TRI40_HUMAN
ID TRI40_HUMAN Reviewed; 258 AA.
AC Q6P9F5; Q5SRJ6; Q5SS36; Q8TD96;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=E3 ubiquitin ligase TRIM40;
DE EC=2.3.2.27 {ECO:0000269|PubMed:29117565};
DE AltName: Full=Probable E3 NEDD8-protein ligase;
DE AltName: Full=RING finger protein 35;
GN Name=TRIM40; Synonyms=RNF35;
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 2).
RX PubMed=12622776; DOI=10.1034/j.1399-0039.2003.610105.x;
RA Meyer M., Gaudieri S., Rhodes D.A., Trowsdale J.;
RT "Cluster of TRIM genes in the human MHC class I region sharing the B30.2
RT domain.";
RL Tissue Antigens 61:63-71(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=16702430; DOI=10.1534/genetics.106.057034;
RA Shiina T., Ota M., Shimizu S., Katsuyama Y., Hashimoto N., Takasu M.,
RA Anzai T., Kulski J.K., Kikkawa E., Naruse T., Kimura N., Yanagiya K.,
RA Watanabe A., Hosomichi K., Kohara S., Iwamoto C., Umehara Y., Meyer A.,
RA Wanner V., Sano K., Macquin C., Ikeo K., Tokunaga K., Gojobori T.,
RA Inoko H., Bahram S.;
RT "Rapid evolution of major histocompatibility complex class I genes in
RT primates generates new disease alleles in humans via hitchhiking
RT diversity.";
RL Genetics 173:1555-1570(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH NEDD8.
RX PubMed=21474709; DOI=10.1093/carcin/bgr068;
RA Noguchi K., Okumura F., Takahashi N., Kataoka A., Kamiyama T., Todo S.,
RA Hatakeyama S.;
RT "TRIM40 promotes neddylation of IKKgamma and is downregulated in
RT gastrointestinal cancers.";
RL Carcinogenesis 32:995-1004(2011).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29117565; DOI=10.1016/j.celrep.2017.10.020;
RA Zhao C., Jia M., Song H., Yu Z., Wang W., Li Q., Zhang L., Zhao W., Cao X.;
RT "The E3 Ubiquitin Ligase TRIM40 Attenuates Antiviral Immune Responses by
RT Targeting MDA5 and RIG-I.";
RL Cell Rep. 21:1613-1623(2017).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a role in the
CC limitation of the innate immune response (PubMed:21474709,
CC PubMed:29117565). Mediates inhibition of the RLR signaling pathway by
CC ubiquitinating DDX58 and IFIH1 receptors, leading to their proteasomal
CC degradation (PubMed:21474709). Promotes also the neddylation of
CC IKBKG/NEMO, stabilizing NFKBIA, and thereby inhibiting of NF-kappa-B
CC nuclear translocation and activation (PubMed:21474709).
CC {ECO:0000269|PubMed:21474709, ECO:0000269|PubMed:29117565}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:29117565};
CC -!- SUBUNIT: Interacts with NEDD8. {ECO:0000269|PubMed:21474709}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P9F5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P9F5-2; Sequence=VSP_012131;
CC -!- TISSUE SPECIFICITY: Highly expressed in normal gastrointestinal
CC epithelia but that is down-regulated in gastrointestinal carcinomas and
CC chronic inflammatory lesions of the gastrointestinal tract.
CC {ECO:0000269|PubMed:21474709}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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DR EMBL; AF489517; AAM09503.1; -; mRNA.
DR EMBL; AB110939; BAD13705.1; -; Genomic_DNA.
DR EMBL; AB110940; BAD13706.1; -; Genomic_DNA.
DR EMBL; AB202084; BAE78604.1; -; Genomic_DNA.
DR EMBL; AL669914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX322644; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL671859; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR788282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX927221; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03265.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03266.1; -; Genomic_DNA.
DR EMBL; BC060785; AAH60785.1; -; mRNA.
DR CCDS; CCDS4675.1; -. [Q6P9F5-2]
DR CCDS; CCDS69069.1; -. [Q6P9F5-1]
DR RefSeq; NP_001273562.1; NM_001286633.1. [Q6P9F5-1]
DR RefSeq; NP_619645.1; NM_138700.4. [Q6P9F5-2]
DR RefSeq; XP_011512607.1; XM_011514305.1. [Q6P9F5-1]
DR RefSeq; XP_011512608.1; XM_011514306.1. [Q6P9F5-1]
DR AlphaFoldDB; Q6P9F5; -.
DR SMR; Q6P9F5; -.
DR BioGRID; 126432; 13.
DR IntAct; Q6P9F5; 1.
DR MINT; Q6P9F5; -.
DR STRING; 9606.ENSP00000379826; -.
DR iPTMnet; Q6P9F5; -.
DR PhosphoSitePlus; Q6P9F5; -.
DR BioMuta; TRIM40; -.
DR DMDM; 229463021; -.
DR MassIVE; Q6P9F5; -.
DR PeptideAtlas; Q6P9F5; -.
DR PRIDE; Q6P9F5; -.
DR ProteomicsDB; 67040; -. [Q6P9F5-1]
DR ProteomicsDB; 67041; -. [Q6P9F5-2]
DR Antibodypedia; 26227; 91 antibodies from 27 providers.
