251
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 120-224 3.27e-07

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: 49.19  E-value: 3.27e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 120 DTDRSGYIEANELKgflSDLLKKANRPYDEpklqEYTQTILRMFDLNGDGKLGLSEMSRLLpvqeNFLlkfqgmkltsEE 199
Cdd:cd16184  10 DRDRSGKISAKELQ---QALVNGNWSHFND----ETCRLMIGMFDKDKSGTIDIYEFQALW----NYI----------QQ 68

                        90       100
                ....*....|....*....|....*
gi 34098931 200 FNAIFTFYDKDGSGYIDENELDALL 224
Cdd:cd16184  69 WKQVFQQFDRDRSGSIDENELHQAL 93
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 23-132 6.62e-07

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: 48.03  E-value: 6.62e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  23 EIWKHF---DADGNGYIEGKELEnffQELEKARkGSgmmsksdNFGEKMKEFMQK-YDKNSDGKIEMAELAQilpteenf 98
Cdd:cd16184   1 EVQQWFqavDRDRSGKISAKELQ---QALVNGN-WS-------HFNDETCRLMIGmFDKDKSGTIDIYEFQA-------- 61

                        90       100       110
                ....*....|....*....|....*....|....
gi 34098931  99 LLCFRQhvgssaEFMEAWRKYDTDRSGYIEANEL 132
Cdd:cd16184  62 LWNYIQ------QWKQVFQQFDRDRSGSIDENEL 89
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
 120-220 9.99e-07

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: 47.63  E-value: 9.99e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 120 DTDRSGYIEANELKGFLSdllkkaN---RPYDEpklqEYTQTILRMFDLNGDGKLGLSEmsrllpvqenfllkFQGMKLT 196
Cdd:cd16183  10 DKDRSGQISATELQQALS------NgtwTPFNP----ETVRLMIGMFDRDNSGTINFQE--------------FAALWKY 65

                        90       100
                ....*....|....*....|....
gi 34098931 197 SEEFNAIFTFYDKDGSGYIDENEL 220
Cdd:cd16183  66 ITDWQNCFRSFDRDNSGNIDKNEL 89
XopAW NF041410
XopAW family type III secretion system calcium-binding effector;
59-225 3.68e-06

XopAW family type III secretion system calcium-binding effector;


Pssm-ID: 469301 [Multi-domain]  Cd Length: 227  Bit Score: 46.98  E-value: 3.68e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931   59 SKSDNFGEKMkefMQKYDKNSDGKIEMAELAQILPTEENfllcfrqhVGSSAEFMEAWRKYDTDRSGYIEANELkgflSD 138
Cdd:NF041410  23 ARSQQFQKQL---FAKLDSDGDGSVSQDELSSALSSKSD--------DGSLIDLSELFSDLDSDGDGSLSSDEL----AA 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  139 LLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLLPVQENfllkfqgmkltSEEFNAIFTFYDKDGSGYIDEN 218
Cdd:NF041410  88 AAPPPPPPPDQAPSTELADDLLSALDTDGDGSISSDELSAGLTSAGS-----------SADSSQLFSALDSDGDGSVSSD 156


                 ....*..
gi 34098931  219 ELDALLK 225
Cdd:NF041410 157 ELAAALQ 163
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 20-215 5.00e-06

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: 45.60  E-value: 5.00e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  20 QFLEIWKHFDADGNGYIEGKELenffQELekarkgsgmMSKSDNFGEKM---KEFMQKYDKNSDGKIEMAELAQILptee 96
Cdd:cd16180   1 ELRRIFQAVDRDRSGRISAKEL----QRA---------LSNGDWTPFSIetvRLMINMFDRDRSGTINFDEFVGLW---- 63

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  97 nfllcfrqhvgssaEFMEAWRK----YDTDRSGYIEANELKGFLSDLlkkanrPYDEPklQEYTQTILRMFDLNGDGKLG 172
Cdd:cd16180  64 --------------KYIQDWRRlfrrFDRDRSGSIDFNELQNALSSF------GYRLS--PQFVQLLVRKFDRRRRGSIS 121

