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Identification
HMDB Protein ID HMDBP02003
Secondary Accession Numbers
  • 7454
Name Vitamin K-dependent protein S
Synonyms Not Available
Gene Name PROS1
Protein Type Enzyme
Biological Properties
General Function Involved in calcium ion binding
Specific Function Anticoagulant 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
extracellular region
Function
ion binding
cation binding
metal ion binding
binding
calcium ion binding
Cellular Location
  1. Secreted
Gene Properties
Chromosome Location Chromosome:3
Locus 3q11.2
SNPs PROS1
Gene Sequence
>2031 bp
ATGAGGGTCCTGGGTGGGCGCTGCGGGGCGTTGCTGGCGTGTCTCCTCCTAGTGCTTCCC
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
Protein Properties
Number of Residues 676
Molecular Weight 75121.9
Theoretical pI 5.37
Pfam Domain Function
Signals
  • 1-24
Transmembrane Regions
  • None
Protein Sequence
>Vitamin K-dependent protein S
MRVLGGRCGALLACLLLVLPVSEANFLSKQQASQVLVRKRRANSLLEETKQGNLERECIE
ELCNKEEAREVFENDPETDYFYPKYLVCLRSFQTGLFTAARQSTNAYPDLRSCVNAIPDQ
CSPLPCNEDGYMSCKDGKASFTCTCKPGWQGEKCEFDINECKDPSNINGGCSQICDNTPG
SYHCSCKNGFVMLSNKKDCKDVDECSLKPSICGTAVCKNIPGDFECECPEGYRYNLKSKS
CEDIDECSENMCAQLCVNYPGGYTCYCDGKKGFKLAQDQKSCEVVSVCLPLNLDTKYELL
YLAEQFAGVVLYLKFRLPEISRFSAEFDFRTYDSEGVILYAESIDHSAWLLIALRGGKIE
VQLKNEHTSKITTGGDVINNGLWNMVSVEELEHSISIKIAKEAVMDINKPGPLFKPENGL
LETKVYFAGFPRKVESELIKPINPRLDGCIRSWNLMKQGASGIKEIIQEKQNKHCLVTVE
KGSYYPGSGIAQFHIDYNNVSSAEGWHVNVTLNIRPSTGTGVMLALVSGNNTVPFAVSLV
DSTSEKSQDILLSVENTVIYRIQALSLCSDQQSHLEFRVNRNNLELSTPLKIETISHEDL
QRQLAVLDKAMKAKVATYLGGLPDVPFSATPVNAFYNGCMEVNINGVQLDLDEAISKHND
IRAHSCPSVWKKTKNS
GenBank ID Protein 36579
UniProtKB/Swiss-Prot ID P07225
UniProtKB/Swiss-Prot Entry Name PROS_HUMAN
PDB IDs Not Available
GenBank Gene ID Y00692
GeneCard ID PROS1
GenAtlas ID PROS1
HGNC ID HGNC:9456
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  4. 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. [PubMed:16335952 ]
  5. 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. [PubMed:2820795 ]
  6. 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. [PubMed:3467362 ]
  7. 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. [PubMed:2148110 ]
  8. 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. [PubMed:2148111 ]
  9. 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. [PubMed:2944113 ]
  10. 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. [PubMed:7482398 ]
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15238143 ]
  36. Biguzzi E, Razzari C, Lane DA, Castaman G, Cappellari A, Bucciarelli P, Fontana G, Margaglione M, D'Andrea G, Simmonds RE, Rezende SM, Preston R, Prisco D, Faioni EM: Molecular diversity and thrombotic risk in protein S deficiency: the PROSIT study. Hum Mutat. 2005 Mar;25(3):259-69. [PubMed:15712227 ]