VKGC_HUMAN
ID VKGC_HUMAN Reviewed; 758 AA.
AC P38435; B4DMC5; E9PEE1; Q14415; Q6GU45;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Vitamin K-dependent gamma-carboxylase;
DE EC=4.1.1.90 {ECO:0000269|PubMed:17073445};
DE AltName: Full=Gamma-glutamyl carboxylase;
DE AltName: Full=Peptidyl-glutamate 4-carboxylase;
DE AltName: Full=Vitamin K gamma glutamyl carboxylase;
GN Name=GGCX; Synonyms=GC;
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), AND VARIANT GLN-325.
RX PubMed=1749935; DOI=10.1126/science.1749935;
RA Wu S.-M., Cheung W.-F., Frazier D., Stafford D.W.;
RT "Cloning and expression of the cDNA for human gamma-glutamyl carboxylase.";
RL Science 254:1634-1636(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9166845;
RA Wu S.-M., Stafford D.W., Frazier L.D., Fu Y.Y., High K.A., Chu K.,
RA Sanchez-Vega B., Solera J.;
RT "Genomic sequence and transcription start site for the human gamma-glutamyl
RT carboxylase.";
RL Blood 89:4058-4062(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Ying L., Lipsky J.J.;
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [7]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=10910912;
RA Tie J., Wu S.-M., Jin D., Nicchitta C.V., Stafford D.W.;
RT "A topological study of the human gamma-glutamyl carboxylase.";
RL Blood 96:973-978(2000).
RN [8]
RP PROPEPTIDE INTERACTION, AND MONOMER.
RX PubMed=11570873; DOI=10.1021/bi010332w;
RA Presnell S.R., Tripathy A., Lentz B.R., Jin D.Y., Stafford D.W.;
RT "A novel fluorescence assay to study propeptide interaction with gamma-
RT glutamyl carboxylase.";
RL Biochemistry 40:11723-11733(2001).
RN [9]
RP DISULFIDE BOND.
RX PubMed=12963724; DOI=10.1074/jbc.m309164200;
RA Tie J.K., Mutucumarana V.P., Straight D.L., Carrick K.L., Pope R.M.,
RA Stafford D.W.;
RT "Determination of disulfide bond assignment of human vitamin K-dependent
RT gamma-glutamyl carboxylase by matrix-assisted laser desorption/ionization
RT time-of-flight mass spectrometry.";
RL J. Biol. Chem. 278:45468-45475(2003).
RN [10]
RP REVIEW.
RX PubMed=16011462; DOI=10.1146/annurev.nutr.25.050304.092713;
RA Berkner K.L.;
RT "The vitamin K-dependent carboxylase.";
RL Annu. Rev. Nutr. 25:127-149(2005).
RN [11]
RP MUTAGENESIS OF HIS-160; LYS-218; HIS-287 AND HIS-381, ACTIVE SITE,
RP FUNCTION, CATALYTIC ACTIVITY, PH DEPENDENCE, AND REACTION MECHANISM.
RX PubMed=17073445; DOI=10.1021/bi0609523;
RA Rishavy M.A., Hallgren K.W., Yakubenko A.V., Shtofman R.L., Runge K.W.,
RA Berkner K.L.;
RT "Bronsted analysis reveals Lys218 as the carboxylase active site base that
RT deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein
RT carboxylation.";
RL Biochemistry 45:13239-13248(2006).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-459 AND ASN-550.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
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 [16]
RP VARIANT VKCFD1 ARG-394.
RX PubMed=9845520;
RA Brenner B., Sanchez-Vega B., Wu S.M., Lanir N., Stafford D.W., Solera J.;
RT "A missense mutation in gamma-glutamyl carboxylase gene causes combined
RT deficiency of all vitamin K-dependent blood coagulation factors.";
RL Blood 92:4554-4559(1998).
RN [17]
RP VARIANT VKCFD1 SER-501.
RX PubMed=11071668;
RA Spronk H.M.H., Farah R.A., Buchanan G.R., Vermeer C., Soute B.A.M.;
RT "Novel mutation in the gamma-glutamyl carboxylase gene resulting in
RT congenital combined deficiency of all vitamin K-dependent blood coagulation
RT factors.";
RL Blood 96:3650-3652(2000).
RN [18]
RP CHARACTERIZATION OF VARIANT VKCFD1 ARG-394.
RX PubMed=10934213; DOI=10.1074/jbc.m006808200;
RA Mutucumarana V.P., Stafford D.W., Stanley T.B., Jin D.-Y., Solera J.,
RA Brenner B., Azerad R., Wu S.-M.;
RT "Expression and characterization of the naturally occurring mutation L394R
RT in human gamma-glutamyl carboxylase.";
RL J. Biol. Chem. 275:32572-32577(2000).
