ID TRI32_HUMAN Reviewed; 653 AA. AC Q13049; Q9NQP8; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 27-MAR-2024, entry version 232. DE RecName: Full=E3 ubiquitin-protein ligase TRIM32; DE EC=2.3.2.27 {ECO:0000269|PubMed:19349376, ECO:0000269|PubMed:21628460, ECO:0000269|PubMed:22745133, ECO:0000269|PubMed:31123703}; DE AltName: Full=72 kDa Tat-interacting protein; DE AltName: Full=RING-type E3 ubiquitin transferase TRIM32 {ECO:0000305}; DE AltName: Full=Tripartite motif-containing protein 32; DE AltName: Full=Zinc finger protein HT2A; GN Name=TRIM32; Synonyms=HT2A; 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], AND FUNCTION (MICROBIAL INFECTION). RX PubMed=7778269; DOI=10.1006/viro.1995.1266; RA Fridell R.A., Harding L.S., Bogerd H.P., Cullen B.R.; RT "Identification of a novel human zinc finger protein that specifically RT interacts with the activation domain of lentiviral Tat proteins."; RL Virology 209:347-357(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; 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 [4] RP PROTEIN SEQUENCE OF 2-15; 51-60; 70-101; 205-238; 248-282; 345-359; RP 467-500; 587-596 AND 605-613, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION RP AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [6] RP FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, CATALYTIC ACTIVITY, PATHWAY, RP UBIQUITINATION, SELF-ASSOCIATION, AND INTERACTION WITH DTNBP1. RX PubMed=19349376; DOI=10.1093/hmg/ddp167; RA Locke M., Tinsley C.L., Benson M.A., Blake D.J.; RT "TRIM32 is an E3 ubiquitin ligase for dysbindin."; RL Hum. Mol. Genet. 18:2344-2358(2009). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY. RX PubMed=21628460; DOI=10.1074/jbc.m111.241893; RA Ryu Y.S., Lee Y., Lee K.W., Hwang C.Y., Maeng J.S., Kim J.H., Seo Y.S., RA You K.H., Song B., Kwon K.S.; RT "TRIM32 protein sensitizes cells to tumor necrosis factor (TNFalpha)- RT induced apoptosis via its RING domain-dependent E3 ligase activity against RT X-linked inhibitor of apoptosis (XIAP)."; RL J. Biol. Chem. 286:25729-25738(2011). RN [8] RP FUNCTION. RX PubMed=22500027; DOI=10.1074/jbc.m112.341487; RA Zhang Q., Yu D., Seo S., Stone E.M., Sheffield V.C.; RT "Intrinsic protein-protein interaction-mediated and chaperonin-assisted RT sequential assembly of stable Bardet-Biedl syndrome protein complex, the RT BBSome."; RL J. Biol. Chem. 287:20625-20635(2012). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-39, AND CATALYTIC RP ACTIVITY. RX PubMed=22745133; DOI=10.1074/jbc.m112.362608; RA Zhang J., Hu M.M., Wang Y.Y., Shu H.B.; RT "TRIM32 protein modulates type I interferon induction and cellular RT antiviral response by targeting MITA/STING protein for K63-linked RT ubiquitination."; RL J. Biol. Chem. 287:28646-28655(2012). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335 AND SER-339, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP INTERACTION WITH S.TYPHIMURIUM SSEK3 (MICROBIAL INFECTION). RX PubMed=26394407; DOI=10.1371/journal.pone.0138529; RA Yang Z., Soderholm A., Lung T.W., Giogha C., Hill M.M., Brown N.F., RA Hartland E., Teasdale R.D.; RT "SseK3 is a Salmonella effector that binds TRIM32 and modulates the host's RT NF-kappaB signalling activity."; RL PLoS ONE 10:e0138529-e0138529(2015). RN [12] RP FUNCTION, AND INTERACTION WITH TICAM1 AND TAX1BP1. RX PubMed=28898289; DOI=10.1371/journal.ppat.1006600; RA Yang Q., Liu T.T., Lin H., Zhang M., Wei J., Luo W.W., Hu Y.H., Zhong B., RA Hu M.M., Shu H.B.; RT "TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF RT negatively regulates TLR3/4-mediated innate immune responses."; RL PLoS Pathog. 13:e1006600-e1006600(2017). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH AMBRA1, AND RP MUTAGENESIS OF CYS-39. RX PubMed=31123703; DOI=10.1126/sciadv.aau8857; RA Di Rienzo M., Antonioli M., Fusco C., Liu Y., Mari M., Orhon I., Refolo G., RA Germani F., Corazzari M., Romagnoli A., Ciccosanti F., Mandriani B., RA Pellico M.T., De La Torre R., Ding H., Dentice M., Neri M., Ferlini A., RA Reggiori F., Kulesz-Martin M., Piacentini M., Merla G., Fimia G.M.; RT "Autophagy induction in atrophic muscle cells requires ULK1 activation by RT TRIM32 through unanchored K63-linked polyubiquitin chains."; RL Sci. Adv. 5:eaau8857-eaau8857(2019). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=32918979; DOI=10.1016/j.cellsig.2020.109777; RA Prajapati P., Gohel D., Shinde A., Roy M., Singh K., Singh R.; RT "TRIM32 regulates mitochondrial mediated ROS levels and sensitizes the RT oxidative stress induced cell death."; RL Cell. Signal. 76:109777-109777(2020). RN [15] RP FUNCTION. RX PubMed=34888944; DOI=10.1096/fj.202100031rr; RA Liu L., Liu T.T., Xie G.G., Zhu X.Q., Wang Y.; RT "Ubiquitin ligase TRIM32 promotes dendrite arborization by mediating RT degradation of the epigenetic factor CDYL."; RL FASEB J. 36:e22087-e22087(2022). RN [16] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=37543647; DOI=10.1038/s41419-023-06026-1; RA Romagnoli A., Di Rienzo M., Petruccioli E., Fusco C., Palucci I., RA Micale L., Mazza T., Delogu G., Merla G., Goletti D., Piacentini M., RA Fimia G.M.; RT "The ubiquitin ligase TRIM32 promotes the autophagic response to RT Mycobacterium tuberculosis infection in macrophages."; RL Cell Death Dis. 14:505-505(2023). RN [17] RP STRUCTURE BY NMR OF 10-84. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the RING domain of the tripartite motif protein RT 32."; RL Submitted (NOV-2005) to the PDB data bank. RN [18] RP VARIANT LGMDR8 ASN-487, AND TISSUE SPECIFICITY. RX PubMed=11822024; DOI=10.1086/339083; RA Frosk P., Weiler T., Nylen E., Sudha T., Greenberg C.R., Morgan K., RA Fujiwara T.M., Wrogemann K.; RT "Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, RT a putative E3-ubiquitin-ligase gene."; RL Am. J. Hum. Genet. 70:663-672(2002). RN [19] RP VARIANT BBS11 SER-130. RX PubMed=16606853; DOI=10.1073/pnas.0600158103; RA Chiang A.P., Beck J.S., Yen H.-J., Tayeh M.K., Scheetz T.E., RA Swiderski R.E., Nishimura D.Y., Braun T.A., Kim K.-Y.A., Huang J., RA Elbedour K., Carmi R., Slusarski D.C., Casavant T.L., Stone E.M., RA Sheffield V.C.; RT "Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin RT ligase, as a Bardet-Biedl syndrome gene (BBS11)."; RL Proc. Natl. Acad. Sci. U.S.A. 103:6287-6292(2006). RN [20] RP VARIANTS LGMDR8 HIS-394 AND ASP-588 DEL. RX PubMed=17994549; DOI=10.1002/humu.20633; RA Saccone V., Palmieri M., Passamano L., Piluso G., Meroni G., Politano L., RA Nigro V.; RT "Mutations that impair interaction properties of TRIM32 associated with RT limb-girdle muscular dystrophy 2H."; RL Hum. Mutat. 29:240-247(2008). RN [21] RP VARIANT GLN-299. RX PubMed=21344540; DOI=10.1002/humu.21480; RA Deveault C., Billingsley G., Duncan J.L., Bin J., Theal R., Vincent A., RA Fieggen K.J., Gerth C., Noordeh N., Traboulsi E.I., Fishman G.A., RA Chitayat D., Knueppel T., Millan J.M., Munier F.L., Kennedy D., RA Jacobson S.G., Innes A.M., Mitchell G.A., Boycott K., Heon E.; RT "BBS genotype-phenotype assessment of a multiethnic patient cohort calls RT for a revision of the disease definition."; RL Hum. Mutat. 32:610-619(2011). CC -!