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 34098931 173 LSEMSRLLpvqenFLLKfqgmKLTSeefnaIFTFYDKDGSGYI 215
Cdd:cd16180 122 FDDFVEAC-----VTLK----RLTD-----AFRKYDTNRTGYA 150
EFh_parvalbumin_like cd16251
EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes ...
 102-179 5.01e-06

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: 44.06  E-value: 5.01e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 102 FRQHVG----SSAEFMEAWRKYDTDRSGYIEANELKGFLSdllkkaNRPYDEPKL-QEYTQTILRMFDLNGDGKLGLSEM 176
Cdd:cd16251  22 FFEHVGlkqkSEDQIKKVFQILDKDKSGFIEEEELKYILK------GFSIAGRDLtDEETKALLAAGDTDGDGKIGVEEF 95


                ...
gi 34098931 177 SRL 179
Cdd:cd16251  96 ATL 98
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 157-252 8.79e-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: 44.20  E-value: 8.79e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 157 QTILRMFDLNGDGKLGLSEMSRLLpvqeNFLLkfqgMKLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKEMN 236
Cdd:cd15898   3 RRQWIKADKDGDGKLSLKEIKKLL----KRLN----IRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELEPI 74

                        90
                ....*....|....*.
gi 34098931 237 IQQLTTYRKSVMSLAE 252
Cdd:cd15898  75 FKKYAGTNRDYMTLEE 90
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
 12-219 1.89e-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: 45.00  E-value: 1.89e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  12 HLAELTASQFLEIW-KHFDADGNGYIEGKELENF----FQELEKarkgsgmmsksdnfgEKMKEFMQKYDKNSDGKIEMA 86
Cdd:cd16227  28 ELPPEEAKRRLAVLaKKMDLNDDGFIDRKELKAWilrsFKMLDE---------------EEANERFEEADEDGDGKVTWE 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  87 ELAQ-------------ILPTEENFLLCFRQHvgssaefMEAWRKYDTDRSGYIEANELKGFLSdllkkanrPYDEPKLQ 153
Cdd:cd16227  93 EYLAdsfgyddedneemIKDSTEDDLKLLEDD-------KEMFEAADLNKDGKLDKTEFSAFQH--------PEEYPHMH 157

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34098931 154 EY-TQTILRMFDLNGDGKLGLSE-MSRLLPVQENFLLKFQgmkltSEEFNAiftFYDKDGSGYIDENE 219
Cdd:cd16227 158 PVlIEQTLRDKDKDNDGFISFQEfLGDRAGHEDKEWLLVE-----KDRFDE---DYDKDGDGKLDGEE 217
EFh_PEF_CAPN12 cd16194
Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed ...
 127-220 2.81e-05

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: 43.33  E-value: 2.81e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 127 IEANELKGFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEmsrllpvqenfllkFQGMKLTSEEFNAIFTF 206
Cdd:cd16194  16 INASELQKILSIALERAHTSKPREFGLRTCRQLIQCFDHGQNGKLALEE--------------FQQLWGYLLEWQAIFTK 81

                        90
                ....*....|....
gi 34098931 207 YDKDGSGYIDENEL 220
Cdd:cd16194  82 FDEDTSGTMDSYEL 95
EFh_parvalbumin_beta cd16255
EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed ...
 108-179 4.10e-05

EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed Oncomodulin-1 (OM), is a small calcium-binding protein that is expressed in hepatomas, as well as in the blastocyst and the cytotrophoblasts of the placenta. It is also found to be expressed in the cochlear outer hair cells of the organ of Corti and frequently expressed in neoplasms. Mammalian beta-parvalbumin is secreted by activated macrophages and neutrophils. It may function as a tissue-specific Ca2+-dependent regulatory protein, and may also serve as a specialized cytosolic Ca2+ buffer. Beta-parvalbumin acts as a potent growth-promoting signal between the innate immune system and neurons in vivo. It has high and specific affinity for its receptor on retinal ganglion cells (RGC) and functions as the principal mediator of optic nerve regeneration. It exerts its effects in a cyclic adenosine monophosphate (cAMP)-dependent manner and can further elevate intracellular cAMP levels. Moreover, beta-parvalbumin is associated with efferent function and outer hair cell electromotility, and can identify different hair cell types in the mammalian inner ear. Beta-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+. The EF site displays a high-affinity for Ca2+/Mg2+, and the CD site is a low-affinity Ca2+-specific site. In addition, beta-parvalbumin is distinguished from other parvalbumins by its unusually low isoelectric point (pI = 3.1) and sequence eccentricities (e.g., Y57-L58-D59 instead of F57-I58-E59).


