ID   ECSIT_MOUSE             Reviewed;         435 AA.
AC   Q9QZH6; Q91V53;
DT   26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   26-JUN-2007, sequence version 2.
DT   25-MAY-2022, entry version 125.
DE   RecName: Full=Evolutionarily conserved signaling intermediate in Toll pathway, mitochondrial {ECO:0000305};
DE   AltName: Full=Protein SITPEC;
DE   Flags: Precursor;
GN   Name=Ecsit {ECO:0000312|MGI:MGI:1349469}; Synonyms=Sitpec;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TRAF6 AND MAP3K1, FUNCTION,
RP   ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=10465784; DOI=10.1101/gad.13.16.2059;
RA   Kopp E., Medzhitov R., Carothers J., Xiao C., Douglas I., Janeway C.A.,
RA   Ghosh S.;
RT   "ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal
RT   transduction pathway.";
RL   Genes Dev. 13:2059-2071(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SMAD1 AND SMAD4,
RP   ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX   PubMed=14633973; DOI=10.1101/gad.1145603;
RA   Xiao C., Shim J.-H., Klueppel M., Zhang S.S.-M., Dong C., Flavell R.A.,
RA   Fu X.-Y., Wrana J.L., Hogan B.L.M., Ghosh S.;
RT   "Ecsit is required for Bmp signaling and mesoderm formation during mouse
RT   embryogenesis.";
RL   Genes Dev. 17:2933-2949(2003).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   INTERACTION WITH TRIM59.
RX   PubMed=22588174; DOI=10.1016/j.bbrc.2012.05.028;
RA   Kondo T., Watanabe M., Hatakeyama S.;
RT   "TRIM59 interacts with ECSIT and negatively regulates NF-kappaB and IRF-
RT   3/7-mediated signal pathways.";
RL   Biochem. Biophys. Res. Commun. 422:501-507(2012).
CC   -!- FUNCTION: Adapter protein of the Toll-like and IL-1 receptor signaling
CC       pathway that is involved in the activation of NF-kappa-B via MAP3K1.
CC       Promotes proteolytic activation of MAP3K1. Involved in the BMP
CC       signaling pathway. Required for normal embryonic development.
CC       {ECO:0000269|PubMed:10465784, ECO:0000269|PubMed:14633973}.
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 (PubMed:14633973, PubMed:10465784). Part of
CC       the mitochondrial complex I assembly/MCIA complex that comprises at
CC       least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and
CC       complement subunits such as COA1 and TMEM186. Interacts with NDUFAF1.
CC       Interacts with ACAD9 (By similarity). Interacts with TRIM59
CC       (PubMed:22588174). Interacts with TMEM70 and TMEM242 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9BQ95, ECO:0000269|PubMed:10465784,
CC       ECO:0000269|PubMed:14633973, ECO:0000269|PubMed:22588174}.
CC   -!- INTERACTION:
CC       Q9QZH6; P70196: Traf6; NbExp=5; IntAct=EBI-527020, EBI-448028;
CC       Q9QZH6; P62991: Ubc; NbExp=2; IntAct=EBI-527020, EBI-413074;
CC       Q9QZH6; Q9Y4K3: TRAF6; Xeno; NbExp=2; IntAct=EBI-527020, EBI-359276;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14633973}. Nucleus
CC       {ECO:0000269|PubMed:14633973}. Mitochondrion {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Detected in heart, brain, lung, liver, skeletal
CC       muscle, kidney and testis. Detected in embryonic mesoderm and epiblast,
CC       and in extraembryonic ectoderm. {ECO:0000269|PubMed:10465784,
CC       ECO:0000269|PubMed:14633973}.
CC   -!- SIMILARITY: Belongs to the ECSIT family. {ECO:0000305}.
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DR   EMBL; AF182510; AAF01219.1; -; mRNA.
DR   EMBL; BC004583; AAH04583.1; -; mRNA.
DR   EMBL; BC016424; AAH16424.1; -; mRNA.
DR   CCDS; CCDS22920.1; -.
DR   RefSeq; NP_001240826.1; NM_001253897.1.
