PROC_HUMAN
ID PROC_HUMAN Reviewed; 461 AA.
AC P04070; B4DPQ7; Q15189; Q15190; Q16001; Q53S74; Q9UC55;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 260.
DE RecName: Full=Vitamin K-dependent protein C;
DE EC=3.4.21.69;
DE AltName: Full=Anticoagulant protein C;
DE AltName: Full=Autoprothrombin IIA;
DE AltName: Full=Blood coagulation factor XIV;
DE Contains:
DE RecName: Full=Vitamin K-dependent protein C light chain;
DE Contains:
DE RecName: Full=Vitamin K-dependent protein C heavy chain;
DE Contains:
DE RecName: Full=Activation peptide;
DE Flags: Precursor;
GN Name=PROC;
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] (ISOFORM 1).
RX PubMed=2991859; DOI=10.1093/nar/13.14.5233;
RA Beckmann R.J., Schmidt R.J., Santerre R.F., Plutzky J., Crabtree G.R.,
RA Long G.L.;
RT "The structure and evolution of a 461 amino acid human protein C precursor
RT and its messenger RNA, based upon the DNA sequence of cloned human liver
RT cDNAs.";
RL Nucleic Acids Res. 13:5233-5247(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], HYDROXYLATION AT ASP-113, GLYCOSYLATION
RP AT ASN-290; ASN-355 AND ASN-371, AND GAMMA-CARBOXYGLUTAMATION AT GLU-48;
RP GLU-49; GLU-56; GLU-58; GLU-61; GLU-62; GLU-67; GLU-68 AND GLU-71.
RX PubMed=2991887; DOI=10.1073/pnas.82.14.4673;
RA Foster D.C., Yoshitake S., Davie E.W.;
RT "The nucleotide sequence of the gene for human protein C.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:4673-4677(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3511471; DOI=10.1073/pnas.83.3.546;
RA Plutzky J., Hoskins J.A., Long G.L., Crabtree G.R.;
RT "Evolution and organization of the human protein C gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:546-550(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 PROTEIN SEQUENCE OF 42-57, AND VARIANT THPH3 SER-42.
RC TISSUE=Blood;
RX PubMed=8560401;
RA Miyata T., Zheng Y.-Z., Sakata T., Kato H.;
RT "Protein C Osaka 10 with aberrant propeptide processing: loss of
RT anticoagulant activity due to an amino acid substitution in the protein C
RT precursor.";
RL Thromb. Haemost. 74:1003-1008(1995).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-64, AND VARIANT PROC DEFICIENCY
RP GLY-57.
RX PubMed=8477066;
RA Mimuro J., Muramatsu S., Kaneko M., Yoshitake S., Iijima K., Nakamura K.,
RA Sakata Y., Matsuda M.;
RT "An abnormal protein C (protein C Yonago) with an amino acid substitution
RT of Gly for Arg-15 caused by a single base mutation of C to G in codon 57
RT (CGG-->GGG). Deteriorated calcium-dependent conformation of the gamma-
RT carboxyglutamic acid domain relevant to a thrombotic tendency.";
RL Int. J. Hematol. 57:9-14(1993).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 106-461 (ISOFORM 1).
RX PubMed=6589623; DOI=10.1073/pnas.81.15.4766;
RA Foster D.C., Davie E.W.;
RT "Characterization of a cDNA coding for human protein C.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4766-4770(1984).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-178 AND 267-332, AND VARIANTS
RP THPH4 PRO-178 AND HIS-328.
RX PubMed=7878626;
RA Long G.L., Tomczak J.A., Rainville I.R., Dreyfus M., Schramm W.,
RA Schwarz H.P.;
RT "Homozygous type I protein C deficiency in two unrelated families
RT exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His
RT mutations.";
RL Thromb. Haemost. 72:526-533(1994).
RN [13]
RP GLYCOSYLATION AT ASN-371.
RX PubMed=1694179; DOI=10.1016/s0021-9258(19)38606-5;
RA Miletich J.P., Broze G.J. Jr.;
RT "Beta protein C is not glycosylated at asparagine 329. The rate of
RT translation may influence the frequency of usage at asparagine-X-cysteine
RT sites.";
RL J. Biol. Chem. 265:11397-11404(1990).
RN [14]
RP HYDROXYLATION.
RX PubMed=1544894; DOI=10.1016/s0021-9258(18)42736-6;
RA Harris R.J., Ling V.T., Spellman M.W.;
RT "O-linked fucose is present in the first epidermal growth factor domain of
RT factor XII but not protein C.";
RL J. Biol. Chem. 267:5102-5107(1992).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-290.
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 [16]
RP GLYCOSYLATION AT THR-19, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [17]
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 [18]
RP PHOSPHORYLATION AT SER-347.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [19]
RP 3D-STRUCTURE MODELING OF 175-450.
RX PubMed=8003977; DOI=10.1002/pro.5560030407;
RA Fisher C.L., Greengard J.S., Griffin J.H.;
RT "Models of the serine protease domain of the human antithrombotic plasma
RT factor activated protein C and its zymogen.";
RL Protein Sci. 3:588-599(1994).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 84-461.
RX PubMed=9003757; DOI=10.1002/j.1460-2075.1996.tb01073.x;
RA Mather T., Oganessyan V., Hof P., Huber R., Foundling S., Esmon C.,
RA Bode W.;
RT "The 2.8 A crystal structure of Gla-domainless activated protein C.";
RL EMBO J. 15:6822-6831(1996).
RN [21]
RP REVIEW ON PROC VARIANTS.
RX PubMed=8446940;
RA Reitsma P.H., Poort S.R., Bernardi F., Gandrille S., Long G.L., Sala N.,
RA Cooper D.N.;
RT "Protein C deficiency: a database of mutations.";
RL Thromb. Haemost. 69:77-84(1993).
RN [22]
RP VARIANT THPH3 CYS-444.
RX PubMed=2437584; DOI=10.1073/pnas.84.9.2829;
RA Romeo G., Hassan H.J., Staempfli S., Roncuzzi L., Cianetti L., Leonardi A.,
RA Vicente V., Mannucci P.M., Bertina R.M., Peschle C., Cortese R.;
RT "Hereditary thrombophilia: identification of nonsense and missense
RT mutations in the protein C gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2829-2832(1987).
RN [23]
RP VARIANT THPH3 TRP-211.
RX PubMed=2602169; DOI=10.1093/nar/17.24.10513;
RA Grundy C.B., Chitolie A., Talbot S., Bevan D., Kakkar V.V., Cooper D.N.;
RT "Protein C London 1: recurrent mutation at Arg-169 (CGG-->TGG) in the
RT protein C gene causing thrombosis.";
RL Nucleic Acids Res. 17:10513-10513(1989).