RN [19]
RP VARIANT VKCFD1 PRO-485.
RX PubMed=15287948; DOI=10.1111/j.1365-2141.2004.05071.x;
RA Rost S., Fregin A., Koch D., Compes M., Mueller C.R., Oldenburg J.;
RT "Compound heterozygous mutations in the gamma-glutamyl carboxylase gene
RT cause combined deficiency of all vitamin K-dependent blood coagulation
RT factors.";
RL Br. J. Haematol. 126:546-549(2004).
RN [20]
RP VARIANTS PXEL-MCFD SER-299; CYS-476; HIS-476; SER-493 AND ARG-558.
RX PubMed=17110937; DOI=10.1038/sj.jid.5700610;
RA Vanakker O.M., Martin L., Gheduzzi D., Leroy B.P., Loeys B.L., Guerci V.I.,
RA Matthys D., Terry S.F., Coucke P.J., Pasquali-Ronchetti I., De Paepe A.;
RT "Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple
RT coagulation factor deficiency represents a separate genetic entity.";
RL J. Invest. Dermatol. 127:581-587(2007).
CC -!- FUNCTION: Mediates the vitamin K-dependent carboxylation of glutamate
CC residues to calcium-binding gamma-carboxyglutamate (Gla) residues with
CC the concomitant conversion of the reduced hydroquinone form of vitamin
CC K to vitamin K epoxide. {ECO:0000269|PubMed:17073445}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2,3-epoxyphylloquinone + 4-carboxy-L-glutamyl-[protein] + H(+)
CC + H2O = CO2 + L-glutamyl-[protein] + O2 + phylloquinol;
CC Xref=Rhea:RHEA:45140, Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:11094,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15759, ChEBI:CHEBI:16526, ChEBI:CHEBI:28433,
CC ChEBI:CHEBI:29973, ChEBI:CHEBI:84990; EC=4.1.1.90;
CC Evidence={ECO:0000269|PubMed:17073445};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:17073445};
CC -!- SUBUNIT: Monomer. May interact with CALU (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10910912}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10910912}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P38435-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P38435-2; Sequence=VSP_046179;
CC -!- DISEASE: Combined deficiency of vitamin K-dependent clotting factors 1
CC (VKCFD1) [MIM:277450]: VKCFD leads to a bleeding tendency that is
CC usually reversed by oral administration of vitamin K.
CC {ECO:0000269|PubMed:10934213, ECO:0000269|PubMed:11071668,
CC ECO:0000269|PubMed:15287948, ECO:0000269|PubMed:9845520}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Pseudoxanthoma elasticum-like disorder with multiple
CC coagulation factor deficiency (PXEL-MCFD) [MIM:610842]: Characterized
CC by hyperlaxity of the skin involving the entire body. Important
CC phenotypic differences with classical PXE include much more severe skin
CC laxity with spreading toward the trunk and limbs with thick, leathery
CC skin folds rather than confinement to flexural areas, and no decrease
CC in visual acuity. Moreover, detailed electron microscopic analyses
CC revealed that alterations of elastic fibers as well as their
CC mineralization are slightly different from those in classic PXE.
CC {ECO:0000269|PubMed:17110937}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The vitamin K-dependent protein substrates of
CC carboxylase have usually a propeptide that binds to a high-affinity
CC site on the carboxylase. CO(2), O(2) and reduced vitamin K are
CC cosubstrates.
CC -!- SIMILARITY: Belongs to the vitamin K-dependent gamma-carboxylase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M81592; AAA58643.1; -; mRNA.
DR EMBL; U65896; AAB39832.1; -; Genomic_DNA.
DR EMBL; L17128; AAA91834.1; -; mRNA.
DR EMBL; AK297397; BAG59837.1; -; mRNA.
DR EMBL; AC016753; AAY24340.1; -; Genomic_DNA.
DR EMBL; BC013979; AAH13979.1; -; mRNA.
DR CCDS; CCDS1978.1; -. [P38435-1]
DR CCDS; CCDS46353.1; -. [P38435-2]
DR PIR; A39283; A39283.
DR RefSeq; NP_000812.2; NM_000821.6. [P38435-1]
DR RefSeq; NP_001135741.1; NM_001142269.3. [P38435-2]
DR AlphaFoldDB; P38435; -.
DR BioGRID; 108945; 85.
DR IntAct; P38435; 30.
DR MINT; P38435; -.
DR STRING; 9606.ENSP00000233838; -.
DR ChEMBL; CHEMBL2012; -.
