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Identification
HMDB Protein ID HMDBP01691
Secondary Accession Numbers
  • 7028
Name Vitamin K-dependent gamma-carboxylase
Synonyms
  1. Gamma-glutamyl carboxylase
  2. Peptidyl-glutamate 4-carboxylase
  3. Vitamin K gamma glutamyl carboxylase
Gene Name GGCX
Protein Type Unknown
Biological Properties
General Function Involved in gamma-glutamyl carboxylase activity
Specific Function Mediates 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.
Pathways
  • Acenocoumarol Action Pathway
  • Alteplase Action Pathway
  • Aminocaproic Acid Action Pathway
  • Anistreplase Action Pathway
  • Aprotinin Action Pathway
  • Ardeparin Action Pathway
  • Argatroban Action Pathway
  • Bivalirudin Action Pathway
  • Coagulation
  • Dicoumarol Action Pathway
  • Dicumarol Action Pathway
  • Enoxaparin Action Pathway
  • Fondaparinux Action Pathway
  • Heparin Action Pathway
  • Lepirudin Action Pathway
  • Phenindione Action Pathway
  • Phenprocoumon Action Pathway
  • Reteplase Action Pathway
  • Streptokinase Action Pathway
  • Tenecteplase Action Pathway
  • Tranexamic Acid Action Pathway
  • Ubiquinone and other terpenoid-quinone biosynthesis
  • Urokinase Action Pathway
  • Vitamin K Metabolism
  • Warfarin Action Pathway
  • Ximelagatran Action Pathway
Reactions
[Peptidyl]-4-carboxyglutamate + Vitamin K1 2,3-epoxide + Water → [peptidyl]-glutamate + CO(2) + Oxygen + Reduced Vitamin K (phylloquinone) details
Gla protein + Vitamin K1 2,3-epoxide + Water → Gla protein precursor + Phylloquinol + Carbon dioxide + Oxygen details
2,3-Epoxymenaquinone + Gla protein + Water → Menaquinol + Gla protein precursor + Carbon dioxide + Oxygen details
GO Classification
Biological Process
embryo development
post-translational protein modification
blood coagulation
peptidyl-glutamic acid carboxylation
response to vitamin K
Cellular Component
endoplasmic reticulum membrane
integral to membrane
Function
catalytic activity
gamma-glutamyl carboxylase activity
lyase activity
carbon-carbon lyase activity
carboxy-lyase activity
Molecular Function
gamma-glutamyl carboxylase activity
Process
metabolic process
macromolecule metabolic process
peptidyl-glutamic acid modification
peptidyl-glutamic acid carboxylation
macromolecule modification
protein modification process
peptidyl-amino acid modification
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location 2
Locus 2p12
SNPs GGCX
Gene Sequence
>2277 bp
ATGGCGGTGTCTGCCGGGTCCGCGCGGACCTCGCCCAGCTCAGATAAAGTACAGAAAGAC
AAGGCTGAACTGATCTCAGGGCCCAGGCAGGACAGCCGAATAGGGAAACTCTTGGGTTTT
GAGTGGACAGATTTGTCCAGTTGGCGGAGGCTGGTGACCCTGCTGAATCGACCAACGGAC
CCTGCAAGCTTAGCTGTCTTTCGTTTTCTTTTTGGGTTCTTGATGGTGCTAGACATTCCC
CAGGAGCGGGGGCTCAGCTCTCTGGACCGGAAATACCTTGATGGGCTGGATGTGTGCCGC
TTCCCCTTGCTGGATGCCCTACGCCCACTGCCACTTGACTGGATGTATCTTGTCTACACC
ATCATGTTTCTGGGGGCACTGGGCATGATGCTGGGCCTGTGCTACCGGATAAGCTGTGTG
TTATTCCTGCTGCCATACTGGTATGTGTTTCTCCTGGACAAGACATCATGGAACAACCAC
TCCTATCTGTATGGGTTGTTGGCCTTTCAGCTAACATTCATGGATGCAAACCACTACTGG
TCTGTGGACGGTCTGCTGAATGCCCATAGGAGGAATGCCCACGTGCCCCTTTGGAACTAT
GCAGTGCTCCGTGGCCAGATCTTCATTGTGTACTTCATTGCGGGTGTGAAAAAGCTGGAT
GCAGACTGGGTTGAAGGCTATTCCATGGAATATTTGTCCCGGCACTGGCTCTTCAGTCCC
TTCAAACTGCTGTTGTCTGAGGAGCTGACTAGCCTGCTGGTCGTGCACTGGGGTGGGCTG
CTGCTTGACCTCTCAGCTGGTTTCCTGCTCTTTTTTGATGTCTCAAGATCCATTGGACTG
TTCTTTGTGTCCTACTTCCACTGCATGAATTCCCAGCTTTTCAGCATTGGTATGTTCTCC
