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Protein

Heparin cofactor 2

Gene

SERPIND1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.1 Publication
Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei463 – 464Reactive bondBy similarity2

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • heparin binding Source: UniProtKB-KW
  • serine-type endopeptidase inhibitor activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding, Protease inhibitor, Serine protease inhibitor
Biological processBlood coagulation, Chemotaxis, Hemostasis

Enzyme and pathway databases

ReactomeiR-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-140875 Common Pathway of Fibrin Clot Formation
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation

Protein family/group databases

MEROPSiI04.019

Names & Taxonomyi

Protein namesi
Recommended name:
Heparin cofactor 2
Alternative name(s):
Heparin cofactor II
Short name:
HC-II
Protease inhibitor leuserpin-2
Short name:
HLS2
Serpin D1
Gene namesi
Name:SERPIND1
Synonyms:HCF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000099937.10
HGNCiHGNC:4838 SERPIND1
MIMi142360 gene
neXtProtiNX_P05546

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Thrombophilia due to heparin cofactor 2 deficiency (THPH10)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hemostatic disorder characterized by a tendency to recurrent thrombosis.
See also OMIM:612356
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007112208R → H in THPH10; Oslo; decreased affinity for dermatan sulfate. 2 PublicationsCorresponds to variant dbSNP:rs5907EnsemblClinVar.1
Natural variantiVAR_054977447E → K in THPH10. 1 PublicationCorresponds to variant dbSNP:rs142451096Ensembl.1
Natural variantiVAR_054978462P → L in THPH10; Tokushima; impaired secretion of the mutant molecules. 1 PublicationCorresponds to variant dbSNP:rs121912420EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi122R → L: Normal thrombin inhibition and glycosaminoglycan affinity. 1 Publication1
Mutagenesisi122R → Q: Greatly reduced thrombin inhibition. Normal glycosaminoglycan affinity. 1 Publication1
Mutagenesisi122R → W: Greatly reduced thrombin inhibition. Normal glycosaminoglycan affinity. 1 Publication1
Mutagenesisi204K → M: Reduced heparin- and no dermatan sulfate-activated inhibition. 1 Publication1
Mutagenesisi204K → N: Reduced heparin- and no dermatan sulfate-activated inhibition. 1 Publication1
Mutagenesisi204K → T: Reduced heparin- and no dermatan sulfate-activated inhibition. 1 Publication1

Keywords - Diseasei

Disease mutation, Thrombophilia

Organism-specific databases

DisGeNETi3053
MalaCardsiSERPIND1
MIMi612356 phenotype
OpenTargetsiENSG00000099937
PharmGKBiPA35053

Chemistry databases

DrugBankiDB00407 Ardeparin
DB06271 Sulodexide

Polymorphism and mutation databases

BioMutaiSERPIND1
DMDMi123055

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 191 PublicationAdd BLAST19
ChainiPRO_000003249420 – 499Heparin cofactor 2Add BLAST480

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37Phosphoserine; by FAM20C1 Publication1
Glycosylationi49N-linked (GlcNAc...) (complex) asparagine3 Publications1
Modified residuei79Sulfotyrosine1 Publication1
Modified residuei92Sulfotyrosine1 Publication1
Glycosylationi188N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi387N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

Phosphorylated by FAM20C in the extracellular medium.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Sulfation

Proteomic databases

EPDiP05546
MaxQBiP05546
PaxDbiP05546
PeptideAtlasiP05546
PRIDEiP05546
ProteomicsDBi51846

PTM databases

GlyConnecti695
iPTMnetiP05546
PhosphoSitePlusiP05546

Miscellaneous databases

PMAP-CutDBiP05546

Expressioni

Tissue specificityi

Expressed predominantly in liver. Also present in plasma.

Gene expression databases

BgeeiENSG00000099937 Expressed in 81 organ(s), highest expression level in liver
CleanExiHS_SERPIND1
GenevisibleiP05546 HS

Organism-specific databases

HPAiCAB008639
HPA055767

Interactioni

Protein-protein interaction databases

BioGridi109303, 4 interactors
CORUMiP05546
IntActiP05546, 5 interactors
STRINGi9606.ENSP00000215727

Structurei

Secondary structure

1499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP05546
SMRiP05546
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05546

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati73 – 831Add BLAST11
Repeati87 – 972Add BLAST11

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni68 – 79Chemotactic activityAdd BLAST12
Regioni73 – 972 X 11 AA approximate repeats, Asp/Glu-rich (acidic) (hirudin-like)Add BLAST25
Regioni192 – 212Glycosaminoglycan-binding siteAdd BLAST21

Domaini

The N-terminal acidic repeat region mediates, in part, the glycosaminoglycan-accelerated thrombin inhibition.

