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Conserved domains on  [gi|826307929|ref|XP_012504786|]
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PREDICTED: calpain-3 isoform X1 [Propithecus coquereli]

Protein Classification

penta-EF hand family protein; EF hand domain-containing protein( domain architecture ID 12004785)

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

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Peptidase_C2 pfam00648
Calpain family cysteine protease;
75-415 0e+00

Calpain family cysteine protease;


:

Pssm-ID: 459889 [Multi-domain]  Cd Length: 295  Bit Score: 564.82  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   75 YVDPEFPPDETSLFY--SQKFPIQFVWKRPPEICENPRFIIGGANRTDICQGDLGDCWFLAAIACLTLNKRLLFRVIPHD 152
Cdd:pfam00648   1 FEDPEFPADDSSLGYppSPPPPRGVEWKRPKEICSNPQFIVDGASRFDICQGELGDCWLLAAIASLTLNPKLLERVVPPD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  153 QSFVENYAGIFHFQFWRYGDWVDVVIDDCLPTYNNQLVFTKSNHRNEFWSALLEKAYAKLHGSYEALKGGNTTEAMEDFT 232
Cdd:pfam00648  81 QSFEENYAGIFHFRFWRFGEWVDVVIDDRLPTRNGKLLFVHSRDKNEFWSALLEKAYAKLHGSYEALKGGSTSEALEDFT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  233 GGVTEFFEIRDAPSDMYKIMKKAIERGSLMGCSIDdgtnmtygtspsGLNMGELiermvrnmdnsllrdsdldprgsddr 312
Cdd:pfam00648 161 GGVAESYDLKEPPPNLFEILLKALERGSLMGCSID------------ATSAAEE-------------------------- 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  313 ptrtivpvqyETRMACGLVKGHAYSVTGLEETLFKDEKVKLVRLRNPWGQVEWNGSWSDGWKDWSFVDKDEKARLQHQVT 392
Cdd:pfam00648 203 ----------EARTPNGLVKGHAYSVTGVRKVNLKGGKVRLIRLRNPWGEVEWNGAWSDGSPEWQTVSPEEKEELGLTKK 272

                         330       340
                  ....*....|....*....|...
gi 826307929  393 EDGEFWMSYDDFIYHFTKLEICN 415
Cdd:pfam00648 273 DDGEFWMSFEDFLKYFTDLEICN 295
EFh_PEF_CAPN3 cd16190
Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), ...
 653-821 1.59e-121

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


:

Pssm-ID: 320065 [Multi-domain]  Cd Length: 169  Bit Score: 363.03  E-value: 1.59e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16190    1 QFRNIFQQIAGDDMEISADELRSVLNRVVKKHKDLKTEGFTLESCRSMIALMDTDGSGKLNLQEFRHLWNKIKQWQKIFK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16190   81 RYDTDKSGTINSYEMRNAVNDAGFRLNNQLYDIITMRYADKHMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVL 160


                 ....*....
gi 826307929 813 EWLQLTMYA 821
Cdd:cd16190  161 EWLQLTMYA 169
Calpain_III pfam01067
Calpain large subunit, domain III; The function of the domain III and I are currently unknown. ...
 435-574 4.39e-74

Calpain large subunit, domain III; The function of the domain III and I are currently unknown. Domain II is a cysteine protease and domain IV is a calcium binding domain. Calpains are believed to participate in intracellular signaling pathways mediated by calcium ions.


:

Pssm-ID: 460050  Cd Length: 136  Bit Score: 237.44  E-value: 4.39e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  435 EGRWVRGCSAGGCRNFPDTFWTNPQYRLKLLEEDDDPDDSEviCSFLVALMQKNRRKDRKLGANLFTIGFAIYEVPKEmh 514
Cdd:pfam01067   2 EGRWVRGSTAGGCRNYPDTFWTNPQYRFTLTEPDDDDDEGE--CTVLVSLMQKNRRKQRRLGENLLTIGFAIYKVPVE-- 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  515 gNKQHLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVF 574
Cdd:pfam01067  78 -LNRKLRKHFFLTNQPVARSSTYINSREVSLRFRLPPGEYVIVPSTFEPNEEGEFLLRVF 136
Calpain_u2 pfam16648
Unstructured region on Calpain-3; Calpain_u2 is a region of natively unstructured sequence ...
 583-653 6.42e-25

Unstructured region on Calpain-3; Calpain_u2 is a region of natively unstructured sequence that lies between the Calpain_III, pfam01067 and the first EF-hand, Pfam;PF13833, domains on higher eukaryote calpain-3 proteins. The function is not known.


:

Pssm-ID: 465216  Cd Length: 67  Bit Score: 98.46  E-value: 6.42e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 826307929  583 EAENTISVDRPVKKKKPKPIIFVSDRANSNKELGVDQESEEGKDKTSPDKQQRSpqprPGNADQESEDQQQ 653
Cdd:pfam16648   1 EVENTIEADRPVEGKKKKPIIFVSDRANSNKELGHDEEEGEKKDKTSPDEKKPK----PLQADEESEEEKQ 67
 
Name Accession Description Interval E-value
Peptidase_C2 pfam00648
Calpain family cysteine protease;
75-415 0e+00

Calpain family cysteine protease;


Pssm-ID: 459889 [Multi-domain]  Cd Length: 295  Bit Score: 564.82  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   75 YVDPEFPPDETSLFY--SQKFPIQFVWKRPPEICENPRFIIGGANRTDICQGDLGDCWFLAAIACLTLNKRLLFRVIPHD 152
Cdd:pfam00648   1 FEDPEFPADDSSLGYppSPPPPRGVEWKRPKEICSNPQFIVDGASRFDICQGELGDCWLLAAIASLTLNPKLLERVVPPD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  153 QSFVENYAGIFHFQFWRYGDWVDVVIDDCLPTYNNQLVFTKSNHRNEFWSALLEKAYAKLHGSYEALKGGNTTEAMEDFT 232
Cdd:pfam00648  81 QSFEENYAGIFHFRFWRFGEWVDVVIDDRLPTRNGKLLFVHSRDKNEFWSALLEKAYAKLHGSYEALKGGSTSEALEDFT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  233 GGVTEFFEIRDAPSDMYKIMKKAIERGSLMGCSIDdgtnmtygtspsGLNMGELiermvrnmdnsllrdsdldprgsddr 312
Cdd:pfam00648 161 GGVAESYDLKEPPPNLFEILLKALERGSLMGCSID------------ATSAAEE-------------------------- 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  313 ptrtivpvqyETRMACGLVKGHAYSVTGLEETLFKDEKVKLVRLRNPWGQVEWNGSWSDGWKDWSFVDKDEKARLQHQVT 392
Cdd:pfam00648 203 ----------EARTPNGLVKGHAYSVTGVRKVNLKGGKVRLIRLRNPWGEVEWNGAWSDGSPEWQTVSPEEKEELGLTKK 272

                         330       340
                  ....*....|....*....|...
gi 826307929  393 EDGEFWMSYDDFIYHFTKLEICN 415
Cdd:pfam00648 273 DDGEFWMSFEDFLKYFTDLEICN 295
CysPc smart00230
Calpain-like thiol protease family; Calpain-like thiol protease family (peptidase family C2). ...
 61-425 2.78e-178

Calpain-like thiol protease family; Calpain-like thiol protease family (peptidase family C2). Calcium activated neutral protease (large subunit).


