Seroatlas · Human Serome Atlas

PROS1

Vitamin K-dependent protein S

Also known as: PROS, PROS_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P07225
Gene
PROS1
Ensembl
ENSG00000184500
Chromosome
3
Canonical length
676 aa
Protein class
Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
Secretome location
Secreted to blood

OverviewNCBI Gene

This gene encodes a vitamin K-dependent plasma protein that functions as a cofactor for the anticoagulant protease, activated protein C (APC) to inhibit blood coagulation. It is found in plasma in both a free, functionally active form and also in an inactive form complexed with C4b-binding protein. Mutations in this gene result in autosomal dominant hereditary thrombophilia. An inactive pseudogene of this locus is located at an adjacent region on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

676 residues, UniProt reviewed canonical sequence.

>P07225|PROS1
     1  MRVLGGRCGA LLACLLLVLP VSEANFLSKQ QASQVLVRKR RANSLLEETK QGNLERECIE
    61  ELCNKEEARE VFENDPETDY FYPKYLVCLR SFQTGLFTAA RQSTNAYPDL RSCVNAIPDQ
   121  CSPLPCNEDG YMSCKDGKAS FTCTCKPGWQ GEKCEFDINE CKDPSNINGG CSQICDNTPG
   181  SYHCSCKNGF VMLSNKKDCK DVDECSLKPS ICGTAVCKNI PGDFECECPE GYRYNLKSKS
   241  CEDIDECSEN MCAQLCVNYP GGYTCYCDGK KGFKLAQDQK SCEVVSVCLP LNLDTKYELL
   301  YLAEQFAGVV LYLKFRLPEI SRFSAEFDFR TYDSEGVILY AESIDHSAWL LIALRGGKIE
   361  VQLKNEHTSK ITTGGDVINN GLWNMVSVEE LEHSISIKIA KEAVMDINKP GPLFKPENGL
   421  LETKVYFAGF PRKVESELIK PINPRLDGCI RSWNLMKQGA SGIKEIIQEK QNKHCLVTVE
   481  KGSYYPGSGI AQFHIDYNNV SSAEGWHVNV TLNIRPSTGT GVMLALVSGN NTVPFAVSLV
   541  DSTSEKSQDI LLSVENTVIY RIQALSLCSD QQSHLEFRVN RNNLELSTPL KIETISHEDL
   601  QRQLAVLDKA MKAKVATYLG GLPDVPFSAT PVNAFYNGCM EVNINGVQLD LDEAISKHND
   661  IRAHSCPSVW KKTKNS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PROS1 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)
0.31
Highest tissue expression
265 nTPM

Expression across tissuesHPA

Tissue

  • liver: 265 nTPM
  • choroid plexus: 133 nTPM
  • heart muscle: 109 nTPM
  • blood vessel: 99 nTPM
  • ovary: 43 nTPM
  • lung: 37 nTPM

Single-cell type

  • choroid plexus epithelial cells: 1,011 nCPM
  • hepatocytes: 460 nCPM
  • platelets: 329 nCPM
  • ependymal cells: 305 nCPM
  • schwann cells: 195 nCPM
  • respiratory ciliated cells: 175 nCPM

Immune cell

  • total PBMC: 3.2 nTPM
  • neutrophil: 0.8 nTPM
  • myeloid DC: 0.3 nTPM
  • classical monocyte: 0.2 nTPM
  • eosinophil: 0.2 nTPM
  • intermediate monocyte: 0.2 nTPM

Brain region

  • choroid plexus: 214 nTPM
  • hippocampal formation: 6.2 nTPM
  • midbrain: 4.5 nTPM
  • thalamus: 4.4 nTPM
  • medulla oblongata: 4.2 nTPM
  • hypothalamus: 4 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PROS1.

Disease | AllUniProt

Conditions PROS1 is implicated in, by any mechanism.

  • Thrombophilia due to protein S deficiency, autosomal dominant (THPH5) MIM:612336
  • Thrombophilia due to protein S deficiency, autosomal recessive (THPH6) MIM:614514

Disease | GeneticClinVar

146 pathogenic / likely-pathogenic of 688 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Thrombophilia due to protein S deficiency, autosomal recessive
  • Thrombophilia due to protein S deficiency, autosomal dominant
  • Protein S deficiency disease
  • PROS1-related disorder
  • Hereditary thrombophilia due to congenital protein S deficiency

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)
0.57
gnomAD pLI
0
gnomAD missense Z
0.58
DepMap mean gene effect
-0.13
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PROS1 as an antibody target. Whether an autoantibody or antibody against PROS1 could matter depends on whether native PROS1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PROS1 is annotated as secreted, so native PROS1 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label PROS1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/PROS1. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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