Vitamin K-dependent gamma-carboxylase

NameVitamin K-dependent gamma-carboxylase
Synonyms4.1.1.90 Gamma-glutamyl carboxylase GC Peptidyl-glutamate 4-carboxylase Vitamin K gamma glutamyl carboxylase
Gene NameGGCX
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000803|Vitamin K-dependent gamma-carboxylase
MAVSAGSARTSPSSDKVQKDKAELISGPRQDSRIGKLLGFEWTDLSSWRRLVTLLNRPTD
PASLAVFRFLFGFLMVLDIPQERGLSSLDRKYLDGLDVCRFPLLDALRPLPLDWMYLVYT
IMFLGALGMMLGLCYRISCVLFLLPYWYVFLLDKTSWNNHSYLYGLLAFQLTFMDANHYW
SVDGLLNAHRRNAHVPLWNYAVLRGQIFIVYFIAGVKKLDADWVEGYSMEYLSRHWLFSP
FKLLLSEELTSLLVVHWGGLLLDLSAGFLLFFDVSRSIGLFFVSYFHCMNSQLFSIGMFS
YVMLASSPLFCSPEWPRKLVSYCPRRLQQLLPLKAAPQPSVSCVYKRSRGKSGQKPGLRH
QLGAAFTLLYLLEQLFLPYSHFLTQGYNNWTNGLYGYSWDMMVHSRSHQHVKITYRDGRT
GELGYLNPGVFTQSRRWKDHADMLKQYATCLSRLLPKYNVTEPQIYFDIWVSINDRFQQR
IFDPRVDIVQAAWSPFQRTSWVQPLLMDLSPWRAKLQEIKSSLDNHTEVVFIADFPGLHL
ENFVSEDLGNTSIQLLQGEVTVELVAEQKNQTLREGEKMQLPAGEYHKVYTTSPSPSCYM
YVYVNTTELALEQDLAYLQELKEKVENGSETGPLPPELQPLLEGEVKGGPEPTPLVQTFL
RRQQRLQEIERRRNTPFHERFFRFLLRKLYVFRRSFLMTCISLRNLILGRPSLEQLAQEV
TYANLRPFEAVGELNPSNTDSSHSNPPESNPDPVHSEF
Number of residues758
Molecular Weight87560.065
Theoretical pI8.1
GO Classification
Functions
    gamma-glutamyl carboxylase activity
Processes
    cellular protein metabolic process
post-translational protein modification
blood coagulation
peptidyl-glutamic acid carboxylation
cellular protein modification process
Components
    membrane
endoplasmic reticulum membrane
integral component of membrane
General FunctionGamma-glutamyl carboxylase activity
Specific FunctionMediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.
Transmembrane Regions61-81 114-134 137-157 293-313 362-382
GenBank Protein ID184028
UniProtKB IDP38435
UniProtKB Entry NameVKGC_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0018949|Vitamin K-dependent gamma-carboxylase (GGCX)
ATGGCGGTGTCTGCCGGGTCCGCGCGGACCTCGCCCAGCTCAGATAAAGTACAGAAAGAC
AAGGCTGAACTGATCTCAGGGCCCAGGCAGGACAGCCGAATAGGGAAACTCTTGGGTTTT
GAGTGGACAGATTTGTCCAGTTGGCGGAGGCTGGTGACCCTGCTGAATCGACCAACGGAC
CCTGCAAGCTTAGCTGTCTTTCGTTTTCTTTTTGGGTTCTTGATGGTGCTAGACATTCCC
CAGGAGCGGGGGCTCAGCTCTCTGGACCGGAAATACCTTGATGGGCTGGATGTGTGCCGC
TTCCCCTTGCTGGATGCCCTACGCCCACTGCCACTTGACTGGATGTATCTTGTCTACACC
ATCATGTTTCTGGGGGCACTGGGCATGATGCTGGGCCTGTGCTACCGGATAAGCTGTGTG
TTATTCCTGCTGCCATACTGGTATGTGTTTCTCCTGGACAAGACATCATGGAACAACCAC
TCCTATCTGTATGGGTTGTTGGCCTTTCAGCTAACATTCATGGATGCAAACCACTACTGG
TCTGTGGACGGTCTGCTGAATGCCCATAGGAGGAATGCCCACGTGCCCCTTTGGAACTAT
GCAGTGCTCCGTGGCCAGATCTTCATTGTGTACTTCATTGCGGGTGTGAAAAAGCTGGAT
GCAGACTGGGTTGAAGGCTATTCCATGGAATATTTGTCCCGGCACTGGCTCTTCAGTCCC
TTCAAACTGCTGTTGTCTGAGGAGCTGACTAGCCTGCTGGTCGTGCACTGGGGTGGGCTG
CTGCTTGACCTCTCAGCTGGTTTCCTGCTCTTTTTTGATGTCTCAAGATCCATTGGCCTG
TTCTTTGTGTCCTACTTCCACTGCATGAATTCCCAGCTTTTCAGCATTGGTATGTTCTCC
TACGTCATGCTGGCCAGCAGCCCTCTCTTCTGCTCCCCTGAGTGGCCTCGGAAGCTGGTG
TCCTACTGCCCCCGAAGGTTGCAACAACTGTTGCCCCTCAAGGCAGCCCCTCAGCCCAGT
GTTTCCTGTGTGTATAAGAGGAGCCGGGGCAAAAGTGGCCAGAAGCCAGGGCTGCGCCAT
CAGCTGGGAGCTGCCTTCACCCTGCTCTACCTCCTGGAGCAGCTATTCCTGCCCTATTCT
CATTTTCTCACCCAGGGCTATAACAACTGGACAAATGGGCTGTATGGCTATTCCTGGGAC
ATGATGGTGCACTCCCGCTCCCACCAGCACGTGAAGATCACCTACCGTGATGGCCGCACT
GGCGAACTGGGCTACCTTAACCCTGGGGTATTTACACAGAGTCGGCGATGGAAGGATCAT
GCAGACATGCTGAAGCAATATGCCACTTGCCTGAGCCGCCTGCTTCCCAAGTATAATGTC
ACTGAGCCCCAGATCTACTTTGATATTTGGGTCTCCATCAATGACCGCTTCCAGCAGAGG
ATTTTTGACCCTCGTGTGGACATCGTGCAGGCCGCTTGGTCACCCTTTCAGCGCACATCC
TGGGTGCAACCACTCTTGATGGACCTGTCTCCCTGGAGGGCCAAGTTACAGGAAATCAAG
AGCAGCCTAGACAACCACACTGAGGTGGTCTTCATTGCAGATTTCCCTGGACTGCACTTG
GAGAATTTTGTGAGTGAAGACCTGGGCAACACTAGCATCCAGCTGCTGCAGGGGGAAGTG
ACTGTGGAGCTTGTGGCAGAACAGAAGAACCAGACTCTTCGAGAGGGAGAAAAAATGCAG
