ID PROS_HUMAN Reviewed; 676 AA. AC P07225; A8KAC9; D3DN28; Q15518; Q7Z715; Q9UCZ8; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 02-OCT-2024, entry version 260. DE RecName: Full=Vitamin K-dependent protein S; DE Flags: Precursor; GN Name=PROS1; Synonyms=PROS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND GAMMA-CARBOXYGLUTAMATION AT GLU-47; GLU-48; RP GLU-55; GLU-57; GLU-60; GLU-61; GLU-66; GLU-67; GLU-70; GLU-73 AND GLU-77. RX PubMed=2820795; DOI=10.1016/0014-5793(87)80217-x; RA Ploos van Amstel H.K., van der Zanden A.L., Reitsma P.H., Bertina R.M.; RT "Human protein S cDNA encodes Phe-16 and Tyr 222 in consensus sequences for RT the post-translational processing."; RL FEBS Lett. 222:186-190(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3467362; DOI=10.1073/pnas.84.2.349; RA Hoskins J., Norman D.K., Beckmann R.J., Long G.L.; RT "Cloning and characterization of human liver cDNA encoding a protein S RT precursor."; RL Proc. Natl. Acad. Sci. U.S.A. 84:349-353(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2148110; DOI=10.1021/bi00486a010; RA Schmidel D.K., Tatro A.V., Phelps L.G., Tomczak J.A., Long G.L.; RT "Organization of the human protein S genes."; RL Biochemistry 29:7845-7852(1990). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Liver; RX PubMed=2148111; DOI=10.1021/bi00486a011; RA Ploos van Amstel H.K., Reitsma P.H., der Logt C.P., Bertina R.M.; RT "Intron-exon organization of the active human protein S gene PS alpha and RT its pseudogene PS beta: duplication and silencing during primate RT evolution."; RL Biochemistry 29:7853-7861(1990). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 27-676. RX PubMed=2944113; DOI=10.1073/pnas.83.18.6716; RA Lundwall A., Dackowski W., Cohen E., Shaffer M., Mahr A., Dahlback B., RA Stenflo J., Wydro R.; RT "Isolation and sequence of the cDNA for human protein S, a regulator of RT blood coagulation."; RL Proc. Natl. Acad. Sci. U.S.A. 83:6716-6720(1986). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-519, AND VARIANTS THPH5 VAL-381 RP AND GLY-508. RX PubMed=7482398; RA Gomez E., Poort S.R., Bertina R.M., Reitsma P.H.; RT "Identification of eight point mutations in protein S deficiency type I RT -- analysis of 15 pedigrees."; RL Thromb. Haemost. 73:750-755(1995). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-530. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP STRUCTURE BY NMR OF 200-286, AND DISULFIDE BONDS. RX PubMed=15952784; DOI=10.1021/bi050101f; RA Drakenberg T., Ghasriani H., Thulin E., Thamlitz A.M., Muranyi A., RA Annila A., Stenflo J.; RT "Solution structure of the Ca2+-binding EGF3-4 pair from vitamin K- RT dependent protein S: identification of an unusual fold in EGF3."; RL Biochemistry 44:8782-8789(2005). RN [14] RP VARIANT PRO-501. RX PubMed=2143091; RA Bertina R.M., Ploos van Amstel H.K., van Wijngaarden A., Coenen J., RA Leemhuis M.P., Deutz-Terlouw P.P., van der Linden I.K., Reitsma P.H.; RT "Heerlen polymorphism of protein S, an immunologic polymorphism due to RT dimorphism of residue 460."; RL Blood 76:538-548(1990). RN [15] RP VARIANT THPH5 SER-258. RA Cooper D.N.; RL Unpublished observations (SEP-1993). RN [16] RP VARIANT THPH5 TOKUSHIMA GLU-196. RX PubMed=8298131; RA Hayashi T., Nishioka J., Shigekiyo T., Saito S., Suzuki K.; RT "Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys- RT 155 in the second epidermal growth factor-like domain of protein S."; RL Blood 83:683-690(1994). RN [17] RP VARIANTS THPH5 LEU-40; HIS-41; ALA-67; CYS-72; MET-78; HIS-90; ASN-144; RP GLY-245; LYS-249; TRP-265; ARG-265 AND ASN-376, AND VARIANTS LEU-76 AND RP VAL-385. RX PubMed=7803790; RA Gandrille S., Borgel D., Eschwege-Gufflet V., Aillaud M., Dreyfus M., RA Matheron C., Gaussem P., Abgrall J.F., Jude B., Sie P., Toulon P., RA Aiach M.; RT "Identification of 15 different candidate causal point mutations and three RT polymorphisms in 19 patients with protein S deficiency using a scanning RT method for the analysis of the protein S active gene."; RL Blood 85:130-138(1995). RN [18] RP VARIANTS THPH5 SER-258 AND THR-611. RX PubMed=7545463; RA Formstone C.J., Wacey A.I., Berg L.-P., Rahman S., Bevan D., Rowley M., RA Voke J., Bernardi F., Legnani C., Simioni P., Girolami A., RA Tuddenham E.G.D., Kakkar V.V., Cooper D.N.; RT "Detection and characterization of seven novel protein S (PROS) gene RT lesions: evaluation of reverse transcript-polymerase chain reaction as a RT mutation screening strategy."; RL Blood 86:2632-2641(1995). RN [19] RP VARIANTS THPH5 PRO-351; SER-552; GLN-584 AND PRO-616. RX PubMed=7579449; RA Mustafa S., Pabinger I., Mannhalter C.; RT "Protein S deficiency type I: identification of point mutations in 9 of 10 RT families."; RL Blood 86:3444-3451(1995). RN [20] RP VARIANT THPH5 SER-644. RX PubMed=8977443; DOI=10.1161/01.atv.16.12.1407; RA Li M., Long G.L.; RT "Identification of two novel point mutations in the human protein S gene RT associated with familial protein S deficiency and thrombosis."; RL Arterioscler. Thromb. Vasc. Biol. 16:1407-1415(1996). RN [21] RP VARIANT THPH5 CYS-515, CHARACTERIZATION OF VARIANT PROS1 DEFICIENCY RP CYS-515, AND MUTAGENESIS OF ARG-515. RX PubMed=8639833; RA Yamazaki T., Katsumi A., Kagami K., Okamoto Y., Sugiura