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00760000118839
HOGENOMiHOG000294159
HOVERGENiHBG101242
InParanoidiP05546
KOiK03912
OMAiWEQKFPK
OrthoDBiEOG091G0ION
PhylomeDBiP05546
TreeFamiTF343094

Family and domain databases

CDDicd02047 HCII, 1 hit
InterProiView protein in InterPro
IPR033831 HCII
IPR023795 Serpin_CS
IPR023796 Serpin_dom
IPR000215 Serpin_fam
IPR036186 Serpin_sf
PANTHERiPTHR11461 PTHR11461, 1 hit
PfamiView protein in Pfam
PF00079 Serpin, 1 hit
SMARTiView protein in SMART
SM00093 SERPIN, 1 hit
SUPFAMiSSF56574 SSF56574, 1 hit
PROSITEiView protein in PROSITE
PS00284 SERPIN, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P05546-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKHSLNALLI FLIITSAWGG SKGPLDQLEK GGETAQSADP QWEQLNNKNL
60 70 80 90 100
SMPLLPADFH KENTVTNDWI PEGEEDDDYL DLEKIFSEDD DYIDIVDSLS
110 120 130 140 150
VSPTDSDVSA GNILQLFHGK SRIQRLNILN AKFAFNLYRV LKDQVNTFDN
160 170 180 190 200
IFIAPVGIST AMGMISLGLK GETHEQVHSI LHFKDFVNAS SKYEITTIHN
210 220 230 240 250
LFRKLTHRLF RRNFGYTLRS VNDLYIQKQF PILLDFKTKV REYYFAEAQI
260 270 280 290 300
ADFSDPAFIS KTNNHIMKLT KGLIKDALEN IDPATQMMIL NCIYFKGSWV
310 320 330 340 350
NKFPVEMTHN HNFRLNEREV VKVSMMQTKG NFLAANDQEL DCDILQLEYV
360 370 380 390 400
GGISMLIVVP HKMSGMKTLE AQLTPRVVER WQKSMTNRTR EVLLPKFKLE
410 420 430 440 450
KNYNLVESLK LMGIRMLFDK NGNMAGISDQ RIAIDLFKHQ GTITVNEEGT
460 470 480 490
QATTVTTVGF MPLSTQVRFT VDRPFLFLIY EHRTSCLLFM GRVANPSRS
Length:499
Mass (Da):57,071
Last modified:November 1, 1991 - v3
Checksum:i3B0E353FE1F6DF05
GO

Sequence cautioni

The sequence CAG30459 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti49Missing AA sequence (PubMed:3907702).Curated1
Sequence conflicti483R → P AA sequence (PubMed:3907702).Curated1
Sequence conflicti486C → T AA sequence (PubMed:3907702).Curated1
Sequence conflicti499S → Q AA sequence (PubMed:3907702).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0117467A → T1 PublicationCorresponds to variant dbSNP:rs5905Ensembl.1
Natural variantiVAR_01174760H → P. Corresponds to variant dbSNP:rs165867Ensembl.1
Natural variantiVAR_05195387S → N. Corresponds to variant dbSNP:rs34324685Ensembl.1
Natural variantiVAR_051954129L → V. Corresponds to variant dbSNP:rs11542069Ensembl.1
Natural variantiVAR_007112208R → H in THPH10; Oslo; decreased affinity for dermatan sulfate. 2 PublicationsCorresponds to variant dbSNP:rs5907EnsemblClinVar.1
Natural variantiVAR_011748237K → R. Corresponds to variant dbSNP:rs1042435Ensembl.1
Natural variantiVAR_011749442T → M1 PublicationCorresponds to variant dbSNP:rs5904Ensembl.1
Natural variantiVAR_054977447E → K in THPH10. 1 PublicationCorresponds to variant dbSNP:rs142451096Ensembl.1
Natural variantiVAR_054978462P → L in THPH10; Tokushima; impaired secretion of the mutant molecules. 1 PublicationCorresponds to variant dbSNP:rs121912420EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12849 mRNA Translation: AAA52642.1
M58600 Genomic DNA Translation: AAA52641.1
CR456573 mRNA Translation: CAG30459.1 Different initiation.
AK314200 mRNA Translation: BAG36878.1
CH471176 Genomic DNA Translation: EAX02941.1
CH471176 Genomic DNA Translation: EAX02942.1
X03498 mRNA Translation: CAA27218.1
M33660 Genomic DNA Translation: AAA36185.1
CCDSiCCDS13783.1
PIRiA37924
RefSeqiNP_000176.2, NM_000185.3
UniGeneiHs.474270

