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Q8C6L5

- CGAS_MOUSE

UniProt

Q8C6L5 - CGAS_MOUSE

Protein

Cyclic GMP-AMP synthase

Gene

Mb21d1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 79 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    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.3 Publications

    Catalytic activityi

    ATP + GTP = 2 diphosphate + cyclic G-P(2'-5')A-P(3'-5').1 Publication

    Cofactori

    Binds 1 Mg2+ per subunit. Is also active with Mn2+.1 Publication

    Enzyme regulationi

    Nucleotidyltransferase activity is stimulated by double-stranded DNA but not RNA.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei197 – 1971GTP
    Binding sitei199 – 1991ATP
    Metal bindingi211 – 2111Magnesium; catalytic
    Metal bindingi213 – 2131Magnesium; catalytic
    Metal bindingi307 – 3071Magnesium; catalytic
    Binding sitei307 – 3071GTP
    Binding sitei371 – 3711ATP
    Metal bindingi378 – 3781Zinc
    Metal bindingi384 – 3841Zinc
    Metal bindingi385 – 3851Zinc
    Metal bindingi392 – 3921Zinc
    Binding sitei402 – 4021ATP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi364 – 3718GTP
    Nucleotide bindingi420 – 4245ATP

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cyclic-GMP-AMP synthase activity Source: UniProtKB
    3. DNA binding Source: UniProtKB-KW
    4. GTP binding Source: UniProtKB-KW
    5. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. activation of innate immune response Source: UniProtKB
    2. cellular response to exogenous dsRNA Source: UniProtKB
    3. cyclic nucleotide biosynthetic process Source: UniProtKB
    4. defense response to virus Source: UniProtKB-KW
    5. innate immune response Source: UniProtKB-KW
    6. positive regulation of defense response to virus by host Source: UniProtKB

    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

    ReactomeiREACT_196457. STING mediated induction of host immune responses.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclic GMP-AMP synthase (EC:2.7.7.86)
    Short name:
    cGAMP synthase
    Short name:
    cGAS
    Short name:
    m-cGAS
    Alternative name(s):
    Mab-21 domain-containing protein 1
    Gene namesi
    Name:Mb21d1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 9

    Organism-specific databases

    MGIiMGI:2442261. Mb21d1.

    Subcellular locationi

    Cytoplasmcytosol 1 Publication

    GO - Cellular componenti

    1. cytosol Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi211 – 2111E → A: Abolishes ability to promote type-I interferon production. 1 Publication
    Mutagenesisi213 – 2131D → A: Abolishes ability to promote type-I interferon production. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 507507Cyclic GMP-AMP synthasePRO_0000421764Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei402 – 4021N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PRIDEiQ8C6L5.

    Expressioni

    Gene expression databases

    ArrayExpressiQ8C6L5.
    GenevestigatoriQ8C6L5.

    Structurei

    Secondary structure

    1
    507
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi147 – 15711
    Helixi161 – 18424
    Beta strandi185 – 1873
    Turni188 – 1914
    Beta strandi193 – 1986
    Turni199 – 2035
    Beta strandi207 – 2093
    Beta strandi211 – 2199
    Beta strandi222 – 2287
    Beta strandi232 – 2398
    Helixi249 – 2513
    Beta strandi252 – 2576
    Helixi259 – 27416
    Beta strandi279 – 2846
    Beta strandi293 – 31422
    Helixi320 – 3223
    Turni329 – 3324
    Helixi334 – 3407
    Beta strandi345 – 3495
    Beta strandi352 – 3543
    Helixi359 – 3613
    Beta strandi363 – 3664
    Helixi368 – 3769
    Turni382 – 3854
    Helixi394 – 41118
    Helixi413 – 4153
    Helixi420 – 43314
    Helixi437 – 4404
    Helixi442 – 4443
    Helixi445 – 46218
    Beta strandi468 – 4703
    Turni478 – 4803
    Helixi483 – 49816
    Helixi502 – 5054

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4K8VX-ray2.00A/B/C/D147-507[»]
    4K96X-ray2.08A/B147-507[»]
    4K97X-ray2.41A147-507[»]
    4K98X-ray1.94A147-507[»]
    4K99X-ray1.95A147-507[»]
    4K9AX-ray2.26A147-507[»]
    4K9BX-ray2.26A147-507[»]
    4LEYX-ray2.50A/B/C/D142-507[»]
    4LEZX-ray2.36A/C142-507[»]
    4O6AX-ray1.86A/B147-507[»]
    ProteinModelPortaliQ8C6L5.
    SMRiQ8C6L5. Positions 147-506.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni158 – 20144DNA-bindingAdd
    BLAST
    Regioni372 – 39524DNA-bindingAdd
    BLAST

    Sequence similaritiesi

    Belongs to the mab-21 family.Curated

    Phylogenomic databases

    GeneTreeiENSGT00710000106842.
    HOVERGENiHBG068840.
    InParanoidiQ8C6L5.
    KOiK17834.
    OMAiPQDSQWD.
    OrthoDBiEOG7S21ZG.
    TreeFamiTF331255.

    Family and domain databases

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

    Sequencei

    Sequence statusi: Complete.

