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Protein

Cyclic GMP-AMP synthase

Gene

MB21D1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. cGAMP can be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but TMEM173/STING-dependent manner (PubMed:26229115).10 Publications

Catalytic activityi

ATP + GTP = 2 diphosphate + cyclic G-P(2'-5')A-P(3'-5').4 Publications

Cofactori

Mg2+By similarityNote: Binds 1 Mg2+ ion per subunit.By similarity

Enzyme regulationi

The enzyme activity is strongly increased by double-stranded DNA, but not by single-stranded DNA or RNA.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei211 – 2111GTPBy similarity
Binding sitei213 – 2131ATPBy similarity
Metal bindingi225 – 2251Magnesium; catalyticCurated
Metal bindingi227 – 2271Magnesium; catalyticCurated
Metal bindingi319 – 3191Magnesium; catalyticBy similarity
Binding sitei319 – 3191GTP1 Publication
Binding sitei383 – 3831ATPBy similarity
Metal bindingi390 – 3901Zinc; via tele nitrogen3 Publications
Metal bindingi396 – 3961Zinc3 Publications
Metal bindingi397 – 3971Zinc3 Publications
Metal bindingi404 – 4041Zinc3 Publications
Binding sitei414 – 4141ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi376 – 3838GTP1 Publication
Nucleotide bindingi435 – 4395ATP1 Publication

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cyclic-GMP-AMP synthase activity Source: UniProtKB
  • DNA binding Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • activation of innate immune response Source: UniProtKB
  • cellular response to exogenous dsRNA Source: UniProtKB
  • cyclic nucleotide biosynthetic process Source: UniProtKB
  • defense response to virus Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • positive regulation of defense response to virus by host Source: UniProtKB
  • positive regulation of type I interferon production Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Nucleotidyltransferase, Transferase

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, DNA-binding, GTP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.7.86. 2681.
ReactomeiR-HSA-1834941. STING mediated induction of host immune responses.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic GMP-AMP synthase (EC:2.7.7.864 Publications)
Short name:
cGAMP synthase
Short name:
cGAS
Short name:
h-cGAS
Alternative name(s):
2'3'-cGAMP synthase
Mab-21 domain-containing protein 1
Gene namesi
Name:MB21D1
Synonyms:C6orf150
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:21367. MB21D1.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication

GO - Cellular componenti

  • cytosol Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi171 – 1711K → A: No effect on stimulation of interferon production. 1 Publication
Mutagenesisi173 – 1731K → A: Strongly reduces enzyme activity and stimulation of interferon production; when associated with A-176. No effect on stimulation of interferon production. 3 Publications
Mutagenesisi173 – 1731K → E: Strongly reduces stimulation of interferon production. 2 Publications
Mutagenesisi174 – 1741L → N: Strongly reduces enzyme activity and stimulation of interferon production. 2 Publications
Mutagenesisi176 – 1761R → A: Strongly reduces enzyme activity and stimulation of interferon production; when associated with A-173. 1 Publication
Mutagenesisi211 – 2111T → Q: Abolishes enzyme activity; when associated with I-376 and I-436. 1 Publication
Mutagenesisi212 – 2132GS → AA: Abolishes enzyme activity. Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi225 – 2251E → A: Abolishes enzyme activity and stimulation of interferon production; when associated with A-227. 3 Publications
Mutagenesisi227 – 2271D → A: Abolishes enzyme activity and stimulation of interferon production; when associated with A-225. 3 Publications
Mutagenesisi236 – 2361R → E: Abolishes stimulation of interferon production; when associated with E-254 and E-327. 1 Publication
Mutagenesisi254 – 2541K → E: Abolishes stimulation of interferon production; when associated with E-236 and E-327. 1 Publication
Mutagenesisi327 – 3271K → E: Abolishes stimulation of interferon production; when associated with E-236 and E-254. 1 Publication
Mutagenesisi347 – 3471K → E: Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi353 – 3531R → E: Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi376 – 3761R → I: Alters enzyme activity, leading to the appearance of 3'-5' linked cGAMP. Abolishes enzyme activity; when associated with Q-211 and I-436. 1 Publication
Mutagenesisi384 – 3841K → A or E: Abolishes stimulation of interferon production. 2 Publications
Mutagenesisi390 – 3901H → A: Strongly reduces stimulation of interferon production. 1 Publication
Mutagenesisi394 – 3941K → A: Abolishes enzyme activity. No effect on stimulation of interferon production. 2 Publications
Mutagenesisi394 – 3941K → E: Abolishes enzyme activity. Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi396 – 3972CC → AA: Abolishes DNA binding and enzyme activity. Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi396 – 3961C → A: Abolishes DNA binding and enzyme activity. 1 Publication
Mutagenesisi397 – 3971C → A: Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi400 – 4001K → E: Abolishes stimulation of interferon production; when associated with E-403. 1 Publication
Mutagenesisi403 – 4031K → E: Abolishes stimulation of interferon production; when associated with E-400. 1 Publication
Mutagenesisi404 – 4041C → A: Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi407 – 4071K → A or E: Abolishes enzyme activity and stimulation of interferon production; when associated with A-411. Abolishes enzyme activity. Abolishes stimulation of interferon production. 2 Publications
Mutagenesisi411 – 4111K → A: Abolishes enzyme activity and stimulation of interferon production; when associated with A-407. 1 Publication
Mutagenesisi414 – 4141K → A or E: Abolishes stimulation of interferon production. 1 Publication
Mutagenesisi436 – 4361Y → I: Abolishes enzyme activity; when associated with Q-211 and I-376. 1 Publication

