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NameVitamin K-dependent protein S
Synonyms
  • PROS
Gene NamePROS1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001878|Vitamin K-dependent protein S
MRVLGGRCGALLACLLLVLPVSEANFLSKQQASQVLVRKRRANSLLEETKQGNLERECIE
ELCNKEEAREVFENDPETDYFYPKYLVCLRSFQTGLFTAARQSTNAYPDLRSCVNAIPDQ
CSPLPCNEDGYMSCKDGKASFTCTCKPGWQGEKCEFDINECKDPSNINGGCSQICDNTPG
SYHCSCKNGFVMLSNKKDCKDVDECSLKPSICGTAVCKNIPGDFECECPEGYRYNLKSKS
CEDIDECSENMCAQLCVNYPGGYTCYCDGKKGFKLAQDQKSCEVVSVCLPLNLDTKYELL
YLAEQFAGVVLYLKFRLPEISRFSAEFDFRTYDSEGVILYAESIDHSAWLLIALRGGKIE
VQLKNEHTSKITTGGDVINNGLWNMVSVEELEHSISIKIAKEAVMDINKPGPLFKPENGL
LETKVYFAGFPRKVESELIKPINPRLDGCIRSWNLMKQGASGIKEIIQEKQNKHCLVTVE
KGSYYPGSGIAQFHIDYNNVSSAEGWHVNVTLNIRPSTGTGVMLALVSGNNTVPFAVSLV
DSTSEKSQDILLSVENTVIYRIQALSLCSDQQSHLEFRVNRNNLELSTPLKIETISHEDL
QRQLAVLDKAMKAKVATYLGGLPDVPFSATPVNAFYNGCMEVNINGVQLDLDEAISKHND
IRAHSCPSVWKKTKNS
Number of residues676
Molecular Weight75121.905
Theoretical pI5.37
GO Classification
Functions
  • calcium ion binding
  • endopeptidase inhibitor activity
Processes
  • negative regulation of endopeptidase activity
  • regulation of complement activation
  • platelet activation
  • innate immune response
  • leukocyte migration
  • cellular protein metabolic process
  • blood coagulation
  • platelet degranulation
  • proteolysis
  • post-translational protein modification
  • fibrinolysis
  • peptidyl-glutamic acid carboxylation
  • positive regulation of phagocytosis
  • response to lipopolysaccharide
Components
  • endoplasmic reticulum membrane
  • extracellular exosome
  • protein complex
  • Golgi membrane
  • platelet alpha granule lumen
  • extracellular region
  • blood microparticle
  • Golgi lumen
  • plasma membrane
  • extracellular space
General FunctionEndopeptidase inhibitor activity
Specific FunctionAnticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID190289
UniProtKB IDP07225
UniProtKB Entry NamePROS_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0016264|Vitamin K-dependent protein S (PROS1)
ATGAGGGTCCTGGGTGGGCGCTGCGGGGCGCTGCTGGCGTGTCTCCTCCTAGTGCTTCCC
GTCTCAGAGGCAAACTTTTTGTCAAAGCAACAGGCTTCACAAGTCCTGGTTAGGAAGCGT
CGTGCAAATTCTTTACTTGAAGAAACCAAACAGGGTAATCTTGAAAGAGAATGCATCGAA
GAACTGTGCAATAAAGAAGAAGCCAGGGAGGTCTTTGAAAATGACCCGGAAACGGATTAT
TTTTATCCAAAATACTTAGTTTGTCTTCGCTCTTTTCAAACTGGGTTATTCACTGCTGCA
CGTCAGTCAACTAATGCTTATCCTGACCTAAGAAGCTGTGTCAATGCCATTCCAGACCAG
TGTAGTCCTCTGCCATGCAATGAAGATGGATATATGAGCTGCAAAGATGGAAAAGCTTCT
TTTACTTGCACTTGTAAACCAGGTTGGCAAGGAGAAAAGTGTGAATTTGACATAAATGAA
TGCAAAGATCCCTCAAATATAAATGGAGGTTGCAGTCAAATTTGTGATAATACACCTGGA
AGTTACCACTGTTCCTGTAAAAATGGTTTTGTTATGCTTTCAAATAAGAAAGATTGTAAA
GATGTGGATGAATGCTCTTTGAAGCCAAGCATTTGTGGCACAGCTGTGTGCAAGAACATC
CCAGGAGATTTTGAATGTGAATGCCCCGAAGGCTACAGATATAATCTCAAATCAAAGTCT
TGTGAAGATATAGATGAATGCTCTGAGAACATGTGTGCTCAGCTTTGTGTCAATTACCCT
GGAGGTTACACTTGCTATTGTGATGGGAAGAAAGGATTCAAACTTGCCCAAGATCAGAAG
AGTTGTGAGGTTGTTTCAGTGTGCCTTCCCTTGAACCTTGACACAAAGTATGAATTACTT
TACTTGGCGGAGCAGTTTGCAGGGGTTGTTTTATATTTAAAATTTCGTTTGCCAGAAATC