Pssm-ID: 128526  Cd Length: 318  Bit Score: 514.57  E-value: 2.78e-178
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929    61 FEQLHKKCLEKKVLYVDPEFPPDETSLFYSQKFPIQFVWKRPPEICENPRFIIGGANRTDICQGDLGDCWFLAAIACLTL 140
Cdd:smart00230   1 YEALRQYCKESGTLFEDPLFPANNGSLFFSQRQRKFVVWKRPHEIFENPPFIVGGASRTDICQGVLGDCWLLAALASLTL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   141 NKRLLFRVIPHDQSFVENYAGIFHFQFWRYGDWVDVVIDDCLPTYNNQLVFTKSNHRNEFWSALLEKAYAKLHGSYEALK 220
Cdd:smart00230  81 REKLLDRVIPHDQEFSENYAGIFHFRFWRFGKWVDVVIDDRLPTYNGELVFMHSNSRNEFWSALLEKAYAKLNGCYEALK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   221 GGNTTEAMEDFTGGVTEFFEIRDA---PSDMYKIMKKAIERGSLMGCSIDDGTnmtygtspsglnmgeliermvrnmdns 297
Cdd:smart00230 161 GGSTTEALEDLTGGVAESIDLKEAskdPDNLFEDLFKAFERGSLMGCSIGAGT--------------------------- 213

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   298 llrdsdldprgsddrptrtivPVQYETRMACGLVKGHAYSVTGLEETLFKdeKVKLVRLRNPWGQVEWNGSWSDGWKDWS 377
Cdd:smart00230 214 ---------------------AVEEEEQKDCGLVKGHAYSVTDVREVQGR--RQELLRLRNPWGQVEWNGPWSDDSPEWR 270

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 826307929   378 FVDKDEKARLQHQVTEDGEFWMSYDDFIYHFTKLEICNLTADALESDK 425
Cdd:smart00230 271 SVSASEKKNLGLTFDDDGEFWMSFEDFLRHFDKVEICNLNPDSLEERS 318
CysPc cd00044
Calpains, domains IIa, IIb; calcium-dependent cytoplasmic cysteine proteinases, papain-like. ...
 63-415 1.58e-144

Calpains, domains IIa, IIb; calcium-dependent cytoplasmic cysteine proteinases, papain-like. Functions in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction.


Pssm-ID: 238004 [Multi-domain]  Cd Length: 315  Bit Score: 427.90  E-value: 1.58e-144
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  63 QLHKKCLEKKVLYVDPEFPPDETSLFY-----SQKFPIQFVWKRPPEICEN-----PRFIIGGANRTDICQGDLGDCWFL 132
Cdd:cd00044    1 TLLQICLLSGVLFEDPDFPPNDSSLGFddslsNGQPKKVIEWKRPSEIFADdgnsnPRLFVNGASPSDVCQGILGDCWFL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 133 AAIACLTLNKRLLFRVIPHDQSFVENYAGIFHFQFWRYGDWVDVVIDDCLPTYNNQLVFTKSNHRNEFWSALLEKAYAKL 212
Cdd:cd00044   81 AALAALAERPELLKRVIPPDQSFEENYAGIYHFRFWKNGEWVEVVIDDRLPTSNGGLLFMHSRDRNELWVALLEKAYAKL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 213 HGSYEALKGGNTTEAMEDFTGGVTEFFEIR-----DAPSDMYKIMKKAIERGSLMGCSIDDGTNMtygtspsglnmgeli 287
Cdd:cd00044  161 HGSYEALVGGNTAEALEDLTGGPTERIDLKsadasSGDNDLFALLLSFLQGGSLIGCSTGSRSEE--------------- 225

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 288 ermvrnmdnsllrdsdldprgsddrptrtivpvqyETRMACGLVKGHAYSVTGLEEtlFKDEKVKLVRLRNPWGQVEWNG 367
Cdd:cd00044  226 -----------------------------------EARTANGLVKGHAYSVLDVRE--VQEEGLRLLRLRNPWGVGEWWG 268

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*...
gi 826307929 368 SWSDGWKDWSFVDKDEKARLQHQvTEDGEFWMSYDDFIYHFTKLEICN 415
Cdd:cd00044  269 GWSDDSSEWWVIDAERKKLLLSG-KDDGEFWMSFEDFLRNFDGLYVCN 315
EFh_PEF_CAPN3 cd16190
Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), ...
 653-821 1.59e-121

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


Pssm-ID: 320065 [Multi-domain]  Cd Length: 169  Bit Score: 363.03  E-value: 1.59e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16190    1 QFRNIFQQIAGDDMEISADELRSVLNRVVKKHKDLKTEGFTLESCRSMIALMDTDGSGKLNLQEFRHLWNKIKQWQKIFK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16190   81 RYDTDKSGTINSYEMRNAVNDAGFRLNNQLYDIITMRYADKHMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVL 160


                 ....*....
gi 826307929 813 EWLQLTMYA 821
Cdd:cd16190  161 EWLQLTMYA 169
Calpain_III pfam01067
Calpain large subunit, domain III; The function of the domain III and I are currently unknown. ...
 435-574 4.39e-74

Calpain large subunit, domain III; The function of the domain III and I are currently unknown. Domain II is a cysteine protease and domain IV is a calcium binding domain. Calpains are believed to participate in intracellular signaling pathways mediated by calcium ions.


Pssm-ID: 460050  Cd Length: 136  Bit Score: 237.44  E-value: 4.39e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  435 EGRWVRGCSAGGCRNFPDTFWTNPQYRLKLLEEDDDPDDSEviCSFLVALMQKNRRKDRKLGANLFTIGFAIYEVPKEmh 514
Cdd:pfam01067   2 EGRWVRGSTAGGCRNYPDTFWTNPQYRFTLTEPDDDDDEGE--CTVLVSLMQKNRRKQRRLGENLLTIGFAIYKVPVE-- 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  515 gNKQHLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVF 574
Cdd:pfam01067  78 -LNRKLRKHFFLTNQPVARSSTYINSREVSLRFRLPPGEYVIVPSTFEPNEEGEFLLRVF 136
Calpain_III cd00214
Calpain, subdomain III. Calpains are calcium-activated cytoplasmic cysteine proteinases, ...
 427-583 6.29e-72

Calpain, subdomain III. Calpains are calcium-activated cytoplasmic cysteine proteinases, participate in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction. Catalytic domain and the two calmodulin-like domains are separated by C2-like domain III. Domain III plays an important role in calcium-induced activation of calpain involving electrostatic interactions with subdomain II. Proposed to mediate calpain's interaction with phospholipids and translocation to cytoplasmic/nuclear membranes. CD includes subdomain III of typical and atypical calpains.


