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 02-SEP-2026, entry version 211. DE RecName: Full=Vitamin K-dependent gamma-carboxylase; DE Short=VKGC {ECO:0000303|PubMed:39880037}; DE EC=4.1.1.90 {ECO:0000269|PubMed:17073445, ECO:0000269|PubMed:39880037, ECO:0000269|PubMed:39880952}; DE AltName: Full=Gamma-glutamyl carboxylase {ECO:0000303|PubMed:39880952}; 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; DOI=10.1182/blood.v89.11.4058; 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; DOI=10.1182/blood.v96.3.973; 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] {ECO:0007744|PDB:9BUM, ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX} RP STRUCTURE BY ELECTRON MICROSCOPY (2.95 ANGSTROMS) IN COMPLEXES WITH VITAMIN RP K HYDROQUINONE; BGLAP AND CHOLESTEROL, FUNCTION, CATALYTIC ACTIVITY, RP ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION RP AT ASN-550; ASN-570 AND ASN-605, DISULFIDE BONDS, AND MUTAGENESIS OF RP HIS-160; LYS-218 AND MET-401. RX PubMed=39880952; DOI=10.1038/s41586-024-08484-9; RA Wang R., Chen B., Elghobashi-Meinhardt N., Tie J.K., Ayala A., Zhou N., RA Qi X.; RT "Structure and mechanism of vitamin-K-dependent gamma-glutamyl RT carboxylase."; RL Nature 639:808-815(2025). RN [17] {ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, ECO:0007744|PDB:9BVR} RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 27-758 IN COMPLEXES RP WITH VITAMIN K HYDROQUINONE; PRRG2; PROC; F9 AND F10, FUNCTION, CATALYTIC RP ACTIVITY, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, RP DISULFIDE BONDS, AND MUTAGENESIS OF HIS-160; PHE-299; TYR-395; MET-401; RP MET-402; TYR-601 AND TYR-603. RX PubMed=39880037; DOI=10.1038/s41586-025-08648-1; RA Cao Q., Ammerman A., Saimi M., Lin Z., Shen G., Chen H., Sun J., Chai M., RA Liu S., Hsu F.F., Krezel A.M., Gross M.L., Xu J., Garcia B.A., Liu B., RA Li W.; RT "Molecular basis of vitamin-K-driven gamma-carboxylation at the membrane RT interface."; RL Nature 639:816-824(2025). RN [18] RP VARIANT VKCFD1 ARG-394. RX PubMed=9845520; DOI=10.1182/blood.v92.12.4554; 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 [19] RP VARIANT VKCFD1 SER-501. RX PubMed=11071668; DOI=10.1182/blood.v96.10.3650; 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 [20] 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 [21] 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 [22] RP VARIANTS PXECD SER-299; CYS-476; HIS-476; SER-493 AND ARG-558, AND RP INVOLVEMENT IN PXECD. 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 epoxidation of vitamin K hydroquinone to vitamin K CC epoxide (PubMed:17073445, PubMed:39880952, PubMed:39880037). Couples CC epoxidation and carboxylation in the same active site (PubMed:39880952, CC PubMed:39880037). Catalyzes gamma-carboxylation of blood coagulation CC factors (F2, F7, F9 and F10) and anticoagulants such as PROC, which are CC essential for thrombosis(PubMed:17073445, PubMed:39880037). Catalyzes CC gamma-carboxylation of osteocalcin/BGLAP, which is essential for bone CC metabolism (PubMed:17073445, PubMed:39880952). Catalyzes gamma- CC carboxylation of matrix Gla protein (MGP) and other transmembrane CC gamma-Gla proteins such as PRRG2, which are essential for calcium CC homeostasis and haemostasis (PubMed:17073445, PubMed:39880037). CC {ECO:0000269|PubMed:17073445, ECO:0000269|PubMed:39880037, CC ECO:0000269|PubMed:39880952}. CC -!- CATALYTIC ACTIVITY: CC Reaction=4-carboxy-L-glutamyl-[protein] + 2,3-epoxyphylloquinone + H2O CC + H(+) = phylloquinol + L-glutamyl-[protein] + CO2 + O2; 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, ECO:0000269|PubMed:39880037, CC ECO:0000269|PubMed:39880952}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45142; CC Evidence={ECO:0000269|PubMed:17073445}; CC -!- ACTIVITY REGULATION: Interacts with lipids such as phosphatidylcholine CC and cholesterol; this interaction is required for optimal carboxylation CC activity. {ECO:0000269|PubMed:39880037, ECO:0000269|PubMed:39880952}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 7. {ECO:0000269|PubMed:17073445}; CC -!