DR DrugBank; DB01125; Anisindione.
DR DrugBank; DB00100; Coagulation Factor IX (Recombinant).
DR DrugBank; DB13152; Coagulation Factor IX Human.
DR DrugBank; DB00036; Coagulation factor VIIa Recombinant Human.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB09332; Kappadione.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB01022; Phylloquinone.
DR DrugCentral; P38435; -.
DR GlyConnect; 1894; 1 N-Linked glycan (1 site).
DR GlyGen; P38435; 5 sites, 1 N-linked glycan (1 site), 2 O-linked glycans (1 site).
DR iPTMnet; P38435; -.
DR PhosphoSitePlus; P38435; -.
DR BioMuta; GGCX; -.
DR DMDM; 84028279; -.
DR EPD; P38435; -.
DR jPOST; P38435; -.
DR MassIVE; P38435; -.
DR MaxQB; P38435; -.
DR PaxDb; P38435; -.
DR PeptideAtlas; P38435; -.
DR PRIDE; P38435; -.
DR ProteomicsDB; 19868; -.
DR ProteomicsDB; 55296; -. [P38435-1]
DR Antibodypedia; 16941; 287 antibodies from 35 providers.
DR DNASU; 2677; -.
DR Ensembl; ENST00000233838.9; ENSP00000233838.3; ENSG00000115486.13. [P38435-1]
DR Ensembl; ENST00000430215.7; ENSP00000408045.3; ENSG00000115486.13. [P38435-2]
DR GeneID; 2677; -.
DR KEGG; hsa:2677; -.
DR MANE-Select; ENST00000233838.9; ENSP00000233838.3; NM_000821.7; NP_000812.2.
DR UCSC; uc002sps.4; human. [P38435-1]
DR CTD; 2677; -.
DR DisGeNET; 2677; -.
DR GeneCards; GGCX; -.
DR HGNC; HGNC:4247; GGCX.
DR HPA; ENSG00000115486; Tissue enriched (liver).
DR MalaCards; GGCX; -.
DR MIM; 137167; gene.
DR MIM; 277450; phenotype.
DR MIM; 610842; phenotype.
DR neXtProt; NX_P38435; -.
DR OpenTargets; ENSG00000115486; -.
DR Orphanet; 91135; Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency.
DR Orphanet; 98434; Hereditary combined deficiency of vitamin K-dependent clotting factors.
DR Orphanet; 436274; Pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa.
DR PharmGKB; PA28660; -.
DR VEuPathDB; HostDB:ENSG00000115486; -.
DR eggNOG; ENOG502QRU2; Eukaryota.
DR GeneTree; ENSGT00390000014909; -.
DR HOGENOM; CLU_020495_0_0_1; -.
DR InParanoid; P38435; -.
DR OMA; TYLNHYY; -.
DR OrthoDB; 304818at2759; -.
DR PhylomeDB; P38435; -.
DR TreeFam; TF323879; -.
DR BioCyc; MetaCyc:HS03897-MON; -.
DR BRENDA; 4.1.1.90; 2681.
DR PathwayCommons; P38435; -.
DR Reactome; R-HSA-159740; Gamma-carboxylation of protein precursors.
DR Reactome; R-HSA-9673240; Defective gamma-carboxylation of F9.
DR SignaLink; P38435; -.
DR SIGNOR; P38435; -.
DR BioGRID-ORCS; 2677; 13 hits in 1083 CRISPR screens.
DR ChiTaRS; GGCX; human.
DR GeneWiki; Gamma-glutamyl_carboxylase; -.
DR GenomeRNAi; 2677; -.
DR Pharos; P38435; Tclin.
DR PRO; PR:P38435; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P38435; protein.
DR Bgee; ENSG00000115486; Expressed in buccal mucosa cell and 205 other tissues.
DR ExpressionAtlas; P38435; baseline and differential.
DR Genevisible; P38435; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0008488; F:gamma-glutamyl carboxylase activity; IBA:GO_Central.
DR GO; GO:0019842; F:vitamin binding; IBA:GO_Central.
DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR GO; GO:0017187; P:peptidyl-glutamic acid carboxylation; IBA:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR011020; HTTM.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR InterPro; IPR007782; VKG_COase.
DR PANTHER; PTHR12639; PTHR12639; 1.
DR Pfam; PF05090; VKG_Carbox; 1.