Pssm-ID: 319998 [Multi-domain]  Cd Length: 101  Bit Score: 41.64  E-value: 4.10e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 34098931 108 SSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKAnRPYDEPKlqeyTQTILRMFDLNGDGKLGLSEMSRL 179
Cdd:cd16255  32 SADDVKKVFEIIDQDKSGFIEEEELKLFLQNFSSGA-RELTDAE----TKAFLKAGDSDGDGKIGVEEFQAL 98
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 23-223 6.18e-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: 42.42  E-value: 6.18e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  23 EIWKHFDAdgngyIEGKELENFFQELEKARKGSGMMSKSDNFG-EKMKEFMQKYDKNSDGKIEMAELAQILpteeNFLLC 101
Cdd:cd15897   1 QLRNVFQA-----VAGDDGEISATELQQALSNVGWTHFDLGFSlETCRSMIAMMDRDHSGKLNFSEFKGLW----NYIKA 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 102 FRqhvgssaefmEAWRKYDTDRSGYIEANELKGFLSDLLKKANrpydepklQEYTQTILRMFDlNGDGKLGLSEMSRLlp 181
Cdd:cd15897  72 WQ----------EIFRTYDTDGSGTIDSNELRQALSGAGYRLS--------EQTYDIIIRRYD-RGRGNIDFDDFIQC-- 130

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 34098931 182 vqenfLLKFQGMkltseeFNAiFTFYDKDGSGYIDENELDAL 223
Cdd:cd15897 131 -----CVRLQRL------TDA-FRRYDKDQDGQIQVNYDEFL 160
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 199-234 9.06e-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: 39.45  E-value: 9.06e-05
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 34098931 199 EFNAIFTFYDKDGSGYIDENELDALLKDLYEKNKKE 234
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEE 36
PTZ00184 PTZ00184
calmodulin; Provisional
 66-224 9.73e-05

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 41.67  E-value: 9.73e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931   66 EKMKEFMQKYDKNSDGKIEMAELAQIL------PTEenfllcfrqhvgssAEFMEAWRKYDTDRSGYIEANElkgFLSDL 139
Cdd:PTZ00184  11 AEFKEAFSLFDKDGDGTITTKELGTVMrslgqnPTE--------------AELQDMINEVDADGNGTIDFPE---FLTLM 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  140 LKKANRPYDEPKLQEytqtILRMFDLNGDGKLGLSEMSRLLpvqenfllKFQGMKLTSEEFNAIFTFYDKDGSGYIDENE 219
Cdd:PTZ00184  74 ARKMKDTDSEEEIKE----AFKVFDRDGNGFISAAELRHVM--------TNLGEKLTDEEVDEMIREADVDGDGQINYEE 141


                 ....*
gi 34098931  220 LDALL 224
Cdd:PTZ00184 142 FVKMM 146
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
 66-231 1.37e-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: 42.19  E-value: 1.37e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  66 EKMKEFMQKYDKNSDGKIEMAEL-AQILpteenfllcFRQHVGSSAEFMEAWRKYDTDRSGYIEANELK----GFLSDLL 140
Cdd:cd16226  35 ERLGIIVDKIDKNGDGFVTEEELkDWIK---------YVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKkatyGFLDDEE 105

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 141 KKANRPYDEPKLQEYTQTILRMFDLNGDGKLGLSEMSRLLPVQEnfllkFQGMK--LTSEEFNAIftfyDKDGSGYIDEN 218
Cdd:cd16226 106 EDDDLHESYKKMIRRDERRWKAADQDGDGKLTKEEFTAFLHPEE-----FPHMRdiVVQETLEDI----DKNKDGFISLE 176

                       170
                ....*....|...
gi 34098931 219 EldaLLKDLYEKN 231
Cdd:cd16226 177 E---YIGDMYRDD 186
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
 29-169 1.58e-04

