ECSIT_HUMAN
ID ECSIT_HUMAN Reviewed; 431 AA.
AC Q9BQ95; E9PAN9; K7EMM0; Q96HQ7; Q9NYI1;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
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|HGNC:HGNC:29548};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT CYS-278.
RA Fitzgerald S.N., Brady K.J., Moynagh P.N.;
RT "Nucleotide sequence of the human ECSIT cDNA.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye, Lung, and Pancreas;
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 [6]
RP SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION
RP WITH NDUFAF1.
RX PubMed=17344420; DOI=10.1101/gad.408407;
RA Vogel R.O., Janssen R.J.R.J., van den Brand M.A.M., Dieteren C.E.J.,
RA Verkaart S., Koopman W.J.H., Willems P.H.G.M., Pluk W.,
RA van den Heuvel L.P.W.J., Smeitink J.A.M., Nijtmans L.G.J.;
RT "Cytosolic signaling protein Ecsit also localizes to mitochondria where it
RT interacts with chaperone NDUFAF1 and functions in complex I assembly.";
RL Genes Dev. 21:615-624(2007).
RN [7]
RP INTERACTION WITH ACAD9.
RX PubMed=20816094; DOI=10.1016/j.cmet.2010.08.002;
RA Nouws J., Nijtmans L., Houten S.M., van den Brand M., Huynen M.,
RA Venselaar H., Hoefs S., Gloerich J., Kronick J., Hutchin T., Willems P.,
RA Rodenburg R., Wanders R., van den Heuvel L., Smeitink J., Vogel R.O.;
RT "Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative
RT phosphorylation complex I.";
RL Cell Metab. 12:283-294(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP IDENTIFICATION IN THE MCIA COMPLEX, AND FUNCTION.
RX PubMed=32320651; DOI=10.1016/j.celrep.2020.107541;
RA Formosa L.E., Muellner-Wong L., Reljic B., Sharpe A.J., Jackson T.D.,
RA Beilharz T.H., Stojanovski D., Lazarou M., Stroud D.A., Ryan M.T.;
RT "Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly
RT Complex Factors in the Biogenesis of Complex I.";
RL Cell Rep. 31:107541-107541(2020).
RN [11]
RP INTERACTION WITH TMEM70 AND TMEM242.
RX PubMed=33753518; DOI=10.1073/pnas.2100558118;
RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.;
RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase
RT and interact with assembly factors for complex I.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
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 (By
CC similarity). {ECO:0000250}.
CC -!- FUNCTION: As part of the MCIA complex, involved in the assembly of the
CC mitochondrial complex I. {ECO:0000269|PubMed:32320651}.
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 (PubMed:32320651). Interacts with NDUFAF1
CC (PubMed:17344420). Interacts with ACAD9 (PubMed:20816094). Interacts
CC with TRIM59 (By similarity). Interacts with TMEM70 and TMEM242
CC (PubMed:33753518). {ECO:0000250|UniProtKB:Q9QZH6,
CC ECO:0000269|PubMed:17344420, ECO:0000269|PubMed:20816094,
CC ECO:0000269|PubMed:32320651, ECO:0000269|PubMed:33753518}.
CC -!- INTERACTION:
CC Q9BQ95; P02649: APOE; NbExp=4; IntAct=EBI-712452, EBI-1222467;
CC Q9BQ95; Q13515: BFSP2; NbExp=3; IntAct=EBI-712452, EBI-10229433;
CC Q9BQ95; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-712452, EBI-8643161;
CC Q9BQ95; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-712452, EBI-11962928;
CC Q9BQ95; Q86UW9: DTX2; NbExp=3; IntAct=EBI-712452, EBI-740376;
CC Q9BQ95; Q9Y285: FARSA; NbExp=2; IntAct=EBI-712452, EBI-725361;
CC Q9BQ95; P55040: GEM; NbExp=3; IntAct=EBI-712452, EBI-744104;
CC Q9BQ95; O15479: MAGEB2; NbExp=3; IntAct=EBI-712452, EBI-1057615;
CC Q9BQ95; Q13064: MKRN3; NbExp=3; IntAct=EBI-712452, EBI-2340269;
CC Q9BQ95; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-712452, EBI-398874;
CC Q9BQ95; P49768: PSEN1; NbExp=4; IntAct=EBI-712452, EBI-297277;
CC Q9BQ95; P49810: PSEN2; NbExp=4; IntAct=EBI-712452, EBI-2010251;
CC Q9BQ95; A2RTX5: TARS3; NbExp=3; IntAct=EBI-712452, EBI-1056629;
CC Q9BQ95; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-712452, EBI-3918381;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17344420}. Nucleus
CC {ECO:0000269|PubMed:17344420}. Mitochondrion
CC {ECO:0000269|PubMed:17344420}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9BQ95-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BQ95-2; Sequence=VSP_026345, VSP_026346;
CC Name=3;
CC IsoId=Q9BQ95-3; Sequence=VSP_046689;
CC Name=4;
CC IsoId=Q9BQ95-4; Sequence=VSP_055626, VSP_026346;
CC -!- SIMILARITY: Belongs to the ECSIT family. {ECO:0000305}.
