ID   VKGC_MOUSE              Reviewed;         757 AA.
AC   Q9QYC7; Q3UXN5; Q8CCB3;
DT   01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-JAN-2024, entry version 154.
DE   RecName: Full=Vitamin K-dependent gamma-carboxylase;
DE            EC=4.1.1.90 {ECO:0000250|UniProtKB:P38435};
DE   AltName: Full=Gamma-glutamyl carboxylase;
DE   AltName: Full=Peptidyl-glutamate 4-carboxylase;
DE   AltName: Full=Vitamin K gamma glutamyl carboxylase;
GN   Name=Ggcx;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Zhu A., Zheng X., Ginsburg D.;
RT   "Characterization of the mouse gamma-carboxylase genomic locus and its
RT   promoter.";
RL   Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Bone, Colon, and Muellerian duct;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, and Lung;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=17327402; DOI=10.1182/blood-2006-12-064188;
RA   Zhu A., Sun H., Raymond R.M. Jr., Furie B.C., Furie B., Bronstein M.,
RA   Kaufman R.J., Westrick R., Ginsburg D.;
RT   "Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase.";
RL   Blood 109:5270-5275(2007).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=25264202; DOI=10.1016/j.bbrc.2014.09.091;
RA   Shiba S., Ikeda K., Azuma K., Hasegawa T., Amizuka N., Horie-Inoue K.,
RA   Inoue S.;
RT   "gamma-Glutamyl carboxylase in osteoblasts regulates glucose metabolism in
RT   mice.";
RL   Biochem. Biophys. Res. Commun. 453:350-355(2014).
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 (By similarity). Catalyzes gamma-carboxylation
CC       of various proteins, such as blood coagulation factors (F2, F7, F9 and
CC       F10), osteocalcin (bglap and bglap2) or matrix Gla protein (MGP)
CC       (PubMed:25264202). {ECO:0000250|UniProtKB:P38435,
CC       ECO:0000269|PubMed:25264202}.
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:0000250|UniProtKB:P38435};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45142;
CC         Evidence={ECO:0000250|UniProtKB:P38435};
CC   -!- SUBUNIT: Monomer (By similarity). May interact with CALU (By
CC       similarity). {ECO:0000250|UniProtKB:O88496,
CC       ECO:0000250|UniProtKB:P38435}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P38435}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P38435}.
CC   -!- DISRUPTION PHENOTYPE: Embryonic lethality between 9.5-18 dpc due to
CC       massive hemorrhage (PubMed:17327402). Conditional deletion in
CC       osteoblasts leads to altered glucose metabolism due to inability to
CC       carboxylate osteocalcin (bglap and bglap2) (PubMed:25264202).
CC       {ECO:0000269|PubMed:17327402, ECO:0000269|PubMed:25264202}.
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}.
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DR   EMBL; AF087938; AAF21291.1; -; mRNA.
DR   EMBL; AK033496; BAC28319.1; -; mRNA.
DR   EMBL; AK036577; BAC29487.1; -; mRNA.
DR   EMBL; AK135425; BAE22528.1; -; mRNA.
DR   CCDS; CCDS20242.1; -.
DR   RefSeq; NP_062776.1; NM_019802.5.
DR   AlphaFoldDB; Q9QYC7; -.
DR   BioGRID; 207897; 6.
DR   STRING; 10090.ENSMUSP00000070109; -.
DR   GlyGen; Q9QYC7; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9QYC7; -.
DR   PhosphoSitePlus; Q9QYC7; -.
DR   jPOST; Q9QYC7; -.
DR   MaxQB; Q9QYC7; -.
DR   PaxDb; 10090-ENSMUSP00000070109; -.
DR   ProteomicsDB; 297960; -.
DR   Pumba; Q9QYC7; -.
DR   Antibodypedia; 16941; 315 antibodies from 35 providers.
DR   DNASU; 56316; -.
DR   Ensembl; ENSMUST00000065906.9; ENSMUSP00000070109.8; ENSMUSG00000053460.9.
DR   GeneID; 56316; -.
DR   KEGG; mmu:56316; -.
DR   UCSC; uc009cio.2; mouse.
DR   AGR; MGI:1927655; -.
DR   CTD; 2677; -.
DR   MGI; MGI:1927655; Ggcx.
DR   VEuPathDB; HostDB:ENSMUSG00000053460; -.
