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    PROS1 protein S [ Homo sapiens (human) ]

    Gene ID: 5627, updated on 2-Nov-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
    mouse all
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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)

    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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