RN [24]
RP VARIANT THPH3 CYS-272.
RX PubMed=1868249;
RA Reitsma P.H., Poort S.R., Allaart C.F., Briet E., Bertina R.M.;
RT "The spectrum of genetic defects in a panel of 40 Dutch families with
RT symptomatic protein C deficiency type I: heterogeneity and founder
RT effects.";
RL Blood 78:890-894(1991).
RN [25]
RP VARIANTS THPH3 ALA-62 AND MET-76.
RX PubMed=1347706;
RA Bovill E.G., Tomczak J.A., Grant B., Bhushan F., Pillemer E.,
RA Rainville I.R., Long G.L.;
RT "Protein CVermont: symptomatic type II protein C deficiency associated with
RT two GLA domain mutations.";
RL Blood 79:1456-1465(1992).
RN [26]
RP VARIANT THPH4 ASP-418.
RX PubMed=1611081;
RA Sugahara Y., Miura O., Yuen P., Aoki N.;
RT "Protein C deficiency Hong Kong 1 and 2: hereditary protein C deficiency
RT caused by two mutant alleles, a 5-nucleotide deletion and a missense
RT mutation.";
RL Blood 80:126-133(1992).
RN [27]
RP VARIANT THPH4 LEU-289.
RX PubMed=1511988; DOI=10.1007/bf00221963;
RA Grundy C.B., Chisholm M., Kakkar V.V., Cooper D.N.;
RT "A novel homozygous missense mutation in the protein C (PROC) gene causing
RT recurrent venous thrombosis.";
RL Hum. Genet. 89:683-684(1992).
RN [28]
RP VARIANTS THPH3 GLN-220 AND TRP-220.
RX PubMed=1511989; DOI=10.1007/bf00221964;
RA Grundy C.B., Schulman S., Tengborn L., Kakkar V.V., Cooper D.N.;
RT "Two different missense mutations at Arg 178 of the protein C (PROC) gene
RT causing recurrent venous thrombosis.";
RL Hum. Genet. 89:685-686(1992).
RN [29]
RP VARIANT THPH3 GLN-220.
RX PubMed=1301959; DOI=10.1002/humu.1380010607;
RA Gandrille S., Vidaud M., Aiach M., Alhenc-Gelas M., Fischer A.M.,
RA Gouault-Heilman M., Toulon P., Fiessinger J.-N., Goossens M.;
RT "Two novel mutations responsible for hereditary type I protein C
RT deficiency: characterization by denaturing gradient gel electrophoresis.";
RL Hum. Mutat. 1:491-500(1992).
RN [30]
RP VARIANT THPH4 SER-334.
RX PubMed=1593215;
RA Yamamoto K., Matsushita T., Sugiura I., Takamatsu J., Iwasaki E., Wada H.,
RA Deguchi K., Shirakawa S., Saito H.;
RT "Homozygous protein C deficiency: identification of a novel missense
RT mutation that causes impaired secretion of the mutant protein C.";
RL J. Lab. Clin. Med. 119:682-689(1992).
RN [31]
RP VARIANTS TRP-38; CYS-42; HIS-42; GLN-271 AND ASN-294.
RX PubMed=8324221;
RA Gandrille S., Alhenc-Gelas M., Gaussem P., Aillaud M.-F., Dupuy E.,
RA Juhan-Vague I., Aiach M.;
RT "Five novel mutations located in exons III and IX of the protein C gene in
RT patients presenting with defective protein C anticoagulant activity.";
RL Blood 82:159-168(1993).
RN [32]
RP VARIANTS GLY-14; GLN-211; TYR-244; GLN-253; LEU-321; CYS-328; ILE-385;
RP THR-388 AND VAL-388.
RX PubMed=8499565; DOI=10.1097/00001721-199304000-00009;
RA Poort S.R., Pabinger-Fasching I., Mannhalter C., Reitsma P.H.,
RA Bertina R.M.;
RT "Twelve novel and two recurrent mutations in 14 Austrian families with
RT hereditary protein C deficiency.";
RL Blood Coagul. Fibrinolysis 4:273-280(1993).
RN [33]
RP VARIANT THPH3 TRP-57.
RX PubMed=8499568; DOI=10.1097/00001721-199304000-00014;
RA Millar D.S., Grundy C.B., Bignell P., Moffat E.H., Martin R., Kakkar V.V.,
RA Cooper D.N.;
RT "A Gla domain mutation (Arg 15-->Trp) in the protein C (PROC) gene causing
RT type 2 protein C deficiency and recurrent venous thrombosis.";
RL Blood Coagul. Fibrinolysis 4:345-347(1993).
RN [34]
RP VARIANTS THPH3 ARG-145; LEU-210; TRP-211; THR-243; LEU-321; MET-340 AND
RP TYR-426.
RX PubMed=8292730;
RA Tsay W., Greengard J.S., Montgomery R.R., McPherson R.A., Fucci J.C.,
RA Koerper M.A., Coughlin J., Griffin J.H.;
RT "Genetic mutations in ten unrelated American patients with symptomatic type
RT 1 protein C deficiency.";
RL Blood Coagul. Fibrinolysis 4:791-796(1993).
RN [35]
RP VARIANT THPH3 SER-423.
RX PubMed=8398832; DOI=10.1111/j.1365-2141.1993.tb03066.x;
RA Marchetti G., Patracchini P., Gemmati D., Castaman G., Rodeghiero F.,
RA Wacey A., Cooper D.N., Tuddenham E.G., Bernardi F.;
RT "Symptomatic type II protein C deficiency caused by a missense mutation
RT (Gly 381-->Ser) in the substrate-binding pocket.";
RL Br. J. Haematol. 84:285-289(1993).
RN [36]
RP VARIANT PRO-312.
RX PubMed=7919373;
RA Gandrille S., Jude B., Alhenc-Gelas M., Emmerich J., Aiach M.;
RT "First de novo mutations in the protein C gene of two patients with type I
RT deficiency: a missense mutation and a splice site deletion.";
RL Blood 84:2566-2570(1994).
RN [37]
RP VARIANT THPH4 144-ASN-GLY-145 DELINS LYS.
RX PubMed=7841323;
RA Millar D.S., Allgrove J., Rodeck C., Kakkar V.V., Cooper D.N.;
RT "A homozygous deletion/insertion mutation in the protein C (PROC) gene
RT causing neonatal Purpura fulminans: prenatal diagnosis in an at-risk
RT pregnancy.";
RL Blood Coagul. Fibrinolysis 5:647-649(1994).
RN [38]
RP VARIANT THPH4 ALA-367.
RX PubMed=7841324;
RA Witt I., Beck S., Seydewitz H.H., Tasangil C., Schenck W.;
RT "A novel homozygous missense mutation (Val 325-->Ala) in the protein C gene
RT causing neonatal purpura fulminans.";
RL Blood Coagul. Fibrinolysis 5:651-653(1994).