I., Hamaguchi M., RA Kojima T., Takamatsu J., Saito H.; RT "Molecular basis of a hereditary type I protein S deficiency caused by a RT substitution of Cys for Arg474."; RL Blood 87:4643-4650(1996). RN [22] RP VARIANTS THPH5 TYR-186; THR-611 AND LEU-665. RX PubMed=8781426; RA Beauchamp N.J., Daly M.E., Cooper P.C., Makris M., Preston F.E., RA Peake I.R.; RT "Molecular basis of protein S deficiency in three families also showing RT independent inheritance of factor V Leiden."; RL Blood 88:1700-1707(1996). RN [23] RP VARIANTS THPH5 GLU-50; ALA-67; GLU-95; TYR-186; SER-241; PRO-324; ASP-381; RP SER-449 AND ARG-666, AND VARIANT PRO-501. RX PubMed=8943854; RG Protein S study group; RA Simmonds R.E., Ireland H., Kunz G., Lane D.A.; RT "Identification of 19 protein S gene mutations in patients with phenotypic RT protein S deficiency and thrombosis."; RL Blood 88:4195-4204(1996). RN [24] RP VARIANTS THPH5 SER-111; GLY-157; GLY-161; GLU-364; PRO-446; ARG-475; RP ALA-501; MET-508; CYS-515; PRO-525; ALA-532; TYR-568; ARG-575 AND ARG-666, RP AND VARIANT PRO-501. RX PubMed=8765219; DOI=10.1016/s0022-2143(96)90015-3; RG The French network on molecular abnormalities responsible for protein C and protein S deficiencies; RA Borgel D., Duchemin J., Alhenc-Gelas M., Matheron C., Aiach M., RA Gandrille S.; RT "Molecular basis for protein S hereditary deficiency: genetic defects RT observed in 118 patients with type I and type IIa deficiencies."; RL J. Lab. Clin. Med. 128:218-227(1996). RN [25] RP VARIANTS THPH5 PRO-300 AND ARG-666. RX PubMed=8701404; RA Duchemin J., Borg J.-Y., Borgel D., Vasse M., Leveque H., Aiach M., RA Gandrille S.; RT "Five novel mutations of the protein S active gene (PROS 1) in 8 Norman RT families."; RL Thromb. Haemost. 75:437-444(1996). RN [26] RP VARIANT THPH5 PHE-639. RX PubMed=9031443; RA Bustorff T.C., Freire I., Gago T., Crespo F., David D.; RT "Identification of three novel mutations in hereditary protein S RT deficiency."; RL Thromb. Haemost. 77:21-25(1997). RN [27] RP VARIANTS THPH5 ASP-68; ARG-95 AND SER-336. RX PubMed=9241758; RG Plasma coagulation inhibitors subcommittee of the scientific and standardization committee of the international society on thrombosis and haemostasis; RA Gandrille S., Borgel D., Ireland H., Lane D.A., Simmonds R., Reitsma P.H., RA Mannhalter C., Pabinger I., Saito H., Suzuki K., Formstone C., Cooper D.N., RA Espinosa Y., Sala N., Bernardi F., Aiach M.; RT "Protein S deficiency: a database of mutations."; RL Thromb. Haemost. 77:1201-1214(1997). RN [28] RP VARIANTS THPH5 CYS-482; CYS-485 AND GLY-561, AND VARIANTS PRO-501 AND RP MET-559. RX PubMed=10447256; RX DOI=10.1002/(sici)1098-1004(1999)14:1<30::aid-humu4>3.0.co;2-x; RA Espinosa-Parrilla Y., Morell M., Souto J.C., Tirado I., Fontcuberta J., RA Estivill X., Sala N.; RT "Protein S gene analysis reveals the presence of a cosegregating mutation RT in most pedigrees with type I but not type III PS deficiency."; RL Hum. Mutat. 14:30-39(1999). RN [29] RP VARIANTS THPH5 ALA-67; GLY-129; PHE-175; PRO-515; LEU-562 AND ASP-638, AND RP VARIANTS LEU-76 AND ASP-638. RX PubMed=10613647; RA Hermida J., Faioni E.M., Mannucci P.M.; RT "Poor relationship between phenotypes of protein S deficiency and mutations RT in the protein S alpha gene."; RL Thromb. Haemost. 82:1634-1638(1999). RN [30] RP VARIANTS THPH5 TYR-166; GLY-247; THR-611; ARG-622 AND ARG-666. RX PubMed=10706858; RA Makris M., Leach M., Beauchamp N.J., Daly M.E., Cooper P.C., Hampton K.K., RA Bayliss P., Peake I.R., Miller G.J., Preston F.E.; RT "Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in RT families with inherited deficiencies of protein S."; RL Blood 95:1935-1941(2000). RN [31] RP VARIANTS THPH5 HIS-15; THR-640 AND LEU-667, AND VARIANTS SER-98; LYS-233 RP AND MET-559. RX PubMed=10790208; RX DOI=10.1002/(sici)1098-1004(200005)15:5<463::aid-humu8>3.0.co;2-e; RA Espinosa-Parrilla Y., Morell M., Borrell M., Souto J.C., Fontcuberta J., RA Estivill X., Sala N.; RT "Optimization of a simple and rapid single-strand conformation analysis for RT detection of mutations in the PROS1 gene: identification of seven novel RT mutations and three novel, apparently neutral, variants."; RL Hum. Mutat. 15:463-473(2000). RN [32] RP VARIANTS THPH5 ASN-243 AND PRO-339. RX PubMed=11372770; DOI=10.1055/s-2001-14075; RA Iwaki T., Mastushita T., Kobayashi T., Yamamoto Y., Nomura Y., Kagami K., RA Nakayama T., Sugiura I., Kojima T., Takamatsu J., Kanayama N., Saito H.; RT "DNA sequence analysis of protein S deficiency -- identification of four RT point mutations in twelve Japanese subjects."; RL Semin. Thromb. Hemost. 27:155-160(2001). RN [33] RP VARIANTS THPH5 CYS-149; ARG-383; LYS-390 AND SER-526. RX PubMed=11776305; RA Andersen B.D., Bisgaard M.L., Lind B., Philips M., Villoutreix B.O., RA Thorsen S.; RT "Characterization and structural impact of five novel PROS1 mutations in RT eleven protein S-deficient families."; RL Thromb. Haemost. 