1JMJ,1JMO


Conserved Protein Domain Family
serpinD1_HCF2

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cd02047: serpinD1_HCF2 
Click on image for an interactive view with Cn3D
serpin family D member 1, Heparin cofactor II
Heparin cofactor II (HCF2/HC-II, also called protease inhibitor leuserpin-2/hLS2) is a protein encoded by the SERPIND1 gene that inhibits thrombin, the final protease of the coagulation cascade. HCII is allosterically activated by binding to cell surface glycosaminoglycans (GAGs). The specificity of HCII for thrombin is conferred by a highly acidic hirudin-like N-terminal tail, which becomes available after GAG binding for interaction with the anion-binding exosite I of thrombin. HCII deficiency can lead to increased thrombin generation and a hypercoagulable state. This subgroup corresponds to clade D of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.
Statistics
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PSSM-Id: 381004
Aligned: 15 rows
Threshold Bit Score: 753.094
Created: 9-Nov-2004
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
reactive centerthrombin
Conserved site includes 26 residues -Click on image for an interactive view with Cn3D
Feature 1:reactive center loop (RCL)
Evidence:
  • Comment:depending on the conformational state, the RC loop is surface accessible in the active form or buried and inserted as the central beta strand in the inactive form.
  • Structure:1JMJ_B: human heparin cofactor II native conformation RCL partially inserted into a beta-sheet and is unfavorable for complex formation with thrombin
  • Structure:1JMO_A: human heparin cofactor II with bound heparin results in the expulsion of the RCL to a favorable conformation for complex formation with thrombin

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                        
1JMJ_B        32 SMPLLPADFHKENTVTNDWi--PEGEEDDDYLDLEKIFSEDdd-yiDIVDSLSVSPT--------------DSDVSAGnI 94  human
AIA57696      38 RYPNNPSDSYMDDTLALDLngfTDEDSIEDYIDFDKLLNEDe----DYPDEIDDINEdgstgvtvnaeklvDASFNKKlF 113 European river ...
AAC16323      38 GSQTQAVENLLDDTVTNDLs--TEGEDEEDYLDFDKIFGEDe----DYIDIIDAAPEi------------kNSETQQGnI 99  African clawed ...
AAI55277      50 DMESIPLDFHRENTVTNDL---PEGQDDEDYVDFDKILGEDdysegDHIDEISTPAPdldlf-----yepsDPKIRRArL 121 zebrafish
AAC16324      28 NMPDLPLEFHRENTITNDLi--PEEEEEEDYLDLDKILGED-----DYSDIIDAAPHi-------------VSEIQQGnI 87  chicken
NP_001279502  37 DTILESGDYLFLDSSVTRN---LISEEEEDYLDWDQILGEDhd-ddDYIDEIDEIEDelefdp---vaeraDPATKRArL 109 elephant shark
XP_005990227  84 STDSIPTEYHQVDTITNDL---MLKEDEMDYLDLDLILGEDd----DYPDEIDEIEPdapds----viesnDREAMRAkL 152 coelacanth
NP_878300     50 DMESIPLDFHRENTVTNDL---PEGQDDEDYVDFDKILGEDdysegDHIDEISTPAPdldlf-----yepsDPKIRRArL 121 zebrafish
AAH49293      38 GSQTQAVENLLDDTVTNDLs--TEGEDEEDYLDFDKIFGEDe----DYIDIIDAAPEi------------kNSETQQGnI 99  African clawed ...
Q64268        33 TVSLLPPNFHKENTVTNDWi--PEGEEDDDYLDLEKLLSEDd----DYIYVVDAVSPt-------------DSESSAGnI 93  Norway rat
Feature 1                                                                                        
1JMJ_B        95 LQLFHGKSRIQRLNILNAKFAFNLYRVLKDQVNTFDNIFIAPVGISTAMGMISLGLKGETHEQVHSILHFKDFVNASSKY 174 human
AIA57696     114 LRRFQGKTRIQRLSIVNSDFAFNLYRSVSESTPPGENLLLAPLGISSTLGMISLGANGGTHEEIYRALGFESLVNSSSKY 193 European river ...
AAC16323     100 FELFHGKTRVQRLNIINANFGFNLYRAIKNNTDASENILLAPVGISTAMATISLGTKGQTLEQVLLTLGFKDFLNASSKY 179 African clawed ...
AAI55277     122 LRLFHGQTRLQRINVVNARFGFRLYRKLRNRLNQTDNILLAPVGISIAMGMMGLGVGPNTQEQLFQTVGFAEFVNASNHY 201 zebrafish
AAC16324      88 LELFQGKTRIQRLNILNANFGFNLYRSVADKANSSDNILMAPVGISTAMAMISLGLKGQTQQEVLSVLGFEDFINASAKY 167 chicken
NP_001279502 110 LGLFHGKTRIQRLNTVNTDFAFDLYRRLSNSSNQYDNILLAPVGISTTLAMISLGAGSHTHQQLFHTLGFGAFVNASTKY 189 elephant shark
XP_005990227 153 LKLFRGKTRIQRLNIVNADFGFRLYRSLRNTINSSENILLAPVGISTILAMISLGAQEETHQQILSTLGFYDFVNASTKY 232 coelacanth
NP_878300    122 LRLFHGQTRLQRINVVNARFGFRLYRKLRNRLNQTDNILLAPVGISIAMGMMGLGVGPNTQEQLFQTVGFAEFVNASNHY 201 zebrafish
AAH49293     100 FELFHGKTRVQRLNIINANFGFNLYRAIKNNTDASENILLAPVGISTAMATISLGTKGQTLEQVLLTLGFKDFLNASSKY 179 African clawed ...