RN [39]
RP VARIANTS THPH3 LEU-369; ARG-392; ASN-401 AND HIS-441.
RX PubMed=7865674; DOI=10.1097/00001721-199410000-00003;
RA Zheng Y.-Z., Sakata T., Matsusue T., Umeyama H., Kato H., Miyata T.;
RT "Six missense mutations associated with type I and type II protein C
RT deficiency and implications obtained from molecular modelling.";
RL Blood Coagul. Fibrinolysis 5:687-696(1994).
RN [40]
RP VARIANT ASP-49.
RX PubMed=7974343;
RA Gaussem P., Gandrille S., Duchemin J., Emmerich J., Alhenc-Gelas M.,
RA Aillaud M.-F., Aiach M.;
RT "Influence of six mutations of the protein C gene on the Gla domain
RT conformation and calcium affinity.";
RL Thromb. Haemost. 71:748-754(1994).
RN [41]
RP VARIANTS CYS-89; PRO-220 AND THR-301.
RX PubMed=7605880; DOI=10.1097/00001721-199504000-00009;
RA Millar D.S., Bevan D., Chitolie A., Reynaud J., Chisholm M., Kakkar V.V.,
RA Cooper D.N.;
RT "Three novel mutations in the protein C (PROC) gene causing venous
RT thrombosis.";
RL Blood Coagul. Fibrinolysis 6:138-140(1995).
RN [42]
RP VARIANTS THPH3 TRP-57; ARG-114; ARG-324; CYS-328 AND LEU-369, AND VARIANT
RP THR-43.
RX PubMed=7792728;
RA Lind B., Schwartz M., Thorsen S.;
RT "Six different point mutations in seven Danish families with symptomatic
RT protein C deficiency.";
RL Thromb. Haemost. 73:186-193(1995).
RN [43]
RP VARIANTS THPH3 CYS-32 AND ASN-436.
RX PubMed=8829639;
RX DOI=10.1002/(sici)1098-1004(1996)7:2<176::aid-humu16>3.0.co;2-#;
RA Ireland H.A., Boisclair M.D., Taylor J., Thompson E., Thein S.L.,
RA Girolami A., de Caterina M., Scopacasa F., de Stefano V., Leone G.,
RA Finazzi G., Cohen H., Lane D.A.;
RT "Two novel (R(-11)C; T394D) and two repeat missense mutations in the
RT protein C gene associated with venous thrombosis in six kindreds.";
RL Hum. Mutat. 7:176-179(1996).
RN [44]
RP VARIANTS THPH3 GLN-220 AND MET-340.
RX PubMed=9798967;
RA Couture P., Demers C., Morissette J., Delage R., Jomphe M., Couture L.,
RA Simard J.;
RT "Type I protein C deficiency in French Canadians: evidence of a founder
RT effect and association of specific protein C gene mutations with plasma
RT protein C levels.";
RL Thromb. Haemost. 80:551-556(1998).
RN [45]
RP VARIANT SER-317, CHARACTERIZATION OF SER-317, AND SUBCELLULAR LOCATION.
RX PubMed=22531345; DOI=10.1097/pat.0b013e328353a218;
RA Yu T., Dai J., Liu H., Wang J., Ding Q., Wang H., Wang X., Fu Q.;
RT "Homozygous protein C deficiency with late onset venous thrombosis:
RT identification and in vitro expression study of a novel Pro275Ser
RT mutation.";
RL Pathology 44:348-353(2012).
RN [46]
RP VARIANTS GLU-70; GLY-106; ALA-118; TYR-175; VAL-181; TRP-189; GLN-211;
RP TRP-220; ARG-223; GLY-240; HIS-297; LEU-312; VAL-327 AND LEU-420.
RX PubMed=22545135; DOI=10.1371/journal.pone.0035773;
RA Tang L., Guo T., Yang R., Mei H., Wang H., Lu X., Yu J., Wang Q., Hu Y.;
RT "Genetic background analysis of protein C deficiency demonstrates a
RT recurrent mutation associated with venous thrombosis in Chinese
RT population.";
RL PLoS ONE 7:E35773-E35773(2012).
RN [47]
RP VARIANT ALA-357, CHARACTERIZATION OF ALA-357, AND FUNCTION.
RX PubMed=25651845; DOI=10.1182/blood-2014-12-617274;
RA Ding Q., Yang L., Dinarvand P., Wang X., Rezaie A.R.;
RT "Protein C Thr315Ala variant results in gain of function but manifests as
RT type II deficiency in diagnostic assays.";
RL Blood 125:2428-2434(2015).
RN [48]
RP VARIANTS THPH3 HIS-297 AND LEU-420, CHARACTERIZATION OF VARIANTS THPH3
RP HIS-297 AND LEU-420, AND SUBCELLULAR LOCATION.
RX PubMed=25748729; DOI=10.1016/j.gene.2015.03.002;
RA Liu H., Wang H.F., Tang L., Yang Y., Wang Q.Y., Zeng W., Wu Y.Y.,
RA Cheng Z.P., Hu B., Guo T., Hu Y.;
RT "Compound heterozygous protein C deficiency in a family with venous
RT thrombosis: Identification and in vitro study of p.Asp297His and
RT p.Val420Leu mutations.";
RL Gene 563:35-40(2015).
RN [49]
RP VARIANTS THPH4 GLY-77 AND GLU-163, VARIANT THPH3 VAL-163, FUNCTION AS
RP ANTICOAGULANT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS THPH4
RP GLY-77 AND GLU-163, AND CHARACTERIZATION OF VARIANT THPH3 VAL-163.
RX PubMed=25618265; DOI=10.1016/j.thromres.2015.01.011;
RA Kovacs K.B., Pataki I., Bardos H., Fekete A., Pfliegler G., Haramura G.,
RA Gindele R., Komaromi I., Balla G., Adany R., Muszbek L., Bereczky Z.;
RT "Molecular characterization of p.Asp77Gly and the novel p.Ala163Val and
RT p.Ala163Glu mutations causing protein C deficiency.";
RL Thromb. Res. 135:718-726(2015).
CC -!- FUNCTION: Protein C is a vitamin K-dependent serine protease that
CC regulates blood coagulation by inactivating factors Va and VIIIa in the
CC presence of calcium ions and phospholipids (PubMed:25618265). Exerts a
CC protective effect on the endothelial cell barrier function
CC (PubMed:25651845). {ECO:0000269|PubMed:25618265,
CC ECO:0000269|PubMed:25651845}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Degradation of blood coagulation factors Va and VIIIa.;
CC EC=3.4.21.69;
CC -!- SUBUNIT: Synthesized as a single chain precursor, which is cleaved into
CC a light chain and a heavy chain held together by a disulfide bond. The
CC enzyme is then activated by thrombin, which cleaves a tetradecapeptide
CC from the amino end of the heavy chain; this reaction, which occurs at
CC the surface of endothelial cells, is strongly promoted by
CC thrombomodulin.
