PROS_HUMAN
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 03-AUG-2022, entry version 248.
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 -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/pros1/";
CC ---------------------------------------------------------------------------
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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; 81.
DR IntAct; P07225; 21.
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 GlyGen; P07225; 5 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (2 sites).
DR iPTMnet; P07225; -.
DR PhosphoSitePlus; P07225; -.
DR BioMuta; PROS1; -.
DR DMDM; 131086; -.
DR CPTAC; non-CPTAC-2705; -.
DR EPD; P07225; -.
DR jPOST; P07225; -.
DR MassIVE; P07225; -.
DR MaxQB; P07225; -.
DR PaxDb; P07225; -.
DR PeptideAtlas; P07225; -.
DR PRIDE; P07225; -.
DR ProteomicsDB; 51975; -.
DR ABCD; P07225; 29 sequenced antibodies.
DR Antibodypedia; 858; 460 antibodies from 39 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 CTD; 5627; -.
DR DisGeNET; 5627; -.
DR GeneCards; PROS1; -.
DR HGNC; HGNC:9456; PROS1.
DR HPA; ENSG00000184500; Group enriched (choroid plexus, heart muscle, 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; 64738; NON RARE IN EUROPE: Non rare thrombophilia.
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; 317733at2759; -.
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 1082 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 194 other tissues.
DR ExpressionAtlas; P07225; baseline and differential.
DR Genevisible; P07225; HS.
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; cd00110; LamG; 1.
DR Gene3D; 4.10.740.10; -; 1.
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; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
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; IPR033189; PROS1.
DR PANTHER; PTHR24040:SF10; PTHR24040:SF10; 1.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF07645; EGF_CA; 2.
DR Pfam; PF00594; Gla; 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; SSF49899; 2.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57630; SSF57630; 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; Reference proteome; Repeat; Secreted; Signal;
KW 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 Ca(2+)-
FT 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; could be associated with
FT THPH5; 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; unknown pathological 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 wild-
FT 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