AGCAGATTTTCAGCAGAATTTGATTTCCGGACATATGATTCAGAAGGCGTGATACTGTAC
GCAGAATCTATCGATCACTCAGCGTGGCTCCTGATTGCACTTCGTGGTGGAAAGATTGAA
GTTCAGCTTAAGAATGAACATACATCCAAAATCACAACTGGAGGTGATGTTATTAATAAT
GGTCTATGGAATATGGTGTCTGTGGAAGAATTAGAACATAGTATTAGCATTAAAATAGCT
AAAGAAGCTGTGATGGATATAAATAAACCTGGACCCCTTTTTAAGCCGGAAAATGGATTG
CTGGAAACCAAAGTATACTTTGCAGGATTCCCTCGGAAAGTGGAAAGTGAACTCATTAAA
CCGATTAACCCTCGTCTAGATGGATGTATACGAAGCTGGAATTTGATGAAGCAAGGAGCT
TCTGGAATAAAGGAAATTATTCAAGAAAAACAAAATAAGCATTGCCTGGTTACTGTGGAG
AAGGGCTCCTACTATCCTGGTTCTGGAATTGCTCAATTTCACATAGATTATAATAATGTA
TCCAGTGCTGAGGGTTGGCATGTAAATGTGACCTTGAATATTCGTCCATCCACGGGCACT
GGTGTTATGCTTGCCTTGGTTTCTGGTAACAACACAGTGCCCTTTGCTGTGTCCTTGGTG
GACTCCACCTCTGAAAAATCACAGGATATTCTGTTATCTGTTGAAAATACTGTAATATAT
CGGATACAGGCCCTAAGTCTATGTTCCGATCAACAATCTCATCTGGAATTTAGAGTCAAC
AGAAACAATCTGGAGTTGTCGACACCACTTAAAATAGAAACCATCTCCCATGAAGACCTT
CAAAGACAACTTGCCGTCTTGGACAAAGCAATGAAAGCAAAAGTGGCCACATACCTGGGT
GGCCTTCCAGATGTTCCATTCAGTGCCACACCAGTGAATGCCTTTTATAATGGCTGCATG
GAAGTGAATATTAATGGTGTACAGTTGGATCTGGATGAAGCCATTTCTAAACATAATGAT
ATTAGAGCTCACTCATGTCCATCAGTTTGGAAAAAGACAAAGAATTCTTAA
GenBank Gene IDM15036
GeneCard IDNot Available
GenAtlas IDPROS1
HGNC IDHGNC:9456
Chromosome Location3
Locus3q11.2
References
  1. Ploos van Amstel HK, van der Zanden AL, Reitsma PH, Bertina RM: Human protein S cDNA encodes Phe-16 and Tyr 222 in consensus sequences for the post-translational processing. FEBS Lett. 1987 Sep 28;222(1):186-90. 2820795
  2. Hoskins J, Norman DK, Beckmann RJ, Long GL: Cloning and characterization of human liver cDNA encoding a protein S precursor. Proc Natl Acad Sci U S A. 1987 Jan;84(2):349-53. 3467362
  3. Schmidel DK, Tatro AV, Phelps LG, Tomczak JA, Long GL: Organization of the human protein S genes. Biochemistry. 1990 Aug 28;29(34):7845-52. 2148110
  4. Ploos van Amstel HK, Reitsma PH, van der Logt CP, Bertina RM: Intron-exon organization of the active human protein S gene PS alpha and its pseudogene PS beta: duplication and silencing during primate evolution. Biochemistry. 1990 Aug 28;29(34):7853-61. 2148111
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  7. Lundwall A, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlback B, Stenflo J, Wydro R: Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6716-20. 2944113
  8. Gomez E, Poort SR, Bertina RM, Reitsma PH: Identification of eight point mutations in protein S deficiency type I--analysis of 15 pedigrees. Thromb Haemost. 1995 May;73(5):750-5. 7482398
  9. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. 16335952
  10. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  11. Drakenberg T, Ghasriani H, Thulin E, Thamlitz AM, Muranyi A, Annila A, Stenflo J: Solution structure of the Ca2+-Binding EGF3-4 pair from vitamin K-dependent protein S: identification of an unusual fold in EGF3. Biochemistry. 2005 Jun 21;44(24):8782-9. 15952784
  12. Bertina RM, Ploos van Amstel HK, van Wijngaarden A, Coenen J, Leemhuis MP, Deutz-Terlouw PP, van der Linden IK, Reitsma PH: Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460. Blood. 1990 Aug 1;76(3):538-48. 2143091