CC -!- INTERACTION:
CC P04070; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1383018, EBI-3867333;
CC P04070; P51511: MMP15; NbExp=2; IntAct=EBI-1383018, EBI-1383043;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25618265}. Golgi
CC apparatus {ECO:0000269|PubMed:22531345, ECO:0000269|PubMed:25748729}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:22531345,
CC ECO:0000269|PubMed:25748729}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P04070-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04070-2; Sequence=VSP_054393, VSP_054394;
CC -!- TISSUE SPECIFICITY: Plasma; synthesized in the liver.
CC -!- PTM: The vitamin K-dependent, enzymatic carboxylation of some Glu
CC residues allows the modified protein to bind calcium.
CC -!- PTM: N- and O-glycosylated. Partial (70%) N-glycosylation of Asn-371
CC with an atypical N-X-C site produces a higher molecular weight form
CC referred to as alpha. The lower molecular weight form, not N-
CC glycosylated at Asn-371, is beta. O-glycosylated with core 1 or
CC possibly core 8 glycans. {ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:1694179, ECO:0000269|PubMed:22171320,
CC ECO:0000269|PubMed:2991887}.
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate
CC and asparagine is (R) stereospecific within EGF domains.
CC {ECO:0000269|PubMed:1544894, ECO:0000269|PubMed:2991887}.
CC -!- PTM: May be phosphorylated on a Ser or Thr in a region (AA 25-30) of
CC the propeptide.
CC -!- DISEASE: Thrombophilia due to protein C deficiency, autosomal dominant
CC (THPH3) [MIM:176860]: A hemostatic disorder characterized by impaired
CC regulation of blood coagulation and a tendency to recurrent venous
CC thrombosis. Individuals with decreased amounts of protein C are
CC classically referred to as having type I protein C deficiency and those
CC with normal amounts of a functionally defective protein as having type
CC II deficiency. {ECO:0000269|PubMed:1301959, ECO:0000269|PubMed:1347706,
CC ECO:0000269|PubMed:1511989, ECO:0000269|PubMed:1868249,
CC ECO:0000269|PubMed:2437584, ECO:0000269|PubMed:25618265,
CC ECO:0000269|PubMed:25748729, ECO:0000269|PubMed:2602169,
CC ECO:0000269|PubMed:7792728, ECO:0000269|PubMed:7865674,
CC ECO:0000269|PubMed:8292730, ECO:0000269|PubMed:8398832,
CC ECO:0000269|PubMed:8499568, ECO:0000269|PubMed:8560401,
CC ECO:0000269|PubMed:8829639, ECO:0000269|PubMed:9798967}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Thrombophilia due to protein C deficiency, autosomal recessive
CC (THPH4) [MIM:612304]: A hemostatic disorder characterized by impaired
CC regulation of blood coagulation and a tendency to recurrent venous
CC thrombosis. It results in a thrombotic condition that can manifest as a
CC severe neonatal disorder or as a milder disorder with late-onset
CC thrombophilia. The severe form leads to neonatal death through massive
CC neonatal venous thrombosis. Often associated with ecchymotic skin
CC lesions which can turn necrotic called purpura fulminans, this disorder
CC is very rare. {ECO:0000269|PubMed:1511988, ECO:0000269|PubMed:1593215,
CC ECO:0000269|PubMed:1611081, ECO:0000269|PubMed:25618265,
CC ECO:0000269|PubMed:7841323, ECO:0000269|PubMed:7841324,
CC ECO:0000269|PubMed:7878626}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Calcium also binds, with stronger affinity to another
CC site, beyond the GLA domain. This GLA-independent binding site is
CC necessary for the recognition of the thrombin-thrombomodulin complex.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=S76088; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Protein C entry;
CC URL="https://en.wikipedia.org/wiki/Protein_C";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/proc/";
CC ---------------------------------------------------------------------------
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DR EMBL; X02750; CAA26528.1; -; mRNA.
DR EMBL; M11228; AAA60166.1; -; Genomic_DNA.
DR EMBL; M12712; AAA60165.1; -; Genomic_DNA.
DR EMBL; M12683; AAA60165.1; JOINED; Genomic_DNA.
DR EMBL; M12684; AAA60165.1; JOINED; Genomic_DNA.
DR EMBL; M12685; AAA60165.1; JOINED; Genomic_DNA.
DR EMBL; M12686; AAA60165.1; JOINED; Genomic_DNA.
DR EMBL; M12687; AAA60165.1; JOINED; Genomic_DNA.
DR EMBL; AF378903; AAK56377.1; -; Genomic_DNA.
DR EMBL; AK298454; BAG60669.1; -; mRNA.
DR EMBL; AC068282; AAY15044.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95320.1; -; Genomic_DNA.
DR EMBL; BC034377; AAH34377.1; -; mRNA.
DR EMBL; S58668; AAB26335.1; -; Genomic_DNA.
DR EMBL; K02059; AAA60164.1; -; mRNA.
DR EMBL; S76088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; S76090; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS2145.1; -. [P04070-1]
DR PIR; A22331; KXHU.
DR RefSeq; NP_000303.1; NM_000312.3. [P04070-1]
DR PDB; 1AUT; X-ray; 2.80 A; C=212-461, L=84-197.
DR PDB; 1LQV; X-ray; 1.60 A; C/D=43-75.
DR PDB; 3F6U; X-ray; 2.80 A; H=212-451, L=91-188.
DR PDB; 3JTC; X-ray; 1.60 A; C/D=43-75.
DR PDB; 4DT7; X-ray; 1.90 A; E/F=204-223.
DR PDB; 6M3B; X-ray; 2.20 A; A=212-461, D=43-197.
DR PDB; 6M3C; X-ray; 3.70 A; A/C/G=212-461, B/D/I=43-197.
DR PDBsum; 1AUT; -.
DR PDBsum; 1LQV; -.
DR PDBsum; 3F6U; -.
DR PDBsum; 3JTC; -.
DR PDBsum; 4DT7; -.
DR PDBsum; 6M3B; -.
DR PDBsum; 6M3C; -.
DR AlphaFoldDB; P04070; -.
DR SASBDB; P04070; -.
DR SMR; P04070; -.
DR BioGRID; 111608; 18.
DR ComplexPortal; CPX-6224; Active Protein C complex.
DR ELM; P04070; -.
DR IntAct; P04070; 11.
DR MINT; P04070; -.