- SUBUNIT: Monomer (PubMed:11570873, PubMed:39880952, PubMed:39880037). CC May interact with CALU (By similarity). {ECO:0000250|UniProtKB:O88496, CC ECO:0000269|PubMed:11570873, ECO:0000269|PubMed:39880037, CC ECO:0000269|PubMed:39880952}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:10910912}; Multi-pass membrane protein CC {ECO:0000269|PubMed:10910912, ECO:0000269|PubMed:39880037, CC ECO:0000269|PubMed:39880952}. 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 (PXECD) [MIM:610842]: An autosomal CC recessive disorder characterized by hyperlaxity of the skin involving CC the entire body. Important phenotypic differences with classical CC pseudoxanthoma elasticum include much more severe skin laxity with CC spreading toward the trunk and limbs with thick, leathery skin folds CC rather than confinement to flexural areas, and no decrease in visual CC acuity. Detailed electron microscopic analyses revealed that CC alterations of elastic fibers as well as their mineralization are CC slightly different from those in classic pseudoxanthoma elasticum. 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 have an N- CC terminal propeptide that is recognized by the carboxylase CC (PubMed:39880952, PubMed:39880037). {ECO:0000269|PubMed:39880037, CC ECO:0000269|PubMed:39880952}. 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_000821.7. [P38435-1] DR RefSeq; NP_001135741.1; NM_001142269.4. [P38435-2] DR PDB; 9BUM; EM; 3.63 A; A=1-758. DR PDB; 9BUR; EM; 2.95 A; A=1-758. DR PDB; 9BUX; EM; 3.06 A; A=1-758. DR PDB; 9BVK; EM; 3.60 A; A=27-758. DR PDB; 9BVL; EM; 3.40 A; A=27-758. DR PDB; 9BVM; EM; 3.40 A; A=27-758. DR PDB; 9BVO; EM; 4.40 A; A=27-758. DR PDB; 9BVP; EM; 3.30 A; A=26-758. DR PDB; 9BVQ; EM; 3.30 A; A=27-758. DR PDB; 9BVR; EM; 3.50 A; A=27-758. DR PDB; 9L1Y; EM; 3.46 A; A=1-758. DR PDB; 9L20; EM; 2.82 A; A=32-729. DR PDB; 9L21; EM; 2.62 A; A=32-729. DR PDB; 9L23; EM; 2.62 A; A=32-729. DR PDB; 9L24; EM; 3.10 A; A=32-729. DR PDB; 9L25; EM; 2.41 A; A=32-729. DR PDB; 9L54; EM; 3.04 A; A=32-729. DR PDB; 9L6Q; EM; 2.78 A; A=1-758. DR PDB; 9L6R; EM; 2.59 A; A=1-758. DR PDB; 9L6S; EM; 2.58 A; A=1-758. DR PDB; 9MQB; EM; 3.37 A; A=1-758. DR PDB; 9MQC; EM; 3.13 A; A=1-758. DR PDB; 9MQE; EM; 3.56 A; A=1-758. DR PDB; 9WF2; EM; 2.94 A; A=32-728. DR PDB; 9WF3; EM; 2.65 A; A=32-728. DR PDB; 9WF9; EM; 2.83 A; A=32-728. DR PDB; 9WFC; EM; 3.33 A; A=32-728. DR PDB; 9WFN; EM; 2.94 A; A=32-727. DR AlphaFoldDB; P38435; -. DR EMDB; EMD-44912; -. DR EMDB; EMD-44917; -. DR EMDB; EMD-44924; -. DR EMDB; EMD-44935; -. DR EMDB; EMD-44936; -. DR EMDB; EMD-44937; -. DR EMDB; EMD-44939; -. DR EMDB; EMD-44940; -. DR EMDB; EMD-44941; -. DR EMDB; EMD-44942; -. DR EMDB; EMD-48519; -. DR EMDB; EMD-48520; -. DR EMDB; EMD-48522; -. DR EMDB; EMD-62758; -. DR EMDB; EMD-62764; -. DR EMDB; EMD-62765; -. DR EMDB; EMD-62767; -. DR EMDB; EMD-62768; -. DR EMDB; EMD-62769; -. DR EMDB; EMD-62822; -. DR EMDB; EMD-62862; -. DR EMDB; EMD-62863; -. DR EMDB; EMD-62864; -. DR EMDB; EMD-65921; -. DR EMDB; EMD-65922; -. DR EMDB; EMD-65923; -. DR EMDB; EMD-65925; -. DR EMDB; EMD-65930; -. DR EMDB; EMD-65932; -. DR SMR; P38435; -. DR BioGRID; 108945; 104. DR FunCoup; P38435; 941. DR IntAct; P38435; 67. DR MINT; P38435; -. DR NDEx; IQUERY-CP-GGCX; 5 NDEx IQuery Curated Pathways. 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; DB00142; Glutamic acid. DR DrugBank; DB09332; Kappadione. DR DrugBank; DB00170; Menadione. DR DrugBank; DB01022; Phylloquinone. DR DrugCentral; P38435; -. DR GlyConnect; P38435; 1 N-Linked glycan (1 site). DR GlyCosmos; P38435; 4 sites, 3 glycans. DR GlyGen; P38435; 5 sites, 5 N-linked glycans (1 site), 2 O-linked glycans (1 site). DR iPTMnet; P38435; -. DR PhosphoSitePlus; P38435; -. DR SwissPalm; P38435; -. DR BioMuta; GGCX; -. DR DMDM; 84028279; -. DR jPOST; P38435; -. DR MassIVE; P38435; -. DR PaxDb; 9606-ENSP00000233838; -. DR PeptideAtlas; P38435; -. DR ProteomicsDB; 19868; -. DR ProteomicsDB; 55296; -. [P38435-1] DR Pumba; P38435; -. DR Antibodypedia; 16941; 280 antibodies from 35 providers. DR DNASU; 2677; -. DR Ensembl; ENST00000233838.9; ENSP00000233838.3; ENSG00000115486.14. [P38435-1] DR Ensembl; ENST00000430215.7; ENSP00000408045.3; ENSG00000115486.14. [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 AGR; HGNC:4247; -. DR ClinPGx; PA28660; -. 