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Protein

Heparin cofactor 2

Gene

SERPIND1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Photoprotein, Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Blood coagulation, Chemotaxis, Hemostasis, Luminescence

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000099937-MONOMER.
ReactomeiR-HSA-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-HSA-140875. Common Pathway of Fibrin Clot Formation.

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

HGNCiHGNC:4838. SERPIND1.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: GO_Central
Complete GO annotation...

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 rs5907dbSNPEnsembl.1
Natural variantiVAR_054977447E → K in THPH10. 1 PublicationCorresponds to variant rs142451096dbSNPEnsembl.1
Natural variantiVAR_054978462P → L in THPH10; Tokushima; impaired secretion of the mutant molecules. 1 PublicationCorresponds to variant rs121912420dbSNPEnsembl.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)3 Publications1
Modified residuei79Sulfotyrosine1 Publication1
Modified residuei92Sulfotyrosine1 Publication1
Glycosylationi188N-linked (GlcNAc...)3 Publications1
Glycosylationi387N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

Phosphorylated by FAM20C in the extracellular medium.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Sulfation

Proteomic databases

MaxQBiP05546.
PaxDbiP05546.
PeptideAtlasiP05546.
PRIDEiP05546.

PTM databases

iPTMnetiP05546.
PhosphoSitePlusiP05546.

Miscellaneous databases

PMAP-CutDBP05546.

Expressioni

Tissue specificityi

Expressed predominantly in liver. Also present in plasma.

Gene expression databases

BgeeiENSG00000099937.
CleanExiHS_SERPIND1.
GenevisibleiP05546. HS.

Organism-specific databases

HPAiCAB008639.
HPA055767.

Interactioni

Protein-protein interaction databases

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

Structurei

Secondary structure

1499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi82 – 87Combined sources6
Helixi90 – 92Combined sources3
Helixi122 – 142Combined sources21
Beta strandi151 – 153Combined sources3
Helixi155 – 165Combined sources11
Helixi166 – 168Combined sources3
Helixi171 – 180Combined sources10
Helixi183 – 189Combined sources7
Helixi195 – 210Combined sources16
Beta strandi214 – 227Combined sources14
Helixi234 – 244Combined sources11
Beta strandi248 – 251Combined sources4
Helixi256 – 269Combined sources14
Turni270 – 272Combined sources3
Turni277 – 280Combined sources4
Beta strandi287 – 296Combined sources10
Beta strandi299 – 301Combined sources3
Helixi305 – 307Combined sources3
Beta strandi309 – 314Combined sources6
Beta strandi316 – 318Combined sources3
Beta strandi320 – 337Combined sources18
Turni338 – 341Combined sources4
Beta strandi342 – 349Combined sources8
Turni350 – 352Combined sources3
Beta strandi353 – 362Combined sources10
Helixi363 – 365Combined sources3
Helixi366 – 372Combined sources7
Helixi375 – 384Combined sources10
Beta strandi386 – 395Combined sources10
Beta strandi397 – 400Combined sources4
Helixi406 – 412Combined sources7
Helixi416 – 418Combined sources3
Turni425 – 427Combined sources3
Beta strandi434 – 445Combined sources12
Beta strandi447 – 451Combined sources5
Beta strandi459 – 462Combined sources4
Beta strandi468 – 470Combined sources3
Beta strandi475 – 481Combined sources7
Turni482 – 485Combined sources4
Beta strandi486 – 494Combined sources9

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[»]
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.
OMAiTNNHIMK.
OrthoDBiEOG091G0ION.
PhylomeDBiP05546.
TreeFamiTF343094.

Family and domain databases

CDDicd02047. HCII. 1 hit.
InterProiIPR033831. HCII.
IPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiPF00079. Serpin. 1 hit.
[Graphical view]
SMARTiSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiPS00284. SERPIN. 1 hit.
[Graphical view]

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.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 → T.1 PublicationCorresponds to variant rs5905dbSNPEnsembl.1
Natural variantiVAR_01174760H → P.Corresponds to variant rs165867dbSNPEnsembl.1
Natural variantiVAR_05195387S → N.Corresponds to variant rs34324685dbSNPEnsembl.1
Natural variantiVAR_051954129L → V.Corresponds to variant rs11542069dbSNPEnsembl.1
Natural variantiVAR_007112208R → H in THPH10; Oslo; decreased affinity for dermatan sulfate. 2 PublicationsCorresponds to variant rs5907dbSNPEnsembl.1
Natural variantiVAR_011748237K → R.Corresponds to variant rs1042435dbSNPEnsembl.1
Natural variantiVAR_011749442T → M.1 PublicationCorresponds to variant rs5904dbSNPEnsembl.1
Natural variantiVAR_054977447E → K in THPH10. 1 PublicationCorresponds to variant rs142451096dbSNPEnsembl.1
Natural variantiVAR_054978462P → L in THPH10; Tokushima; impaired secretion of the mutant molecules. 1 PublicationCorresponds to variant rs121912420dbSNPEnsembl.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

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[»]
ProteinModelPortaliP05546.
SMRiP05546.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

DrugBankiDB00407. Ardeparin.
DB06271. Sulodexide.

Protein family/group databases

MEROPSiI04.019.

PTM databases

iPTMnetiP05546.
PhosphoSitePlusiP05546.

Polymorphism and mutation databases

BioMutaiSERPIND1.
DMDMi123055.

Proteomic databases

MaxQBiP05546.
PaxDbiP05546.
PeptideAtlasiP05546.
PRIDEiP05546.

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.
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.
OMAiTNNHIMK.
OrthoDBiEOG091G0ION.
PhylomeDBiP05546.
TreeFamiTF343094.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000099937-MONOMER.
ReactomeiR-HSA-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-HSA-140875. Common Pathway of Fibrin Clot Formation.

Miscellaneous databases

EvolutionaryTraceiP05546.
GeneWikiiHeparin_cofactor_II.
GenomeRNAii3053.
PMAP-CutDBP05546.
PROiP05546.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000099937.
CleanExiHS_SERPIND1.
GenevisibleiP05546. HS.

Family and domain databases

CDDicd02047. HCII. 1 hit.
InterProiIPR033831. HCII.
IPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiPF00079. Serpin. 1 hit.
[Graphical view]
SMARTiSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiPS00284. SERPIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHEP2_HUMAN
AccessioniPrimary (citable) accession number: P05546
Secondary accession number(s): B2RAI1, D3DX34, Q6IBZ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1991
Last modified: November 30, 2016
This is version 181 of the entry and version 3 of the sequence. [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. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.