DR STRING; 9606.ENSP00000234071; -.
DR BindingDB; P04070; -.
DR ChEMBL; CHEMBL4444; -.
DR DrugBank; DB13192; Antihemophilic factor human.
DR DrugBank; DB00025; Antihemophilic factor, human recombinant.
DR DrugBank; DB09131; Cupric Chloride.
DR DrugBank; DB09332; Kappadione.
DR DrugBank; DB13998; Lonoctocog alfa.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB13999; Moroctocog alfa.
DR DrugBank; DB13149; Protein S human.
DR DrugBank; DB00464; Sodium tetradecyl sulfate.
DR DrugBank; DB14738; Turoctocog alfa pegol.
DR DrugCentral; P04070; -.
DR GuidetoPHARMACOLOGY; 2396; -.
DR MEROPS; S01.218; -.
DR GlyConnect; 620; 17 N-Linked glycans (2 sites), 1 O-Linked glycan (1 site).
DR GlyGen; P04070; 7 sites, 43 N-linked glycans (5 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; P04070; -.
DR PhosphoSitePlus; P04070; -.
DR BioMuta; PROC; -.
DR DMDM; 131067; -.
DR jPOST; P04070; -.
DR MassIVE; P04070; -.
DR MaxQB; P04070; -.
DR PaxDb; P04070; -.
DR PeptideAtlas; P04070; -.
DR PRIDE; P04070; -.
DR ProteomicsDB; 4804; -.
DR ProteomicsDB; 51646; -. [P04070-1]
DR ABCD; P04070; 2 sequenced antibodies.
DR Antibodypedia; 791; 696 antibodies from 41 providers.
DR DNASU; 5624; -.
DR Ensembl; ENST00000234071.8; ENSP00000234071.4; ENSG00000115718.18. [P04070-1]
DR GeneID; 5624; -.
DR KEGG; hsa:5624; -.
DR MANE-Select; ENST00000234071.8; ENSP00000234071.4; NM_000312.4; NP_000303.1.
DR UCSC; uc002tok.4; human. [P04070-1]
DR CTD; 5624; -.
DR DisGeNET; 5624; -.
DR GeneCards; PROC; -.
DR HGNC; HGNC:9451; PROC.
DR HPA; ENSG00000115718; Tissue enriched (liver).
DR MalaCards; PROC; -.
DR MIM; 176860; phenotype.
DR MIM; 612283; gene.
DR MIM; 612304; phenotype.
DR neXtProt; NX_P04070; -.
DR OpenTargets; ENSG00000115718; -.
DR Orphanet; 64738; NON RARE IN EUROPE: Non rare thrombophilia.
DR Orphanet; 745; Severe hereditary thrombophilia due to congenital protein C deficiency.
DR PharmGKB; PA33799; -.
DR VEuPathDB; HostDB:ENSG00000115718; -.
DR eggNOG; ENOG502QQ3W; Eukaryota.
DR GeneTree; ENSGT00940000154505; -.
DR HOGENOM; CLU_006842_19_5_1; -.
DR InParanoid; P04070; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P04070; -.
DR TreeFam; TF327329; -.
DR BRENDA; 3.4.21.69; 2681.
DR PathwayCommons; P04070; -.
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-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SABIO-RK; P04070; -.
DR SignaLink; P04070; -.
DR SIGNOR; P04070; -.
DR BioGRID-ORCS; 5624; 6 hits in 1068 CRISPR screens.
DR ChiTaRS; PROC; human.
DR EvolutionaryTrace; P04070; -.
DR GeneWiki; Protein_C; -.
DR GenomeRNAi; 5624; -.
DR Pharos; P04070; Tchem.
DR PRO; PR:P04070; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P04070; protein.
DR Bgee; ENSG00000115718; Expressed in right lobe of liver and 101 other tissues.
DR ExpressionAtlas; P04070; baseline and differential.
DR Genevisible; P04070; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:ComplexPortal.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IPI:ComplexPortal.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:ComplexPortal.
DR GO; GO:0050819; P:negative regulation of coagulation; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:1903142; P:positive regulation of establishment of endothelial barrier; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:ComplexPortal.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 4.10.740.10; -; 1.
DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
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; IPR012224; Pept_S1A_FX.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001143; Factor_X; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00001; GLABLOOD.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57630; SSF57630; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood coagulation; Calcium;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disease variant; Disulfide bond; EGF-like domain; Endoplasmic reticulum;
KW Gamma-carboxyglutamic acid; Glycoprotein; Golgi apparatus; Hemostasis;
KW Hydrolase; Hydroxylation; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Secreted; Serine protease; Signal; Thrombophilia; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..42
FT /id="PRO_0000028107"
FT CHAIN 43..461
FT /note="Vitamin K-dependent protein C"
FT /id="PRO_0000028108"
FT CHAIN 43..197
FT /note="Vitamin K-dependent protein C light chain"
FT /id="PRO_0000028109"
FT CHAIN 200..461
FT /note="Vitamin K-dependent protein C heavy chain"
FT /id="PRO_0000028110"
FT PEPTIDE 200..211
FT /note="Activation peptide"
FT /id="PRO_0000028111"
FT DOMAIN 43..88
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 97..132
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 136..176
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 212..450
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 253
FT /note="Charge relay system"
FT ACT_SITE 299
FT /note="Charge relay system"
FT ACT_SITE 402
FT /note="Charge relay system"
FT SITE 211..212
FT /note="Cleavage; by thrombin"
FT MOD_RES 48
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 49
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 56
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 58
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 61
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 62
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 67
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 68
