Identification |
HMDB Protein ID
| HMDBP00702 |
Secondary Accession Numbers
| |
Name
| Glutamate decarboxylase 2 |
Synonyms
|
- 65 kDa glutamic acid decarboxylase
- GAD-65
- Glutamate decarboxylase 65 kDa isoform
|
Gene Name
| GAD2 |
Protein Type
| Enzyme |
Biological Properties |
General Function
| Involved in carboxy-lyase activity |
Specific Function
| Catalyzes the production of GABA.
|
Pathways
|
- Alanine, aspartate and glutamate metabolism
- beta-Alanine metabolism
- Butanoate metabolism
- GABAergic synapse
- Taurine and hypotaurine metabolism
- Type I diabetes mellitus
|
Reactions
|
L-Glutamic acid → gamma-Aminobutyric acid + CO(2) |
details
|
L-Glutamic acid → gamma-Aminobutyric acid + Carbon dioxide |
details
|
L-Aspartic acid → beta-Alanine + Carbon dioxide |
details
|
Cysteic acid → Taurine + Carbon dioxide |
details
|
3-Sulfinoalanine → Hypotaurine + Carbon dioxide |
details
|
|
GO Classification
|
Biological Process |
neurotransmitter biosynthetic process |
response to drug |
neurotransmitter secretion |
glutamate decarboxylation to succinate |
Cellular Component |
cytosol |
anchored to membrane |
plasma membrane |
cell junction |
perinuclear region of cytoplasm |
presynaptic membrane |
axon |
clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane |
Golgi membrane |
synaptic vesicle membrane |
Function |
binding |
catalytic activity |
lyase activity |
carbon-carbon lyase activity |
carboxy-lyase activity |
cofactor binding |
pyridoxal phosphate binding |
Molecular Function |
pyridoxal phosphate binding |
glutamate decarboxylase activity |
Process |
metabolic process |
cellular metabolic process |
organic acid metabolic process |
oxoacid metabolic process |
carboxylic acid metabolic process |
|
Cellular Location
|
- Lipid-anchor
- Cytoplasm
- Golgi apparatus membrane
- Peripheral membrane protein
- Cytoplasmic vesicle
- Cytoplasmic side
- cytosol
- Cell junction
- synapse
- presynaptic cell membrane
|
Gene Properties |
Chromosome Location
| 10 |
Locus
| 10p11.23 |
SNPs
| GAD2 |
Gene Sequence
|
>1758 bp
ATGGCATCTCCGGGCTCTGGCTTTTGGTCTTTCGGGTCGGAAGATGGCTCTGGGGATTCC
GAGAATCCCGGCACAGCGCGAGCCTGGTGCCAAGTGGCTCAGAAGTTCACGGGCGGCATC
GGAAACAAACTGTGCGCCCTGCTCTACGGAGACGCCGAGAAGCCGGCGGAGAGCGGCGGG
AGCCAACCCCCGCGGGCCGCCGCCCGGAAGGCCGCCTGCGCCTGCGACCAGAAGCCCTGC
AGCTGCTCCAAAGTGGATGTCAACTACGCGTTTCTCCATGCAACAGACCTGCTGCCGGCG
TGTGATGGAGAAAGGCCCACTTTGGCGTTTCTGCAAGATGTTATGAACATTTTACTTCAG
TATGTGGTGAAAAGTTTCGATAGATCAACCAAAGTGATTGATTTCCATTATCCTAATGAG
CTTCTCCAAGAATATAATTGGGAATTGGCAGACCAACCACAAAATTTGGAGGAAATTTTG
ATGCATTGCCAAACAACTCTAAAATATGCAATTAAAACAGGGCATCCTAGATACTTCAAT
CAACTTTCTACTGGTTTGGATATGGTTGGATTAGCAGCAGACTGGCTGACATCAACAGCA
AATACTAACATGTTCACCTATGAAATTGCTCCAGTATTTGTGCTTTTGGAATATGTCACA
CTAAAGAAAATGAGAGAAATCATTGGCTGGCCAGGGGGCTCTGGCGATGGGATATTTTCT
CCCGGTGGCGCCATATCTAACATGTATGCCATGATGATCGCACGCTTTAAGATGTTCCCA
GAAGTCAAGGAGAAAGGAATGGCTGCTCTTCCCAGGCTCATTGCCTTCACGTCTGAACAT
AGTCATTTTTCTCTCAAGAAGGGAGCTGCAGCCTTAGGGATTGGAACAGACAGCGTGATT
CTGATTAAATGTGATGAGAGAGGGAAAATGATTCCATCTGATCTTGAAAGAAGGATTCTT
GAAGCCAAACAGAAAGGGTTTGTTCCTTTCCTCGTGAGTGCCACAGCTGGAACCACCGTG
TACGGAGCATTTGACCCCCTCTTAGCTGTCGCTGACATTTGCAAAAAGTATAAGATCTGG
ATGCATGTGGATGCAGCTTGGGGTGGGGGATTACTGATGTCCCGAAAACACAAGTGGAAA
CTGAGTGGCGTGGAGAGGGCCAACTCTGTGACGTGGAATCCACACAAGATGATGGGAGTC
CCTTTGCAGTGCTCTGCTCTCCTGGTTAGAGAAGAGGGATTGATGCAGAATTGCAACCAA
ATGCATGCCTCCTACCTCTTTCAGCAAGATAAACATTATGACCTGTCCTATGACACTGGA
GACAAGGCCTTACAGTGCGGACGCCACGTTGATGTTTTTAAACTATGGCTGATGTGGAGG
GCAAAGGGGACTACCGGGTTTGAAGCGCATGTTGATAAATGTTTGGAGTTGGCAGAGTAT
TTATACAACATCATAAAAAACCGAGAAGGATATGAGATGGTGTTTGATGGGAAGCCTCAG
CACACAAATGTCTGCTTCTGGTACATTCCTCCAAGCTTGCGTACTCTGGAAGACAATGAA
