MAVS_HUMAN » Mitochondrial antiviral-signaling protein

MAVS_HUMAN » Mitochondrial antiviral-signaling protein
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Topology in Mitochondrial outer membrane
Topologyintermembrane space
cytoplasmic side
MAVS_HUMAN » Mitochondrial antiviral-signaling protein » MAVS; CARD adapter inducing interferon beta;Cardif; Interferon beta promoter stimulator protein 1;IPS-1; Putative NF-kappa-B-activating protein 031N;Virus-induced-signaling adapter;VISA;
Hydrophobic Thickness 32.4 ± 3.8 Å
Tilt Angle 4 ± 1°
ΔGtransfer -21.9 kcal/mol
ΔGfold -15.5 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome
Topology In
TM Segments 515-536 (515-539)
Pathways

Cytosolic DNA-sensing pathway (KEGG)

Hepatitis B (KEGG)

Hepatitis C (KEGG)

Herpes simplex infection (KEGG)

Immune System (Reactome)

Influenza A (KEGG)

Measles (KEGG)

RIG-I-like receptor signaling pathway (KEGG)

PDB 2vgq (1-93), 3j6j (1-97), 3j6c (3-93), 4p4h (I/J...=1-99)
OPM none
Complexes none
Interactions

COA3, Complex: MAVS:COA3

HRSL4, Complex: HRSL4:MAVS, PubMed

PPR3A, Complex: IFIH1:PPR3A:MAVS, PubMed

TOM70, Complex: TOM70:MAVS, PubMed

Domains

AA: 5-92, PDBID: 2MS7, Subunit N, Seq Identity:100%, Caspase recruitment domain

UniProt annotation for MAVS_HUMAN » Mitochondrial antiviral-signaling protein
FUNCTION: Required for innate immune defense against viruses. Acts downstream of DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon- independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon- dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis.

SUBUNIT: Self-associates and polymerizes (via CARD domains) to form 400 nM long three-stranded helical filaments on mitochondria, filament nucleation requires interaction with DDX58/RIG-I whose CARD domains act as a template for filament assembly. Interacts with DDX58/RIG-I, IFIH1/MDA5, TRAF2, TRAF6 and C1QBP. May interact with IRF3, FADD, RIPK1, CHUK and IKBKB. Interacts with and is cleaved by HCV and hepatitis GB virus B NS3/4A proteases. Interacts with and is cleaved by HHAV protein 3ABC. Interacts with NLRX1. Interaction with NLRX1 requires the CARD domain. Interacts with PSMA7. Interacts with TRAFD1 (By similarity). Interacts (via C-terminus) with PCBP2 in a complex containing MAVS/IPS1, PCBP2 and ITCH. Interacts with CYLD. Interacts with SRC. Interacts with DHX58/LGP2 and IKBKE. Interacts with TMEM173/MITA. Interacts with IFIT3 (via N-terminus). Interacts with TBK1 only in the presence of IFIT3. Interacts with MUL1. Interacts with human respiratory syncytial virus (HRSV) NS1 protein; this interaction disrupts MAVS binding to DDX58/RIG-I. Interacts with ANKRD17.

TISSUE SPECIFICITY: Present in T-cells, monocytes, epithelial cells and hepatocytes (at protein level). Ubiquitously expressed, with highest levels in heart, skeletal muscle, liver, placenta and peripheral blood leukocytes.

DOMAIN: Both CARD and transmembrane domains are essential for antiviral function. The CARD domain is responsible for interaction with DDX58/RIG-I and IFIH1/MDA5.

DOMAIN: The transmembrane domain and residues 300-444 are essential for its interaction with DHX58/LGP2.

MISCELLANEOUS: Cleavage by HCV protease complex leads to inactivation.

UniProt features for MAVS_HUMAN » Mitochondrial antiviral-signaling protein
CHAIN 1 540 Mitochondrial antiviral-signaling protein.
DOMAIN 10 77 CARD.
REGION 10 77 Required for interaction with NLRX1.
REGION 143 147 Interaction with TRAF2.
REGION 153 158 Interaction with TRAF6.
REGION 455 460 Interaction with TRAF6.
SITE 427 428 Cleavage; by HHAV protein 3ABC.
SITE 508 509 Cleavage; by HCV and hepatitis GB virus B NS3/4A protease complex.
Amino Acid Sequence for MAVS_HUMAN » Mitochondrial antiviral-signaling protein
MPFAEDKTYK YICRNFSNFC NVDVVEILPY LPCLTARDQD RLRATCTLSG NRDTLWHLFN TLQRRPGWVE YFIAALRGCE LVDLADEVAS VYQSYQPRTS DRPPDPLEPP SLPAERPGPP TPAAAHSIPY NSCREKEPSY PMPVQETQAP ESPGENSEQA LQTLSPRAIP RNPDGGPLES SSDLAALSPL TSSGHQEQDT ELGSTHTAGA TSSLTPSRGP VSPSVSFQPL ARSTPRASRL PGPTGSVVST GTSFSSSSPG LASAGAAEGK QGAESDQAEP IICSSGAEAP ANSLPSKVPT TLMPVNTVAL KVPANPASVS TVPSKLPTSS KPPGAVPSNA LTNPAPSKLP INSTRAGMVP SKVPTSMVLT KVSASTVPTD GSSRNEETPA APTPAGATGG SSAWLDSSSE NRGLGSELSK PGVLASQVDS PFSGCFEDLA ISASTSLGMG PCHGPEENEY KSEGTFGIHV AENPSIQLLE GNPGPPADPD GGPRPQADRK FQEREVPCHR PSPGALWLQV AVTGVLVVTL LVVLYRRRLH