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 71
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:2991887"
FT MOD_RES 113
FT /note="(3R)-3-hydroxyaspartate"
FT /evidence="ECO:0000269|PubMed:2991887"
FT MOD_RES 347
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 19
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:2991887"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2991887"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine; atypical; partial"
FT /evidence="ECO:0000269|PubMed:1694179,
FT ECO:0000269|PubMed:2991887"
FT DISULFID 59..64
FT DISULFID 92..111
FT DISULFID 101..106
FT DISULFID 105..120
FT DISULFID 122..131
FT DISULFID 140..151
FT DISULFID 147..160
FT DISULFID 162..175
FT DISULFID 183..319
FT /note="Interchain (between light and heavy chains)"
FT DISULFID 238..254
FT DISULFID 373..387
FT DISULFID 398..426
FT VAR_SEQ 1
FT /note="M -> MAAGRRTCSISTTRPCASASRM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054393"
FT VAR_SEQ 133
FT /note="R -> RGEGERWMLAGGGAGLGPGWGRGTSTSCPRPPLPA (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054394"
FT VARIANT 14
FT /note="W -> G (in patients with PROC deficiency)"
FT /evidence="ECO:0000269|PubMed:8499565"
FT /id="VAR_006634"
FT VARIANT 32
FT /note="R -> C (in THPH3)"
FT /evidence="ECO:0000269|PubMed:8829639"
FT /id="VAR_006635"
FT VARIANT 38
FT /note="R -> W (in patients with PROC deficiency;
FT dbSNP:rs769900251)"
FT /evidence="ECO:0000269|PubMed:8324221"
FT /id="VAR_006636"
FT VARIANT 42
FT /note="R -> C (in patients with PROC deficiency;
FT dbSNP:rs774572099)"
FT /evidence="ECO:0000269|PubMed:8324221"
FT /id="VAR_006638"
FT VARIANT 42
FT /note="R -> H (in Malakoff; low anticoagulant activity;
FT dbSNP:rs369504169)"
FT /evidence="ECO:0000269|PubMed:8324221"
FT /id="VAR_006637"
FT VARIANT 42
FT /note="R -> S (in THPH3; type II; Osaka-10; alters
FT proteolytic processing so that S-42 is the N-terminus of
FT the mature protein; dbSNP:rs774572099)"
FT /evidence="ECO:0000269|PubMed:8560401"
FT /id="VAR_055074"
FT VARIANT 43
FT /note="A -> T (in dbSNP:rs767626189)"
FT /evidence="ECO:0000269|PubMed:7792728"
FT /id="VAR_006639"
FT VARIANT 49
FT /note="E -> D (in patients with PROC deficiency)"
FT /evidence="ECO:0000269|PubMed:7974343"
FT /id="VAR_006640"
FT VARIANT 51
FT /note="R -> C (in patients with PROC deficiency;
FT dbSNP:rs764546127)"
FT /id="VAR_006641"
FT VARIANT 57
FT /note="R -> G (in Yonago; defective anticoagulant
FT activity)"
FT /evidence="ECO:0000269|PubMed:8477066"
FT /id="VAR_006643"
FT VARIANT 57
FT /note="R -> Q (in patients with PROC deficiency;
FT dbSNP:rs574949343)"
FT /id="VAR_006644"
FT VARIANT 57
FT /note="R -> W (in THPH3; dbSNP:rs757583846)"
FT /evidence="ECO:0000269|PubMed:7792728,
FT ECO:0000269|PubMed:8499568"
FT /id="VAR_006642"
FT VARIANT 62
FT /note="E -> A (in THPH3; Vermont-1; dbSNP:rs121918148)"
FT /evidence="ECO:0000269|PubMed:1347706"
FT /id="VAR_006645"
FT VARIANT 70
FT /note="K -> E (in patients with PROC deficiency;
FT dbSNP:rs199469481)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074296"
FT VARIANT 76
FT /note="V -> M (in THPH3; Vermont-1; dbSNP:rs121918149)"
FT /evidence="ECO:0000269|PubMed:1347706"
FT /id="VAR_006646"
FT VARIANT 77
FT /note="D -> G (in THPH4; no effect on secretion; no effect
FT on catalytic activity in vitro)"
FT /evidence="ECO:0000269|PubMed:25618265"
FT /id="VAR_073145"
FT VARIANT 89
FT /note="G -> C (in patients with PROC deficiency)"
FT /evidence="ECO:0000269|PubMed:7605880"
FT /id="VAR_006647"
FT VARIANT 106
FT /note="C -> G (in patients with PROC deficiency;
FT dbSNP:rs199469479)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074297"
FT VARIANT 108
FT /note="H -> N (in patients with PROC deficiency; La Jolla-
FT 1; dbSNP:rs200234655)"
FT /id="VAR_006648"
FT VARIANT 109
FT /note="G -> R (in patients with PROC deficiency)"
FT /id="VAR_006649"
FT VARIANT 114..118
FT /note="Missing (in patients with PROC deficiency)"
FT /id="VAR_006650"
FT VARIANT 114
FT /note="G -> R (in THPH3; dbSNP:rs374476971)"
FT /evidence="ECO:0000269|PubMed:7792728"
FT /id="VAR_006651"
FT VARIANT 118
FT /note="F -> A (in patients with PROC deficiency; requires 2
FT nucleotide substitutions)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074298"
FT VARIANT 118
FT /note="F -> L (in patients with PROC deficiency;
FT dbSNP:rs1553424043)"
FT /id="VAR_006652"
FT VARIANT 119..124
FT /note="Missing (in patients with PROC deficiency; St Louis-
FT 2)"
FT /id="VAR_006653"
FT VARIANT 120..125
FT /note="Missing (in patients with PROC deficiency; St Louis-
FT 3)"
FT /id="VAR_006654"
FT VARIANT 144..145
FT /note="NG -> K (in THPH4; neonatal purpura fulminans)"
FT /evidence="ECO:0000269|PubMed:7841323"
FT /id="VAR_006655"
FT VARIANT 145
FT /note="G -> R (in THPH3; dbSNP:rs370813536)"
FT /evidence="ECO:0000269|PubMed:8292730"
FT /id="VAR_006656"
FT VARIANT 147
FT /note="C -> Y (in patients with PROC deficiency;
FT dbSNP:rs1247269491)"
FT /id="VAR_006657"
FT VARIANT 149
FT /note="H -> P (in patients with PROC deficiency;
FT dbSNP:rs121918159)"
FT /id="VAR_006658"
FT VARIANT 161
FT /note="S -> R (in patients with PROC deficiency;
FT dbSNP:rs1433503391)"
FT /id="VAR_006659"
FT VARIANT 163
FT /note="A -> E (in THPH4; drastically reduced secretion;
FT colocalizes with 26S proteasome)"
FT /evidence="ECO:0000269|PubMed:25618265"
FT /id="VAR_073146"
FT VARIANT 163