    Q8C6L5-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEDPRRRTTA PRAKKPSAKR APTQPSRTRA HAESCGPQRG ARSRRAERDG    50
    DTTEKPRAPG PRVHPARATE LTKDAQPSAM DAAGATARPA VRVPQQQAIL 100
    DPELPAVREP QPPADPEARK VVRGPSHRRG ARSTGQPRAP RGSRKEPDKL 150
    KKVLDKLRLK RKDISEAAET VNKVVERLLR RMQKRESEFK GVEQLNTGSY 200
    YEHVKISAPN EFDVMFKLEV PRIELQEYYE TGAFYLVKFK RIPRGNPLSH 250
    FLEGEVLSAT KMLSKFRKII KEEVKEIKDI DVSVEKEKPG SPAVTLLIRN 300
    PEEISVDIIL ALESKGSWPI STKEGLPIQG WLGTKVRTNL RREPFYLVPK 350
    NAKDGNSFQG ETWRLSFSHT EKYILNNHGI EKTCCESSGA KCCRKECLKL 400
    MKYLLEQLKK EFQELDAFCS YHVKTAIFHM WTQDPQDSQW DPRNLSSCFD 450
    KLLAFFLECL RTEKLDHYFI PKFNLFSQEL IDRKSKEFLS KKIEYERNNG 500
    FPIFDKL 507
    Length:507
    Mass (Da):58,194
    Last modified:March 1, 2003 - v1
    Checksum:i9FDA84DF5E4859CA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti6 – 61R → I in BAE26335. (PubMed:16141072)Curated
    Sequence conflicti471 – 4711P → R in BAE26335. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    KC294567 mRNA. Translation: AGB51854.1.
    AK054330 mRNA. Translation: BAC35733.1.
    AK145268 mRNA. Translation: BAE26335.1.
    AC158987 Genomic DNA. No translation available.
    CH466522 Genomic DNA. Translation: EDL26396.1.
    BC052196 mRNA. Translation: AAH52196.1.
    BC145651 mRNA. Translation: AAI45652.1.
    BC145653 mRNA. Translation: AAI45654.1.
    CCDSiCCDS40702.1.
    RefSeqiNP_775562.2. NM_173386.4.
    UniGeneiMm.101559.

    Genome annotation databases

    EnsembliENSMUST00000070742; ENSMUSP00000063331; ENSMUSG00000032344.
    GeneIDi214763.
    KEGGimmu:214763.
    UCSCiuc009quj.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    KC294567 mRNA. Translation: AGB51854.1 .
    AK054330 mRNA. Translation: BAC35733.1 .
    AK145268 mRNA. Translation: BAE26335.1 .
    AC158987 Genomic DNA. No translation available.
    CH466522 Genomic DNA. Translation: EDL26396.1 .
    BC052196 mRNA. Translation: AAH52196.1 .
    BC145651 mRNA. Translation: AAI45652.1 .
    BC145653 mRNA. Translation: AAI45654.1 .
    CCDSi CCDS40702.1.
    RefSeqi NP_775562.2. NM_173386.4.
    UniGenei Mm.101559.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4K8V X-ray 2.00 A/B/C/D 147-507 [» ]
    4K96 X-ray 2.08 A/B 147-507 [» ]
    4K97 X-ray 2.41 A 147-507 [» ]
    4K98 X-ray 1.94 A 147-507 [» ]
    4K99 X-ray 1.95 A 147-507 [» ]
    4K9A X-ray 2.26 A 147-507 [» ]
    4K9B X-ray 2.26 A 147-507 [» ]
    4LEY X-ray 2.50 A/B/C/D 142-507 [» ]
    4LEZ X-ray 2.36 A/C 142-507 [» ]
    4O6A X-ray 1.86 A/B 147-507 [» ]
    ProteinModelPortali Q8C6L5.
    SMRi Q8C6L5. Positions 147-506.
    ModBasei Search...
    MobiDBi Search...

    Proteomic databases

    PRIDEi Q8C6L5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000070742 ; ENSMUSP00000063331 ; ENSMUSG00000032344 .
    GeneIDi 214763.
    KEGGi mmu:214763.
    UCSCi uc009quj.1. mouse.

    Organism-specific databases

    CTDi 115004.
    MGIi MGI:2442261. Mb21d1.

    Phylogenomic databases

    GeneTreei ENSGT00710000106842.
    HOVERGENi HBG068840.
    InParanoidi Q8C6L5.
    KOi K17834.
    OMAi PQDSQWD.
    OrthoDBi EOG7S21ZG.
    TreeFami TF331255.

    Enzyme and pathway databases

    Reactomei REACT_196457. STING mediated induction of host immune responses.

    Miscellaneous databases

    NextBioi 374454.
    PROi Q8C6L5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8C6L5.
    Genevestigatori Q8C6L5.

    Family and domain databases

    InterProi IPR024810. Mab-21_dom.
    [Graphical view ]
    Pfami PF03281. Mab-21. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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, DNA-BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF GLU-211 AND ASP-213.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Mammary gland and Ovary.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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].
      Tissue: Brain and Limb.
    6. "cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING."
      Ablasser A., Goldeck M., Cavlar T., Deimling T., Witte G., Rohl I., Hopfner K.P., Ludwig J., Hornung V.
      Nature 498:380-384(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase."
      Gao P., Ascano M., Wu Y., Barchet W., Gaffney B.L., Zillinger T., Serganov A.A., Liu Y., Jones R.A., Hartmann G., Tuschl T., Patel D.J.
      Cell 153:1094-1107(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 147-507 IN COMPLEXES WITH DNA; GMP; GTP; ATP; CYCLIC GMP-AMP; MAGNESIUM AND ZINC IONS, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, DNA-BINDING.

    Entry informationi

    Entry nameiCGAS_MOUSE
    AccessioniPrimary (citable) accession number: Q8C6L5
    Secondary accession number(s): Q3ULW3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 6, 2013
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 79 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3