UniProt Accession

 CGAS_HUMAN; Q8N884; L0L2J9; Q14CV6; Q32NC9; Q5SWL0; Q5SWL1; Q96E45 

Genbank Protein ID

 KC294566; AK097148; AL603910; AC019205; AL603910; AC019205; BC012928; BC108714; BC113606; BC113608; BC143694 

Genbank Nucleotide ID

 AGB51853.1; BAC04965.1; CAI14878.1; CAI14878.1; CAI14879.1; CAI14879.1; AAH12928.1; AAI08715.1; AAI13607.1; AAI13609.1; AAI43695.1 

Protein Name

 Cyclic GMP-AMP synthase 

Protein Synonyms/Alias

 cGAMP synthase; cGAS; h-cGAS; Mab-21 domain-containing protein 1 

Gene Name

 MB21D1 

Gene Synonyms/Alias

 C6orf150 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
7	*MQPWHGKAMQRASE	acetylation	[1]
50	AALPKAGKFGPARKS	acetylation	[1]
347	IQNWLSAKVRKQLRL	ubiquitination	[2, 3]
355	VRKQLRLKPFYLVPK	ubiquitination	[2, 3]
384	LSFSHIEKEILNNHG	acetylation	[4]
392	EILNNHGKSKTCCEN	acetylation	[4]
394	LNNHGKSKTCCENKE	acetylation	[4]
414	KDCLKLMKYLLEQLK	acetylation	[1]
414	KDCLKLMKYLLEQLK	ubiquitination	[2, 3, 5, 6]
506	RSKEFLTKQIEYERN	ubiquitination	[2, 3]

Reference

 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [5] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 

Functional Description

 Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP. Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p]. Has antiviral activity by acting as a key cytosolic DNA sensor, the presence of double- stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses. Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production. 

Sequence Annotation

 NP_BIND 376 383 GTP (By similarity).
 NP_BIND 435 439 ATP (By similarity).
 REGION 173 215 DNA-binding region.
 REGION 384 407 DNA-binding.
 METAL 225 225 Magnesium; catalytic (Probable).
 METAL 227 227 Magnesium; catalytic (Probable).
 METAL 319 319 Magnesium; catalytic (By similarity).
 METAL 390 390 Zinc.
 METAL 396 396 Zinc.
 METAL 397 397 Zinc.
 METAL 404 404 Zinc.
 BINDING 211 211 GTP (By similarity).
 BINDING 213 213 ATP (By similarity).
 BINDING 319 319 GTP (By similarity).
 BINDING 383 383 ATP (By similarity).
 BINDING 414 414 ATP (By similarity).
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 7 7 N6-acetyllysine.
 MOD_RES 143 143 Phosphoserine.
 MOD_RES 414 414 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Antiviral defense; ATP-binding; Complete proteome; Cytoplasm; DNA-binding; GTP-binding; Immunity; Innate immunity; Magnesium; Metal-binding; Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Polymorphism; Reference proteome; Transferase; Zinc. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 522 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0061501; F:cyclic-GMP-AMP synthase activity; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0002218; P:activation of innate immune response; IMP:UniProtKB.
 GO:0071360; P:cellular response to exogenous dsRNA; IDA:UniProtKB.
 GO:0009190; P:cyclic nucleotide biosynthetic process; IDA:UniProtKB.
 GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB. 

Interpro

 IPR020950; Mab-21-rel.
 IPR024810; Mab-21_dom.
 IPR024805; MB21D1. 

Pfam

 PF03281; Mab-21 

SMART

  

PROSITE

  

PRINTS