Pssm-ID: 238132  Cd Length: 150  Bit Score: 232.19  E-value: 6.29e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 427 QTWTVSVNEGRWVRGCSAGGCRNFPDTFWTNPQYRLKLLEEDDDPddseVICSFLVALMQKNRRKDRKLGANLFTIGFAI 506
Cdd:cd00214    1 RKWHTKSFNGEWRRGQTAGGCRNNPDTFWTNPQFRIRVPEPDDDE----GKCTVLIALMQKNRRHLRKKGLDLLTIGFHV 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 826307929 507 YEVPKEMHgnkqHLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVFSEKRNLSEE 583
Cdd:cd00214   77 YKVPGENR----HLRRDFFLHKAPRARSSTFINTREVSLRFRLPPGEYVIVPSTFEPGEEGEFLLRVFSEKSIKSSE 149
calpain_III smart00720
calpain_III domain;
429-578 1.95e-66

calpain_III domain;


Pssm-ID: 214786  Cd Length: 143  Bit Score: 217.23  E-value: 1.95e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   429 WTVSVNEGRWVRGCSAGGCRNFPDTFWTNPQYRLKLLEEDDDPddseviCSFLVALMQKNRRKDRKLGANLFTIGFAIYE 508
Cdd:smart00720   1 WHTKSVQGSWTRGQTAGGCRNYPATFWTNPQFRITLEEPDDDD------CTVLIALMQKNRRRLRRKGADFLTIGFAVYK 74

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   509 VPKEMHgnkqhLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVFSEKR 578
Cdd:smart00720  75 VPKELH-----LRRDFFLSNAPRASSGDYINGREVSERFRLPPGEYVIVPSTFEPNQEGDFLLRVFSEGP 139
Calpain_u2 pfam16648
Unstructured region on Calpain-3; Calpain_u2 is a region of natively unstructured sequence ...
 583-653 6.42e-25

Unstructured region on Calpain-3; Calpain_u2 is a region of natively unstructured sequence that lies between the Calpain_III, pfam01067 and the first EF-hand, Pfam;PF13833, domains on higher eukaryote calpain-3 proteins. The function is not known.


Pssm-ID: 465216  Cd Length: 67  Bit Score: 98.46  E-value: 6.42e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 826307929  583 EAENTISVDRPVKKKKPKPIIFVSDRANSNKELGVDQESEEGKDKTSPDKQQRSpqprPGNADQESEDQQQ 653
Cdd:pfam16648   1 EVENTIEADRPVEGKKKKPIIFVSDRANSNKELGHDEEEGEKKDKTSPDEKKPK----PLQADEESEEEKQ 67
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
698-753 1.72e-06

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 48.25  E-value: 1.72e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 698 RSMIALMDTDGSGRLNLQEFHHLWKKIKAW----QKIFKHYDTDQSGTINSYEMRNAVND 753
Cdd:COG5126   72 RAAFDLLDTDGDGKISADEFRRLLTALGVSeeeaDELFARLDTDGDGKISFEEFVAAVRD 131
PTZ00183 PTZ00183
centrin; Provisional
 731-812 1.92e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 42.75  E-value: 1.92e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 731 FKHYDTDQSGTINSYEMRNAVNDAGFHL-NSQLYDIITMRYADRHMNIDFDSFI-CCFIRL------EGMFRAFNAFDKD 802
Cdd:PTZ00183  23 FDLFDTDGSGTIDPKELKVAMRSLGFEPkKEEIKQMIADVDKDGSGKIDFEEFLdIMTKKLgerdprEEILKAFRLFDDD 102

                         90
                 ....*....|
gi 826307929 803 GDGIIKLNVL 812
Cdd:PTZ00183 103 KTGKISLKNL 112
EF-hand_6 pfam13405
EF-hand domain;
727-755 1.57e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 36.77  E-value: 1.57e-03
                          10        20
                  ....*....|....*....|....*....
gi 826307929  727 WQKIFKHYDTDQSGTINSYEMRNAVNDAG 755
Cdd:pfam13405   2 LREAFKLFDKDGDGKISLEELRKALRSLG 30
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
 647-720 2.94e-03

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


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 37.64  E-value: 2.94e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 826307929   647 ESEDQQQFRNIFKQIAGD-DMEICADELKNVLntvvnKHKDLKSQgfTLEScrsmI-ALMDTDGSGRLNLQEF---HHL 720
Cdd:smart00027   5 SPEDKAKYEQIFRSLDKNqDGTVTGAQAKPIL-----LKSGLPQT--LLAK----IwNLADIDNDGELDKDEFalaMHL 72
 
Name Accession Description Interval E-value
Peptidase_C2 pfam00648
Calpain family cysteine protease;
75-415 0e+00

Calpain family cysteine protease;


Pssm-ID: 459889 [Multi-domain]  Cd Length: 295  Bit Score: 564.82  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   75 YVDPEFPPDETSLFY--SQKFPIQFVWKRPPEICENPRFIIGGANRTDICQGDLGDCWFLAAIACLTLNKRLLFRVIPHD 152
Cdd:pfam00648   1 FEDPEFPADDSSLGYppSPPPPRGVEWKRPKEICSNPQFIVDGASRFDICQGELGDCWLLAAIASLTLNPKLLERVVPPD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  153 QSFVENYAGIFHFQFWRYGDWVDVVIDDCLPTYNNQLVFTKSNHRNEFWSALLEKAYAKLHGSYEALKGGNTTEAMEDFT 232
Cdd:pfam00648  81 QSFEENYAGIFHFRFWRFGEWVDVVIDDRLPTRNGKLLFVHSRDKNEFWSALLEKAYAKLHGSYEALKGGSTSEALEDFT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  233 GGVTEFFEIRDAPSDMYKIMKKAIERGSLMGCSIDdgtnmtygtspsGLNMGELiermvrnmdnsllrdsdldprgsddr 312
Cdd:pfam00648 161 GGVAESYDLKEPPPNLFEILLKALERGSLMGCSID------------ATSAAEE-------------------------- 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  313 ptrtivpvqyETRMACGLVKGHAYSVTGLEETLFKDEKVKLVRLRNPWGQVEWNGSWSDGWKDWSFVDKDEKARLQHQVT 392
Cdd:pfam00648 203 ----------EARTPNGLVKGHAYSVTGVRKVNLKGGKVRLIRLRNPWGEVEWNGAWSDGSPEWQTVSPEEKEELGLTKK 272

                         330       340
                  ....*....|....*....|...
gi 826307929  393 EDGEFWMSYDDFIYHFTKLEICN 415
Cdd:pfam00648 273 DDGEFWMSFEDFLKYFTDLEICN 295
CysPc smart00230
Calpain-like thiol protease family; Calpain-like thiol protease family (peptidase family C2). ...
 61-425 2.78e-178

Calpain-like thiol protease family; Calpain-like thiol protease family (peptidase family C2). Calcium activated neutral protease (large subunit).