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: 41.09  E-value: 1.58e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  29 DADGNGYIEGKELEnffQELEkarkgSGMMSKSDnfGEKMKEFMQKYDKNSDGKIEMAELAQILPTEENFLLCFRqhvgs 108
Cdd:cd16183  10 DKDRSGQISATELQ---QALS-----NGTWTPFN--PETVRLMIGMFDRDNSGTINFQEFAALWKYITDWQNCFR----- 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34098931 109 saefmeawrKYDTDRSGYIEANELK------GF-LSDllkkanrpydepklqEYTQTILRMFDLNGDG 169
Cdd:cd16183  75 ---------SFDRDNSGNIDKNELKqaltsfGYrLSD---------------QFYDILVRKFDRQGRG 118
EFh_parvalbumin_alpha cd16254
EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2 ...
 108-180 2.07e-04

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: 39.81  E-value: 2.07e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34098931 108 SSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPklqeyTQTILRMFDLNGDGKLGLSEMSRLL 180
Cdd:cd16254  32 SADDVKKVFHILDKDKSGFIEEDELKFVLKGFSPDGRDLSDKE-----TKALLAAGDKDGDGKIGIDEFATLV 99
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
 23-176 2.09e-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: 41.80  E-value: 2.09e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  23 EIWKHFDADGNGYIEGKELENF---FQELEkarkgsgmmSKSDNFGEKMKEFMQK-------YDKNSDGKIEMAELAQIL 92
Cdd:cd16226  75 RQWKEYDPNKDGKLSWEEYKKAtygFLDDE---------EEDDDLHESYKKMIRRderrwkaADQDGDGKLTKEEFTAFL 145

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  93 PTEENfllcfrQHVgssAEF--MEAWRKYDTDRSGYIEANElkgFLSDLLKKANRPYDEPKLQEYTQTILRMFDLNGDGK 170
Cdd:cd16226 146 HPEEF------PHM---RDIvvQETLEDIDKNKDGFISLEE---YIGDMYRDDDEEEDPDWVKSEREQFKEFRDKNKDGK 213


                ....*.
gi 34098931 171 LGLSEM 176
Cdd:cd16226 214 MDREEV 219
PTZ00183 PTZ00183
centrin; Provisional
 111-225 2.18e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 40.83  E-value: 2.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  111 EFMEAWRKYDTDRSGYIEANELK------GF----------LSDLLKKANRPYD-------------EPKLQEYTQTILR 161
Cdd:PTZ00183  18 EIREAFDLFDTDGSGTIDPKELKvamrslGFepkkeeikqmIADVDKDGSGKIDfeefldimtkklgERDPREEILKAFR 97

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34098931  162 MFDLNGDGKLGLSEMSRllpvqenfLLKFQGMKLTSEEFNAIFTFYDKDGSGYIDENELDALLK 225
Cdd:PTZ00183  98 LFDDDKTGKISLKNLKR--------VAKELGETITDEELQEMIDEADRNGDGEISEEEFYRIMK 153
EF-hand_7 pfam13499
EF-hand domain pair;
157-219 2.36e-04

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 38.39  E-value: 2.36e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34098931   157 QTILRMFDLNGDGKLGLSEMSRLLpvqENFLLkfqGMKLTSEEFNAIFTFYDKDGSGYIDENE 219
Cdd:pfam13499   5 KEAFKLLDSDGDGYLDVEELKKLL---RKLEE---GEPLSDEEVEELFKEFDLDKDGRISFEE 61
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
 117-220 5.04e-04

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: 39.88  E-value: 5.04e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 117 RKYdTDRSGYIEANELKGFLSD-LLKKANRPYDEPKLqEYTQTILRMFDLNGDGKLGLSEMSRLLpvqeNFLLKFQgmkl 195
Cdd:cd16195   7 LKY-ADQGGELDAEQLQKLLNEnLLKGLAGSGGGFSL-DACRSMVALMDLSVNGRLSLEEFSRLW----KKLRKYK---- 76

                        90       100
                ....*....|....*....|....*
gi 34098931 196 tseefnAIFTFYDKDGSGYIDENEL 220
Cdd:cd16195  77 ------DIFQKADVSKSGFLSLSEL 95
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 111-139 5.64e-04