DR DNASU; 135644; -.
DR Ensembl; ENST00000307859.4; ENSP00000308310.4; ENSG00000204614.9. [Q6P9F5-2]
DR Ensembl; ENST00000376724.6; ENSP00000365914.2; ENSG00000204614.9. [Q6P9F5-1]
DR Ensembl; ENST00000383610.6; ENSP00000373105.2; ENSG00000172524.12. [Q6P9F5-1]
DR Ensembl; ENST00000396581.6; ENSP00000379826.1; ENSG00000204614.9. [Q6P9F5-1]
DR Ensembl; ENST00000400651.7; ENSP00000383492.3; ENSG00000172524.12. [Q6P9F5-2]
DR Ensembl; ENST00000421981.6; ENSP00000403025.2; ENSG00000237046.8. [Q6P9F5-2]
DR Ensembl; ENST00000429471.6; ENSP00000393674.2; ENSG00000228001.8. [Q6P9F5-2]
DR Ensembl; ENST00000433713.5; ENSP00000389607.1; ENSG00000224496.7. [Q6P9F5-1]
DR Ensembl; ENST00000434151.5; ENSP00000388460.1; ENSG00000237046.8. [Q6P9F5-1]
DR Ensembl; ENST00000436951.6; ENSP00000416663.2; ENSG00000224496.7. [Q6P9F5-2]
DR Ensembl; ENST00000437563.5; ENSP00000416950.1; ENSG00000228001.8. [Q6P9F5-1]
DR Ensembl; ENST00000547289.2; ENSP00000446663.1; ENSG00000172524.12. [Q6P9F5-1]
DR Ensembl; ENST00000549728.2; ENSP00000447016.1; ENSG00000237046.8. [Q6P9F5-1]
DR Ensembl; ENST00000552119.2; ENSP00000448967.1; ENSG00000228001.8. [Q6P9F5-1]
DR Ensembl; ENST00000616351.1; ENSP00000483120.1; ENSG00000224496.7. [Q6P9F5-1]
DR GeneID; 135644; -.
DR KEGG; hsa:135644; -.
DR MANE-Select; ENST00000396581.6; ENSP00000379826.1; NM_001286633.2; NP_001273562.1.
DR UCSC; uc003npk.2; human. [Q6P9F5-1]
DR CTD; 135644; -.
DR DisGeNET; 135644; -.
DR GeneCards; TRIM40; -.
DR HGNC; HGNC:18736; TRIM40.
DR HPA; ENSG00000204614; Group enriched (intestine, liver, testis).
DR MIM; 616976; gene.
DR neXtProt; NX_Q6P9F5; -.
DR OpenTargets; ENSG00000204614; -.
DR PharmGKB; PA38663; -.
DR VEuPathDB; HostDB:ENSG00000204614; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00710000106875; -.
DR HOGENOM; CLU_013137_3_0_1; -.
DR InParanoid; Q6P9F5; -.
DR OMA; PEHVSHH; -.
DR OrthoDB; 251004at2759; -.
DR PhylomeDB; Q6P9F5; -.
DR TreeFam; TF333491; -.
DR PathwayCommons; Q6P9F5; -.
DR SignaLink; Q6P9F5; -.
DR BioGRID-ORCS; 135644; 13 hits in 1104 CRISPR screens.
DR ChiTaRS; TRIM40; human.
DR GenomeRNAi; 135644; -.
DR Pharos; Q6P9F5; Tbio.
DR PRO; PR:Q6P9F5; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q6P9F5; protein.
DR Bgee; ENSG00000204614; Expressed in duodenum and 27 other tissues.
DR ExpressionAtlas; Q6P9F5; baseline and differential.
DR Genevisible; Q6P9F5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0008385; C:IkappaB kinase complex; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; NAS:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:UniProtKB.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IDA:UniProtKB.
DR GO; GO:0045116; P:protein neddylation; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Metal-binding; Reference proteome;
KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..258
FT /note="E3 ubiquitin ligase TRIM40"
FT /id="PRO_0000056260"
FT ZN_FING 14..56
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 66..107
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT COILED 107..159
FT /evidence="ECO:0000255"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT VAR_SEQ 148..176
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12622776"
FT /id="VSP_012131"
FT VARIANT 142
FT /note="K -> Q (in dbSNP:rs12528473)"
FT /id="VAR_055309"
FT VARIANT 215
FT /note="E -> K (in dbSNP:rs757259)"
FT /id="VAR_055310"
FT VARIANT 244
FT /note="E -> K (in dbSNP:rs757259)"
FT /id="VAR_057222"
SQ SEQUENCE 258 AA; 29336 MW; C360BECD4411F1DB CRC64;
MIPLQKDNQE EGVCPICQES LKEAVSTNCG HLFCRVCLTQ HVEKASASGV FCCPLCRKPC
SEEVLGTGYI CPNHQKRVCR FCEESRLLLC VECLVSPEHM SHHELTIENA LSHYKERLNR
RSRKLRKDIA ELQRLKAQQE KKLQALQFQV DHGNHRLEAG PESQHQTREQ LGALPQQWLG
QLEHMPAEAA RILDISRAVT QLRSLVIDLE RTAKELDTNT LKNAGDLLNR SAPQKLEVIY
PQLEKGVSEL LLQPPQKL