Organism-specific databases

PharmGKBiPA134956015.

Polymorphism and mutation databases

BioMutaiMB21D1.
DMDMi68565218.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 522522Cyclic GMP-AMP synthasePRO_0000089543Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei7 – 71N6-acetyllysineCombined sources
Modified residuei143 – 1431PhosphoserineCombined sources
Modified residuei286 – 28615-glutamyl polyglutamateBy similarity
Modified residuei314 – 31415-glutamyl glutamateBy similarity
Modified residuei414 – 4141N6-acetyllysineCombined sources

Post-translational modificationi

Polyglutamylated by TTLL6 at Glu-286, leading to impair DNA-binding activity. Monoglutamylated at Glu-314 by TTLL4, leading to impair the nucleotidyltransferase activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein

Proteomic databases

EPDiQ8N884.
MaxQBiQ8N884.
PaxDbiQ8N884.
PeptideAtlasiQ8N884.
PRIDEiQ8N884.

PTM databases

iPTMnetiQ8N884.
PhosphoSiteiQ8N884.

Expressioni

Tissue specificityi

Expressed in the monocytic cell line THP1.1 Publication

Inductioni

By type I interferons.1 Publication

Gene expression databases

BgeeiQ8N884.
CleanExiHS_C6orf150.
GenevisibleiQ8N884. HS.

Organism-specific databases

HPAiHPA031700.
HPA031702.

Interactioni

Subunit structurei

Monomer in the absence of DNA. Homodimer when bound to DNA.By similarity

Protein-protein interaction databases

BioGridi125408. 7 interactions.
IntActiQ8N884. 5 interactions.
STRINGi9606.ENSP00000359339.