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: 36.59  E-value: 5.64e-04
                           10        20
                   ....*....|....*....|....*....
gi 34098931    111 EFMEAWRKYDTDRSGYIEANELKGFLSDL 139
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 199-227 5.75e-04

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: 36.59  E-value: 5.75e-04
                           10        20
                   ....*....|....*....|....*....
gi 34098931    199 EFNAIFTFYDKDGSGYIDENELDALLKDL 227
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 112-226 6.22e-04

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: 39.19  E-value: 6.22e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 112 FMEAWRKYDTDRSGYIEANELKGflsdLLKKANRPYDEPKLQEytqtILRMFDLNGDGKLGLSEMSRLLpvqenfllkfq 191
Cdd:cd15898   2 LRRQWIKADKDGDGKLSLKEIKK----LLKRLNIRVSEKELKK----LFKEVDTNGDGTLTFDEFEELY----------- 62

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 34098931 192 gMKLTS-EEFNAIFTFYDKDGSGYIDENELDALLKD 226
Cdd:cd15898  63 -KSLTErPELEPIFKKYAGTNRDYMTLEEFIRFLRE 97
EFh_parvalbumins cd16253
EF-hand, calcium binding motif, found in parvalbumins; Parvalbumins are small, acidic, ...
 102-179 6.85e-04

EF-hand, calcium binding motif, found in parvalbumins; 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: 319996 [Multi-domain]  Cd Length: 101  Bit Score: 38.31  E-value: 6.85e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 102 FRQHVG----SSAEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANRPYDEPklqeyTQTILRMFDLNGDGKLGLSEMS 177
Cdd:cd16253  22 FFKAVGlskkSPADIKKVFNILDQDKSGFIEEEELKLFLKNFSDGARVLSDKE-----TKNFLAAGDSDGDGKIGVDEFK 96


                ..
gi 34098931 178 RL 179
Cdd:cd16253  97 SM 98
PLN02964 PLN02964
phosphatidylserine decarboxylase
 153-230 7.11e-04

phosphatidylserine decarboxylase


Pssm-ID: 215520 [Multi-domain]  Cd Length: 644  Bit Score: 40.61  E-value: 7.11e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34098931  153 QEYTQTILRMFDLNGDGKLGLSEMSRLLpvqenfllKFQGMKLTSEEFNAIFTFYDKDGSGYIDENELDALLKDLYEK 230
Cdd:PLN02964 178 RSFARRILAIVDYDEDGQLSFSEFSDLI--------KAFGNLVAANKKEELFKAADLNGDGVVTIDELAALLALQQEQ 247
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 199-227 7.31e-04

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 36.22  E-value: 7.31e-04
                          10        20
                  ....*....|....*....|....*....
gi 34098931   199 EFNAIFTFYDKDGSGYIDENELDALLKDL 227
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EF-hand_6 pfam13405
EF-hand domain;
111-139 1.01e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 35.62  E-value: 1.01e-03
                          10        20
                  ....*....|....*....|....*....
gi 34098931   111 EFMEAWRKYDTDRSGYIEANELKGFLSDL 139
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 67-137 1.23e-03

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: 36.37  E-value: 1.23e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 34098931  67 KMKEFMQKYDKNSDGKIEMAELAQILP-TEENFllcfrqhvgSSAEFMEAWRKYDTDRSGYIEANELKGFLS 137
Cdd:cd00051   1 ELREAFRLFDKDGDGTISADELKAALKsLGEGL---------SEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 111-139 1.24e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 35.45  E-value: 1.24e-03
                          10        20
                  ....*....|....*....|....*....
gi 34098931   111 EFMEAWRKYDTDRSGYIEANELKGFLSDL 139
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EF-hand_6 pfam13405
EF-hand domain;
199-227 1.47e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 35.23  E-value: 1.47e-03
                          10        20
                  ....*....|....*....|....*....
gi 34098931   199 EFNAIFTFYDKDGSGYIDENELDALLKDL 227
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29
EF-hand_7 pfam13499
EF-hand domain pair;
66-137 1.50e-03