Genome annotation databases

EnsembliENST00000215727; ENSP00000215727; ENSG00000099937
ENST00000406799; ENSP00000384050; ENSG00000099937
GeneIDi3053
KEGGihsa:3053
UCSCiuc002ztb.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12849 mRNA Translation: AAA52642.1
M58600 Genomic DNA Translation: AAA52641.1
CR456573 mRNA Translation: CAG30459.1 Different initiation.
AK314200 mRNA Translation: BAG36878.1
CH471176 Genomic DNA Translation: EAX02941.1
CH471176 Genomic DNA Translation: EAX02942.1
X03498 mRNA Translation: CAA27218.1
M33660 Genomic DNA Translation: AAA36185.1
CCDSiCCDS13783.1
PIRiA37924
RefSeqiNP_000176.2, NM_000185.3
UniGeneiHs.474270

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JMJX-ray2.35A/B20-499[»]
1JMOX-ray2.20A20-499[»]
2NATNMR-A192-219[»]
2NCUNMR-A192-212[»]
2NCVNMR-A192-212[»]
2NCWNMR-A189-212[»]
ProteinModelPortaliP05546
SMRiP05546
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109303, 4 interactors
CORUMiP05546
IntActiP05546, 5 interactors
STRINGi9606.ENSP00000215727

Chemistry databases

DrugBankiDB00407 Ardeparin
DB06271 Sulodexide

Protein family/group databases

MEROPSiI04.019

PTM databases

GlyConnecti695
iPTMnetiP05546
PhosphoSitePlusiP05546

Polymorphism and mutation databases

BioMutaiSERPIND1
DMDMi123055

Proteomic databases

EPDiP05546
MaxQBiP05546
PaxDbiP05546
PeptideAtlasiP05546
PRIDEiP05546
ProteomicsDBi51846

Protocols and materials databases

DNASUi3053
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000215727; ENSP00000215727; ENSG00000099937
ENST00000406799; ENSP00000384050; ENSG00000099937
GeneIDi3053
KEGGihsa:3053
UCSCiuc002ztb.2 human

Organism-specific databases

CTDi3053
DisGeNETi3053
EuPathDBiHostDB:ENSG00000099937.10
GeneCardsiSERPIND1
HGNCiHGNC:4838 SERPIND1
HPAiCAB008639
HPA055767
MalaCardsiSERPIND1
MIMi142360 gene
612356 phenotype
neXtProtiNX_P05546
OpenTargetsiENSG00000099937
PharmGKBiPA35053
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00760000118839
HOGENOMiHOG000294159
HOVERGENiHBG101242
InParanoidiP05546
KOiK03912
OMAiWEQKFPK
OrthoDBiEOG091G0ION
PhylomeDBiP05546
TreeFamiTF343094

Enzyme and pathway databases

ReactomeiR-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-140875 Common Pathway of Fibrin Clot Formation
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation

Miscellaneous databases

EvolutionaryTraceiP05546
GeneWikiiHeparin_cofactor_II
GenomeRNAii3053
PMAP-CutDBiP05546
PROiPR:P05546
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000099937 Expressed in 81 organ(s), highest expression level in liver
CleanExiHS_SERPIND1
GenevisibleiP05546 HS

Family and domain databases

CDDicd02047 HCII, 1 hit
InterProiView protein in InterPro
IPR033831 HCII
IPR023795 Serpin_CS
IPR023796 Serpin_dom
IPR000215 Serpin_fam
IPR036186 Serpin_sf
PANTHERiPTHR11461 PTHR11461, 1 hit
PfamiView protein in Pfam
PF00079 Serpin, 1 hit
SMARTiView protein in SMART
SM00093 SERPIN, 1 hit
SUPFAMiSSF56574 SSF56574, 1 hit
PROSITEiView protein in PROSITE
PS00284 SERPIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHEP2_HUMAN
AccessioniPrimary (citable) accession number: P05546
Secondary accession number(s): B2RAI1, D3DX34, Q6IBZ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1991
Last modified: November 7, 2018
This is version 199 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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