FT /note="A -> V (in THPH3; drastically reduced secretion;
FT colocalizes with 26S proteasome)"
FT /evidence="ECO:0000269|PubMed:25618265"
FT /id="VAR_073147"
FT VARIANT 175
FT /note="C -> Y (in patients with PROC deficiency;
FT dbSNP:rs199469474)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074299"
FT VARIANT 178
FT /note="A -> P (in THPH4; Clamart; dbSNP:rs1254257945)"
FT /evidence="ECO:0000269|PubMed:7878626"
FT /id="VAR_006660"
FT VARIANT 181
FT /note="F -> V (in patients with PROC deficiency;
FT dbSNP:rs199469470)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074300"
FT VARIANT 183
FT /note="C -> R (in patients with PROC deficiency;
FT dbSNP:rs748920874)"
FT /id="VAR_006661"
FT VARIANT 189
FT /note="R -> W (in patients with PROC deficiency; La Jolla-
FT 3; dbSNP:rs146922325)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_006662"
FT VARIANT 194
FT /note="R -> C (in patients with PROC deficiency;
FT dbSNP:rs371071104)"
FT /id="VAR_006663"
FT VARIANT 210
FT /note="P -> L (in THPH3; dbSNP:rs121918145)"
FT /evidence="ECO:0000269|PubMed:8292730"
FT /id="VAR_006664"
FT VARIANT 211
FT /note="R -> Q (in patients with PROC deficiency;
FT dbSNP:rs199469476)"
FT /evidence="ECO:0000269|PubMed:22545135,
FT ECO:0000269|PubMed:8499565"
FT /id="VAR_006666"
FT VARIANT 211
FT /note="R -> W (in THPH3; London-1/Tochigi;
FT dbSNP:rs121918143)"
FT /evidence="ECO:0000269|PubMed:2602169,
FT ECO:0000269|PubMed:8292730"
FT /id="VAR_006665"
FT VARIANT 220
FT /note="R -> P (in patients with PROC deficiency)"
FT /evidence="ECO:0000269|PubMed:7605880"
FT /id="VAR_006667"
FT VARIANT 220
FT /note="R -> Q (in THPH3; Vermont-3; dbSNP:rs121918153)"
FT /evidence="ECO:0000269|PubMed:1301959,
FT ECO:0000269|PubMed:1511989, ECO:0000269|PubMed:9798967"
FT /id="VAR_006669"
FT VARIANT 220
FT /note="R -> W (in THPH3; dbSNP:rs121918152)"
FT /evidence="ECO:0000269|PubMed:1511989,
FT ECO:0000269|PubMed:22545135"
FT /id="VAR_006668"
FT VARIANT 223
FT /note="S -> R (in patients with PROC deficiency;
FT dbSNP:rs199469483)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074301"
FT VARIANT 226
FT /note="Q -> H (in patients with PROC deficiency;
FT dbSNP:rs121918155)"
FT /id="VAR_006670"
FT VARIANT 240
FT /note="A -> G (in patients with PROC deficiency)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074302"
FT VARIANT 243
FT /note="I -> T (in THPH3; dbSNP:rs774584131)"
FT /evidence="ECO:0000269|PubMed:8292730"
FT /id="VAR_006671"
FT VARIANT 244
FT /note="H -> Y (in patients with PROC deficiency;
FT dbSNP:rs759557871)"
FT /evidence="ECO:0000269|PubMed:8499565"
FT /id="VAR_006672"
FT VARIANT 253
FT /note="H -> Q (in patients with PROC deficiency;
FT dbSNP:rs1458669732)"
FT /evidence="ECO:0000269|PubMed:8499565"
FT /id="VAR_006673"
FT VARIANT 265
FT /note="L -> F (in patients with PROC deficiency;
FT dbSNP:rs121918156)"
FT /id="VAR_006674"
FT VARIANT 271
FT /note="R -> Q (in Marseille; low anticoagulant activity;
FT dbSNP:rs752290840)"
FT /evidence="ECO:0000269|PubMed:8324221"
FT /id="VAR_006675"
FT VARIANT 271
FT /note="R -> W (in patients with PROC deficiency;
FT dbSNP:rs767112991)"
FT /id="VAR_006676"
FT VARIANT 272
FT /note="R -> C (in THPH3; dbSNP:rs121918154)"
FT /evidence="ECO:0000269|PubMed:1868249"
FT /id="VAR_006677"
FT VARIANT 281
FT /note="D -> DLD (in patients with PROC deficiency)"
FT /id="VAR_006678"
FT VARIANT 289
FT /note="P -> L (in THPH4; dbSNP:rs121918151)"
FT /evidence="ECO:0000269|PubMed:1511988"
FT /id="VAR_006679"
FT VARIANT 294
FT /note="S -> N (in Paris; low anticoagulant activity;
FT dbSNP:rs200721675)"
FT /evidence="ECO:0000269|PubMed:8324221"
FT /id="VAR_006680"
FT VARIANT 297
FT /note="D -> H (in THPH3; also found in patients with PROC
FT deficiency; decrease in vitamin-K dependent serine protease
FT activity; decreased Golgi localization; dbSNP:rs199469471)"
FT /evidence="ECO:0000269|PubMed:22545135,
FT ECO:0000269|PubMed:25748729"
FT /id="VAR_074303"
FT VARIANT 298
FT /note="N -> D (in patients with PROC deficiency)"
FT /id="VAR_006681"
FT VARIANT 301
FT /note="A -> T (in patients with PROC deficiency;
FT dbSNP:rs1343264503)"
FT /evidence="ECO:0000269|PubMed:7605880"
FT /id="VAR_006682"
FT VARIANT 301
FT /note="A -> V (in patients with PROC deficiency;
FT dbSNP:rs121918144)"
FT /id="VAR_006683"
FT VARIANT 309
FT /note="A -> T (in patients with PROC deficiency;
FT dbSNP:rs121918146)"
FT /id="VAR_006684"
FT VARIANT 312
FT /note="S -> L (in patients with PROC deficiency;
FT dbSNP:rs121918160)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_006685"
FT VARIANT 312
FT /note="S -> P (in a patient with PROC deficiency; sporadic
FT case)"
FT /evidence="ECO:0000269|PubMed:7919373"
FT /id="VAR_006686"
FT VARIANT 317
FT /note="P -> S (in patients with PROC deficiency; abolishes
FT Golgi localization)"
FT /evidence="ECO:0000269|PubMed:22531345"
FT /id="VAR_074304"
FT VARIANT 321
FT /note="P -> L (in THPH3; dbSNP:rs1321566264)"
FT /evidence="ECO:0000269|PubMed:8292730,
FT ECO:0000269|PubMed:8499565"
FT /id="VAR_006687"
FT VARIANT 324
FT /note="G -> R (in THPH3)"
FT /evidence="ECO:0000269|PubMed:7792728"
FT /id="VAR_006688"
FT VARIANT 327
FT /note="E -> V (in patients with PROC deficiency;
FT dbSNP:rs199469480)"
FT /evidence="ECO:0000269|PubMed:22545135"
FT /id="VAR_074305"
FT VARIANT 328
FT /note="R -> C (in THPH3; dbSNP:rs201907715)"
FT /evidence="ECO:0000269|PubMed:7792728,
