SERPINC1

Protein identityUniProt · HPA

UniProt accession

P01008

Gene

SERPINC1

Ensembl

ENSG00000117601

Chromosome

1

Canonical length

464 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene, antithrombin III, is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. Numerous mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency which constitutes a strong risk factor for thrombosis. A reduction in the serum level of this protein is associated with severe cases of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Sep 2020]

Canonical amino-acid sequenceUniProt

464 residues, UniProt reviewed canonical sequence.

>P01008|SERPINC1
     1  MYSNVIGTVT SGKRKVYLLS LLLIGFWDCV TCHGSPVDIC TAKPRDIPMN PMCIYRSPEK
    61  KATEDEGSEQ KIPEATNRRV WELSKANSRF ATTFYQHLAD SKNDNDNIFL SPLSISTAFA
   121  MTKLGACNDT LQQLMEVFKF DTISEKTSDQ IHFFFAKLNC RLYRKANKSS KLVSANRLFG
   181  DKSLTFNETY QDISELVYGA KLQPLDFKEN AEQSRAAINK WVSNKTEGRI TDVIPSEAIN
   241  ELTVLVLVNT IYFKGLWKSK FSPENTRKEL FYKADGESCS ASMMYQEGKF RYRRVAEGTQ
   301  VLELPFKGDD ITMVLILPKP EKSLAKVEKE LTPEVLQEWL DELEEMMLVV HMPRFRIEDG
   361  FSLKEQLQDM GLVDLFSPEK SKLPGIVAEG RDDLYVSDAF HKAFLEVNEE GSEAAASTAV
   421  VIAGRSLNPN RVTFKANRPF LVFIREVPLN TIIFMGRVAN PCVK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SERPINC1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

4,727 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SERPINC1.

Disease | AllUniProt

Conditions SERPINC1 is implicated in, by any mechanism.

• Antithrombin III deficiency (AT3D) MIM:613118

Disease | GeneticClinVar

174 pathogenic / likely-pathogenic of 487 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary antithrombin deficiency
• SERPINC1-related disorder
• Deep venous thrombosis
• Tuberous sclerosis 2
• Thrombophilia with a likely monogenic cause

Disease | ImmuneIEDB

Conditions an epitope on SERPINC1 was assayed in.

• rheumatoid arthritis B cell

ReferencesPubMed · IEDB

Publications for SERPINC1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.15

gnomAD pLI

1

gnomAD missense Z

1.36

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• regulation of blood coagulation

Molecular functions

• heparin binding
• identical protein binding
• protease binding
• serine-type endopeptidase inhibitor activity

Cellular components

• blood microparticle
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Serpin family
• Serpin, conserved site
• Serpin domain
• Serpin superfamily
• Serpin superfamily, domain 1
• Serpin superfamily, domain 2
• Serpin (serine protease inhibitor)
• Antithrombin-III, serpin domain

KeywordsUniProt

• Blood coagulation
• Disulfide bond
• Glycoprotein
• Hemostasis
• Heparin-binding
• Phosphoprotein
• Protease inhibitor
• Secreted
• Serine protease inhibitor
• Signal
• Thrombophilia

InteractionsUniProt · HPA

Protein binding partners of SERPINC1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• F9