  13. Hayashi T, Nishioka J, Shigekiyo T, Saito S, Suzuki K: Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. Blood. 1994 Feb 1;83(3):683-90. 8298131
  14. Gandrille S, Borgel D, Eschwege-Gufflet V, Aillaud M, Dreyfus M, Matheron C, Gaussem P, Abgrall JF, Jude B, Sie P, et al.: Identification of 15 different candidate causal point mutations and three polymorphisms in 19 patients with protein S deficiency using a scanning method for the analysis of the protein S active gene. Blood. 1995 Jan 1;85(1):130-8. 7803790
  15. Formstone CJ, Wacey AI, Berg LP, Rahman S, Bevan D, Rowley M, Voke J, Bernardi F, Legnani C, Simioni P, Girolami A, Tuddenham EG, Kakkar VV, Cooper DN: Detection and characterization of seven novel protein S (PROS) gene lesions: evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy. Blood. 1995 Oct 1;86(7):2632-41. 7545463
  16. Mustafa S, Pabinger I, Mannhalter C: Protein S deficiency type I: identification of point mutations in 9 of 10 families. Blood. 1995 Nov 1;86(9):3444-51. 7579449
  17. Li M, Long GL: Identification of two novel point mutations in the human protein S gene associated with familial protein S deficiency and thrombosis. Arterioscler Thromb Vasc Biol. 1996 Dec;16(12):1407-15. 8977443
  18. Yamazaki T, Katsumi A, Kagami K, Okamoto Y, Sugiura I, Hamaguchi M, Kojima T, Takamatsu J, Saito H: Molecular basis of a hereditary type I protein S deficiency caused by a substitution of Cys for Arg474. Blood. 1996 Jun 1;87(11):4643-50. 8639833
  19. Beauchamp NJ, Daly ME, Cooper PC, Makris M, Preston FE, Peake IR: Molecular basis of protein S deficiency in three families also showing independent inheritance of factor V leiden. Blood. 1996 Sep 1;88(5):1700-7. 8781426
  20. Simmonds RE, Ireland H, Kunz G, Lane DA: Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. Protein S Study Group. Blood. 1996 Dec 1;88(11):4195-204. 8943854
  21. Borgel D, Duchemin J, Alhenc-Gelas M, Matheron C, Aiach M, Gandrille S: Molecular basis for protein S hereditary deficiency: genetic defects observed in 118 patients with type I and type IIa deficiencies. The French Network on Molecular Abnormalities Responsible for Protein C and Protein S Deficiencies. J Lab Clin Med. 1996 Aug;128(2):218-27. 8765219
  22. Duchemin J, Borg JY, Borgel D, Vasse M, Leveque H, Aiach M, Gandrille S: Five novel mutations of the protein S active gene (PROS 1) in 8 Norman families. Thromb Haemost. 1996 Mar;75(3):437-44. 8701404
  23. Bustorff TC, Freire I, Gago T, Crespo F, David D: Identification of three novel mutations in hereditary protein S deficiency. Thromb Haemost. 1997 Jan;77(1):21-5. 9031443
  24. Gandrille S, Borgel D, Ireland H, Lane DA, Simmonds R, Reitsma PH, Mannhalter C, Pabinger I, Saito H, Suzuki K, Formstone C, Cooper DN, Espinosa Y, Sala N, Bernardi F, Aiach M: Protein S deficiency: a database of mutations. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1997 Jun;77(6):1201-14. 9241758