Structurei

Secondary structure

1
522
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi157 – 1593Combined sources
Helixi162 – 17413Combined sources
Turni175 – 1784Combined sources
Helixi180 – 19718Combined sources
Helixi201 – 2033Combined sources
Beta strandi207 – 2104Combined sources
Helixi212 – 2165Combined sources
Beta strandi220 – 2223Combined sources
Beta strandi225 – 2339Combined sources
Beta strandi237 – 2426Combined sources
Beta strandi246 – 2549Combined sources
Helixi263 – 2653Combined sources
Helixi273 – 28816Combined sources
Beta strandi292 – 2943Combined sources
Beta strandi296 – 2983Combined sources
Beta strandi304 – 3063Combined sources
Beta strandi308 – 3125Combined sources
Turni313 – 3153Combined sources
Beta strandi316 – 32611Combined sources
Helixi332 – 3343Combined sources
Turni341 – 3444Combined sources
Helixi346 – 3538Combined sources
Beta strandi357 – 3615Combined sources
Beta strandi375 – 3784Combined sources
Helixi380 – 3889Combined sources
Beta strandi391 – 3933Combined sources
Turni394 – 3974Combined sources
Beta strandi398 – 4003Combined sources
Helixi406 – 42318Combined sources
Helixi425 – 4273Combined sources
Turni429 – 4324Combined sources
Helixi435 – 44814Combined sources
Helixi452 – 4554Combined sources
Helixi457 – 4593Combined sources
Helixi460 – 47718Combined sources
Turni493 – 4953Combined sources
Helixi498 – 51316Combined sources
Helixi518 – 5214Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KM5X-ray2.50A157-522[»]
4LEVX-ray1.95A/B157-522[»]
4LEWX-ray2.04A/B157-522[»]
4MKPX-ray1.95A161-522[»]
4O67X-ray2.44A/B161-522[»]
4O68X-ray2.44A147-522[»]
4O69X-ray2.25A161-522[»]
ProteinModelPortaliQ8N884.
SMRiQ8N884. Positions 157-522.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni173 – 21543DNA-binding1 PublicationAdd
BLAST
Regioni384 – 40724DNA-binding1 PublicationAdd
BLAST

Sequence similaritiesi

Belongs to the mab-21 family.Curated

Phylogenomic databases

eggNOGiENOG410IE27. Eukaryota.
ENOG410XTKD. LUCA.
GeneTreeiENSGT00710000106842.
HOGENOMiHOG000293423.
HOVERGENiHBG068840.
InParanoidiQ8N884.
KOiK17834.
OMAiPQDSQWD.
OrthoDBiEOG7S21ZG.
PhylomeDBiQ8N884.
TreeFamiTF331255.

Family and domain databases

InterProiIPR024810. Mab-21_dom.
[Graphical view]
PfamiPF03281. Mab-21. 1 hit.
[Graphical view]
SMARTiSM01265. Mab-21. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N884-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQPWHGKAMQ RASEAGATAP KASARNARGA PMDPTESPAA PEAALPKAGK
60 70 80 90 100
FGPARKSGSR QKKSAPDTQE RPPVRATGAR AKKAPQRAQD TQPSDATSAP
110 120 130 140 150
GAEGLEPPAA REPALSRAGS CRQRGARCST KPRPPPGPWD VPSPGLPVSA
160 170 180 190 200
PILVRRDAAP GASKLRAVLE KLKLSRDDIS TAAGMVKGVV DHLLLRLKCD
210 220 230 240 250
SAFRGVGLLN TGSYYEHVKI SAPNEFDVMF KLEVPRIQLE EYSNTRAYYF
260 270 280 290 300
VKFKRNPKEN PLSQFLEGEI LSASKMLSKF RKIIKEEIND IKDTDVIMKR
310 320 330 340 350
KRGGSPAVTL LISEKISVDI TLALESKSSW PASTQEGLRI QNWLSAKVRK
360 370 380 390 400
QLRLKPFYLV PKHAKEGNGF QEETWRLSFS HIEKEILNNH GKSKTCCENK
410 420 430 440 450
EEKCCRKDCL KLMKYLLEQL KERFKDKKHL DKFSSYHVKT AFFHVCTQNP
460 470 480 490 500
QDSQWDRKDL GLCFDNCVTY FLQCLRTEKL ENYFIPEFNL FSSNLIDKRS
510 520
KEFLTKQIEY ERNNEFPVFD EF
Length:522
Mass (Da):58,814
Last modified:July 5, 2005 - v2
Checksum:i808FF6F9F3BF8C50
GO
Isoform 2 (identifier: Q8N884-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     445-447: VCT → RLY
     448-522: Missing.