DR   RefSeq; NP_001240827.1; NM_001253898.1.
DR   RefSeq; NP_036159.1; NM_012029.2.
DR   RefSeq; XP_006510433.1; XM_006510370.3.
DR   RefSeq; XP_011240840.1; XM_011242538.2.
DR   AlphaFoldDB; Q9QZH6; -.
DR   BioGRID; 205076; 6.
DR   CORUM; Q9QZH6; -.
DR   DIP; DIP-33901N; -.
DR   IntAct; Q9QZH6; 16.
DR   STRING; 10090.ENSMUSP00000137424; -.
DR   iPTMnet; Q9QZH6; -.
DR   PhosphoSitePlus; Q9QZH6; -.
DR   EPD; Q9QZH6; -.
DR   jPOST; Q9QZH6; -.
DR   MaxQB; Q9QZH6; -.
DR   PaxDb; Q9QZH6; -.
DR   PeptideAtlas; Q9QZH6; -.
DR   PRIDE; Q9QZH6; -.
DR   ProteomicsDB; 277544; -.
DR   DNASU; 26940; -.
DR   GeneID; 26940; -.
DR   KEGG; mmu:26940; -.
DR   UCSC; uc009ons.2; mouse.
DR   CTD; 51295; -.
DR   MGI; MGI:1349469; Ecsit.
DR   eggNOG; KOG3941; Eukaryota.
DR   InParanoid; Q9QZH6; -.
DR   OrthoDB; 995360at2759; -.
DR   PhylomeDB; Q9QZH6; -.
DR   TreeFam; TF314943; -.
DR   Reactome; R-MMU-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR   Reactome; R-MMU-6799198; Complex I biogenesis.
DR   Reactome; R-MMU-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR   Reactome; R-MMU-975871; MyD88 cascade initiated on plasma membrane.
DR   BioGRID-ORCS; 26940; 17 hits in 73 CRISPR screens.
DR   ChiTaRS; Ecsit; mouse.
DR   PRO; PR:Q9QZH6; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q9QZH6; protein.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR   GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0001707; P:mesoderm formation; IMP:MGI.
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:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IDA:MGI.
DR   InterPro; IPR029342; ECIST_C.
DR   InterPro; IPR010418; ECSIT.
DR   PANTHER; PTHR13113; PTHR13113; 1.
DR   Pfam; PF06239; ECSIT; 1.
DR   Pfam; PF14784; ECSIT_C; 1.
DR   SMART; SM01284; ECSIT_Cterm; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Immunity; Innate immunity; Mitochondrion; Nucleus;
KW   Reference proteome; Transit peptide.
FT   TRANSIT         1..48
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           49..435
FT                   /note="Evolutionarily conserved signaling intermediate in
FT                   Toll pathway, mitochondrial"
FT                   /id="PRO_0000291987"
FT   REGION          401..435
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        75
FT                   /note="L -> S (in Ref. 1; AAF01219)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   435 AA;  49799 MW;  A2ABA68F1E2C6BF3 CRC64;
     MSWVQVNLLV RSLSRGWGGL CRPALSGTPF AQVSLQALRG LHCSAATHKD EPWLVPRPPE
     PQRKPIKVPA MHEDLFKPSG NRERDKASFL NAVRSFGAHN VRKRGHVDFI YLALRKMPEF
     GVERDLSVYN LLLDVFPKEV FRPRNVIQRI FVHYPRQQEC GVAVLEQMER HGVMPSAETE
     FLLIQIFGRK SYPMLKFLRM KLWFTRFKNI NPYPVPRDLP QDPLDLAKLG LRHMEPDLSA
     KVTVYQMSLP SDSTGMEDPT QPHIVGIQSP DQQAALARHN PSRPVFVEGP FPLWLRNKCV
     YYHILRADLP PPEEEKVEEI PEEWELYYPQ KLDLEYSRSG WDDYEFDVDE VTEGPVFAMC
     MAGAHDQATL IKWIQGLQET NPTLAQIPVV FRLARSTGEL LTTSRLEGQS PPHSPPKGPE
     EDDETIQAEQ QQGQS