TACGTCATGCTGGCCAGCAGCCCTCTCTTCTGCTCCCCTGAGTGGCCTCGGAAGCTGGTG
TCCTACTGCCCCCGAAGGTTGCAACAACTGTTGCCCCTCAAGGCAGCCCCTCAGCCCAGT
GTTTCCTGTGTGTATAAGAGGAGCCGGGGCAAAAGTGGCCAGAAGCCAGGGCTGCGCCAT
CAGCTGGGAGCTGCCTTCACCCTGCTCTACCTCCTGGAGCAGCTATTCCTGCCCTATTCT
CATTTTCTCACCCAGGGCTATAACAACTGGACAAATGGGCTGTATGGCTATTCCTGGGAC
ATGATGGTGCACTCCCGCTCCCACCAGCACGTGAAGATCACCTACCGTGATGGCCGCACT
GGCGAACTGGGCTACCTTAACCCTGGGGTATTTACACAGAGTCGGCGATGGAAGGATCAT
GCAGACATGCTGAAGCAATATGCCACTTGCCTGAGCCGCCTGCTTCCCAAGTATAATGTC
ACTGAGCCCCAGATCTACTTTGATATTTGGGTCTCCATCAATGACCGCTTCCAGCAGAGG
ATTTTTGACCCTCGTGTGGACATCGTGCAGGCCGCTTGGTCACCCTTTCAGCGCACATCC
TGGGTGCAACCACTCTTGATGGACCTGTCTCCCTGGAGGGCCAAGTTACAGGAAATCAAG
AGCAGCCTAGACAACCACACTGAGGTGGTCTTCATTGCAGATTTCCCTGGACTGCACTTG
GAGAATTTTGTGAGTGAAGACCTGGGCAACACTAGCATCCAGCTGCTGCAGGGGGAAGTG
ACTGTGGAGCTTGTGGCAGAACAGAAGAACCAGACTCTTCGAGAGGGAGAAAAAATGCAG
TTGCCTGCTGGTGAGTACCATAAGGTGTATACGACATCACCTAGCCCTTCTTGCTACATG
TACGTCTATGTCAACACTACAGAGCTTGCACTGGAGCAAGACCTGGCATATCTGCAAGAA
TTAAAGGAAAAGGTGGAGAATGGAAGTGAAACAGGGCCTCTACCCCCAGAGCTGCAGCCT
CTGTTGGAAGGGGAAGTAAAAGGGGGCCCTGAGCCAACACCTCTGGTTCAGACCTTTCTT
AGACGCCAACAAAGGCTCCAGGAGATTGAACGCCGGCGAAATACTCCTTTCCATGAGCGA
TTCTTCCGCTTCTTGTTGCGAAAGCTCTATGTCTTTCGCCGCAGCTTCCTGATGACTTGT
ATCTCACTTCGAAATCTGATATTAGGCCGTCCTTCCCTGGAGCAGCTGGCCCAGGAGGTG
ACTTATGCAAACTTGAGACCCTTTGAGGCAGTTGGAGAACTGAATCCCTCAAACACGGAT
TCTTCACATTCTAATCCTCCTGAGTCAAATCCTGATCCTGTCCACTCAGAGTTCTGA
Protein Properties
Number of Residues 758
Molecular Weight 87560.065
Theoretical pI 8.011
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Vitamin K-dependent gamma-carboxylase
MAVSAGSARTSPSSDKVQKDKAELISGPRQDSRIGKLLGFEWTDLSSWRRLVTLLNRPTD
PASLAVFRFLFGFLMVLDIPQERGLSSLDRKYLDGLDVCRFPLLDALRPLPLDWMYLVYT
IMFLGALGMMLGLCYRISCVLFLLPYWYVFLLDKTSWNNHSYLYGLLAFQLTFMDANHYW
SVDGLLNAHRRNAHVPLWNYAVLRGQIFIVYFIAGVKKLDADWVEGYSMEYLSRHWLFSP
FKLLLSEELTSLLVVHWGGLLLDLSAGFLLFFDVSRSIGLFFVSYFHCMNSQLFSIGMFS
YVMLASSPLFCSPEWPRKLVSYCPRRLQQLLPLKAAPQPSVSCVYKRSRGKSGQKPGLRH
QLGAAFTLLYLLEQLFLPYSHFLTQGYNNWTNGLYGYSWDMMVHSRSHQHVKITYRDGRT
GELGYLNPGVFTQSRRWKDHADMLKQYATCLSRLLPKYNVTEPQIYFDIWVSINDRFQQR
IFDPRVDIVQAAWSPFQRTSWVQPLLMDLSPWRAKLQEIKSSLDNHTEVVFIADFPGLHL
ENFVSEDLGNTSIQLLQGEVTVELVAEQKNQTLREGEKMQLPAGEYHKVYTTSPSPSCYM
YVYVNTTELALEQDLAYLQELKEKVENGSETGPLPPELQPLLEGEVKGGPEPTPLVQTFL
RRQQRLQEIERRRNTPFHERFFRFLLRKLYVFRRSFLMTCISLRNLILGRPSLEQLAQEV
TYANLRPFEAVGELNPSNTDSSHSNPPESNPDPVHSEF
GenBank ID Protein 62988953
UniProtKB/Swiss-Prot ID P38435
UniProtKB/Swiss-Prot Entry Name VKGC_HUMAN
PDB IDs Not Available
GenBank Gene ID AC016753
GeneCard ID GGCX
GenAtlas ID GGCX
HGNC ID HGNC:4247
References
General References
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  4. 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. [PubMed:19413330 ]
  5. 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. [PubMed:1749935 ]
  6. 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. [PubMed:9166845 ]
  7. 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. [PubMed:10910912 ]
  8. 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. [PubMed:11570873 ]
  9. 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. [PubMed:12963724 ]
  10. Berkner KL: The vitamin K-dependent carboxylase. Annu Rev Nutr. 2005;25:127-49. [PubMed:16011462 ]
  11. 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. [PubMed:17073445 ]
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15287948 ]
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