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 36.46  E-value: 1.50e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 34098931    66 EKMKEFMQKYDKNSDGKIEMAELaqilpteENFLLCFRQHVGSSAEFMEAW-RKYDTDRSGYIEANELKGFLS 137
Cdd:pfam13499   2 EKLKEAFKLLDSDGDGYLDVEEL-------KKLLRKLEEGEPLSDEEVEELfKEFDLDKDGRISFEEFLELYS 67
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 20-48 3.09e-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: 34.28  E-value: 3.09e-03
                           10        20
                   ....*....|....*....|....*....
gi 34098931     20 QFLEIWKHFDADGNGYIEGKELENFFQEL 48
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_calglandulin_like cd16252
EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The ...
 102-180 3.12e-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: 36.35  E-value: 3.12e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931 102 FRQHVGSSAEFMEAWRK----YDTDRSGYIEANELKGFLSDLlkKANRPYdEPKLQEYTQTILRMFDLNGDGKLGLSEMS 177
Cdd:cd16252  25 YMQKFQTSEQQEEAIRKafqmLDKDKSGFIEWNEIKYILSTV--PSSMPV-APLSDEEAEAMIQAADTDGDGRIDFQEFS 101


                ...
gi 34098931 178 RLL 180
Cdd:cd16252 102 DMV 104
EFh_parvalbumin_beta cd16255
EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed ...
 13-87 3.80e-03

EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed Oncomodulin-1 (OM), is a small calcium-binding protein that is expressed in hepatomas, as well as in the blastocyst and the cytotrophoblasts of the placenta. It is also found to be expressed in the cochlear outer hair cells of the organ of Corti and frequently expressed in neoplasms. Mammalian beta-parvalbumin is secreted by activated macrophages and neutrophils. It may function as a tissue-specific Ca2+-dependent regulatory protein, and may also serve as a specialized cytosolic Ca2+ buffer. Beta-parvalbumin acts as a potent growth-promoting signal between the innate immune system and neurons in vivo. It has high and specific affinity for its receptor on retinal ganglion cells (RGC) and functions as the principal mediator of optic nerve regeneration. It exerts its effects in a cyclic adenosine monophosphate (cAMP)-dependent manner and can further elevate intracellular cAMP levels. Moreover, beta-parvalbumin is associated with efferent function and outer hair cell electromotility, and can identify different hair cell types in the mammalian inner ear. Beta-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+. The EF site displays a high-affinity for Ca2+/Mg2+, and the CD site is a low-affinity Ca2+-specific site. In addition, beta-parvalbumin is distinguished from other parvalbumins by its unusually low isoelectric point (pI = 3.1) and sequence eccentricities (e.g., Y57-L58-D59 instead of F57-I58-E59).


Pssm-ID: 319998 [Multi-domain]  Cd Length: 101  Bit Score: 36.25  E-value: 3.80e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34098931  13 LAELTASQFLEIWKHFDADGNGYIEGKELENFFQELEkarkgSGMMSKSDnfgEKMKEFMQKYDKNSDGKIEMAE 87
Cdd:cd16255  28 LSKKSADDVKKVFEIIDQDKSGFIEEEELKLFLQNFS-----SGARELTD---AETKAFLKAGDSDGDGKIGVEE 94
EF-hand_6 pfam13405
EF-hand domain;
20-48 4.34e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 34.07  E-value: 4.34e-03
                          10        20
                  ....*....|....*....|....*....
gi 34098931    20 QFLEIWKHFDADGNGYIEGKELENFFQEL 48
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29
PTZ00184 PTZ00184
calmodulin; Provisional
 110-230 7.29e-03

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 36.28  E-value: 7.29e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34098931  110 AEFMEAWRKYDTDRSGYIEANELKGFLSDLLKKANrpydEPKLQEYTQTIlrmfDLNGDGKLGLSEMSRLLPVQenfllk 189
Cdd:PTZ00184  11 AEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPT----EAELQDMINEV----DADGNGTIDFPEFLTLMARK------ 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 34098931  190 fqgMKLT--SEEFNAIFTFYDKDGSGYIDENELDALLKDLYEK 230
Cdd:PTZ00184  77 ---MKDTdsEEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEK 116
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 21-48 8.55e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 33.14  E-value: 8.55e-03
                          10        20
                  ....*....|....*....|....*...
gi 34098931    21 FLEIWKHFDADGNGYIEGKELENFFQEL 48
Cdd:pfam00036   2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29
 
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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