86:1392-1399(2001). RN [34] RP VARIANTS THPH5 ASP-52 AND MET-78, AND CHARACTERIZATION OF VARIANTS THPH5 RP ASP-52 AND MET-78. RX PubMed=12351389; DOI=10.1182/blood-2002-03-0909; RA Rezende S.M., Lane D.A., Mille-Baker B., Samama M.M., Conard J., RA Simmonds R.E.; RT "Protein S Gla-domain mutations causing impaired Ca(2+)-induced RT phospholipid binding and severe functional protein S deficiency."; RL Blood 100:2812-2819(2002). RN [35] RP VARIANTS THPH5 GLU-18; CYS-90; SER-258; VAL-336 AND PRO-664, AND RP CHARACTERIZATION OF VARIANTS THPH5 GLU-18; CYS-90; SER-258 VAL-336 AND RP PRO-664. RX PubMed=11858485; DOI=10.1055/s-0037-1612982; RA Rezende S.M., Lane D.A., Zoeller B., Mille-Baker B., Laffan M., RA Dalhbaeck B., Simmonds R.E.; RT "Genetic and phenotypic variability between families with hereditary RT protein S deficiency."; RL Thromb. Haemost. 87:258-265(2002). RN [36] RP VARIANTS THPH5 ARG-95; GLU-196; ILE-630 AND CYS-636, AND CHARACTERIZATION RP OF VARIANTS THPH5 ARG-95; GLU-196; ILE-630 AND CYS-636. RX PubMed=11927129; DOI=10.1016/s0049-3848(02)00015-4; RA Tsuda H., Urata M., Tsuda T., Wakiyama M., Iida H., Nakahara M., RA Kinoshita S., Hamasaki N.; RT "Four missense mutations identified in the protein S gene of thrombosis RT patients with protein S deficiency: effects on secretion and anticoagulant RT activity of protein S."; RL Thromb. Res. 105:233-239(2002). RN [37] RP VARIANTS THPH5 CYS-101 AND ASN-144, AND VARIANT SER-168. RX PubMed=12632031; DOI=10.1097/01.mbc.0000046180.72384.39; RA Boinot C., Borgel D., Kitzis A., Guicheteau M., Aiach M., Alhenc-Gelas M.; RT "Familial thrombophilia is an oligogenetic disease: involvement of the RT prothrombin G20210A, PROC and PROS gene mutations."; RL Blood Coagul. Fibrinolysis 14:191-196(2003). RN [38] RP VARIANTS THPH5 LEU-87; TYR-121; GLU-196; HIS-355 AND LEU-667. RX PubMed=15238143; DOI=10.1111/j.1365-2141.2004.05026.x; RA Okada H., Takagi A., Murate T., Adachi T., Yamamoto K., Matsushita T., RA Takamatsu J., Sugita K., Sugimoto M., Yoshioka A., Yamazaki T., Saito H., RA Kojima T.; RT "Identification of protein Salpha gene mutations including four novel RT mutations in eight unrelated patients with protein S deficiency."; RL Br. J. Haematol. 126:219-225(2004). RN [39] RP VARIANTS THPH5 ALA-67; TYR-88; GLY-129; ASN-144; PHE-175; GLY-204; CYS-266; RP SER-267; ASP-336; ARG-357; PRO-446; PRO-515; ASP-521; LYS-611; ASP-638 AND RP TYR-639, VARIANTS LEU-76; PRO-501; MET-559; LEU-562 AND HIS-583, RP CHARACTERIZATION OF VARIANTS PROS1 DEFICIENCY ALA-67; TYR-88; GLY-129; RP PHE-175; GLY-204; CYS-266; SER-267; ASP-336; ARG-357; PRO-446; PRO-515; RP ASP-521; LYS-611; ASP-638 AND TYR-639, AND CHARACTERIZATION OF VARIANTS RP LEU-76; LEU-562 AND HIS-583. RX PubMed=15712227; DOI=10.1002/humu.20136; RG Protein S Italian team (PROSIT); RA Biguzzi E., Razzari C., Lane D.A., Castaman G., Cappellari A., RA Bucciarelli P., Fontana G., Margaglione M., D'Andrea G., Simmonds R.E., RA Rezende S.M., Preston R., Prisco D., Faioni E.M.; RT "Molecular diversity and thrombotic risk in protein S deficiency: the RT PROSIT study."; RL Hum. Mutat. 25:259-269(2005). RN [40] RP VARIANT [LARGE SCALE ANALYSIS] GLY-545. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [41] RP CHARACTERIZATION OF VARIANTS THPH5 HIS-15 AND THR-640, AND CHARACTERIZATION RP OF VARIANT LYS-233. RX PubMed=18322254; DOI=10.3324/haematol.12090; RA Hurtado B., Munoz X., Mulero M.C., Navarro G., Domenech P., RA Garcia de Frutos P., Perez-Riba M., Sala N.; RT "Functional characterization of twelve natural PROS1 mutations associated RT with anticoagulant protein S deficiency."; RL Haematologica 93:574-580(2008). RN [42] RP VARIANT THPH6 CYS-234. RX PubMed=20484936; DOI=10.1159/000298282; RA Fischer D., Porto L., Stoll H., Geisen C., Schloesser R.L.; RT "Intracerebral mass bleeding in a term neonate: manifestation of hereditary RT protein S deficiency with a new mutation in the PROS1 gene."; RL Neonatology 98:337-340(2010). RN [43] RP VARIANT LYS-233. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). CC -!- FUNCTION: Anticoagulant plasma protein; it is a cofactor to activated CC protein C in the degradation of coagulation factors Va and VIIIa. It CC helps to prevent coagulation and stimulating fibrinolysis. CC -!- INTERACTION: CC P07225; Q5SUL5: HLA-A; NbExp=3; IntAct=EBI-2803380, EBI-8561769; CC P07225; Q92993: KAT5; NbExp=3; IntAct=EBI-2803380, EBI-399080; CC P07225; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-2803380, EBI-11742507; CC P07225; Q96CV9: OPTN; NbExp=3; IntAct=EBI-2803380, EBI-748974; CC P07225; P62937-2: PPIA; NbExp=3; IntAct=EBI-2803380, EBI-25884072; CC P07225; P17252: PRKCA; NbExp=3; IntAct=EBI-2803380, EBI-1383528; CC P07225; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-2803380, EBI-9090795; CC P07225; P61981: YWHAG; NbExp=3; IntAct=EBI-2803380, EBI-359832; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Plasma. CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate CC and asparagine is (R) stereospecific within EGF domains. {ECO:0000250}. CC -!