GAGAGAATGAGTCGCCTCTCGAAGGTGGCTCCAGTGATTAAAGCCAGAATGATGGAGTAT
GGAACCACAATGGTCAGCTACCAACCCTTGGGAGACAAGGTCAATTTCTTCCGCATGGTC
ATCTCAAACCCAGCGGCAACTCACCAAGACATTGACTTCCTGATTGAAGAAATAGAACGC
CTTGGACAAGATTTATAA
|
Protein Properties |
Number of Residues
| 585 |
Molecular Weight
| 65410.77 |
Theoretical pI
| 6.899 |
Pfam Domain Function
|
|
Signals
|
Not Available
|
Transmembrane Regions
|
Not Available
|
Protein Sequence
|
>Glutamate decarboxylase 2
MASPGSGFWSFGSEDGSGDSENPGTARAWCQVAQKFTGGIGNKLCALLYGDAEKPAESGG
SQPPRAAARKAACACDQKPCSCSKVDVNYAFLHATDLLPACDGERPTLAFLQDVMNILLQ
YVVKSFDRSTKVIDFHYPNELLQEYNWELADQPQNLEEILMHCQTTLKYAIKTGHPRYFN
QLSTGLDMVGLAADWLTSTANTNMFTYEIAPVFVLLEYVTLKKMREIIGWPGGSGDGIFS
PGGAISNMYAMMIARFKMFPEVKEKGMAALPRLIAFTSEHSHFSLKKGAAALGIGTDSVI
LIKCDERGKMIPSDLERRILEAKQKGFVPFLVSATAGTTVYGAFDPLLAVADICKKYKIW
MHVDAAWGGGLLMSRKHKWKLSGVERANSVTWNPHKMMGVPLQCSALLVREEGLMQNCNQ
MHASYLFQQDKHYDLSYDTGDKALQCGRHVDVFKLWLMWRAKGTTGFEAHVDKCLELAEY
LYNIIKNREGYEMVFDGKPQHTNVCFWYIPPSLRTLEDNEERMSRLSKVAPVIKARMMEY
GTTMVSYQPLGDKVNFFRMVISNPAATHQDIDFLIEEIERLGQDL
|
External Links |
GenBank ID Protein
| Not Available |
UniProtKB/Swiss-Prot ID
| Q05329 |
UniProtKB/Swiss-Prot Entry Name
| DCE2_HUMAN |
PDB IDs
|
|
GenBank Gene ID
| M81882 |
GeneCard ID
| GAD2 |
GenAtlas ID
| GAD2 |
HGNC ID
| HGNC:4093 |
References |
General References
| - Karlsen AE, Hagopian WA, Grubin CE, Dube S, Disteche CM, Adler DA, Barmeier H, Mathewes S, Grant FJ, Foster D, et al.: Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8337-41. [PubMed:1924293 ]
- Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, Wagner-McPherson CB, Evans GA, Tobin AJ: Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2115-9. [PubMed:1549570 ]
- Bu DF, Tobin AJ: The exon-intron organization of the genes (GAD1 and GAD2) encoding two human glutamate decarboxylases (GAD67 and GAD65) suggests that they derive from a common ancestral GAD. Genomics. 1994 May 1;21(1):222-8. [PubMed:8088791 ]
- Mauch L, Abney CC, Berg H, Scherbaum WA, Liedvogel B, Northemann W: Characterization of a linear epitope within the human pancreatic 64-kDa glutamic acid decarboxylase and its autoimmune recognition by sera from insulin-dependent diabetes mellitus patients. Eur J Biochem. 1993 Mar 1;212(2):597-603. [PubMed:7680313 ]
- Kim J, Richter W, Aanstoot HJ, Shi Y, Fu Q, Rajotte R, Warnock G, Baekkeskov S: Differential expression of GAD65 and GAD67 in human, rat, and mouse pancreatic islets. Diabetes. 1993 Dec;42(12):1799-808. [PubMed:8243826 ]
- Namchuk M, Lindsay L, Turck CW, Kanaani J, Baekkeskov S: Phosphorylation of serine residues 3, 6, 10, and 13 distinguishes membrane anchored from soluble glutamic acid decarboxylase 65 and is restricted to glutamic acid decarboxylase 65alpha. J Biol Chem. 1997 Jan 17;272(3):1548-57. [PubMed:8999827 ]
- Kanaani J, el-Husseini Ael-D, Aguilera-Moreno A, Diacovo JM, Bredt DS, Baekkeskov S: A combination of three distinct trafficking signals mediates axonal targeting and presynaptic clustering of GAD65. J Cell Biol. 2002 Sep 30;158(7):1229-38. [PubMed:12356867 ]
- Corper AL, Stratmann T, Apostolopoulos V, Scott CA, Garcia KC, Kang AS, Wilson IA, Teyton L: A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science. 2000 Apr 21;288(5465):505-11. [PubMed:10775108 ]
- Fenalti G, Law RH, Buckle AM, Langendorf C, Tuck K, Rosado CJ, Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI, Mackay IR, Rowley MJ, Whisstock JC: GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop. Nat Struct Mol Biol. 2007 Apr;14(4):280-6. Epub 2007 Mar 25. [PubMed:17384644 ]
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