DR SMART; SM00752; HTTM; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Lyase; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:21406692"
FT CHAIN 2..758
FT /note="Vitamin K-dependent gamma-carboxylase"
FT /id="PRO_0000191823"
FT TOPO_DOM 2..60
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..81
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..113
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..136
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 158..292
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 314..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..758
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..758
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 734..751
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 218
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:17073445"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:21406692"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 550
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT DISULFID 99..450
FT /evidence="ECO:0000269|PubMed:12963724"
FT VAR_SEQ 15..71
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046179"
FT VARIANT 299
FT /note="F -> S (in PXEL-MCFD; dbSNP:rs121909677)"
FT /evidence="ECO:0000269|PubMed:17110937"
FT /id="VAR_032979"
FT VARIANT 325
FT /note="R -> Q (in dbSNP:rs699664)"
FT /evidence="ECO:0000269|PubMed:1749935"
FT /id="VAR_005780"
FT VARIANT 394
FT /note="L -> R (in VKCFD1; affects glutamate binding;
FT dbSNP:rs121909675)"
FT /evidence="ECO:0000269|PubMed:10934213,
FT ECO:0000269|PubMed:9845520"
FT /id="VAR_005781"
FT VARIANT 476
FT /note="R -> C (in PXEL-MCFD; dbSNP:rs121909681)"
FT /evidence="ECO:0000269|PubMed:17110937"
FT /id="VAR_032980"
FT VARIANT 476
FT /note="R -> H (in PXEL-MCFD; dbSNP:rs121909682)"
FT /evidence="ECO:0000269|PubMed:17110937"
FT /id="VAR_032981"
FT VARIANT 485
FT /note="R -> P (in VKCFD1; dbSNP:rs121909676)"
FT /evidence="ECO:0000269|PubMed:15287948"
FT /id="VAR_021826"
FT VARIANT 493
FT /note="W -> S (in PXEL-MCFD; dbSNP:rs121909679)"
FT /evidence="ECO:0000269|PubMed:17110937"
FT /id="VAR_032982"
FT VARIANT 501
FT /note="W -> S (in VKCFD1; dbSNP:rs28928872)"
FT /evidence="ECO:0000269|PubMed:11071668"
FT /id="VAR_015218"
FT VARIANT 558
FT /note="G -> R (in PXEL-MCFD; dbSNP:rs121909678)"
FT /evidence="ECO:0000269|PubMed:17110937"
FT /id="VAR_032983"
FT MUTAGEN 160
FT /note="H->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:17073445"
FT MUTAGEN 218
FT /note="K->A: No activity."
FT /evidence="ECO:0000269|PubMed:17073445"
FT MUTAGEN 287
FT /note="H->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:17073445"
FT MUTAGEN 381
FT /note="H->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:17073445"
FT CONFLICT 400
FT /note="D -> N (in Ref. 3; AAA91834)"
FT /evidence="ECO:0000305"
FT CONFLICT 659
FT /note="F -> S (in Ref. 4; BAG59837)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 758 AA; 87561 MW; 720D5B08E9B558C8 CRC64;
MAVSAGSART SPSSDKVQKD KAELISGPRQ DSRIGKLLGF EWTDLSSWRR LVTLLNRPTD
PASLAVFRFL FGFLMVLDIP QERGLSSLDR KYLDGLDVCR FPLLDALRPL PLDWMYLVYT
IMFLGALGMM LGLCYRISCV LFLLPYWYVF LLDKTSWNNH SYLYGLLAFQ LTFMDANHYW
SVDGLLNAHR RNAHVPLWNY AVLRGQIFIV YFIAGVKKLD ADWVEGYSME YLSRHWLFSP
FKLLLSEELT SLLVVHWGGL LLDLSAGFLL FFDVSRSIGL FFVSYFHCMN SQLFSIGMFS
YVMLASSPLF CSPEWPRKLV SYCPRRLQQL LPLKAAPQPS VSCVYKRSRG KSGQKPGLRH
QLGAAFTLLY LLEQLFLPYS HFLTQGYNNW TNGLYGYSWD MMVHSRSHQH VKITYRDGRT
GELGYLNPGV FTQSRRWKDH ADMLKQYATC LSRLLPKYNV TEPQIYFDIW VSINDRFQQR
IFDPRVDIVQ AAWSPFQRTS WVQPLLMDLS PWRAKLQEIK SSLDNHTEVV FIADFPGLHL
ENFVSEDLGN TSIQLLQGEV TVELVAEQKN QTLREGEKMQ LPAGEYHKVY TTSPSPSCYM
YVYVNTTELA LEQDLAYLQE LKEKVENGSE TGPLPPELQP LLEGEVKGGP EPTPLVQTFL
RRQQRLQEIE RRRNTPFHER FFRFLLRKLY VFRRSFLMTC ISLRNLILGR PSLEQLAQEV
TYANLRPFEA VGELNPSNTD SSHSNPPESN PDPVHSEF