- DISEASE: Thrombophilia due to protein S deficiency, autosomal dominant CC (THPH5) [MIM:612336]: A hemostatic disorder characterized by impaired CC regulation of blood coagulation and a tendency to recurrent venous CC thrombosis. Based on the plasma levels of total and free PROS1 as well CC as the serine protease-activated protein C cofactor activity, three CC types of THPH5 have been described: type I, characterized by reduced CC total and free PROS1 levels together with reduced anticoagulant CC activity; type III, in which only free PROS1 antigen and PROS1 activity CC levels are reduced; and the rare type II which is characterized by CC normal concentrations of both total and free PROS1 antigen, but low CC cofactor activity. {ECO:0000269|PubMed:10447256, CC ECO:0000269|PubMed:10613647, ECO:0000269|PubMed:10706858, CC ECO:0000269|PubMed:10790208, ECO:0000269|PubMed:11372770, CC ECO:0000269|PubMed:11776305, ECO:0000269|PubMed:11858485, CC ECO:0000269|PubMed:11927129, ECO:0000269|PubMed:12351389, CC ECO:0000269|PubMed:12632031, ECO:0000269|PubMed:15238143, CC ECO:0000269|PubMed:15712227, ECO:0000269|PubMed:18322254, CC ECO:0000269|PubMed:7482398, ECO:0000269|PubMed:7545463, CC ECO:0000269|PubMed:7579449, ECO:0000269|PubMed:7803790, CC ECO:0000269|PubMed:8298131, ECO:0000269|PubMed:8639833, CC ECO:0000269|PubMed:8701404, ECO:0000269|PubMed:8765219, CC ECO:0000269|PubMed:8781426, ECO:0000269|PubMed:8943854, CC ECO:0000269|PubMed:8977443, ECO:0000269|PubMed:9031443, CC ECO:0000269|PubMed:9241758, ECO:0000269|Ref.15}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Thrombophilia due to protein S deficiency, autosomal recessive CC (THPH6) [MIM:614514]: A very rare and severe hematologic disorder CC resulting in thrombosis and secondary hemorrhage usually beginning in CC early infancy. Some affected individuals develop neonatal purpura CC fulminans, multifocal thrombosis, or intracranial hemorrhage. CC {ECO:0000269|PubMed:20484936}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAP45054.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y00692; CAA68687.1; -; mRNA. DR EMBL; Y00692; CAA68688.1; ALT_SEQ; mRNA. DR EMBL; M15036; AAA36479.1; -; mRNA. DR EMBL; M57853; AAA60357.1; -; Genomic_DNA. DR EMBL; M57840; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57841; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57842; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57844; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57845; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57846; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57847; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57848; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57849; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57850; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57851; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; M57852; AAA60357.1; JOINED; Genomic_DNA. DR EMBL; AH002948; AAA60180.1; -; Genomic_DNA. DR EMBL; AK292994; BAF85683.1; -; mRNA. DR EMBL; AY308744; AAP45054.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471052; EAW79903.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79905.1; -; Genomic_DNA. DR EMBL; BC015801; AAH15801.1; -; mRNA. DR CCDS; CCDS2923.1; -. DR PIR; A35610; KXHUS. DR RefSeq; NP_000304.2; NM_000313.3. DR RefSeq; NP_001301006.1; NM_001314077.1. DR PDB; 1Z6C; NMR; -; A=200-286. DR PDBsum; 1Z6C; -. DR AlphaFoldDB; P07225; -. DR SMR; P07225; -. DR BioGRID; 111611; 85. DR IntAct; P07225; 44. DR STRING; 9606.ENSP00000377783; -. DR DrugBank; DB00055; Drotrecogin alfa. DR DrugBank; DB09332; Kappadione. DR DrugBank; DB00170; Menadione. DR DrugBank; DB00464; Sodium tetradecyl sulfate. DR GlyConnect; 2090; 1 N-Linked glycan (1 site). DR GlyCosmos; P07225; 5 sites, 3 glycans. DR GlyGen; P07225; 7 sites, 2 N-linked glycans (1 site), 3 O-linked glycans (4 sites). DR iPTMnet; P07225; -. DR PhosphoSitePlus; P07225; -. DR BioMuta; PROS1; -. DR DMDM; 131086; -. DR CPTAC; non-CPTAC-2705; -. DR jPOST; P07225; -. DR MassIVE; P07225; -. DR PaxDb; 9606-ENSP00000377783; -. DR PeptideAtlas; P07225; -. DR ProteomicsDB; 51975; -. DR ABCD; P07225; 29 sequenced antibodies. DR Antibodypedia; 858; 486 antibodies from 40 providers. DR DNASU; 5627; -. DR Ensembl; ENST00000348974.5; ENSP00000330021.7; ENSG00000184500.16. DR Ensembl; ENST00000394236.9; ENSP00000377783.3; ENSG00000184500.16. DR GeneID; 5627; -. DR KEGG; hsa:5627; -. DR MANE-Select; ENST00000394236.9; ENSP00000377783.3; NM_000313.4; NP_000304.2. DR UCSC; uc003drb.5; human. DR AGR; HGNC:9456; -. DR CTD; 5627; -. DR DisGeNET; 5627; -. DR GeneCards; PROS1; -. DR HGNC; HGNC:9456; PROS1. DR HPA; ENSG00000184500; Tissue enhanced (choroid plexus, liver). DR MalaCards; PROS1; -. DR MIM; 176880; gene. DR MIM; 612336; phenotype. DR MIM; 614514; phenotype. DR neXtProt; NX_P07225; -. DR OpenTargets; ENSG00000184500; -. DR Orphanet; 743; Severe hereditary thrombophilia due to congenital protein S deficiency. DR PharmGKB; PA33809; -. DR VEuPathDB; HostDB:ENSG00000184500; -. DR eggNOG; ENOG502QSNF; Eukaryota. DR GeneTree; ENSGT00940000154035; -. DR HOGENOM; CLU_026236_0_0_1; -. DR InParanoid; P07225; -. DR OMA; GQAAFTC; -. DR OrthoDB; 19806at2759; -. DR PhylomeDB; P07225; -. DR TreeFam; TF352157; -. DR PathwayCommons; P07225; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation. DR Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation. DR Reactome; R-HSA-159740; Gamma-carboxylation of protein precursors. DR Reactome; R-HSA-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus. DR Reactome; R-HSA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins. DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P07225; -. DR SIGNOR; P07225; -. DR BioGRID-ORCS; 5627; 18 hits in 1164 CRISPR screens. DR ChiTaRS; PROS1; human. DR EvolutionaryTrace; P07225; -. DR GeneWiki; Protein_S; -. DR GenomeRNAi; 5627; -. DR Pharos; P07225; Tbio. DR PRO; PR:P07225; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P07225; protein. DR Bgee; ENSG00000184500; Expressed in choroid plexus epithelium and 196 other cell types or tissues. DR ExpressionAtlas; P07225; baseline and differential. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc. DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc. DR GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW. DR CDD; cd00054; EGF_CA; 3. DR CDD; cd00110; LamG; 1. DR Gene3D; 2.60.120.200; -; 2. DR Gene3D; 4.10.740.10; Coagulation Factor IX; 1. DR Gene3D; 2.10.25.10; Laminin; 4. DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR051145; GAS-SHBG-PROS. DR InterPro; IPR035972; GLA-like_dom_SF. DR InterPro; IPR000294; GLA_domain. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR001791; Laminin_G. DR InterPro; IPR049883; NOTCH1_EGF-like. DR PANTHER; PTHR24040; LAMININ G-LIKE DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR24040:SF0; VITAMIN K-DEPENDENT PROTEIN S; 1. DR Pfam; PF07645; EGF_CA; 2. DR Pfam; PF14670; FXa_inhibition; 1. DR Pfam; PF00594; Gla; 1. DR Pfam; PF12661; hEGF; 1. DR Pfam; PF00054; Laminin_G_1; 1. DR Pfam; PF02210; Laminin_G_2; 1. DR PRINTS; PR00001; GLABLOOD. DR SMART; SM00181; EGF; 4. DR SMART; SM00179; EGF_CA; 4. DR SMART; SM00069; GLA; 1. DR SMART; SM00282; LamG; 2. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 2. DR SUPFAM; SSF57630; GLA-domain; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 4. DR PROSITE; PS00022; EGF_1; 1. DR PROSITE; PS01186; EGF_2; 3. DR PROSITE; PS50026; EGF_3; 4. DR PROSITE; PS01187; EGF_CA; 3. DR PROSITE; PS00011; GLA_1; 1. DR PROSITE; PS50998; GLA_2; 1. DR PROSITE; PS50025; LAM_G_DOMAIN; 2. PE 1: Evidence at protein level; KW 3D-structure; Blood coagulation; Calcium; KW Cleavage on pair of basic residues; Disease variant; Disulfide bond; KW EGF-like domain; Fibrinolysis; Gamma-carboxyglutamic acid; Glycoprotein; KW Hemostasis; Hydroxylation; Proteomics identification; Reference proteome; KW Repeat; Secreted; Signal; Thrombophilia; Zymogen. FT SIGNAL 1..24 FT PROPEP 25..41 FT /id="PRO_0000022119" FT CHAIN 42..676 FT /note="Vitamin K-dependent protein S" FT /id="PRO_0000022120" FT DOMAIN 42..87 FT /note="Gla" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463" FT DOMAIN 117..155 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 157..200 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 201..242 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 243..283 FT /note="EGF-like 4; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 299..475 FT /note="Laminin G-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT DOMAIN 484..666 FT /note="Laminin G-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122" FT REGION 88..116 FT /note="Thrombin-sensitive" FT SITE 499 FT /note="Not glycosylated; in variant Heerlen" FT MOD_RES 47 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 48 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 55 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 57 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 60 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 61 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 66 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 67 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 70 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 73 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 77 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463, FT ECO:0000269|PubMed:2820795" FT MOD_RES 136 FT /note="(3R)-3-hydroxyaspartate" FT /evidence="ECO:0000250" FT CARBOHYD 499 FT /note="N-linked (GlcNAc...) asparagine" FT CARBOHYD 509 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 530 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT DISULFID 58..63 FT /evidence="ECO:0000250" FT DISULFID 121..134 FT /evidence="ECO:0000250" FT DISULFID 126..143 FT /evidence="ECO:0000250" FT DISULFID 145..154 FT /evidence="ECO:0000250" FT DISULFID 161..175 FT /evidence="ECO:0000250" FT DISULFID 171..184 FT /evidence="ECO:0000250" FT DISULFID 186..199 FT /evidence="ECO:0000250" FT DISULFID 205..217 FT /evidence="ECO:0000269|PubMed:15952784" FT DISULFID 212..226 FT /evidence="ECO:0000269|PubMed:15952784" FT DISULFID 228..241 FT /evidence="ECO:0000269|PubMed:15952784" FT DISULFID 247..256 FT /evidence="ECO:0000269|PubMed:15952784" FT DISULFID 252..265 FT /evidence="ECO:0000269|PubMed:15952784" FT DISULFID 267..282 FT /evidence="ECO:0000269|PubMed:15952784" FT DISULFID 449..475 FT /evidence="ECO:0000250" FT DISULFID 639..666 FT /evidence="ECO:0000250" FT VARIANT 15 FT /note="L -> H (in THPH5; reduced mutant protein levels and FT secretion)" FT /evidence="ECO:0000269|PubMed:10790208, FT ECO:0000269|PubMed:18322254" FT /id="VAR_046802" FT VARIANT 18 FT /note="V -> E (in THPH5; expresses very low/undetectable FT PROS1 levels compared to wild-type; has impaired secretion; FT intracellular degradation of unsecreted material is found)" FT /evidence="ECO:0000269|PubMed:11858485" FT /id="VAR_046803" FT VARIANT 40 FT /note="R -> L (in