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 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 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; 206689at2759; -. DR PAN-GO; P38435; 3 GO annotations based on evolutionary models. DR PhylomeDB; P38435; -. DR BioCyc; MetaCyc:HS03897-MONOMER; -. 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 Agora; ENSG00000115486; -. DR BioGRID-ORCS; 2677; 14 hits in 1167 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 207 other cell types or tissues. DR ExpressionAtlas; P38435; baseline and differential. DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:Ensembl. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProt. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0008488; F:gamma-glutamyl carboxylase activity; IDA:UniProt. DR GO; GO:0019842; F:vitamin binding; IBA:GO_Central. DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc. DR GO; GO:1903011; P:negative regulation of bone development; IEA:Ensembl. DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IDA:UniProt. DR GO; GO:2000225; P:negative regulation of testosterone biosynthetic process; IEA:Ensembl. DR GO; GO:0017187; P:peptidyl-glutamic acid carboxylation; TAS:Reactome. DR GO; GO:0051604; P:protein maturation; IEA:Ensembl. DR GO; GO:0036211; P:protein modification process; TAS:ProtInc. DR GO; GO:0042373; P:vitamin K metabolic process; IDA:UniProt. DR Gene3D; 2.60.120.10; Jelly Rolls; 1. DR InterPro; IPR011020; HTTM-like. DR InterPro; IPR053934; HTTM_dom. DR InterPro; IPR014710; RmlC-like_jellyroll. DR InterPro; IPR011051; RmlC_Cupin_sf. DR InterPro; IPR007782; VKG_COase. DR InterPro; IPR053935; VKGC_lumenal_dom. DR PANTHER; PTHR12639; VITAMIN K-DEPENDENT GAMMA-CARBOXYLASE; 1. DR PANTHER; PTHR12639:SF6; VITAMIN K-DEPENDENT GAMMA-CARBOXYLASE; 1. DR Pfam; PF05090; HTTM; 1. DR Pfam; PF22777; VKGC_lumenal_dom; 1. DR SMART; SM00752; HTTM; 1. DR SUPFAM; SSF51182; RmlC-like cupins; 1. DR PDBsum; 9BUM; -. DR PDBsum; 9BUR; -. DR PDBsum; 9BUX; -. DR PDBsum; 9BVK; -. DR PDBsum; 9BVL; -. DR PDBsum; 9BVM; -. DR PDBsum; 9BVO; -. DR PDBsum; 9BVP; -. DR PDBsum; 9BVQ; -. DR PDBsum; 9BVR; -. DR PDBsum; 9L1Y; -. DR PDBsum; 9L20; -. DR PDBsum; 9L21; -. DR PDBsum; 9L23; -. DR PDBsum; 9L24; -. DR PDBsum; 9L25; -. DR PDBsum; 9L54; -. DR PDBsum; 9L6Q; -. DR PDBsum; 9L6R; -. DR PDBsum; 9L6S; -. DR PDBsum; 9MQB; -. DR PDBsum; 9MQC; -. DR PDBsum; 9MQE; -. DR PDBsum; 9WF2; -. DR PDBsum; 9WF3; -. DR PDBsum; 9WF9; -. DR PDBsum; 9WFC; -. DR PDBsum; 9WFN; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Disease variant; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Lipid-binding; Lyase; KW Membrane; Proteomics identification; Reference proteome; Transmembrane; KW 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..64 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 65..80 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 81..114 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 115..131 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 132..136 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 137..150 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 151..161 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 162..173 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 174..201 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 202..216 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 217..251 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 252..272 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 273..276 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 277..289 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 290..295 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 296..305 FT /note="Helical; Name=8" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 306..364 