TTGCCTGCTGGTGAGTACCATAAGGTGTATACGACATCACCTAGCCCTTCTTGCTACATG
TACGTCTATGTCAACACTACAGAGCTTGCACTGGAGCAAGACCTGGCATATCTGCAAGAA
TTAAAGGAAAAGGTGGAGAATGGAAGTGAAACAGGGCCTCTACCCCCAGAGCTGCAGCCT
CTGTTGGAAGGGGAAGTAAAAGGGGGCCCTGAGCCAACACCTCTGGTTCAGACCTTTCTT
AGACGCCAACAAAGGCTCCAGGAGATTGAACGCCGGCGAAATACTCCTTTCCATGAGCGA
TTCTTCCGCTTCTTGTTGCGAAAGCTCTATGTCTTTCGCCGCAGCTTCCTGATGACTTGT
ATCTCACTTCGAAATCTGATATTAGGCCGTCCTTCCCTGGAGCAGCTGGCCCAGGAGGTG
ACTTATGCAAACTTGAGACCCTTTGAGGCAGTTGGAGAACTGAATCCCTCAAACACGGAT
TCTTCACATTCTAATCCTCCTGAGTCAAATCCTGATCCTGTCCACTCAGAGTTCTGA
GenBank Gene IDM81592
GeneCard IDNone
GenAtlas IDGGCX
HGNC IDHGNC:4247
Chromosome Location2
Locus2p12
References
  1. Wu SM, Cheung WF, Frazier D, Stafford DW: Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science. 1991 Dec 13;254(5038):1634-6.[1749935 ]
  2. Wu SM, Stafford DW, Frazier LD, Fu YY, High KA, Chu K, Sanchez-Vega B, Solera J: Genomic sequence and transcription start site for the human gamma-glutamyl carboxylase. Blood. 1997 Jun 1;89(11):4058-62.[9166845 ]
  3. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31.[15815621 ]
  4. Tie J, Wu SM, Jin D, Nicchitta CV, Stafford DW: A topological study of the human gamma-glutamyl carboxylase. Blood. 2000 Aug 1;96(3):973-8.[10910912 ]
  5. Presnell SR, Tripathy A, Lentz BR, Jin DY, Stafford DW: A novel fluorescence assay to study propeptide interaction with gamma-glutamyl carboxylase. Biochemistry. 2001 Oct 2;40(39):11723-33.[11570873 ]
  6. Berkner KL: The vitamin K-dependent carboxylase. Annu Rev Nutr. 2005;25:127-49.[16011462 ]
  7. Rishavy MA, Hallgren KW, Yakubenko AV, Shtofman RL, Runge KW, Berkner KL: Bronsted analysis reveals Lys218 as the carboxylase active site base that deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein carboxylation. Biochemistry. 2006 Nov 7;45(44):13239-48.[17073445 ]
  8. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309.[19413330 ]
  9. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012.[19159218 ]
  10. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570.[21406692 ]
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22.[24275569 ]
  12. Brenner B, Sanchez-Vega B, Wu SM, Lanir N, Stafford DW, Solera J: A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors. Blood. 1998 Dec 15;92(12):4554-9.[9845520 ]
  13. Spronk HM, Farah RA, Buchanan GR, Vermeer C, Soute BA: Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors. Blood. 2000 Nov 15;96(10):3650-2.[11071668 ]
  14. Mutucumarana VP, Stafford DW, Stanley TB, Jin DY, Solera J, Brenner B, Azerad R, Wu SM: Expression and characterization of the naturally occurring mutation L394R in human gamma-glutamyl carboxylase. J Biol Chem. 2000 Oct 20;275(42):32572-7.[10934213 ]
  15. Rost S, Fregin A, Koch D, Compes M, Muller CR, Oldenburg J: Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. Br J Haematol. 2004 Aug;126(4):546-9.[15287948 ]
  16. Vanakker OM, Martin L, Gheduzzi D, Leroy BP, Loeys BL, Guerci VI, Matthys D, Terry SF, Coucke PJ, Pasquali-Ronchetti I, De Paepe A: Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity. J Invest Dermatol. 2007 Mar;127(3):581-7. Epub 2006 Nov 16.[17110937 ]
  17. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7.[15489334 ]
  18. Tie JK, Mutucumarana VP, Straight DL, Carrick KL, Pope RM, Stafford DW: Determination of disulfide bond assignment of human vitamin K-dependent gamma-glutamyl carboxylase by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Biol Chem. 2003 Nov 14;278(46):45468-75. Epub 2003 Sep 8.[12963724 ]
  19. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21.[14702039 ]

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