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Aliases for MB21D1 Gene

Aliases for MB21D1 Gene

  • Mab-21 Domain Containing 1 2 3 5
  • Mab-21 Domain-Containing Protein 1 3 4
  • Cyclic GMP-AMP Synthase 2 3
  • 23-CGAMP Synthase 3 4
  • CGAMP Synthase 3 4
  • C6orf150 3 4
  • H-CGAS 3 4
  • CGAS 3 4
  • Chromosome 6 Open Reading Frame 150 2
  • Protein MB21D1 3
  • EC 2.7.7.86 4

External Ids for MB21D1 Gene

Previous HGNC Symbols for MB21D1 Gene

  • C6orf150

Previous GeneCards Identifiers for MB21D1 Gene

  • GC06M074123

Summaries for MB21D1 Gene

GeneCards Summary for MB21D1 Gene

MB21D1 (Mab-21 Domain Containing 1) is a Protein Coding gene. Diseases associated with MB21D1 include Aicardi-Goutieres Syndrome and Renpenning Syndrome. Among its related pathways are Cytosolic sensors of pathogen-associated DNA and RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways. GO annotations related to this gene include GTP binding and cyclic-GMP-AMP synthase activity.

UniProtKB/Swiss-Prot for MB21D1 Gene

  • Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP (PubMed:28314590). 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] (PubMed:28363908, PubMed:28214358). 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 (PubMed:28363908). 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 (PubMed:28363908, PubMed:28314590). 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).

  • (Microbial infection) Upon M.tuberculosis infection THP-1 cells knocked-out for this gene have impaired type-I interferon production (IF-1 beta), nor do they produce type-I IFN upon transfection with dsDNA (PubMed:26048138).

Additional gene information for MB21D1 Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MB21D1 Gene

Genomics for MB21D1 Gene

Regulatory Elements for MB21D1 Gene

Enhancers for MB21D1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06H073584 2 FANTOM5 Ensembl ENCODE dbSUPER 12.1 -133.8 -133806 3 HDGF PKNOX1 FOXA2 MLX ARNT FEZF1 ZNF2 YY1 SMARCB1 ZNF592 SLC17A5 EEF1A1 LOC105377857 MB21D1 CD109 GC06P073601 GC06P073558
GH06H073577 2 FANTOM5 Ensembl ENCODE dbSUPER 7.2 -127.4 -127358 5 HDGF FOXA2 ARNT ARID4B DMAP1 YY1 ZNF766 ZNF143 ZNF207 ZNF548 SLC17A5 MTO1 EEF1A1 LOC105377857 CD109 MB21D1 GC06P073601 GC06P073558
GH06H073720 1.6 FANTOM5 Ensembl ENCODE dbSUPER 3.7 -271.0 -271033 5 CBFB ZBED1 JUN JUNB ELF1 EBF1 BATF ATF2 FOSL1 JUND CD109 LOC101928489 SLC17A5 MB21D1 EEF1A1 PIR44699
GH06H072824 0.9 Ensembl ENCODE 5.3 +626.0 626018 2 ZNF146 JUNB BATF ATF2 JUND IKZF1 SCRT2 FOS ATF7 IKZF2 KCNQ5 MB21D1 GC06M072905 GC06P072687
GH06H073665 0.6 ENCODE 5.6 -213.8 -213843 1 FOSL1 IKZF1 JUN CEBPB JUNB TRIM28 SLC17A5 MB21D1 GC06M073661 CD109
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MB21D1 on UCSC Golden Path with GeneCards custom track

Promoters for MB21D1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000198842 830 2201 TBP RB1 SIN3A BATF GTF3C2 RCOR1 ETV6 RUNX3 CREM IKZF2

Genomic Location for MB21D1 Gene

Chromosome:
6
Start:
73,413,515 bp from pter
End:
73,452,330 bp from pter
Size:
38,816 bases
Orientation:
Minus strand

Genomic View for MB21D1 Gene

Genes around MB21D1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MB21D1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MB21D1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MB21D1 Gene

Proteins for MB21D1 Gene

  • Protein details for MB21D1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N884-CGAS_HUMAN
    Recommended name:
    Cyclic GMP-AMP synthase
    Protein Accession:
    Q8N884
    Secondary Accessions:
    • L0L2J9
    • Q14CV6
    • Q32NC9
    • Q5SWL0
    • Q5SWL1
    • Q96E45

    Protein attributes for MB21D1 Gene

    Size:
    522 amino acids
    Molecular mass:
    58814 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Monomer in the absence of DNA and when bound to dsDNA.
    SequenceCaution:
    • Sequence=AAH12928.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for MB21D1 Gene

    Alternative splice isoforms for MB21D1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MB21D1 Gene

Post-translational modifications for MB21D1 Gene

  • Cleaved by CASP1 at Asp-140 and Asp-157 upon DNA virus infection; the cleavage impairs cGAMP production (PubMed:28314590). Also cleaved by the pyroptotic CASP4 and CASP5 during non-canonical inflammasome activation; they dont cut at the same sites than CASP1 (PubMed:28314590).
  • 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.
  • Ubiquitination at posLast=347347, posLast=355355, and posLast=414414
  • Modification sites at PhosphoSitePlus