Q64268        94 LQLFQGKSRIQRLNILNAKFAFNLYRVLKDQATSSDNIFIAPVGISTAMGMISLGLRGETHEEVHSVLHFKDFVNASSKY 173 Norway rat
Feature 1                                                                                        
1JMJ_B       175 EITTIHNLFRKLTHRLFRRNFGYTLRSVNDLYIQKQFPILLDFKTKVREYYFAEAQIADFSDPAFISKTNNHIMKLTKGL 254 human
AIA57696     194 NISTVHKLFHRLNHRLFRHNFGYTLKSASALYLQRRWPLLPSYQQCLRKTYFAEAHTVDFKDPATVQRISHWVSSSTKGT 273 European river ...
AAC16323     180 EILTLHNVFRKLTHRLFRRNFGYTLRSVNDIYVKRDFLIREPFKNNLKNYYFAEAQTVDFGYKDFLTKANKRIQQLTKGL 259 African clawed ...
AAI55277     202 DNSTVHKLFRKLTHRLFRRNFGYTLRSVNDLYVKRNVQIQDSFRADAKTYYFAEPQSVDFADPAFLVKANQRIQKITKGL 281 zebrafish
AAC16324     168 ELMTVHNLFRKLTHRLFRRNFGYTLRSVNDLYIRKDFSILNDFRNNMKTYYFADAQPADFSDPNFITKTNERILKLTKGL 247 chicken
NP_001279502 190 DVITVHNLFRRLTHRLFRHKFGYTLHSVNGLFVRQDTNLLGNFTENMKTYYFAEAQLSNFSDPGLVTKLNQRILKLTKGM 269 elephant shark
XP_005990227 233 EVITVHKLFRKLTHRLFRRNFGYTLHSVNDLYIRQNFNILDTFRNSMKNYYFAEPLLVDFSDPAFITKANQRVLKLTKGL 312 coelacanth
NP_878300    202 DNSTVHKLFRKLTHRLFRRNFGYTLRSVNDLYVKRNVQIQDSFRADAKTYYFAEPQSVDFADPAFLVKANQRIQKITKGL 281 zebrafish
AAH49293     180 EILTLHNVFRKLTHRLFRRNFGYTLRSVNDIYVKRDFLIREPFKNNLKNYYFAEAQTVDFGNKDFLTKANKRIQQLTKGL 259 African clawed ...
Q64268       174 EVTTIHNLFRKLTHRLFRRNFGYTLQSVNDLYIQKQFPIREDFKAAMREFYFAEAQEADFSDPAFISKANSHILKLTKGL 253 Norway rat
Feature 1                                                                                        
1JMJ_B       255 IKDALENIDPATQMMILNCIYFKGSWVNKFPVEMTHNHNFRLNEREVVKVSMMQTKGNFLAANDQELDCDILQLEYVGGI 334 human
AIA57696     274 ISDAVTNIDPSTVFLVINSVYFKGPWEIKFSKHQTSMRSFRLNDKESVKVQMMQTKASFLVTTDHELGCDILQLAYQGNV 353 European river ...
AAC16323     260 IEEALTNVDPALLMLLVNCIYFKGTWENKFPVEYTQNMNFRLNEKELVKVPMMKTKGNFLVAADPELDCAVLQLPYVGNI 339 African clawed ...
AAI55277     282 IKEPLKSVDPNMAVMLLNYLYFKGTWEQKFPKELTHHRQFRVNEKKQVRVLMMQNKGSYLAAADHELNCDILQLPYAGNI 361 zebrafish
AAC16324     248 IKEALVNVNPTTLMMILNCLYFKGTWENKFPVEMTTKRSFRLNEKQTIKVPMMQTKGNFLAAADPELDCGVIQLPFVGNI 327 chicken
NP_001279502 270 IRDSIQAIDPRTLLMILNCLYFKGTWENKFPVEKTYRRVFRVSEKVTVKVPMMHTKGNFLTAVDPELECDILQLPYVGNS 349 elephant shark
XP_005990227 313 IREALKKVDPHTLMMVLNSLYFKGSWENKFPPDLTRYDSFRLNEKETVRVQMMQTKRNFLATVDHELDCDVLQMPYVGNI 392 coelacanth
NP_878300    282 IKEPLKSVDPNMAVMLLNYLYFKGTWEQKFPKELTHHRQFRVNEKKQVRVLMMQNKGSYLAAADHELNCDILQLPYAGNI 361 zebrafish
AAH49293     260 IKEALTNVDPALLMLLVNCIYFKGTWENKFPVEYTQNMNFRLNEKELVKVPMMKTKGNFLVAADPELDCAVLQLPYVGNI 339 African clawed ...