Pssm-ID: 128526  Cd Length: 318  Bit Score: 514.57  E-value: 2.78e-178
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929    61 FEQLHKKCLEKKVLYVDPEFPPDETSLFYSQKFPIQFVWKRPPEICENPRFIIGGANRTDICQGDLGDCWFLAAIACLTL 140
Cdd:smart00230   1 YEALRQYCKESGTLFEDPLFPANNGSLFFSQRQRKFVVWKRPHEIFENPPFIVGGASRTDICQGVLGDCWLLAALASLTL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   141 NKRLLFRVIPHDQSFVENYAGIFHFQFWRYGDWVDVVIDDCLPTYNNQLVFTKSNHRNEFWSALLEKAYAKLHGSYEALK 220
Cdd:smart00230  81 REKLLDRVIPHDQEFSENYAGIFHFRFWRFGKWVDVVIDDRLPTYNGELVFMHSNSRNEFWSALLEKAYAKLNGCYEALK 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   221 GGNTTEAMEDFTGGVTEFFEIRDA---PSDMYKIMKKAIERGSLMGCSIDDGTnmtygtspsglnmgeliermvrnmdns 297
Cdd:smart00230 161 GGSTTEALEDLTGGVAESIDLKEAskdPDNLFEDLFKAFERGSLMGCSIGAGT--------------------------- 213

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   298 llrdsdldprgsddrptrtivPVQYETRMACGLVKGHAYSVTGLEETLFKdeKVKLVRLRNPWGQVEWNGSWSDGWKDWS 377
Cdd:smart00230 214 ---------------------AVEEEEQKDCGLVKGHAYSVTDVREVQGR--RQELLRLRNPWGQVEWNGPWSDDSPEWR 270

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 826307929   378 FVDKDEKARLQHQVTEDGEFWMSYDDFIYHFTKLEICNLTADALESDK 425
Cdd:smart00230 271 SVSASEKKNLGLTFDDDGEFWMSFEDFLRHFDKVEICNLNPDSLEERS 318
CysPc cd00044
Calpains, domains IIa, IIb; calcium-dependent cytoplasmic cysteine proteinases, papain-like. ...
 63-415 1.58e-144

Calpains, domains IIa, IIb; calcium-dependent cytoplasmic cysteine proteinases, papain-like. Functions in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction.


Pssm-ID: 238004 [Multi-domain]  Cd Length: 315  Bit Score: 427.90  E-value: 1.58e-144
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  63 QLHKKCLEKKVLYVDPEFPPDETSLFY-----SQKFPIQFVWKRPPEICEN-----PRFIIGGANRTDICQGDLGDCWFL 132
Cdd:cd00044    1 TLLQICLLSGVLFEDPDFPPNDSSLGFddslsNGQPKKVIEWKRPSEIFADdgnsnPRLFVNGASPSDVCQGILGDCWFL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 133 AAIACLTLNKRLLFRVIPHDQSFVENYAGIFHFQFWRYGDWVDVVIDDCLPTYNNQLVFTKSNHRNEFWSALLEKAYAKL 212
Cdd:cd00044   81 AALAALAERPELLKRVIPPDQSFEENYAGIYHFRFWKNGEWVEVVIDDRLPTSNGGLLFMHSRDRNELWVALLEKAYAKL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 213 HGSYEALKGGNTTEAMEDFTGGVTEFFEIR-----DAPSDMYKIMKKAIERGSLMGCSIDDGTNMtygtspsglnmgeli 287
Cdd:cd00044  161 HGSYEALVGGNTAEALEDLTGGPTERIDLKsadasSGDNDLFALLLSFLQGGSLIGCSTGSRSEE--------------- 225

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 288 ermvrnmdnsllrdsdldprgsddrptrtivpvqyETRMACGLVKGHAYSVTGLEEtlFKDEKVKLVRLRNPWGQVEWNG 367
Cdd:cd00044  226 -----------------------------------EARTANGLVKGHAYSVLDVRE--VQEEGLRLLRLRNPWGVGEWWG 268

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*...
gi 826307929 368 SWSDGWKDWSFVDKDEKARLQHQvTEDGEFWMSYDDFIYHFTKLEICN 415
Cdd:cd00044  269 GWSDDSSEWWVIDAERKKLLLSG-KDDGEFWMSFEDFLRNFDGLYVCN 315
EFh_PEF_CAPN3 cd16190
Calcium-activated neutral; CAPN3, also termed calcium-activated neutral proteinase 3 (CANP 3), ...
 653-821 1.59e-121

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


Pssm-ID: 320065 [Multi-domain]  Cd Length: 169  Bit Score: 363.03  E-value: 1.59e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16190    1 QFRNIFQQIAGDDMEISADELRSVLNRVVKKHKDLKTEGFTLESCRSMIALMDTDGSGKLNLQEFRHLWNKIKQWQKIFK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16190   81 RYDTDKSGTINSYEMRNAVNDAGFRLNNQLYDIITMRYADKHMNIDFDSFICCFVRLEGMFRAFHAFDKDGDGIIKLNVL 160


                 ....*....
gi 826307929 813 EWLQLTMYA 821
Cdd:cd16190  161 EWLQLTMYA 169
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
 653-820 1.81e-88

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: 276.62  E-value: 1.81e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLksqGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd15897    1 QLRNVFQAVAGDDGEISATELQQALSNVGWTHFDL---GFSLETCRSMIAMMDRDHSGKLNFSEFKGLWNYIKAWQEIFR 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd15897   78 TYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYDRGRGNIDFDDFIQCCVRLQRLTDAFRRYDKDQDGQIQVNYD 157


                 ....*...
gi 826307929 813 EWLQLTMY 820
Cdd:cd15897  158 EFLQGTMS 165
EFh_PEF_CPNS1_2 cd16188
Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit ...
 653-821 4.11e-82

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


Pssm-ID: 320063 [Multi-domain]  Cd Length: 169  Bit Score: 260.06  E-value: 4.11e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16188    1 QFRRLFVQLAGDDMEVSATELMNILNKVVTRHPDLKTDGFGIDTCRSMVAVMDSDTTGKLGFEEFKYLWNNIKKWQGIYK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16188   81 QFDTDRSGTIGSQELPGAFEAAGFHLNEQLYQMIIRRYSDEDGNMDFDNFISCLVRLDAMFRAFKSLDKDGTGQIQVNIQ 160


                 ....*....
gi 826307929 813 EWLQLTMYA 821
Cdd:cd16188  161 EWLQLTMYS 169
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
 653-820 1.74e-78

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


Pssm-ID: 320057 [Multi-domain]  Cd Length: 167  Bit Score: 250.22  E-value: 1.74e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHkDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16182    1 QVRELFEKLAGEDEEIDAVELQKLLNASLLKD-MPKFDGFSLETCRSLIALMDTNGSGRLDLEEFKTLWSDLKKWQAIFK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16182   80 KFDTDRSGTLSSYELRKALESAGFHLSNKVLQALVLRYADSTGRITFEDFVSCLVRLKTAFETFSALDKKNEGVIPLTLE 159