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DR EMBL; AF243044; AAF62100.1; -; mRNA.
DR EMBL; AK314905; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CR457204; CAG33485.1; -; mRNA.
DR EMBL; AC008481; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000193; AAH00193.1; -; mRNA.
DR EMBL; BC005119; AAH05119.1; -; mRNA.
DR EMBL; BC008279; AAH08279.1; -; mRNA.
DR CCDS; CCDS12262.1; -. [Q9BQ95-1]
DR CCDS; CCDS45979.1; -. [Q9BQ95-3]
DR CCDS; CCDS45980.1; -. [Q9BQ95-2]
DR CCDS; CCDS59353.1; -. [Q9BQ95-4]
DR RefSeq; NP_001135936.1; NM_001142464.2. [Q9BQ95-2]
DR RefSeq; NP_001135937.1; NM_001142465.2. [Q9BQ95-3]
DR RefSeq; NP_001230133.1; NM_001243204.1. [Q9BQ95-4]
DR RefSeq; NP_057665.2; NM_016581.4. [Q9BQ95-1]
DR AlphaFoldDB; Q9BQ95; -.
DR SASBDB; Q9BQ95; -.
DR BioGRID; 119446; 265.
DR ComplexPortal; CPX-6322; Mitochondrial complex I intermediate assembly (MCIA) complex.
DR CORUM; Q9BQ95; -.
DR IntAct; Q9BQ95; 106.
DR MINT; Q9BQ95; -.
DR STRING; 9606.ENSP00000270517; -.
DR iPTMnet; Q9BQ95; -.
DR PhosphoSitePlus; Q9BQ95; -.
DR SwissPalm; Q9BQ95; -.
DR BioMuta; ECSIT; -.
DR DMDM; 74752234; -.
DR EPD; Q9BQ95; -.
DR jPOST; Q9BQ95; -.
DR MassIVE; Q9BQ95; -.
DR MaxQB; Q9BQ95; -.
DR PaxDb; Q9BQ95; -.
DR PeptideAtlas; Q9BQ95; -.
DR PRIDE; Q9BQ95; -.
DR ProteomicsDB; 19054; -.
DR ProteomicsDB; 78645; -. [Q9BQ95-1]
DR ProteomicsDB; 78646; -. [Q9BQ95-2]
DR TopDownProteomics; Q9BQ95-1; -. [Q9BQ95-1]
DR Antibodypedia; 13189; 227 antibodies from 30 providers.
DR DNASU; 51295; -.
DR Ensembl; ENST00000252440.11; ENSP00000252440.6; ENSG00000130159.15. [Q9BQ95-2]
DR Ensembl; ENST00000270517.12; ENSP00000270517.6; ENSG00000130159.15. [Q9BQ95-1]
DR Ensembl; ENST00000417981.6; ENSP00000412712.1; ENSG00000130159.15. [Q9BQ95-3]
DR Ensembl; ENST00000591104.5; ENSP00000466559.1; ENSG00000130159.15. [Q9BQ95-4]
DR Ensembl; ENST00000688351.1; ENSP00000508502.1; ENSG00000130159.15. [Q9BQ95-1]
DR Ensembl; ENST00000690346.1; ENSP00000510792.1; ENSG00000130159.15. [Q9BQ95-1]
DR GeneID; 51295; -.
DR KEGG; hsa:51295; -.
DR MANE-Select; ENST00000270517.12; ENSP00000270517.6; NM_016581.5; NP_057665.2.