Note: No experimental confirmation available.
Show »
Length:447
Mass (Da):49,762
Checksum:i61504BFBBB6FD338
GO

Sequence cautioni

The sequence AAH12928.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti35 – 351T → N.2 Publications
Corresponds to variant rs9352000 [ dbSNP | Ensembl ].
VAR_050811
Natural varianti261 – 2611P → H.1 Publication
Corresponds to variant rs610913 [ dbSNP | Ensembl ].
VAR_033677

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei445 – 4473VCT → RLY in isoform 2. 1 PublicationVSP_014388
Alternative sequencei448 – 52275Missing in isoform 2. 1 PublicationVSP_014389Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
KC294566 mRNA. Translation: AGB51853.1.
AK097148 mRNA. Translation: BAC04965.1.
AL603910, AC019205 Genomic DNA. Translation: CAI14878.1.
AL603910, AC019205 Genomic DNA. Translation: CAI14879.1.
BC012928 mRNA. Translation: AAH12928.1. Different initiation.
BC108714 mRNA. Translation: AAI08715.1.
BC113606 mRNA. Translation: AAI13607.1.
BC113608 mRNA. Translation: AAI13609.1.
BC143694 mRNA. Translation: AAI43695.1.
CCDSiCCDS4978.1. [Q8N884-1]
RefSeqiNP_612450.2. NM_138441.2. [Q8N884-1]
UniGeneiHs.658405.

Genome annotation databases

EnsembliENST00000370315; ENSP00000359339; ENSG00000164430. [Q8N884-1]
ENST00000370318; ENSP00000359342; ENSG00000164430. [Q8N884-2]
GeneIDi115004.
KEGGihsa:115004.
UCSCiuc003pgx.2. human. [Q8N884-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
KC294566 mRNA. Translation: AGB51853.1.
AK097148 mRNA. Translation: BAC04965.1.
AL603910, AC019205 Genomic DNA. Translation: CAI14878.1.
AL603910, AC019205 Genomic DNA. Translation: CAI14879.1.
BC012928 mRNA. Translation: AAH12928.1. Different initiation.
BC108714 mRNA. Translation: AAI08715.1.
BC113606 mRNA. Translation: AAI13607.1.
BC113608 mRNA. Translation: AAI13609.1.
BC143694 mRNA. Translation: AAI43695.1.
CCDSiCCDS4978.1. [Q8N884-1]
RefSeqiNP_612450.2. NM_138441.2. [Q8N884-1]
UniGeneiHs.658405.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4KM5X-ray2.50A157-522[»]
4LEVX-ray1.95A/B157-522[»]
4LEWX-ray2.04A/B157-522[»]
4MKPX-ray1.95A161-522[»]
4O67X-ray2.44A/B161-522[»]
4O68X-ray2.44A147-522[»]
4O69X-ray2.25A161-522[»]
ProteinModelPortaliQ8N884.
SMRiQ8N884. Positions 157-522.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125408. 7 interactions.
IntActiQ8N884. 5 interactions.
STRINGi9606.ENSP00000359339.

PTM databases

iPTMnetiQ8N884.
PhosphoSiteiQ8N884.

Polymorphism and mutation databases

BioMutaiMB21D1.
DMDMi68565218.

Proteomic databases

EPDiQ8N884.
MaxQBiQ8N884.
PaxDbiQ8N884.
PeptideAtlasiQ8N884.
PRIDEiQ8N884.

Protocols and materials databases

DNASUi115004.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370315; ENSP00000359339; ENSG00000164430. [Q8N884-1]
ENST00000370318; ENSP00000359342; ENSG00000164430. [Q8N884-2]
GeneIDi115004.
KEGGihsa:115004.
UCSCiuc003pgx.2. human. [Q8N884-1]

Organism-specific databases

CTDi115004.
GeneCardsiMB21D1.
H-InvDBHIX0022366.
HGNCiHGNC:21367. MB21D1.
HPAiHPA031700.
HPA031702.
MIMi613973. gene.
neXtProtiNX_Q8N884.
PharmGKBiPA134956015.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE27. Eukaryota.
ENOG410XTKD. LUCA.
GeneTreeiENSGT00710000106842.
HOGENOMiHOG000293423.
HOVERGENiHBG068840.
InParanoidiQ8N884.
KOiK17834.
OMAiPQDSQWD.
OrthoDBiEOG7S21ZG.
PhylomeDBiQ8N884.
TreeFamiTF331255.

Enzyme and pathway databases

BRENDAi2.7.7.86. 2681.
ReactomeiR-HSA-1834941. STING mediated induction of host immune responses.

Miscellaneous databases

ChiTaRSiMB21D1. human.
GenomeRNAii115004.
PROiQ8N884.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N884.
CleanExiHS_C6orf150.
GenevisibleiQ8N884. HS.