                 ....*...
gi 826307929 813 EWLQLTMY 820
Cdd:cd16182  160 EWLLLTLY 167
EFh_PEF_CAPN1_like cd16189
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1), m-type calpain (CAPN2) ...
 654-819 3.79e-77

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


Pssm-ID: 320064 [Multi-domain]  Cd Length: 168  Bit Score: 246.88  E-value: 3.79e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 654 FRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKH 733
Cdd:cd16189    2 FRNLFTQLAGEDSEISAFELQTILNKVLSKRKDIKTDGFSLETCRNMVNLLDKDGSGKLGLVEFQILWTKIQKYLKIYKK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 734 YDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLE 813
Cdd:cd16189   82 FDTDGSGTMSSYEMRLALEEAGFKLNNQLHQVLVARYADQELTIDFDNFVRCLVRLELLFKIFKQLDKDNTGTIELDLIQ 161


                 ....*.
gi 826307929 814 WLQLTM 819
Cdd:cd16189  162 WLSFSL 167
EFh_PEF_CAPN1 cd16198
Penta-EF hand, calcium binding motifs, found in mu-type calpain (CAPN1); CAPN1, also termed ...
 654-821 2.82e-75

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


Pssm-ID: 320073 [Multi-domain]  Cd Length: 169  Bit Score: 242.01  E-value: 2.82e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 654 FRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKH 733
Cdd:cd16198    2 FKNLFRQLAGEDMEISVFELKTILNRIISKHKDLRTDGFSLESCRSMVNLMDKDGNGKLGLVEFNILWNKIRNYLTIFRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 734 YDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLE 813
Cdd:cd16198   82 FDLDKSGSMSAYEMRLALESAGFKLNNRLHQVIVARYADPNLAIDFDNFVCCLVRLETMFRFFKQLDTEETGTIEMDLFE 161


                 ....*...
gi 826307929 814 WLQLTMYA 821
Cdd:cd16198  162 WLQLTMFG 169
Calpain_III pfam01067
Calpain large subunit, domain III; The function of the domain III and I are currently unknown. ...
 435-574 4.39e-74

Calpain large subunit, domain III; The function of the domain III and I are currently unknown. Domain II is a cysteine protease and domain IV is a calcium binding domain. Calpains are believed to participate in intracellular signaling pathways mediated by calcium ions.


Pssm-ID: 460050  Cd Length: 136  Bit Score: 237.44  E-value: 4.39e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  435 EGRWVRGCSAGGCRNFPDTFWTNPQYRLKLLEEDDDPDDSEviCSFLVALMQKNRRKDRKLGANLFTIGFAIYEVPKEmh 514
Cdd:pfam01067   2 EGRWVRGSTAGGCRNYPDTFWTNPQYRFTLTEPDDDDDEGE--CTVLVSLMQKNRRKQRRLGENLLTIGFAIYKVPVE-- 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929  515 gNKQHLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVF 574
Cdd:pfam01067  78 -LNRKLRKHFFLTNQPVARSSTYINSREVSLRFRLPPGEYVIVPSTFEPNEEGEFLLRVF 136
Calpain_III cd00214
Calpain, subdomain III. Calpains are calcium-activated cytoplasmic cysteine proteinases, ...
 427-583 6.29e-72

Calpain, subdomain III. Calpains are calcium-activated cytoplasmic cysteine proteinases, participate in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction. Catalytic domain and the two calmodulin-like domains are separated by C2-like domain III. Domain III plays an important role in calcium-induced activation of calpain involving electrostatic interactions with subdomain II. Proposed to mediate calpain's interaction with phospholipids and translocation to cytoplasmic/nuclear membranes. CD includes subdomain III of typical and atypical calpains.


Pssm-ID: 238132  Cd Length: 150  Bit Score: 232.19  E-value: 6.29e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 427 QTWTVSVNEGRWVRGCSAGGCRNFPDTFWTNPQYRLKLLEEDDDPddseVICSFLVALMQKNRRKDRKLGANLFTIGFAI 506
Cdd:cd00214    1 RKWHTKSFNGEWRRGQTAGGCRNNPDTFWTNPQFRIRVPEPDDDE----GKCTVLIALMQKNRRHLRKKGLDLLTIGFHV 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 826307929 507 YEVPKEMHgnkqHLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVFSEKRNLSEE 583
Cdd:cd00214   77 YKVPGENR----HLRRDFFLHKAPRARSSTFINTREVSLRFRLPPGEYVIVPSTFEPGEEGEFLLRVFSEKSIKSSE 149
calpain_III smart00720
calpain_III domain;
429-578 1.95e-66

calpain_III domain;


Pssm-ID: 214786  Cd Length: 143  Bit Score: 217.23  E-value: 1.95e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   429 WTVSVNEGRWVRGCSAGGCRNFPDTFWTNPQYRLKLLEEDDDPddseviCSFLVALMQKNRRKDRKLGANLFTIGFAIYE 508
Cdd:smart00720   1 WHTKSVQGSWTRGQTAGGCRNYPATFWTNPQFRITLEEPDDDD------CTVLIALMQKNRRRLRRKGADFLTIGFAVYK 74

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929   509 VPKEMHgnkqhLQKDFFLYNASKARSKTYINMREVSQRFRLPPSEYVIVPSTYEPHQEGEFILRVFSEKR 578
Cdd:smart00720  75 VPKELH-----LRRDFFLSNAPRASSGDYINGREVSERFRLPPGEYVIVPSTFEPNQEGDFLLRVFSEGP 139
EFh_PEF_CAPN9 cd16192
Penta-EF hand, calcium binding motifs, found in calpain-9 (CAPN9); CAPN9, also termed ...
 653-819 1.04e-64

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


Pssm-ID: 320067 [Multi-domain]  Cd Length: 169  Bit Score: 213.51  E-value: 1.04e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16192    1 QFRKLFEQISGEDLEISAEELQYVLNAVLARTKEIKFKKLSLLSCKNIISLMDTSGNGKLGFSEFKVFWDKLKKWIGLFL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16192   81 KYDADRSGTMSSYELRSALKAAGFQLNNQLLQLIVLRYADDYLQIDFDDFLNCLVRLENSFRVFQALDTKNTGEISLNML 160


                 ....*..
gi 826307929 813 EWLQLTM 819
Cdd:cd16192  161 EFILLTM 167
EFh_PEF_CAPN2 cd16199
Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2); CAPN2, also termed ...
 654-819 1.72e-62