  25. Espinosa-Parrilla Y, Morell M, Souto JC, Tirado I, Fontcuberta J, Estivill X, Sala N: Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency. Hum Mutat. 1999;14(1):30-9. 10447256
  26. Hermida J, Faioni EM, Mannucci PM: Poor relationship between phenotypes of protein S deficiency and mutations in the protein S alpha gene. Thromb Haemost. 1999 Dec;82(6):1634-8. 10613647
  27. Makris M, Leach M, Beauchamp NJ, Daly ME, Cooper PC, Hampton KK, Bayliss P, Peake IR, Miller GJ, Preston FE: Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S. Blood. 2000 Mar 15;95(6):1935-41. 10706858
  28. Espinosa-Parrilla Y, Morell M, Borrell M, Souto JC, Fontcuberta J, Estivill X, Sala N: Optimization of a simple and rapid single-strand conformation analysis for detection of mutations in the PROS1 gene: identification of seven novel mutations and three novel, apparently neutral, variants. Hum Mutat. 2000;15(5):463-73. 10790208
  29. Iwaki T, Mastushita T, Kobayashi T, Yamamoto Y, Nomura Y, Kagami K, Nakayama T, Sugiura I, Kojima T, Takamatsu J, Kanayama N, Saito H: DNA sequence analysis of protein S deficiency--identification of four point mutations in twelve Japanese subjects. Semin Thromb Hemost. 2001;27(2):155-60. 11372770
  30. Andersen BD, Bisgaard ML, Lind B, Philips M, Villoutreix B, Thorsen S: Characterization and structural impact of five novel PROS1 mutations in eleven protein S-deficient families. Thromb Haemost. 2001 Dec;86(6):1392-9. 11776305
  31. Rezende SM, Lane DA, Mille-Baker B, Samama MM, Conard J, Simmonds RE: Protein S Gla-domain mutations causing impaired Ca(2+)-induced phospholipid binding and severe functional protein S deficiency. Blood. 2002 Oct 15;100(8):2812-9. 12351389
  32. Rezende SM, Lane DA, Zoller B, Mille-Baker B, Laffan M, Dalhback B, Simmonds RE: Genetic and phenotypic variability between families with hereditary protein S deficiency. Thromb Haemost. 2002 Feb;87(2):258-65. 11858485
  33. Tsuda H, Urata M, Tsuda T, Wakiyama M, Iida H, Nakahara M, Kinoshita S, Hamasaki N: Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency: effects on secretion and anticoagulant activity of protein S. Thromb Res. 2002 Feb 1;105(3):233-9. 11927129
  34. Boinot C, Borgel D, Kitzis A, Guicheteau M, Aiach M, Alhenc-Gelas M: Familial thrombophilia is an oligogenetic disease: involvement of the prothrombin G20210A, PROC and PROS gene mutations. Blood Coagul Fibrinolysis. 2003 Feb;14(2):191-6. 12632031
  35. Okada H, Takagi A, Murate T, Adachi T, Yamamoto K, Matsushita T, Takamatsu J, Sugita K, Sugimoto M, Yoshioka A, Yamazaki T, Saito H, Kojima T: Identification of protein Salpha gene mutations including four novel mutations in eight unrelated patients with protein S deficiency. Br J Haematol. 2004 Jul;126(2):219-25. 15238143
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  38. Fischer D, Porto L, Stoll H, Geisen C, Schloesser RL: Intracerebral mass bleeding in a term neonate: manifestation of hereditary protein S deficiency with a new mutation in the PROS1 gene. Neonatology. 2010;98(4):337-40. doi: 10.1159/000298282. Epub 2010 May 20. 20484936