Other Protein References for MB21D1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for MB21D1 Gene

Domains & Families for MB21D1 Gene

Gene Families for MB21D1 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for MB21D1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MB21D1 Gene

Graphical View of Domain Structure for InterPro Entry

Q8N884

UniProtKB/Swiss-Prot:

CGAS_HUMAN :
  • The N-terminal part (1-160) binds unspecifically dsDNA and expand the binding and moving range of MB21D1 on dsDNA. Enhances the enzyme activity and activation of innate immune signaling upon cytosolic recognition of dsDNA (PubMed:28363908, PubMed:28214358). When the N-terminal part (1-160) is missing the protein bound to dsDNA homodimerizes (By similarity).
  • Belongs to the mab-21 family.
Domain:
  • The N-terminal part (1-160) binds unspecifically dsDNA and expand the binding and moving range of MB21D1 on dsDNA. Enhances the enzyme activity and activation of innate immune signaling upon cytosolic recognition of dsDNA (PubMed:28363908, PubMed:28214358). When the N-terminal part (1-160) is missing the protein bound to dsDNA homodimerizes (By similarity).
Family:
  • Belongs to the mab-21 family.
genes like me logo Genes that share domains with MB21D1: view

Function for MB21D1 Gene

Molecular function for MB21D1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + GTP = 2 diphosphate + cyclic G-P(2-5)A-P(3-5).
UniProtKB/Swiss-Prot EnzymeRegulation:
The enzyme activity is strongly increased by double-stranded DNA, but not by single-stranded DNA or RNA (PubMed:23258413, PubMed:23707061, PubMed:26300263). The enzyme activity is impaired by the cleavage at Asp-140 and Asp-157 produced by CASP1 (PubMed:28314590).
UniProtKB/Swiss-Prot Function:
Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP (PubMed:28314590). 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] (PubMed:28363908, PubMed:28214358). 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 (PubMed:28363908). 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 (PubMed:28363908, PubMed:28314590). 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).
UniProtKB/Swiss-Prot Function:
(Microbial infection) Upon M.tuberculosis infection THP-1 cells knocked-out for this gene have impaired type-I interferon production (IF-1 beta), nor do they produce type-I IFN upon transfection with dsDNA (PubMed:26048138).
UniProtKB/Swiss-Prot Induction:
By type I interferons.

Enzyme Numbers (IUBMB) for MB21D1 Gene

Phenotypes From GWAS Catalog for MB21D1 Gene

Gene Ontology (GO) - Molecular Function for MB21D1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA,IDA 23258413
GO:0003682 chromatin binding IDA 28738408
GO:0003690 double-stranded DNA binding IDA,IEA 24077100
GO:0005515 protein binding IPI 26046437
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with MB21D1: view
genes like me logo Genes that share phenotypes with MB21D1: view

Animal Models for MB21D1 Gene

MGI Knock Outs for MB21D1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for MB21D1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MB21D1 Gene

Localization for MB21D1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MB21D1 Gene

Cytoplasm, cytosol. Note=Upon transfection with dsDNA forms punctate structures that co-localize with DNA and Beclin-1 (BECN1) (PubMed:26048138). {ECO:0000269 PubMed:26048138}.
Note=(Microbial infection) Upon infection with virulent M.tuberculosis forms aggregates with dsDNA, non-virulent bacteria (without the ESX-1 locus) do not form these aggregates (PubMed:26048138). .

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MB21D1 gene
Compartment Confidence
cytosol 5
nucleus 3
cytoskeleton 2
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Microtubule organizing center (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MB21D1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MB21D1: view

Pathways & Interactions for MB21D1 Gene

genes like me logo Genes that share pathways with MB21D1: view

Pathways by source for MB21D1 Gene

Interacting Proteins for MB21D1 Gene

Gene Ontology (GO) - Biological Process for MB21D1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002218 activation of innate immune response IEA,IMP 23258413
GO:0002230 positive regulation of defense response to virus by host IEA,IMP 23258413
GO:0002376 immune system process IEA --
GO:0006974 cellular response to DNA damage stimulus IDA 28738408
GO:0009190 cyclic nucleotide biosynthetic process IDA 23258413
genes like me logo Genes that share ontologies with MB21D1: view

No data available for SIGNOR curated interactions for MB21D1 Gene

Drugs & Compounds for MB21D1 Gene

(2) Drugs for MB21D1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine triphosphate Experimental Pharma 0
ATP Nutra Agonist 0

(2) Additional Compounds for MB21D1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
cyclic GMP-AMP
pyrophosphate
  • (4-)Diphosphoric acid ion
  • (P2O74-)Diphosphate
  • Diphosphate
  • Diphosphoric acid
  • PPi
14000-31-8
genes like me logo Genes that share compounds with MB21D1: view

Transcripts for MB21D1 Gene

mRNA/cDNA for MB21D1 Gene

(2) REFSEQ mRNAs :
(7) Additional mRNA sequences :
(4) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for MB21D1 Gene

Mab-21 domain containing 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for MB21D1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

Alternative Splicing Database (ASD) splice patterns (SP) for MB21D1 Gene

No ASD Table

Relevant External Links for MB21D1 Gene

GeneLoc Exon Structure for
MB21D1
ECgene alternative splicing isoforms for
MB21D1

Expression for MB21D1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MB21D1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MB21D1 Gene

This gene is overexpressed in Whole Blood (x7.2).