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


Pssm-ID: 320074 [Multi-domain]  Cd Length: 168  Bit Score: 207.45  E-value: 1.72e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 654 FRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKH 733
Cdd:cd16199    2 FRRLFAQLAGEDAEISAFELQTILRRVLAKREDIKSDGFSIETCKIMVDMLDSDGSGKLGLKEFYILWTKIQKYQKIYRE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 734 YDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLE 813
Cdd:cd16199   82 IDVDRSGTMNSYEMRKALEEAGFKLPCQLHQVIVARFADDDLIIDFDNFVRCLVRLETLFKIFKQLDPENTGTIELDLIS 161


                 ....*.
gi 826307929 814 WLQLTM 819
Cdd:cd16199  162 WLSFSV 167
EFh_PEF_CAPN8 cd16191
Penta-EF hand, calcium binding motifs, found in calpain-8 (CAPN8); CAPN8, also termed new ...
 653-819 9.67e-62

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


Pssm-ID: 320066 [Multi-domain]  Cd Length: 168  Bit Score: 205.40  E-value: 9.67e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16191    1 EFKNIFQKLAGKKCEVTANELQTILNRVLSKRKDIKSDGFTINTCREMISLLDTDGTGTLGLVEFRILWMKIQKYLAIYK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16191   81 KVDSDRSGTIDAHEMRNALQEAGFTLNNKIQQSIVQRYASNKLTINFDGFIACMIRLETLFKMFQLLDKDKSGVVQLSLA 160


                 ....*..
gi 826307929 813 EWLQLTM 819
Cdd:cd16191  161 EWLCCTL 167
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
 653-821 4.57e-61

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


Pssm-ID: 320071 [Multi-domain]  Cd Length: 167  Bit Score: 203.59  E-value: 4.57e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKhkDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16196    1 RLRRLFDKIAGEDMEIDAYELQDILNTAFKK--DFPFDGFSLDACRSMVAMMDVDRSGKLGFEEFKKLWEDLRSWKRVFK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16196   79 LFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVLRYSNKDGRISFDDFIMCAVKLKTMFEIFKEKDPRGGGRATFNLD 158


                 ....*....
gi 826307929 813 EWLQLTMYA 821
Cdd:cd16196  159 EFLESTMYS 167
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
 653-820 5.55e-59

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: 197.81  E-value: 5.55e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16195    1 SSRALFLKYADQGGELDAEQLQKLLNENLLKGLAGSGGGFSLDACRSMVALMDLSVNGRLSLEEFSRLWKKLRKYKDIFQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGdGIIKLNVL 812
Cdd:cd16195   81 KADVSKSGFLSLSELRNAIQAAGIRVSDDLLNLMALRYGDSSGRISFESFICLMLRLECMAKIFRNLSKDG-GGIYLTES 159


                 ....*...
gi 826307929 813 EWLQLTMY 820
Cdd:cd16195  160 EWMQLTMY 167
EFh_PEF_CAPN11 cd16193
Penta-EF hand, calcium binding motifs, found in calpain-11 (CAPN11); CAPN11, also termed ...
 654-820 1.50e-54

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


Pssm-ID: 320068 [Multi-domain]  Cd Length: 169  Bit Score: 185.89  E-value: 1.50e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 654 FRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKH 733
Cdd:cd16193    2 SLHLFKIVANEDKEVDMYELQKLLNRMAIKFKSFKTKGFSLDVCRRMINLMDKDGSGKLGLHEFKILWKKIKKWMEIFKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 734 YDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLE 813
Cdd:cd16193   82 CDQDRSGNLNSYEMRLAIEKAGIKMNNRVTEVVVARYADDNMIVDFDSFINCFLRLKAMFAFFLSMDTKKTGSICLSINQ 161


                 ....*..
gi 826307929 814 WLQLTMY 820
Cdd:cd16193  162 WLQITMW 168
EFh_PEF_CAPN12 cd16194
Penta-EF hand, calcium binding motifs, found in calpain-12 (CAPN12); CAPN12, also termed ...
 653-817 7.13e-54

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: 183.92  E-value: 7.13e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16194    1 ELEQLFQELAGEDEEINASELQKILSIALERAHTSKPREFGLRTCRQLIQCFDHGQNGKLALEEFQQLWGYLLEWQAIFT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16194   81 KFDEDTSGTMDSYELRLALNAAGFHLNNQLTETLTSRYRDSRLRVDFESFLSCLAHLTCIFCQCSQHDDGGEGVICLTHR 160


                 ....*
gi 826307929 813 EWLQL 817
Cdd:cd16194  161 QWLEL 165
EFh_PEF_Group_II_sorcin_like cd16181
Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The ...
 658-819 2.88e-33

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


Pssm-ID: 320056 [Multi-domain]  Cd Length: 165  Bit Score: 125.95  E-value: 2.88e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 658 FKQIAGDDMEICADELKNVLnTVVNKHKDLksQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYDTD 737
Cdd:cd16181    6 FSAVAGQDGQIDADELQRCL-TQSGISGNY--QPFSLETCRLMIAMLDRDHSGKMGFNEFKELWAALNQWKTTFMQYDRD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 738 QSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHmNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLEWLQL 817
Cdd:cd16181   83 RSGTVEPQELQQAIRSFGYNLSPQALNVIVKRYSKNG-RITFDDFVACAVRLRALTDRFRRRDTQQNGTATFQYDDFIQV 161


                 ..
gi 826307929 818 TM 819
Cdd:cd16181  162 TM 163
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 668-810 8.09e-32

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: 121.48  E-value: 8.09e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 668 ICADELKNVLNTVVNkhkdlksQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYDTDQSGTINSYEM 747
Cdd:cd16180   17 ISAKELQRALSNGDW-------TPFSIETVRLMINMFDRDRSGTINFDEFVGLWKYIQDWRRLFRRFDRDRSGSIDFNEL 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 826307929 748 RNAVNDAGFHLNSQLYDIITMRYaDRHMN--IDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLN 810
Cdd:cd16180   90 QNALSSFGYRLSPQFVQLLVRKF-DRRRRgsISFDDFVEACVTLKRLTDAFRKYDTNRTGYATIS 153
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
 668-817 2.28e-28

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: 111.58  E-value: 2.28e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 668 ICADELKNVLntvvnkhkdlkSQG----FTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYDTDQSGTIN 743
Cdd:cd16183   17 ISATELQQAL-----------SNGtwtpFNPETVRLMIGMFDRDNSGTINFQEFAALWKYITDWQNCFRSFDRDNSGNID 85

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 826307929 744 SYEMRNAVNDAGFHLNSQLYDIItMRYADR--HMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLEWLQL 817
Cdd:cd16183   86 KNELKQALTSFGYRLSDQFYDIL-VRKFDRqgRGTIAFDDFIQCCVVLQTLTDSFRRYDTDQDGWIQISYEQFLEM 160
EFh_PEF_sorcin cd16187
Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2 ...
 658-819 2.57e-28

