ID ECSIT_BOVIN Reviewed; 433 AA.
AC Q3SX05;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 24-JAN-2024, entry version 96.
DE RecName: Full=Evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial {ECO:0000250|UniProtKB:Q9BQ95};
DE Flags: Precursor;
GN Name=ECSIT {ECO:0000250|UniProtKB:Q9BQ95};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Adapter protein that plays a role in different signaling
CC pathways including TLRs and IL-1 pathways or innate antiviral induction
CC signaling. Plays a role in the activation of NF-kappa-B by forming a
CC signal complex with TRAF6 and TAK1/MAP3K7 to activate TAK1/MAP3K7
CC leading to activation of IKKs. Once ubiquitinated, interacts with the
CC dissociated RELA and NFKB1 proteins and translocates to the nucleus
CC where it induces NF-kappa-B-dependent gene expression. Plays a role in
CC innate antiviral immune response by bridging the pattern recognition
CC receptors RIGI and MDA5/IFIT1 to the MAVS complex at the mitochondrion
CC (By similarity). Promotes proteolytic activation of MAP3K1. Involved in
CC the BMP signaling pathway. Required for normal embryonic development
CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q9BQ95}.
CC -!- FUNCTION: As part of the MCIA complex, involved in the assembly of the
CC mitochondrial complex I. {ECO:0000250|UniProtKB:Q9BQ95}.
CC -!- SUBUNIT: Interacts with MAP3K1, SMAD4 and TRAF6. Interacts with SMAD1
CC only after BMP4-treatment (By similarity). Part of the mitochondrial
CC complex I assembly/MCIA complex that comprises at least the core
CC subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits
CC such as COA1 and TMEM186. Interacts with NDUFAF1. Interacts with ACAD9.
CC Interacts with TRIM59. Interacts with TMEM70 and TMEM242. Interacts
CC (when ubiquitinated) with NF-kappa-B subunits RELA and NFKB1. Interacts
CC with RIGI, IFIT1 and MAVS; these interactions promote RLR-mediated type
CC I IFN induction. Interacts with SQSTM1; this interaction inhibits TLR4
CC signaling via functional regulation of the TRAF6-ECSIT complex.
CC Interacts with cereblon/CRBN; this interaction inhibits the
CC ubiquitination of ECSIT (By similarity). {ECO:0000250|UniProtKB:Q9BQ95,
CC ECO:0000250|UniProtKB:Q9QZH6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BQ95}. Nucleus
CC {ECO:0000250|UniProtKB:Q9BQ95}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9BQ95}.
CC -!- PTM: Ubiquitinated on Lys-372; leading to translocation in the nucleus
CC together with RELA and NFKB1 and expression of NF-kappa-B-dependent
CC genes. {ECO:0000250|UniProtKB:Q9BQ95}.
CC -!- SIMILARITY: Belongs to the ECSIT family. {ECO:0000305}.
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DR EMBL; BC104572; AAI04573.1; -; mRNA.
DR RefSeq; NP_001029458.1; NM_001034286.1.
DR RefSeq; XP_010805109.1; XM_010806807.2.
DR AlphaFoldDB; Q3SX05; -.
DR STRING; 9913.ENSBTAP00000020029; -.
DR PaxDb; 9913-ENSBTAP00000020029; -.
DR Ensembl; ENSBTAT00000020029.3; ENSBTAP00000020029.2; ENSBTAG00000015049.5.
DR GeneID; 507245; -.
DR KEGG; bta:507245; -.
DR CTD; 51295; -.
DR VEuPathDB; HostDB:ENSBTAG00000015049; -.
DR VGNC; VGNC:28313; ECSIT.
DR eggNOG; KOG3941; Eukaryota.
DR GeneTree; ENSGT00390000005147; -.
DR HOGENOM; CLU_046917_0_0_1; -.
DR InParanoid; Q3SX05; -.
DR OMA; NMADFGV; -.
DR OrthoDB; 4098911at2759; -.
DR TreeFam; TF314943; -.
DR Reactome; R-BTA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-BTA-6799198; Complex I biogenesis.
DR Reactome; R-BTA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR Reactome; R-BTA-975871; MyD88 cascade initiated on plasma membrane.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000015049; Expressed in infraspinatus muscle and 104 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0051341; P:regulation of oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0061635; P:regulation of protein complex stability; ISS:UniProtKB.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IEA:Ensembl.
DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IBA:GO_Central.
DR InterPro; IPR029342; ECIST_C.
DR InterPro; IPR010418; ECSIT.
DR InterPro; IPR046448; ECSIT_N.
DR PANTHER; PTHR13113; ECSIT EVOLUTIONARILY CONSERVED SIGNALING INTERMEDIATE IN TOLL PATHWAYS; 1.
DR PANTHER; PTHR13113:SF1; EVOLUTIONARILY CONSERVED SIGNALING INTERMEDIATE IN TOLL PATHWAY, MITOCHONDRIAL; 1.
DR Pfam; PF14784; ECSIT_C; 1.
DR Pfam; PF06239; ECSIT_N; 1.
DR SMART; SM01284; ECSIT_Cterm; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Immunity; Innate immunity; Isopeptide bond; Mitochondrion;
KW Nucleus; Reference proteome; Transit peptide; Ubl conjugation.
FT TRANSIT 1..48
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 49..433
FT /note="Evolutionarily conserved signaling intermediate in
FT Toll pathway, mitochondrial"
FT /id="PRO_0000291984"
FT REGION 36..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 372
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9BQ95"
SQ SEQUENCE 433 AA; 49251 MW; 8698F263AB81E449 CRC64;
MSWAQAILLA RGASRGWGGI CSTALTGAPF SQVPPQAPRG LRCSAAAHNP DSSLVPHPPE
PPRRPVKALA VHEELFRPAL DGARNKANFV RAVQNFTEYN VHKRGHVDFI YLALRKMREY
GVERDLSVYN LLLDIFPKEV FRPRNIFHSI FLHYPRQQEC GIAVLEQMEN HGVMPNKETE
FLLLQIFGRK SYPMLKLVRM KLWFTRFKNI NPFPVPRDLP QDPVDLASLA LRHMEPDLSA
RVTTYQMPLL KDSPNAMDPT ETHIVGIQSP EQQSALARHD PARPIFVEGP FSLWLRDKCV
YYHILRADLL PPEEREVEEI PEEWNLYYPM QLDLAYGRSS WDDYEFNIDE VEEGPVFAIC
VAGAHDQATL AKWIQGLQET NPALARIPVV FRLSGSSGEL LPSSSELEEP PPPPPEGQEE
EEDSQQRQQQ GQS
//