DR   eggNOG; ENOG502QRU2; Eukaryota.
DR   GeneTree; ENSGT00390000014909; -.
DR   HOGENOM; CLU_020495_0_0_1; -.
DR   InParanoid; Q9QYC7; -.
DR   OMA; TYLNHYY; -.
DR   OrthoDB; 2904328at2759; -.
DR   PhylomeDB; Q9QYC7; -.
DR   TreeFam; TF323879; -.
DR   Reactome; R-MMU-159740; Gamma-carboxylation of protein precursors.
DR   BioGRID-ORCS; 56316; 2 hits in 78 CRISPR screens.
DR   PRO; PR:Q9QYC7; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q9QYC7; Protein.
DR   Bgee; ENSMUSG00000053460; Expressed in humerus cartilage element and 110 other cell types or tissues.
DR   ExpressionAtlas; Q9QYC7; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR   GO; GO:0008488; F:gamma-glutamyl carboxylase activity; IDA:UniProtKB.
DR   GO; GO:0019842; F:vitamin binding; ISO:MGI.
DR   GO; GO:0042373; P:vitamin K metabolic process; ISO:MGI.
DR   InterPro; IPR011020; HTTM.
DR   InterPro; IPR011051; RmlC_Cupin_sf.
DR   InterPro; IPR007782; VKG_COase.
DR   PANTHER; PTHR12639; VITAMIN K-DEPENDENT GAMMA-CARBOXYLASE; 1.
DR   PANTHER; PTHR12639:SF6; VITAMIN K-DEPENDENT GAMMA-CARBOXYLASE; 1.
DR   Pfam; PF05090; VKG_Carbox; 1.
DR   SMART; SM00752; HTTM; 1.
DR   SUPFAM; SSF51182; RmlC-like cupins; 1.
DR   Genevisible; Q9QYC7; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Disulfide bond; Endoplasmic reticulum; Lyase; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P38435"
FT   CHAIN           2..757
FT                   /note="Vitamin K-dependent gamma-carboxylase"
FT                   /id="PRO_0000191824"
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..757
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   REGION          729..757
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P38435"
FT   DISULFID        99..450
FT                   /evidence="ECO:0000250"
FT   CONFLICT        525
FT                   /note="N -> K (in Ref. 2; BAC28319)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   757 AA;  87195 MW;  178CDDCEE5CFBA34 CRC64;
     MAVHRGSALV APASDKVQKN KSAQTSGLKQ GSRMEKILGF EWTDLSSWQS VVTLLNKPTD
     PANLAVFRFL FAFLMLLDIP QERGLSSLDR KYLDGLDVCR FPLLDALRPL PLDWMYLVYT
     IMFLGALGMM LGLCYRLSCV LFLLPYWYVF LLDKTSWNNH SYLYGLLAFQ LTFMDANHYW
     SVDGLLNARK KNAHVPLWNY TVLRGQIFIV YFIAGVKKLD ADWVGGYSME HLSRHWLFSP
     FKLVLSEELT SLLVVHWCGL LLDLSAGFLL FFDASRPVGL FFVSYFHCMN SQLFSIGMFP
     YVMLASSPLF CSAEWPRKLV ARCPKRLQEL LPTKAAPRPS ASCVYKRSRG KAGPKPGLRH
     QLGAIFTLLY LLEQLFLPYS HFLTQGYNNW TNGLYGYSWD MMVHSRSHQH VKITYRDGLT
     GELGYLNPGV FTQSRRWKDH ADMLKQYATC LSLLLPKYNV TEPQIYFDIW VSINDRFQQR
     LFDPRVDIVQ AVWSPFQRTP WVQPLLMDLS PWRTKLQDIK SSLDNHTEVV FIADFPGLHL
     ENFVSEDLGN TSIQLLQGEV TVELVAEQKN QTLQEGEKMQ LPAGEYHKVY TVSSSPSCYM
     YVYVNTTEVA LEQDLAYLQE LKEKVENGSE TGPLPPELQP LLEGEVKGGP EPTPLVQTFL
     RRQRKLQEIE RRRNSPFHER FLRFVLRKLY VFRRSFLMTR ISLRNLLLGR PSLEQLAQEV
     TYANLRPFEP VDESSASNTD SSNHPSEPDS EHVHSEF
//