FT ECO:0000269|PubMed:8499565"
FT /id="VAR_006689"
FT VARIANT 328
FT /note="R -> H (in THPH4; Muenchen)"
FT /evidence="ECO:0000269|PubMed:7878626"
FT /id="VAR_006690"
FT VARIANT 334
FT /note="G -> S (in THPH4; dbSNP:rs121918150)"
FT /evidence="ECO:0000269|PubMed:1593215"
FT /id="VAR_006691"
FT VARIANT 340
FT /note="T -> M (in THPH3; Vermont-2; dbSNP:rs766261022)"
FT /evidence="ECO:0000269|PubMed:8292730,
FT ECO:0000269|PubMed:9798967"
FT /id="VAR_006692"
FT VARIANT 343
FT /note="G -> D (in patients with PROC deficiency)"
FT /id="VAR_006693"
FT VARIANT 357
FT /note="T -> A (gain of function mutation; abolishes
FT glycosylation at N-313; decreases its catalytic activity;
FT significant loss of its protective effect on endothelial
FT barrier function; increased activation by thrombin)"
FT /evidence="ECO:0000269|PubMed:25651845"
FT /id="VAR_074306"
FT VARIANT 363
FT /note="Missing (in patients with PROC deficiency)"
FT /id="VAR_006694"
FT VARIANT 367
FT /note="V -> A (in THPH4; neonatal purpura fulminans;
FT dbSNP:rs767730328)"
FT /evidence="ECO:0000269|PubMed:7841324"
FT /id="VAR_006695"
FT VARIANT 369
FT /note="P -> L (in THPH3; Osaka-6; dbSNP:rs1211098698)"
FT /evidence="ECO:0000269|PubMed:7792728,
FT ECO:0000269|PubMed:7865674"
FT /id="VAR_006696"
FT VARIANT 385
FT /note="M -> I (in patients with PROC deficiency)"
FT /evidence="ECO:0000269|PubMed:8499565"
FT /id="VAR_006697"
FT VARIANT 388
FT /note="A -> T (in patients with PROC deficiency)"
FT /evidence="ECO:0000269|PubMed:8499565"
FT /id="VAR_006698"
FT VARIANT 388
FT /note="A -> V (in patients with PROC deficiency;
FT dbSNP:rs769277939)"
FT /evidence="ECO:0000269|PubMed:8499565"
FT /id="VAR_006699"
FT VARIANT 392
FT /note="G -> R (in THPH3; Osaka-9; dbSNP:rs756467027)"
FT /evidence="ECO:0000269|PubMed:7865674"
FT /id="VAR_006700"
FT VARIANT 394
FT /note="R -> W (in patients with PROC deficiency;
FT dbSNP:rs759316085)"
FT /id="VAR_006701"
FT VARIANT 401
FT /note="D -> N (in THPH3; La Jolla-2/Osaka-7 and -8;
FT dbSNP:rs142742242)"
FT /evidence="ECO:0000269|PubMed:7865674"
FT /id="VAR_006702"
FT VARIANT 418
FT /note="G -> D (in THPH4; Hong Kong-2)"
FT /evidence="ECO:0000269|PubMed:1611081"
FT /id="VAR_006703"
FT VARIANT 420
FT /note="V -> L (in THPH3; also found in patients with PROC
FT deficiency; decrease in vitamin-K dependent serine protease
FT activity; dbSNP:rs199469472)"
FT /evidence="ECO:0000269|PubMed:22545135,
FT ECO:0000269|PubMed:25748729"
FT /id="VAR_074307"
FT VARIANT 423
FT /note="G -> S (in THPH3)"
FT /evidence="ECO:0000269|PubMed:8398832"
FT /id="VAR_006704"
FT VARIANT 426
FT /note="C -> Y (in THPH3)"
FT /evidence="ECO:0000269|PubMed:8292730"
FT /id="VAR_006705"
FT VARIANT 433
FT /note="G -> S (in patients with PROC deficiency; Purmerend;
FT dbSNP:rs1266965698)"
FT /id="VAR_006706"
FT VARIANT 436
FT /note="T -> N (in THPH3)"
FT /evidence="ECO:0000269|PubMed:8829639"
FT /id="VAR_006707"
FT VARIANT 441
FT /note="Y -> H (in THPH3; Osaka-4; dbSNP:rs753436021)"
FT /evidence="ECO:0000269|PubMed:7865674"
FT /id="VAR_006708"
FT VARIANT 444
FT /note="W -> C (in THPH3; dbSNP:rs121918142)"
FT /evidence="ECO:0000269|PubMed:2437584"
FT /id="VAR_006709"
FT VARIANT 445
FT /note="I -> M (in patients with PROC deficiency;
FT dbSNP:rs121918157)"
FT /id="VAR_006710"
FT CONFLICT 106
FT /note="C -> Q (in Ref. 11; AAA60164)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="I -> IL (in Ref. 3; AAA60165)"
FT /evidence="ECO:0000305"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:1LQV"
FT HELIX 55..59
FT /evidence="ECO:0007829|PDB:1LQV"
FT HELIX 66..73
FT /evidence="ECO:0007829|PDB:1LQV"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6M3B"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:6M3B"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 236..244
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:6M3B"
FT HELIX 252..255
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 278..287
FT /evidence="ECO:0007829|PDB:6M3B"
FT TURN 293..295
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 301..307
FT /evidence="ECO:0007829|PDB:6M3B"
FT HELIX 323..328
FT /evidence="ECO:0007829|PDB:6M3B"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 336..341
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 357..359
FT /evidence="ECO:0007829|PDB:1AUT"
FT STRAND 361..368
FT /evidence="ECO:0007829|PDB:6M3B"
FT HELIX 370..376
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:6M3B"
FT TURN 399..403
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 405..410
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 413..422
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 424..427
FT /evidence="ECO:0007829|PDB:6M3B"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:6M3B"
FT HELIX 438..441
FT /evidence="ECO:0007829|PDB:6M3B"
FT HELIX 442..449
FT /evidence="ECO:0007829|PDB:6M3B"
SQ SEQUENCE 461 AA; 52071 MW; 3531B0AE5345B39A CRC64;
MWQLTSLLLF VATWGISGTP APLDSVFSSS ERAHQVLRIR KRANSFLEEL RHSSLERECI
EEICDFEEAK EIFQNVDDTL AFWSKHVDGD QCLVLPLEHP CASLCCGHGT CIDGIGSFSC
DCRSGWEGRF CQREVSFLNC SLDNGGCTHY CLEEVGWRRC SCAPGYKLGD DLLQCHPAVK
FPCGRPWKRM EKKRSHLKRD TEDQEDQVDP RLIDGKMTRR GDSPWQVVLL DSKKKLACGA
VLIHPSWVLT AAHCMDESKK LLVRLGEYDL RRWEKWELDL DIKEVFVHPN YSKSTTDNDI
ALLHLAQPAT LSQTIVPICL PDSGLAEREL NQAGQETLVT GWGYHSSREK EAKRNRTFVL
NFIKIPVVPH NECSEVMSNM VSENMLCAGI LGDRQDACEG DSGGPMVASF HGTWFLVGLV
SWGEGCGLLH NYGVYTKVSR YLDWIHGHIR DKEAPQKSWA P
