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PROS1 protein S [ Homo sapiens (human) ]

Gene ID: 5627, updated on 28-Oct-2024

Summary

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Official Symbol
PROS1provided by HGNC
Official Full Name
protein Sprovided by HGNC
Primary source
HGNC:HGNC:9456
See related
Ensembl:ENSG00000184500 MIM:176880; AllianceGenome:HGNC:9456
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PSA; PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6
Summary
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]
Expression
Broad expression in liver (RPKM 79.4), heart (RPKM 44.6) and 21 other tissues See more
Orthologs
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Genomic context

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See PROS1 in Genome Data Viewer
Location:
3q11.1
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (93873051..93973896, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (96571223..96678047, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (93591895..93692740, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene DNA primase large subunit-like Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:93505591-93506187 Neighboring gene OCT4 hESC enhancer GRCh37_chr3:93515463-93515964 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:93624998-93625498 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:93625499-93625999 Neighboring gene RNA, U6 small nuclear 488, pseudogene Neighboring gene Sharpr-MPRA regulatory region 12381 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20122 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20123 Neighboring gene heat shock protein family E (Hsp10) member 1 pseudogene 17 Neighboring gene RNA, U6 small nuclear 511, pseudogene Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 7 Neighboring gene ARF like GTPase 13B

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Confirmation of inherited protein S deficiency by PROS1 mutational screening: Identification of three novel PROS1 mutations and haplotype analysis of p.Q279X recurrence. Hurtado B, et al. Thromb Haemost, 2008 Oct. PMID 18841302
  2. Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from mixed type I/III families. Castoldi E, et al. Haematologica, 2010 Apr 7. PMID 20378562
  3. PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis. Shi H, et al. Aging (Albany NY), 2024 Apr 10. PMID 38613800, Free PMC Article
  4. A novel splice site mutation in intron C of PROS1 leads to markedly reduced mutant mRNA level, absence of thrombin-sensitive region, and impaired secretion and cofactor activity of mutant protein S. Okada H, et al. Thromb Res, 2010 May. PMID 20022358
  5. Membrane binding and anticoagulant properties of protein S natural variants. Baroni M, et al. Thromb Res, 2010 Feb. PMID 19878975

See all (259) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily.
    Title: Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily.
  2. PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.
    Title: PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.
  3. The Protein S Erlangen Mutation PROS1c.1904T>C (F635S) Suppresses Secretion.
    Title: The Protein S Erlangen Mutation PROS1c.1904T>C (F635S) Suppresses Secretion.
  4. Replication Study of the Association of GAS6 and PROS1 Polymorphisms with Behcet's Disease in a Japanese Population.
    Title: Replication Study of the Association of GAS6 and PROS1 Polymorphisms with Behçet's Disease in a Japanese Population.
  5. Analysis of PROS1 mutations and clinical characteristics in three Chinese families with hereditary protein S deficiency.
    Title: Analysis of PROS1 mutations and clinical characteristics in three Chinese families with hereditary protein S deficiency.
  6. Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.
    Title: Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.
  7. Protein C and S levels in patients with Thalassemia intermedia.
    Title: Protein C and S levels in patients with Thalassemia intermedia.
  8. Dysregulation of Protein S in COVID-19.
    Title: Dysregulation of Protein S in COVID-19.
  9. AXL, along with PROS1, is overexpressed in papillary thyroid carcinoma and regulates its biological behaviour.
    Title: AXL, along with PROS1, is overexpressed in papillary thyroid carcinoma and regulates its biological behaviour.
  10. LncRNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated low PROS1 expression is an onco-immunological biomarker in low-grade gliomas: a pan-cancer analysis with experimental verification.
    Title: LncRNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated low PROS1 expression is an onco-immunological biomarker in low-grade gliomas: a pan-cancer analysis with experimental verification.
Submit: New GeneRIF Correction See all GeneRIFs (194)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Thrombophilia due to protein S deficiency, autosomal dominant
MedGen: C3278211 OMIM: 612336 GeneReviews: Not available
Compare labs
Thrombophilia due to protein S deficiency, autosomal recessive
MedGen: C3281092 OMIM: 614514 GeneReviews: Not available
Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables endopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in blood coagulation IEA
Inferred from Electronic Annotation
more info
  
involved_in fibrinolysis IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in Golgi lumen TAS
Traceable Author Statement
more info
  
located_in Golgi membrane TAS
Traceable Author Statement
more info
  
located_in blood microparticle HDA PubMed 
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in platelet alpha granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
vitamin K-dependent protein S
Names
protein S (alpha)
protein Sa
vitamin K-dependent plasma protein S

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009813.1 RefSeqGene

    Range
    5001..106054
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_572

mRNA and Protein(s)

  1. NM_000313.4 → NP_000304.2  vitamin K-dependent protein S isoform 2 preproprotein

    See identical proteins and their annotated locations for NP_000304.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC144562, AI139337, BC015801
    Consensus CDS
    CCDS2923.1
    UniProtKB/Swiss-Prot
    A8KAC9, D3DN28, P07225, Q15518, Q7Z715, Q9UCZ8
    UniProtKB/TrEMBL
    A0A0S2Z4K3, Q16519
    Related
    ENSP00000377783.3, ENST00000394236.9
    Conserved Domains (7) summary
    smart00069
    Location:23 → 85
    GLA; Domain containing Gla (gamma-carboxyglutamate) residues
    cd00054
    Location:119 → 155
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    pfam00054
    Location:329 → 459
    Laminin_G_1; Laminin G domain
    pfam02210
    Location:514 → 647
    Laminin_G_2; Laminin G domain
    pfam06247
    Location:134 → 293
    Plasmod_Pvs28; Plasmodium ookinete surface protein Pvs28
    pfam07645
    Location:201 → 241
    EGF_CA; Calcium-binding EGF domain
    pfam14670
    Location:168 → 199
    FXa_inhibition; Coagulation Factor Xa inhibitory site

  2. NM_001314077.2 → NP_001301006.1  vitamin K-dependent protein S isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1). This isoform (1) may undergo proteolytic processing similar to isoform 2.
    Source sequence(s)
    AC144562, AI139337, BC015801, BG702968, DA408604, DB076220
    Consensus CDS
    CCDS93325.1
    UniProtKB/TrEMBL
    A0A0S2Z4L3, Q16519
    Related
    ENSP00000497376.1, ENST00000650591.1
    Conserved Domains (7) summary
    smart00069
    Location:58 → 117
    GLA; Domain containing Gla (gamma-carboxyglutamate) residues
    cd00054
    Location:151 → 187
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    pfam00054
    Location:361 → 491
    Laminin_G_1; Laminin G domain
    pfam02210
    Location:546 → 679
    Laminin_G_2; Laminin G domain
    pfam06247
    Location:166 → 325
    Plasmod_Pvs28; Plasmodium ookinete surface protein Pvs28
    pfam07645
    Location:233 → 273
    EGF_CA; Calcium-binding EGF domain
    pfam14670
    Location:200 → 231
    FXa_inhibition; Coagulation Factor Xa inhibitory site

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    93873051..93973896 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    96571223..96678047 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054347264.1 → XP_054203239.1  vitamin K-dependent protein S isoform X1

    UniProtKB/TrEMBL
    A0A0S2Z4L3
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P07225.1 GenPept UniProtKB/Swiss-Prot:P07225

Gene LinkOut

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