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


Pssm-ID: 320062 [Multi-domain]  Cd Length: 165  Bit Score: 111.54  E-value: 2.57e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 658 FKQIAGDDMEICADELKNVLNT--VVNKHKDlksqgFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYD 735
Cdd:cd16187    6 FAAVAGQDGQIDADELQRCLTQsgIAGGYKP-----FNLETCRLMISMLDRDMSGTMGFNEFKELWAVLNGWRQHFISFD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 736 TDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADrHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLEWL 815
Cdd:cd16187   81 SDRSGTVDPQELQKALTTMGFRLSPQAVNSIAKRYST-NGKITFDDYIACCVKLRALTDSFRRRDTSQQGVVNFPYDDFI 159


                 ....
gi 826307929 816 QLTM 819
Cdd:cd16187  160 QCVM 163
EFh_PEF_grancalcin cd16186
Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic ...
 658-819 1.62e-26

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


Pssm-ID: 320061 [Multi-domain]  Cd Length: 165  Bit Score: 106.49  E-value: 1.62e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 658 FKQIAGDDMEICADELKNVLnTVVNKHKDLKSqgFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYDTD 737
Cdd:cd16186    6 FSAVAGQDGEVDAEELQRCL-TQSGINGTYTP--FSLETCRIMIAMLDRDHTGKMGFNEFKELWAALNAWKQNFMTVDQD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 738 QSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYAdRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLEWLQL 817
Cdd:cd16186   83 RSGTVEPHELRQAIGAMGYRLSPQTLTTIVKRYS-KNGRIYFDDYVACCVKLRALTDFFRRRDHMQQGSVNFIYDDFLQC 161


                 ..
gi 826307929 818 TM 819
Cdd:cd16186  162 TM 163
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
 667-819 9.90e-26

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: 104.27  E-value: 9.90e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 667 EICADELKNVLntvVNkhkdlkSQG--FTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFKHYDTDQSGTINS 744
Cdd:cd16184   16 KISAKELQQAL---VN------GNWshFNDETCRLMIGMFDKDKSGTIDIYEFQALWNYIQQWKQVFQQFDRDRSGSIDE 86

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 826307929 745 YEMRNAVNDAGFHLNSQLYDIITMRYADR-HMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVLEWLQLTM 819
Cdd:cd16184   87 NELHQALSQMGYRLSPQFVQFLVSKYDPRaRRSLTLDQFIQVCVQLQSLTDAFRQRDTQMTGTITISYEDFLTMAL 162
EFh_PEF_CalpC cd16197
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-C (CalpC) and ...
 653-816 9.94e-26

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


Pssm-ID: 320072 [Multi-domain]  Cd Length: 166  Bit Score: 104.11  E-value: 9.94e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 653 QFRNIFKQIAGDDMEICADELKNVLNTVVNKhkDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAWQKIFK 732
Cdd:cd16197    1 QYEPVFLQLADEHRTVNAFELQELLEACLPN--DYIKSCANIDVCRQVVLLMDNSGLGRLKFQDFKDFMCSLKWWQGVFK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 733 HYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRYADRHMNIDFDSFICCFIRLEGMFRAFNAFDKDGDGIIKLNVL 812
Cdd:cd16197   79 MHTKEKTGILRAERLRDALEDVGFQLNTDVLSILILRYMRKDGTLRFGDFVSAVLHLTAAFGSFEKKDPLQNGFIKLSLT 158


                 ....
gi 826307929 813 EWLQ 816
Cdd:cd16197  159 EWLK 162
Calpain_u2 pfam16648
Unstructured region on Calpain-3; Calpain_u2 is a region of natively unstructured sequence ...
 583-653 6.42e-25

Unstructured region on Calpain-3; Calpain_u2 is a region of natively unstructured sequence that lies between the Calpain_III, pfam01067 and the first EF-hand, Pfam;PF13833, domains on higher eukaryote calpain-3 proteins. The function is not known.


Pssm-ID: 465216  Cd Length: 67  Bit Score: 98.46  E-value: 6.42e-25
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 826307929  583 EAENTISVDRPVKKKKPKPIIFVSDRANSNKELGVDQESEEGKDKTSPDKQQRSpqprPGNADQESEDQQQ 653
Cdd:pfam16648   1 EVENTIEADRPVEGKKKKPIIFVSDRANSNKELGHDEEEGEKKDKTSPDEKKPK----PLQADEESEEEKQ 67
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 651-820 4.90e-19

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: 84.96  E-value: 4.90e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 651 QQQFRNIFKQIAGddmEICADELKNVLntvvnkhkdlkSQG---FTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIKAW 727
Cdd:cd16185    3 RQWFRAVDRDRSG---SIDVNELQKAL-----------AGGgllFSLATAEKLIRMFDRDGNGTIDFEEFAALHQFLSNM 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 728 QKIFKHYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIITMRY-ADRHMNIDFDSFI--CCFIRLegMFRAFNAFDKDGD 804
Cdd:cd16185   69 QNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFdPDRGGSLGFDDYIelCIFLAS--ARNLFQAFDRQRT 146

                        170
                 ....*....|....*.
gi 826307929 805 GIIKLNVLEWLQLTMY 820
Cdd:cd16185  147 GRVTLDFNQFVYAAAN 162
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 697-751 1.50e-10

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: 57.56  E-value: 1.50e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 826307929 697 CRSMIALMDTDGSGRLNLQEFHHLWKKI------KAWQKIFKHYDTDQSGTINSYEMRNAV 751
Cdd:cd00051    2 LREAFRLFDKDGDGTISADELKAALKSLgeglseEEIDEMIREVDKDGDGKIDFEEFLELM 62
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
698-753 1.72e-06

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 48.25  E-value: 1.72e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 698 RSMIALMDTDGSGRLNLQEFHHLWKKIKAW----QKIFKHYDTDQSGTINSYEMRNAVND 753
Cdd:COG5126   72 RAAFDLLDTDGDGKISADEFRRLLTALGVSeeeaDELFARLDTDGDGKISFEEFVAAVRD 131
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
692-817 8.22e-06

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 46.32  E-value: 8.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 692 FTLESCRSMIALMDTDGSGRLNLQEFHHLWKKIkaWQKIFKHYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDIItMRYA 771
Cdd:COG5126    2 LQRRKLDRRFDLLDADGDGVLERDDFEALFRRL--WATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAA-FDLL 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 826307929 772 DRhmniDFDSFI----------CCFIRLEGMFRAFNAFDKDGDGiiKLNVLEWLQL 817
Cdd:COG5126   79 DT----DGDGKIsadefrrlltALGVSEEEADELFARLDTDGDG--KISFEEFVAA 128
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 653-722 8.85e-06

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


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 43.69  E-value: 8.85e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 826307929 653 QFRNIFKQI-AGDDMEICADELKNVLNTVvnkhkdlkSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWK 722
Cdd:cd00051    1 ELREAFRLFdKDGDGTISADELKAALKSL--------GEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 728-817 6.25e-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: 41.38  E-value: 6.25e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 728 QKIFKHYDTDQSGTINSYEMRNAVNDAGFHLNSQLYDiitmryadrhmnidfdsficcfirlegmfRAFNAFDKDGDGII 807
Cdd:cd00051    3 REAFRLFDKDGDGTISADELKAALKSLGEGLSEEEID-----------------------------EMIREVDKDGDGKI 53