DR UCSC; uc002msb.4; human. [Q9BQ95-1]
DR CTD; 51295; -.
DR DisGeNET; 51295; -.
DR GeneCards; ECSIT; -.
DR HGNC; HGNC:29548; ECSIT.
DR HPA; ENSG00000130159; Low tissue specificity.
DR MIM; 608388; gene.
DR neXtProt; NX_Q9BQ95; -.
DR OpenTargets; ENSG00000130159; -.
DR PharmGKB; PA147358104; -.
DR VEuPathDB; HostDB:ENSG00000130159; -.
DR eggNOG; KOG3941; Eukaryota.
DR GeneTree; ENSGT00390000005147; -.
DR HOGENOM; CLU_046917_0_0_1; -.
DR InParanoid; Q9BQ95; -.
DR OMA; FGQHNVH; -.
DR OrthoDB; 995360at2759; -.
DR PhylomeDB; Q9BQ95; -.
DR TreeFam; TF314943; -.
DR PathwayCommons; Q9BQ95; -.
DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR Reactome; R-HSA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR Reactome; R-HSA-975871; MyD88 cascade initiated on plasma membrane.
DR SignaLink; Q9BQ95; -.
DR SIGNOR; Q9BQ95; -.
DR BioGRID-ORCS; 51295; 88 hits in 1097 CRISPR screens.
DR ChiTaRS; ECSIT; human.
DR GenomeRNAi; 51295; -.
DR Pharos; Q9BQ95; Tbio.
DR PRO; PR:Q9BQ95; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BQ95; protein.
DR Bgee; ENSG00000130159; Expressed in apex of heart and 191 other tissues.
DR ExpressionAtlas; Q9BQ95; baseline and differential.
DR Genevisible; Q9BQ95; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IC:ComplexPortal.
DR GO; GO:0051341; P:regulation of oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0061635; P:regulation of protein complex stability; IDA:UniProtKB.
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 Alternative splicing; Cytoplasm; Immunity; Innate immunity; Mitochondrion;
KW Nucleus; Reference proteome; Transit peptide.
FT TRANSIT 1..48
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 49..431
FT /note="Evolutionarily conserved signaling intermediate in
FT Toll pathway, mitochondrial"
FT /id="PRO_0000291985"
FT REGION 400..431
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 35..248
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046689"
FT VAR_SEQ 266..296
FT /note="GIQSPDQQAALARHNPARPVFVEGPFSLWLR -> ELTCCPRRRGKWKRRRR
FT SGTSTTRCSWTWSM (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055626"
FT VAR_SEQ 267..296
FT /note="IQSPDQQAALARHNPARPVFVEGPFSLWLR -> SGRDAGGVEPLLPDAAGP
FT GVCEEWLGQLRV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026345"
FT VAR_SEQ 297..431
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_026346"
FT VARIANT 278
FT /note="R -> C (in dbSNP:rs34803265)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_032907"
FT VARIANT 406
FT /note="G -> R (in dbSNP:rs2302971)"
FT /id="VAR_032908"
FT CONFLICT 242
FT /note="V -> A (in Ref. 2; AK314905)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 431 AA; 49148 MW; 42AFEBFFA6953C80 CRC64;
MSWVQATLLA RGLCRAWGGT CGAALTGTSI SQVPRRLPRG LHCSAAAHSS EQSLVPSPPE
PRQRPTKALV PFEDLFGQAP GGERDKASFL QTVQKFAEHS VRKRGHIDFI YLALRKMREY
GVERDLAVYN QLLNIFPKEV FRPRNIIQRI FVHYPRQQEC GIAVLEQMEN HGVMPNKETE
FLLIQIFGRK SYPMLKLVRL KLWFPRFMNV NPFPVPRDLP QDPVELAMFG LRHMEPDLSA
RVTIYQVPLP KDSTGAADPP QPHIVGIQSP DQQAALARHN PARPVFVEGP FSLWLRNKCV
YYHILRADLL PPEEREVEET PEEWNLYYPM QLDLEYVRSG WDNYEFDINE VEEGPVFAMC
MAGAHDQATM AKWIQGLQET NPTLAQIPVV FRLAGSTREL QTSSAGLEEP PLPEDHQEED
DNLQRQQQGQ S