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TRANSMEM 365..377 FT /note="Helical; Name=9" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT TOPO_DOM 378..758 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUM, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX, FT ECO:0007744|PDB:9BVK, ECO:0007744|PDB:9BVL, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" 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 735..747 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 BINDING 373 FT /ligand="cholesterol" FT /ligand_id="ChEBI:CHEBI:16113" FT /evidence="ECO:0000269|PubMed:39880952, FT ECO:0007744|PDB:9BUM, ECO:0007744|PDB:9BUX" FT BINDING 374 FT /ligand="cholesterol" FT /ligand_id="ChEBI:CHEBI:16113" FT /evidence="ECO:0000269|PubMed:39880952, FT ECO:0007744|PDB:9BUM, ECO:0007744|PDB:9BUX" 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 ECO:0000269|PubMed:39880037, ECO:0007744|PDB:9BVK, FT ECO:0007744|PDB:9BVM, ECO:0007744|PDB:9BVO, FT ECO:0007744|PDB:9BVP, ECO:0007744|PDB:9BVQ, FT ECO:0007744|PDB:9BVR" FT CARBOHYD 550 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:39880952, ECO:0007744|PDB:9BUR, FT ECO:0007744|PDB:9BUX" FT CARBOHYD 570 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:39880952" FT CARBOHYD 605 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:39880952, FT ECO:0007744|PDB:9BUR, ECO:0007744|PDB:9BUX" FT DISULFID 99..450 FT /evidence="ECO:0000269|PubMed:12963724, FT ECO:0000269|PubMed:39880037, ECO:0000269|PubMed:39880952, FT ECO:0007744|PDB:9BUM, ECO:0007744|PDB:9BUR, FT ECO:0007744|PDB:9BUX, ECO:0007744|PDB:9BVK, FT ECO:0007744|PDB:9BVL, ECO:0007744|PDB:9BVM, FT ECO:0007744|PDB:9BVO, ECO:0007744|PDB:9BVP, FT ECO:0007744|PDB:9BVQ, ECO:0007744|PDB:9BVR" 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 PXECD; 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 PXECD; dbSNP:rs121909681)" FT /evidence="ECO:0000269|PubMed:17110937" FT /id="VAR_032980" FT VARIANT 476 FT /note="R -> H (in PXECD; 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 PXECD; 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 PXECD; dbSNP:rs121909678)" FT /evidence="ECO:0000269|PubMed:17110937" FT /id="VAR_032983" FT MUTAGEN 160 FT /note="H->A: No effect on epoxidase activity. Impairs FT carboxylase activity." FT /evidence="ECO:0000269|PubMed:17073445, FT ECO:0000269|PubMed:39880037, ECO:0000269|PubMed:39880952" FT MUTAGEN 160 FT /note="H->K,R,N: Abolishes carboxylase activity." FT /evidence="ECO:0000269|PubMed:39880037" FT MUTAGEN 218 FT /note="K->A: Abolishes epoxidase activity. Impairs FT carboxylase activity." FT /evidence="ECO:0000269|PubMed:17073445, FT ECO:0000269|PubMed:39880952" FT MUTAGEN 287 FT /note="H->A: No effect on epoxidase activity." FT /evidence="ECO:0000269|PubMed:17073445" FT MUTAGEN 299 FT /note="F->S,A: Abolishes carboxylase activity. No effect on FT epoxidase activity." FT /evidence="ECO:0000269|PubMed:39880037" FT MUTAGEN 381 FT /note="H->A: No effect on epoxidase activity." FT /evidence="ECO:0000269|PubMed:17073445" FT MUTAGEN 395 FT /note="Y->F,A: Impairs carboxylase activity." FT /evidence="ECO:0000269|PubMed:39880037" FT MUTAGEN 401 FT /note="M->C,I,A: Abolishes carboxylase activity. No effect FT on epoxidase activity." FT /evidence="ECO:0000269|PubMed:39880037, FT ECO:0000269|PubMed:39880952" FT MUTAGEN 402 FT /note="M->C,I,A: Abolishes carboxylase activity. No effect FT on epoxidase activity." FT /evidence="ECO:0000269|PubMed:39880037" FT MUTAGEN 601 FT /note="Y->A: Abolishes carboxylase activity; when FT associated with A-603." FT /evidence="ECO:0000269|PubMed:39880037" FT MUTAGEN 603 FT /note="Y->A: Abolishes carboxylase activity; when FT associated with A-601." FT /evidence="ECO:0000269|PubMed:39880037" 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" FT HELIX 33..38 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 42..45 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 48..55 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 62..76 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 78..81 