                         90
                 ....*....|
gi 826307929 808 KLNvlEWLQL 817
Cdd:cd00051   54 DFE--EFLEL 61
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 728-810 1.67e-04

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: 42.90  E-value: 1.67e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 728 QKIFKHYDTDQSGTINSYEMRNA-VNDAGFHLNSQ-------LYDiitmryADRHMNIDFDSFICCFIRLEGMFRAFNAF 799
Cdd:cd16180    3 RRIFQAVDRDRSGRISAKELQRAlSNGDWTPFSIEtvrlminMFD------RDRSGTINFDEFVGLWKYIQDWRRLFRRF 76

                         90
                 ....*....|.
gi 826307929 800 DKDGDGIIKLN 810
Cdd:cd16180   77 DRDRSGSIDFN 87
PTZ00183 PTZ00183
centrin; Provisional
 731-812 1.92e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 42.75  E-value: 1.92e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 731 FKHYDTDQSGTINSYEMRNAVNDAGFHL-NSQLYDIITMRYADRHMNIDFDSFI-CCFIRL------EGMFRAFNAFDKD 802
Cdd:PTZ00183  23 FDLFDTDGSGTIDPKELKVAMRSLGFEPkKEEIKQMIADVDKDGSGKIDFEEFLdIMTKKLgerdprEEILKAFRLFDDD 102

                         90
                 ....*....|
gi 826307929 803 GDGIIKLNVL 812
Cdd:PTZ00183 103 KTGKISLKNL 112
PTZ00183 PTZ00183
centrin; Provisional
 687-783 1.05e-03

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 40.44  E-value: 1.05e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 687 LKSQGFTL--ESCRSMIALMDTDGSGRLNLQEFHHLW-KKI------KAWQKIFKHYDTDQSGTINSYEMRNAVNDAGFH 757
Cdd:PTZ00183  43 MRSLGFEPkkEEIKQMIADVDKDGSGKIDFEEFLDIMtKKLgerdprEEILKAFRLFDDDKTGKISLKNLKRVAKELGET 122

                         90       100
                 ....*....|....*....|....*....
gi 826307929 758 L-NSQLYDIItmRYADRHMN--IDFDSFI 783
Cdd:PTZ00183 123 ItDEELQEMI--DEADRNGDgeISEEEFY 149
EF-hand_6 pfam13405
EF-hand domain;
727-755 1.57e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 36.77  E-value: 1.57e-03
                          10        20
                  ....*....|....*....|....*....
gi 826307929  727 WQKIFKHYDTDQSGTINSYEMRNAVNDAG 755
Cdd:pfam13405   2 LREAFKLFDKDGDGKISLEELRKALRSLG 30
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 697-724 2.17e-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: 36.22  E-value: 2.17e-03
                          10        20
                  ....*....|....*....|....*...
gi 826307929  697 CRSMIALMDTDGSGRLNLQEFHHLWKKI 724
Cdd:pfam00036   2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29
PTZ00184 PTZ00184
calmodulin; Provisional
 723-807 2.31e-03

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 39.36  E-value: 2.31e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 723 KIKAWQKIFKHYDTDQSGTINSYEMRNAVNDAGFH-LNSQLYDIITMRYADRHMNIDFDSFICCFIRL-------EGMFR 794
Cdd:PTZ00184   9 QIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNpTEAELQDMINEVDADGNGTIDFPEFLTLMARKmkdtdseEEIKE 88

                         90
                 ....*....|...
gi 826307929 795 AFNAFDKDGDGII 807
Cdd:PTZ00184  89 AFKVFDRDGNGFI 101
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
 647-720 2.94e-03

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


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 37.64  E-value: 2.94e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 826307929   647 ESEDQQQFRNIFKQIAGD-DMEICADELKNVLntvvnKHKDLKSQgfTLEScrsmI-ALMDTDGSGRLNLQEF---HHL 720
Cdd:smart00027   5 SPEDKAKYEQIFRSLDKNqDGTVTGAQAKPIL-----LKSGLPQT--LLAK----IwNLADIDNDGELDKDEFalaMHL 72
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
 668-753 4.19e-03

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


Pssm-ID: 320079 [Multi-domain]  Cd Length: 261  Bit Score: 39.70  E-value: 4.19e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 668 ICADELKNVLNTVVN--KHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQE----------------FHHLWKKIKA-WQ 728
Cdd:cd16179  112 IEADELKNFLKHLLKeaKRDNDVSEDKLIEYTDTILQLFDRNKDGKLQLSEmarllpvkenflcrpiFKGAGKLTREdID 191

                         90       100
                 ....*....|....*....|....*
gi 826307929 729 KIFKHYDTDQSGTINSYEMRNAVND 753
Cdd:cd16179  192 RVFALYDRDNNGTIENEELTGFLKD 216
EF-hand_7 pfam13499
EF-hand domain pair;
652-722 4.96e-03

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 36.08  E-value: 4.96e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 826307929  652 QQFRNIFKQI--AGDDMeICADELKNVLntvvnkHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHLWK 722
Cdd:pfam13499   2 EKLKEAFKLLdsDGDGY-LDVEELKKLL------RKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 698-724 6.19e-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: 35.05  E-value: 6.19e-03
                           10        20
                   ....*....|....*....|....*..
gi 826307929   698 RSMIALMDTDGSGRLNLQEFHHLWKKI 724
Cdd:smart00054   3 KEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
 668-807 7.80e-03

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: 38.87  E-value: 7.80e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 668 ICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQEFHHL------------------WKKiKAWQK 729
Cdd:cd15902  107 IEAKELKGFLKDLLLKNKKHVSPPKLDEYTKLILKEFDANKDGKLELDEMAKLlpvqenfllkfqilgamdLTK-EDFEK 185

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 826307929 730 IFKHYDTDQSGTINSYEmrnavndagfhLNSQLYDIITMRYADRHMNiDFDSFICCFIRlegmfrafnAFDKDGDGII 807
Cdd:cd15902  186 VFEHYDKDNNGVIEGNE-----------LDALLKDLLEKNKADIDKP-DLENFRDAILR---------ACDKNKDGKI 242
EFh_HEF_SCGN cd16178
EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand ...
 668-753 8.13e-03

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: 38.92  E-value: 8.13e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 826307929 668 ICADELKNVLNTVVNKHKDLKSQGFTLESCRSMIALMDTDGSGRLNLQE----------FHHLWK--------KIKAWQK 729
Cdd:cd16178  109 ISAAELKNFLRDLFLQHKKVITEDKLDEYTDTMMKIFDKNKDGRLDLNDmarilalqenFLLQFKmdamseeeRKRDFEK 188

                         90       100
                 ....*....|....*....|....
gi 826307929 730 IFKHYDTDQSGTINSYEMRNAVND 753
Cdd:cd16178  189 IFAHYDVSKTGALEGPEVDGFVKD 212
 
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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