THPH5; dbSNP:rs7614835)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046804" FT VARIANT 41 FT /note="R -> H (in THPH5; dbSNP:rs963668412)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046805" FT VARIANT 50 FT /note="K -> E (in THPH5; dbSNP:rs748630360)" FT /evidence="ECO:0000269|PubMed:8943854" FT /id="VAR_046806" FT VARIANT 52 FT /note="G -> D (in THPH5; does not affect PROS1 production FT but results in 15.2-fold reduced PROS1 activity; has 5.4 FT fold reduced affinity for anionic phospholipid vesicles (P FT < 0.0001) and decreased affinity for an antibody specific FT for the Ca(2+)-dependent conformation of the PROS1 Gla FT domain)" FT /evidence="ECO:0000269|PubMed:12351389" FT /id="VAR_046807" FT VARIANT 67 FT /note="E -> A (in THPH5; dbSNP:rs766423432)" FT /evidence="ECO:0000269|PubMed:10613647, FT ECO:0000269|PubMed:15712227, ECO:0000269|PubMed:7803790, FT ECO:0000269|PubMed:8943854" FT /id="VAR_046808" FT VARIANT 68 FT /note="A -> D (in THPH5)" FT /evidence="ECO:0000269|PubMed:9241758" FT /id="VAR_046809" FT VARIANT 72 FT /note="F -> C (in THPH5)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046810" FT VARIANT 76 FT /note="P -> L (in dbSNP:rs73846070)" FT /evidence="ECO:0000269|PubMed:10613647, FT ECO:0000269|PubMed:15712227, ECO:0000269|PubMed:7803790" FT /id="VAR_046811" FT VARIANT 78 FT /note="T -> M (in THPH5; reduces expression of PROS1 by FT 33.2% (P < 0.001) and activity by 3.6-fold; has only a FT modest 1.5-fold (P < 0.001) reduced affinity for FT phospholipid and an antibody specific for the FT Ca(2+)-dependent conformation of the PROS1 Gla domain; FT dbSNP:rs6122)" FT /evidence="ECO:0000269|PubMed:12351389, FT ECO:0000269|PubMed:7803790" FT /id="VAR_014666" FT VARIANT 87 FT /note="V -> L (in THPH5; dbSNP:rs557733421)" FT /evidence="ECO:0000269|PubMed:15238143" FT /id="VAR_046812" FT VARIANT 88 FT /note="C -> Y (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046813" FT VARIANT 90 FT /note="R -> C (in THPH5; produces around 50% of PROS1 FT levels compared to wild-type; has impaired secretion; FT intracellular degradation of unsecreted material is found; FT dbSNP:rs765935815)" FT /evidence="ECO:0000269|PubMed:11858485" FT /id="VAR_046814" FT VARIANT 90 FT /note="R -> H (in THPH5; dbSNP:rs200886866)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046815" FT VARIANT 95 FT /note="G -> E (in THPH5; dbSNP:rs144526169)" FT /evidence="ECO:0000269|PubMed:8943854" FT /id="VAR_046816" FT VARIANT 95 FT /note="G -> R (in THPH5; the activated protein cofactor FT activity is inhibited by C4BPB with a dose dependency FT similar to that of wild-type PROS1)" FT /evidence="ECO:0000269|PubMed:11927129, FT ECO:0000269|PubMed:9241758" FT /id="VAR_046817" FT VARIANT 98 FT /note="T -> S (in dbSNP:rs142805170)" FT /evidence="ECO:0000269|PubMed:10790208" FT /id="VAR_046818" FT VARIANT 101 FT /note="R -> C (in THPH5; dbSNP:rs778731080)" FT /evidence="ECO:0000269|PubMed:12632031" FT /id="VAR_046819" FT VARIANT 111 FT /note="R -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046820" FT VARIANT 121 FT /note="C -> Y (in THPH5)" FT /evidence="ECO:0000269|PubMed:15238143" FT /id="VAR_046821" FT VARIANT 129 FT /note="D -> G (in THPH5; dbSNP:rs749024073)" FT /evidence="ECO:0000269|PubMed:10613647, FT ECO:0000269|PubMed:15712227" FT /id="VAR_046822" FT VARIANT 144 FT /note="T -> N (in THPH5; dbSNP:rs146366248)" FT /evidence="ECO:0000269|PubMed:12632031, FT ECO:0000269|PubMed:15712227, ECO:0000269|PubMed:7803790" FT /id="VAR_046823" FT VARIANT 149 FT /note="W -> C (in THPH5)" FT /evidence="ECO:0000269|PubMed:11776305" FT /id="VAR_046824" FT VARIANT 157 FT /note="D -> G (in THPH5; dbSNP:rs751090951)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046825" FT VARIANT 161 FT /note="C -> G (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046826" FT VARIANT 166 FT /note="N -> Y (in THPH5)" FT /evidence="ECO:0000269|PubMed:10706858" FT /id="VAR_046827" FT VARIANT 168 FT /note="N -> S (in dbSNP:rs144430063)" FT /evidence="ECO:0000269|PubMed:12632031" FT /id="VAR_046828" FT VARIANT 175 FT /note="C -> F (in THPH5)" FT /evidence="ECO:0000269|PubMed:10613647, FT ECO:0000269|PubMed:15712227" FT /id="VAR_046829" FT VARIANT 186 FT /note="C -> Y (in THPH5; dbSNP:rs779391826)" FT /evidence="ECO:0000269|PubMed:8781426, FT ECO:0000269|PubMed:8943854" FT /id="VAR_046830" FT VARIANT 196 FT /note="K -> E (in THPH5; Tokushima; the specific activity FT decreases to 58% of that of the wild-type PROS1; the FT activated protein cofactor activity is inhibited by C4BPB FT with a dose dependency similar to that of wild-type PROS1; FT dbSNP:rs121918474)" FT /evidence="ECO:0000269|PubMed:11927129, FT ECO:0000269|PubMed:15238143, ECO:0000269|PubMed:8298131" FT /id="VAR_005566" FT VARIANT 204 FT /note="E -> G (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046831" FT VARIANT 233 FT /note="R -> K (does not affect protein levels; the mutant FT is normally secreted; dbSNP:rs41267007)" FT /evidence="ECO:0000269|PubMed:10790208, FT ECO:0000269|PubMed:18322254, ECO:0000269|PubMed:27535533" FT /id="VAR_046832" FT VARIANT 234 FT /note="Y -> C (in THPH6; dbSNP:rs387906675)" FT /evidence="ECO:0000269|PubMed:20484936" FT /id="VAR_067302" FT VARIANT 241 FT /note="C -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:8943854" FT /id="VAR_046833" FT VARIANT 243 FT /note="D -> N (in THPH5)" FT /evidence="ECO:0000269|PubMed:11372770" FT /id="VAR_046834" FT VARIANT 245 FT /note="D -> G (in THPH5; dbSNP:rs1211117206)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046835" FT VARIANT 247 FT /note="C -> G (in THPH5)" FT /evidence="ECO:0000269|PubMed:10706858" FT /id="VAR_046836" FT VARIANT 249 FT /note="E -> K (in THPH5; dbSNP:rs1455675811)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046837" FT VARIANT 258 FT /note="N -> S (in THPH5; produces around 30% of PROS1 FT levels compared to wild-type; has impaired secretion; FT intracellular degradation of unsecreted material is found; FT dbSNP:rs121918473)" FT /evidence="ECO:0000269|PubMed:11858485, FT ECO:0000269|PubMed:7545463, ECO:0000269|Ref.15" FT /id="VAR_005567" FT VARIANT 265 FT /note="C -> R (in THPH5)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046838" FT VARIANT 265 FT /note="C -> W (in THPH5)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046839" FT VARIANT 266 FT /note="Y -> C (in THPH5; dbSNP:rs777616039)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046840" FT VARIANT 267 FT /note="C -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046841" FT VARIANT 300 FT /note="L -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:8701404" FT /id="VAR_046842" FT VARIANT 324 FT /note="S -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:8943854" FT /id="VAR_046843" FT VARIANT 336 FT /note="G -> D (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046844" FT VARIANT 336 FT /note="G -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:9241758" FT /id="VAR_046845" FT VARIANT 336 FT /note="G -> V (in THPH5; expresses very low/undetectable FT PROS1 levels compared to wild-type; has impaired secretion; FT intracellular degradation of unsecreted material is found)" FT /evidence="ECO:0000269|PubMed:11858485" FT /id="VAR_046846" FT VARIANT 339 FT /note="L -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:11372770" FT /id="VAR_046847" FT VARIANT 351 FT /note="L -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:7579449" FT /id="VAR_046848" FT VARIANT 355 FT /note="R -> H (in THPH5; dbSNP:rs780863931)" FT /evidence="ECO:0000269|PubMed:15238143" FT /id="VAR_046849" FT VARIANT 357 FT /note="G -> R (in THPH5; dbSNP:rs941433523)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046850" FT VARIANT 364 FT /note="K -> E (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046851" FT VARIANT 376 FT /note="D -> N (in THPH5)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046852" FT VARIANT 381 FT /note="G -> D (in THPH5; dbSNP:rs1223579199)" FT /evidence="ECO:0000269|PubMed:8943854" FT /id="VAR_046853" FT VARIANT 381 FT /note="G -> V (in THPH5)" FT /evidence="ECO:0000269|PubMed:7482398" FT /id="VAR_046854" FT VARIANT 383 FT /note="W -> R (in THPH5)" FT /evidence="ECO:0000269|PubMed:11776305" FT /id="VAR_046855" FT VARIANT 385 FT /note="M -> V (in dbSNP:rs767653920)" FT /evidence="ECO:0000269|PubMed:7803790" FT /id="VAR_046856" FT VARIANT 390 FT /note="E -> K (in THPH5)" FT /evidence="ECO:0000269|PubMed:11776305" FT /id="VAR_046857" FT VARIANT 446 FT /note="L -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227, FT ECO:0000269|PubMed:8765219" FT /id="VAR_046858" FT VARIANT 449 FT /note="C -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:8943854" FT /id="VAR_046859" FT VARIANT 475 FT /note="C -> R (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046860" FT VARIANT 482 FT /note="G -> C (in THPH5)" FT /evidence="ECO:0000269|PubMed:10447256" FT /id="VAR_014116" FT VARIANT 485 FT /note="Y -> C (in THPH5; dbSNP:rs1323663956)" FT /evidence="ECO:0000269|PubMed:10447256" FT /id="VAR_014117" FT VARIANT 501 FT /note="S -> A (in THPH5; dbSNP:rs121918472)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046862" FT VARIANT 501 FT /note="S -> P (variant Heerlen; dbSNP:rs121918472)" FT /evidence="ECO:0000269|PubMed:10447256, FT ECO:0000269|PubMed:15712227, ECO:0000269|PubMed:2143091, FT ECO:0000269|PubMed:8765219, ECO:0000269|PubMed:8943854" FT /id="VAR_005568" FT VARIANT 508 FT /note="V -> G (in THPH5)" FT /evidence="ECO:0000269|PubMed:7482398" FT /id="VAR_046863" FT VARIANT 508 FT /note="V -> M (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046864" FT VARIANT 515 FT /note="R -> C (in THPH5; secretion of the mutant markedly FT decreased compared with that of the wild-type; FT intracellular degradation and impaired secretion of the FT mutant; dbSNP:rs199469500)" FT /evidence="ECO:0000269|PubMed:8639833, FT ECO:0000269|PubMed:8765219" FT /id="VAR_046865" FT VARIANT 515 FT /note="R -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:10613647, FT ECO:0000269|PubMed:15712227" FT /id="VAR_046866" FT VARIANT 521 FT /note="G -> D (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046867" FT VARIANT 525 FT /note="A -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046868" FT VARIANT 526 FT /note="L -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:11776305" FT /id="VAR_046869" FT VARIANT 532 FT /note="T -> A (in THPH5; dbSNP:rs371028997)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046870" FT VARIANT 545 FT /note="E -> G (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs1396452003)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035981" FT VARIANT 552 FT /note="L -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:7579449" FT /id="VAR_046871" FT VARIANT 559 FT /note="I -> M (in dbSNP:rs184798444)" FT /evidence="ECO:0000269|PubMed:10447256, FT ECO:0000269|PubMed:10790208, ECO:0000269|PubMed:15712227" FT /id="VAR_014118" FT VARIANT 561 FT /note="R -> G (in THPH5; dbSNP:rs121918476)" FT /evidence="ECO:0000269|PubMed:10447256" FT /id="VAR_014119" FT VARIANT 562 FT /note="I -> L (in THPH5; uncertain significance; FT dbSNP:rs1380889353)" FT /evidence="ECO:0000269|PubMed:10613647, FT ECO:0000269|PubMed:15712227" FT /id="VAR_046872" FT VARIANT 568 FT /note="C -> Y (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046873" FT VARIANT 575 FT /note="L -> R (in THPH5)" FT /evidence="ECO:0000269|PubMed:8765219" FT /id="VAR_046874" FT VARIANT 583 FT /note="N -> H (in dbSNP:rs139479630)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046875" FT VARIANT 584 FT /note="L -> Q (in THPH5)" FT /evidence="ECO:0000269|PubMed:7579449" FT /id="VAR_046876" FT VARIANT 611 FT /note="M -> K (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046877" FT VARIANT 611 FT /note="M -> T (in THPH5; dbSNP:rs750531364)" FT /evidence="ECO:0000269|PubMed:10706858, FT ECO:0000269|PubMed:7545463, ECO:0000269|PubMed:8781426" FT /id="VAR_046878" FT VARIANT 616 FT /note="A -> P (in THPH5)" FT /evidence="ECO:0000269|PubMed:7579449" FT /id="VAR_046879" FT VARIANT 622 FT /note="L -> R (in THPH5)" FT /evidence="ECO:0000269|PubMed:10706858" FT /id="VAR_046880" FT VARIANT 630 FT /note="T -> I (in THPH5; the activated protein cofactor FT activity is inhibited by C4BPB with a dose dependency FT similar to that of wild-type PROS1; dbSNP:rs202190731)" FT /evidence="ECO:0000269|PubMed:11927129" FT /id="VAR_046881" FT VARIANT 636 FT /note="Y -> C (in THPH5; shows intracellular degradation FT and decreased secretion; dbSNP:rs368173480)" FT /evidence="ECO:0000269|PubMed:11927129" FT /id="VAR_046882" FT VARIANT 638 FT /note="G -> D (in THPH5)" FT /evidence="ECO:0000269|PubMed:10613647, FT ECO:0000269|PubMed:15712227" FT /id="VAR_046883" FT VARIANT 639 FT /note="C -> F (in THPH5)" FT /evidence="ECO:0000269|PubMed:9031443" FT /id="VAR_046884" FT VARIANT 639 FT /note="C -> Y (in THPH5)" FT /evidence="ECO:0000269|PubMed:15712227" FT /id="VAR_046885" FT VARIANT 640 FT /note="M -> T (in THPH5; does not affect protein levels; FT the mutant is secreted at lower levels compared to FT wild-type)" FT /evidence="ECO:0000269|PubMed:10790208, FT ECO:0000269|PubMed:18322254" FT /id="VAR_046886" FT VARIANT 644 FT /note="I -> S (in THPH5)" FT /evidence="ECO:0000269|PubMed:8977443" FT /id="VAR_046887" FT VARIANT 664 FT /note="H -> P (in THPH5; expresses very low/undetectable FT PROS1 levels compared to wild-type; has impaired secretion; FT intracellular degradation of unsecreted material is found)" FT /evidence="ECO:0000269|PubMed:11858485" FT /id="VAR_046888" FT VARIANT 665 FT /note="S -> L (in THPH5; dbSNP:rs778685576)" FT /evidence="ECO:0000269|PubMed:8781426" FT /id="VAR_046889" FT VARIANT 666 FT /note="C -> R (in THPH5; dbSNP:rs1302089144)" FT /evidence="ECO:0000269|PubMed:10706858, FT ECO:0000269|PubMed:8701404, ECO:0000269|PubMed:8765219, FT ECO:0000269|PubMed:8943854" FT /id="VAR_046890" FT VARIANT 667 FT /note="P -> L (in THPH5; dbSNP:rs1220553873)" FT /evidence="ECO:0000269|PubMed:10790208, FT ECO:0000269|PubMed:15238143" FT /id="VAR_046891" FT MUTAGEN 515 FT /note="R->A,E: Markedly reduced secretion of the mutant." FT /evidence="ECO:0000269|PubMed:8639833" FT MUTAGEN 515 FT /note="R->K: No change in secretion of the mutant." FT /evidence="ECO:0000269|PubMed:8639833" FT CONFLICT 11 FT /note="L -> P (in Ref. 2; AAA36479)" FT /evidence="ECO:0000305" FT CONFLICT 26 FT /note="F -> L (in Ref. 2; AAA36479)" FT /evidence="ECO:0000305" FT STRAND 204..212 FT /evidence="ECO:0007829|PDB:1Z6C" FT STRAND 227..229 FT /evidence="ECO:0007829|PDB:1Z6C" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:1Z6C" FT TURN 236..239 FT /evidence="ECO:0007829|PDB:1Z6C" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:1Z6C" FT HELIX 246..249 FT /evidence="ECO:0007829|PDB:1Z6C" FT STRAND 253..256 FT /evidence="ECO:0007829|PDB:1Z6C" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:1Z6C" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:1Z6C" FT STRAND 279..281 FT /evidence="ECO:0007829|PDB:1Z6C" SQ SEQUENCE 676 AA; 75123 MW; 2B88A04F85403F25 CRC64; MRVLGGRCGA LLACLLLVLP VSEANFLSKQ QASQVLVRKR RANSLLEETK QGNLERECIE ELCNKEEARE VFENDPETDY FYPKYLVCLR SFQTGLFTAA RQSTNAYPDL RSCVNAIPDQ CSPLPCNEDG YMSCKDGKAS FTCTCKPGWQ GEKCEFDINE CKDPSNINGG CSQICDNTPG SYHCSCKNGF VMLSNKKDCK DVDECSLKPS ICGTAVCKNI PGDFECECPE GYRYNLKSKS CEDIDECSEN MCAQLCVNYP GGYTCYCDGK KGFKLAQDQK SCEVVSVCLP LNLDTKYELL YLAEQFAGVV LYLKFRLPEI SRFSAEFDFR TYDSEGVILY AESIDHSAWL LIALRGGKIE VQLKNEHTSK ITTGGDVINN GLWNMVSVEE LEHSISIKIA KEAVMDINKP GPLFKPENGL LETKVYFAGF PRKVESELIK PINPRLDGCI RSWNLMKQGA SGIKEIIQEK QNKHCLVTVE KGSYYPGSGI AQFHIDYNNV SSAEGWHVNV TLNIRPSTGT GVMLALVSGN NTVPFAVSLV DSTSEKSQDI LLSVENTVIY RIQALSLCSD QQSHLEFRVN RNNLELSTPL KIETISHEDL QRQLAVLDKA MKAKVATYLG GLPDVPFSAT PVNAFYNGCM EVNINGVQLD LDEAISKHND IRAHSCPSVW KKTKNS //