Q64268       254 IKEALENTDSATQMMILNCIYFKGAWMNKFPVEMTHNHNFRLNEREVVKVSMMQTKGNFLAANDQELDCDILQLEYVGGI 333 Norway rat
Feature 1                                                                                        
1JMJ_B       335 SMLIVVPHKM-SGMKTLEAQLTPRVVERWQKSMTNRTREVLLPKFKLEKNYNLVESLKLMGIRMLFDKNGNMAg-ISDQR 412 human
AIA57696     354 SMILAVPHKLkGGLKTLERALSFDLLEKWLQAMTNRTRDVIIPKFNLQQKYDLKNNLKEMGVTELFQANADLSgmTGAKD 433 European river ...
AAC16323     340 SMLIVLPHKL-SGMKLLEKQISPQVVERWQNIMTNRTREVFLPRFKLEKSYDLQKVLSNMGATDLFTHGDFSG--VSDKD 416 African clawed ...
AAI55277     362 SMLIAVPQKL-SGMRSLEQEISPTLVNKWLSNMTNRTREVVFPRFKLEQNYDLIEHLKEMGMTDIFTEKGDFSp-MTSEK 439 zebrafish
AAC16324     328 SMLIVLPHKL-SGMKALEKQITPQVVEKWQKSMTNRTREVVLPKFKLEKNYNLIGFLRSMGIEELFSEKGNYCg-VSEEK 405 chicken
NP_001279502 350 SMLAVLPHKL-SGMKSLEKRLVAEVVVKWQSKMTNRSREVVFPKFSLAKQYDLMPYLKGMGLTLPFQAGADFSriSTQED 428 elephant shark
XP_005990227 393 SMFVAVPRLF-SGMKNLENKLTSAEVEKWINNMTNRTREVLFPRFKLEKNYNLIEYLEDLGLMDMFHANADFSg-IADKQ 470 coelacanth
NP_878300    362 SMLIAVPQKL-SGMRSLEQEISPTLVNKWLSNMTNRTREVVFPRFKLEQNYDLIEHLKEMGMTDIFTEKGDFSp-MTSEK 439 zebrafish
AAH49293     340 SMLIVLPHKL-SGMKLLEKQISPQVVERWQNIMTNRTREVFLPRFKLEKSYDLQKVLSNMGATDLFTHGDFSG--VSDKD 416 African clawed ...
Q64268       334 SMLIVIPRKL-SGMKTLEAQLTPQVVERWQKSMTNRTREVLLPKFKLEKNYNLVEVLKSMGITKLFNKNGNMSg-ISDQR 411 Norway rat
Feature 1                         ##########################                         
1JMJ_B       413 IAIDLFKHQGTITVNEEGTQATTVTTVGFMPLSTQVRFTVDRPFLFLIYEHRTSCLLFMGRVANPSRS 480 human
AIA57696     434 VQVSSFQHQGFIKIDEEGSEAAAVTTVGFTPLTSHNRFVADRPFVFIVYEHHTMSVLFLGQVSNPAKN 501 European river lamprey
AAC16323     417 INIGLFQHQGTITVNEEGTEAAAVTVVGFMPLSTQARFVADRPFLFLIYEHRTNCLVFMGRVANPTKS 484 African clawed frog
AAI55277     440 VIINWFKHQGSITVNEEGTEAAAMTHIGFMPLSTQTRFIVDRPFPFLIYEHRTGCVVFMGRVVDPSQT 507 zebrafish
AAC16324     406 VSIDRFNHQGTITVNEEGTEAGAITNVGFMPLSTQIRFIVDRPFLFLIYEHRTNCLLFMGRVVNPAKP 473 chicken
NP_001279502 429 LIINLLKHQGSITVNEEGTTAASLTKASFMPLSIQNDFVVNRPFLFLIYEHRTECLLFMGRVMNPESS 496 elephant shark
XP_005990227 471 LIIKLLNHQGKINVNEEGTEAAAQTHAGFTPLTTQNRFTANRPFLFLIYEHRTSCLLFMGRVANPLKS 538 coelacanth
NP_878300    440 VIINWFKHQGSITVNEEGTEAAAMTHIGFMPLSTQTRFIVDRPFLFLIYEHRTGCVVFMGRVVDPSQT 507 zebrafish
AAH49293     417 INIGLFQHQGTITVNEEGTEAAAVTVVGFMPLSTQARFVADRPFLFLIYEHRTNCLVFMGRVANPTKS 484 African clawed frog
Q64268       412 IIIDLFKHQSTITVNEEGTQAAAVTTVGFMPLSTQVRFTVDRPFLFLVYEHRTSCLLFMGRVANPAKS 479 Norway rat

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