Protein differential expression in normal tissues from HIPED for MB21D1 Gene

This gene is overexpressed in Lung (48.5) and Peripheral blood mononuclear cells (10.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MB21D1 Gene



Protein tissue co-expression partners for MB21D1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MB21D1 Gene:

MB21D1

SOURCE GeneReport for Unigene cluster for MB21D1 Gene:

Hs.658405

mRNA Expression by UniProt/SwissProt for MB21D1 Gene:

Q8N884-CGAS_HUMAN
Tissue specificity: Expressed in the monocytic cell line THP1.

Evidence on tissue expression from TISSUES for MB21D1 Gene

  • Spleen(4.4)
  • Nervous system(4.3)
  • Lymph node(2)
genes like me logo Genes that share expression patterns with MB21D1: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for MB21D1 Gene

Orthologs for MB21D1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for MB21D1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MB21D1 33 34
  • 98.79 (n)
cow
(Bos Taurus)
Mammalia MB21D1 33 34
  • 75.15 (n)
mouse
(Mus musculus)
Mammalia Mb21d1 33 16 34
  • 73.8 (n)
rat
(Rattus norvegicus)
Mammalia Mb21d1 33
  • 69.63 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia MB21D1 34
  • 61 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MB21D1 34
  • 60 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MB21D1 34
  • 51 (a)
OneToOne
chicken
(Gallus gallus)
Aves MB21D1 33 34
  • 59.81 (n)
lizard
(Anolis carolinensis)
Reptilia MB21D1 34
  • 40 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100488048 33
  • 50.23 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC557043 33
  • 48.68 (n)
mb21d1 34
  • 38 (a)
OneToOne
Species where no ortholog for MB21D1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MB21D1 Gene

ENSEMBL:
Gene Tree for MB21D1 (if available)
TreeFam:
Gene Tree for MB21D1 (if available)

Paralogs for MB21D1 Gene

No data available for Paralogs for MB21D1 Gene

Variants for MB21D1 Gene

Sequence variations from dbSNP and Humsavar for MB21D1 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs1000039180 -- 73,442,523(+) AGCAT(C/T)GTATG intron-variant
rs1000039962 -- 73,425,916(+) TTGCA(C/G)TGAGC intron-variant
rs1000145966 -- 73,427,092(+) TGATC(G/T)ACCTG intron-variant
rs1000175681 -- 73,425,686(+) ACATA(A/C)ATATA intron-variant
rs1000306634 -- 73,438,992(+) TCTTA(C/T)AGAAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MB21D1 Gene

Variant ID Type Subtype PubMed ID
esv1755651 CNV deletion 17803354
esv2264885 CNV deletion 18987734
esv2461232 CNV deletion 19546169
esv2665458 CNV deletion 23128226
esv2732293 CNV deletion 23290073
esv3539974 CNV deletion 23714750
esv3609510 CNV loss 21293372
esv4605 CNV loss 18987735
esv6440 CNV loss 19470904
nsv1074410 CNV deletion 25765185
nsv1140666 CNV deletion 24896259
nsv1151530 CNV deletion 26484159
nsv830693 CNV loss 17160897
nsv957546 CNV deletion 24416366

Variation tolerance for MB21D1 Gene

Residual Variation Intolerance Score: 80.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.51; 43.92% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MB21D1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MB21D1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MB21D1 Gene

Disorders for MB21D1 Gene

MalaCards: The human disease database

(4) MalaCards diseases for MB21D1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
aicardi-goutieres syndrome
  • cree encephalitis
renpenning syndrome
  • golabi-ito-hall syndrome
separation anxiety disorder
  • separation anxiety disorder of childhood
chilblain lupus
  • lupus erythematosus, cutaneous
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for MB21D1

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MB21D1
genes like me logo Genes that share disorders with MB21D1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MB21D1 Gene

Publications for MB21D1 Gene

  1. Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation. (PMID: 28363908) Tao J … Su XD (Journal of immunology (Baltimore, Md. : 1950) 2017) 3 4 60
  2. The N terminus of cGAS de-oligomerizes the cGAS:DNA complex and lifts the DNA size restriction of core-cGAS activity. (PMID: 28214358) Lee A … Kang SJ (FEBS letters 2017) 3 4 60
  3. Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1. (PMID: 26048138) Wassermann R … Ablasser A (Cell host & microbe 2015) 3 4 60
  4. Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling. (PMID: 26300263) Kranzusch PJ … Vance RE (Molecular cell 2015) 3 4 60
  5. The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop. (PMID: 24462292) Zhang X … Chen ZJ (Cell reports 2014) 3 4 60

Products for MB21D1 Gene

Sources for MB21D1 Gene

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