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:9BVM" FT HELIX 88..91 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 108..111 FT /evidence="ECO:0007829|PDB:9BUX" FT HELIX 112..131 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 132..134 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 135..151 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 161..170 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 178..181 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 182..186 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:9BVP" FT HELIX 198..217 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 221..224 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 228..231 FT /evidence="ECO:0007829|PDB:9BVP" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 240..243 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 247..250 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 251..257 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 258..263 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 267..271 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 276..293 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 299..306 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 307..310 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 313..316 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 317..320 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 327..329 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 341..343 FT /evidence="ECO:0007829|PDB:9BUX" FT HELIX 358..361 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 363..376 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 377..382 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:9BVQ" FT STRAND 389..393 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 395..398 FT /evidence="ECO:0007829|PDB:9BVR" FT STRAND 405..416 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 418..420 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 423..426 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 430..433 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 437..439 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 441..454 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 455..458 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 466..475 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 478..482 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 488..490 FT /evidence="ECO:0007829|PDB:9BUX" FT STRAND 500..502 FT /evidence="ECO:0007829|PDB:9BVP" FT HELIX 503..505 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 507..512 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 513..522 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 525..534 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 539..543 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 550..558 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 560..564 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 565..568 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 569..573 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 578..581 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 583..591 FT /evidence="ECO:0007829|PDB:9BUR" FT STRAND 593..595 FT /evidence="ECO:0007829|PDB:9BUX" FT STRAND 597..604 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 606..611 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 612..614 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 615..618 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 619..622 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 633..635 FT /evidence="ECO:0007829|PDB:9BVP" FT HELIX 636..638 FT /evidence="ECO:0007829|PDB:9BVP" FT HELIX 639..643 FT /evidence="ECO:0007829|PDB:9BVP" FT HELIX 650..653 FT /evidence="ECO:0007829|PDB:9BVP" FT HELIX 655..668 FT /evidence="ECO:0007829|PDB:9BUR" FT TURN 669..673 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 677..707 FT /evidence="ECO:0007829|PDB:9BUR" FT HELIX 713..723 FT /evidence="ECO:0007829|PDB:9BUR" 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 //