Family and domain databases

InterProiIPR024810. Mab-21_dom.
[Graphical view]
PfamiPF03281. Mab-21. 1 hit.
[Graphical view]
SMARTiSM01265. Mab-21. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway."
    Sun L., Wu J., Du F., Chen X., Chen Z.J.
    Science 339:786-791(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, DNA-BINDING, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    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 T.-O., 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.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASN-35.
    Tissue: Spleen.
  3. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS ASN-35 AND HIS-261.
    Tissue: Brain, Prostate and Testis.
  5. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-7 AND LYS-414, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. "A diverse range of gene products are effectors of the type I interferon antiviral response."
    Schoggins J.W., Wilson S.J., Panis M., Murphy M.Y., Jones C.T., Bieniasz P., Rice C.M.
    Nature 472:481-485(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  8. "The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING."
    Diner E.J., Burdette D.L., Wilson S.C., Monroe K.M., Kellenberger C.A., Hyodo M., Hayakawa Y., Hammond M.C., Vance R.E.
    Cell Rep. 3:1355-1361(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-173; LEU-174; ARG-176; 212-GLY-SER-213; GLU-225; ASP-227; 396-CYS-CYS-397; LYS-407 AND LYS-411.
  10. "Structure-guided reprogramming of human cGAS dinucleotide linkage specificity."
    Kranzusch P.J., Lee A.S., Wilson S.C., Solovykh M.S., Vance R.E., Berger J.M., Doudna J.A.
    Cell 158:1011-1021(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF THR-211; ARG-376 AND TYR-436.
  11. "Ancient origin of cGAS-STING reveals mechanism of universal 2',3' cGAMP signaling."
    Kranzusch P.J., Wilson S.C., Lee A.S., Berger J.M., Doudna J.A., Vance R.E.
    Mol. Cell 59:891-903(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION.
  12. "Transmission of innate immune signaling by packaging of cGAMP in viral particles."
    Gentili M., Kowal J., Tkach M., Satoh T., Lahaye X., Conrad C., Boyron M., Lombard B., Durand S., Kroemer G., Loew D., Dalod M., Thery C., Manel N.
    Science 349:1232-1236(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF GLU-225 AND ASP-227.
  13. "Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity."
    Kranzusch P.J., Lee A.S., Berger J.M., Doudna J.A.
    Cell Rep. 3:1362-1368(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 157-222 IN COMPLEX WITH ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, DOMAIN, ENZYME REGULATION, DNA-BINDING, MUTAGENESIS OF LYS-171; LYS-173; GLU-225; ASP-227; LYS-384; HIS-390; LYS-394; CYS-396; CYS-397; CYS-404; LYS-407 AND LYS-414.
  14. "Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization."
    Li X., Shu C., Yi G., Chaton C.T., Shelton C.L., Diao J., Zuo X., Kao C.C., Herr A.B., Li P.
    Immunity 39:1019-1031(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 157-522 IN COMPLEX WITH ZINC.
  15. "Structural and functional analyses of DNA-sensing and immune activation by human cGAS."
    Kato K., Ishii R., Goto E., Ishitani R., Tokunaga F., Nureki O.
    PLoS ONE 8:E76983-E76983(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 161-522 IN COMPLEX WITH ZINC, FUNCTION, DNA-BINDING, MUTAGENESIS OF LYS-384; LYS-400; LYS-403; LYS-407 AND LYS-411.
  16. "The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop."
    Zhang X., Wu J., Du F., Xu H., Sun L., Chen Z., Brautigam C.A., Zhang X., Chen Z.J.
    Cell Rep. 6:421-430(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 161-522 IN COMPLEX WITH ZINC AND CYCLIC GMP-AMP, FUNCTION, MUTAGENESIS OF ARG-236; LYS-254; LYS-327; LYS-347; ARG-353 AND LYS-394.

Entry informationi

Entry nameiCGAS_HUMAN
AccessioniPrimary (citable) accession number: Q8N884
Secondary accession number(s): L0L2J9
, Q14CV6, Q32NC9, Q5SWL0, Q5SWL1, Q96E45
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: July 6, 2016
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.