- FUNCTION: E3 ubiquitin ligase that plays a role in various biological CC processes including neural stem cell differentiation, innate immunity, CC inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703). CC Plays a role in virus-triggered induction of IFN-beta and TNF-alpha by CC mediating the ubiquitination of STING1. Mechanistically, targets STING1 CC for 'Lys-63'-linked ubiquitination which promotes the interaction of CC STING1 with TBK1 (PubMed:22745133). Regulates bacterial clearance and CC promotes autophagy in Mycobacterium tuberculosis-infected macrophages CC (PubMed:37543647). Negatively regulates TLR3/4-mediated innate immune CC and inflammatory response by triggering the autophagic degradation of CC TICAM1 in an E3 activity-independent manner (PubMed:28898289). Plays an CC essential role in oxidative stress induced cell death by inducing loss CC of transmembrane potential and enhancing mitochondrial reactive oxygen CC species (ROS) production during oxidative stress conditions CC (PubMed:32918979). Ubiquitinates XIAP and targets it for proteasomal CC degradation (PubMed:21628460). Ubiquitinates DTNBP1 (dysbindin) and CC promotes its degradation (PubMed:19349376). May ubiquitinate BBS2 CC (PubMed:22500027). Ubiquitinates PIAS4/PIASY and promotes its CC degradation in keratinocytes treated with UVB and TNF-alpha (By CC similarity). Also acts as a regulator of autophagy by mediating CC formation of unanchored 'Lys-63'-linked polyubiquitin chains that CC activate ULK1: interaction with AMBRA1 is required for ULK1 activation CC (PubMed:31123703). Positively regulates dendritic branching by CC promoting ubiquitination and subsequent degradation of the epigenetic CC factor CDYL (PubMed:34888944). {ECO:0000250|UniProtKB:Q8CH72, CC ECO:0000269|PubMed:19349376, ECO:0000269|PubMed:21628460, CC ECO:0000269|PubMed:22500027, ECO:0000269|PubMed:22745133, CC ECO:0000269|PubMed:28898289, ECO:0000269|PubMed:31123703, CC ECO:0000269|PubMed:32918979, ECO:0000269|PubMed:34888944, CC ECO:0000269|PubMed:37543647}. CC -!- FUNCTION: (Microbial infection) May play a significant role in CC mediating the biological activity of the HIV-1 Tat protein in vivo CC (PubMed:7778269). Binds specifically to the activation domain of HIV-1 CC Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo CC (PubMed:7778269). {ECO:0000269|PubMed:7778269}. 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:19349376, CC ECO:0000269|PubMed:21628460, ECO:0000269|PubMed:22745133, CC ECO:0000269|PubMed:31123703}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:19349376, ECO:0000269|PubMed:31123703}. CC -!- SUBUNIT: It self-associates (PubMed:19349376). Interacts with DTNBP1 CC (PubMed:19349376). Interacts with PIAS4/PIASY upon treatment with UVB CC and TNF-alpha (By similarity). Interacts with AMBRA1; promoting CC activation of ULK1 through unanchored 'Lys-63'-linked polyubiquitin CC chains (PubMed:31123703). Interacts with TICAM1 and TAX1BP1; these CC interactions target TICAM1 to TAX1BP1-mediated selective autophagic CC degradation (PubMed:28898289). {ECO:0000250|UniProtKB:Q8CH72, CC ECO:0000269|PubMed:19349376, ECO:0000269|PubMed:28898289, CC ECO:0000269|PubMed:31123703}. CC -!- SUBUNIT: (Microbial infection) Interacts with S.typhimurium protein CC SseK3; SseK3 does not glycosylate TRIM32. CC {ECO:0000269|PubMed:26394407}. CC -!- INTERACTION: CC Q13049; Q9NYB9: ABI2; NbExp=6; IntAct=EBI-742790, EBI-743598; CC Q13049; Q9NYB9-2: ABI2; NbExp=8; IntAct=EBI-742790, EBI-11096309; CC Q13049; P54253: ATXN1; NbExp=5; IntAct=EBI-742790, EBI-930964; CC Q13049; P13569: CFTR; NbExp=5; IntAct=EBI-742790, EBI-349854; CC Q13049; Q8N3C7: CLIP4; NbExp=6; IntAct=EBI-742790, EBI-5655540; CC Q13049; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-742790, EBI-398977; CC Q13049; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-742790, EBI-781551; CC Q13049; Q8N9I5: FADS6; NbExp=3; IntAct=EBI-742790, EBI-3943864; CC Q13049; P55040: GEM; NbExp=3; IntAct=EBI-742790, EBI-744104; CC Q13049; O60478: GPR137B; NbExp=3; IntAct=EBI-742790, EBI-18945347; CC Q13049; O60725: ICMT; NbExp=3; IntAct=EBI-742790, EBI-11721771; CC Q13049; Q7L273: KCTD9; NbExp=6; IntAct=EBI-742790, EBI-4397613; CC Q13049; P80188: LCN2; NbExp=3; IntAct=EBI-742790, EBI-11911016; CC Q13049; Q9H8S9: MOB1A; NbExp=3; IntAct=EBI-742790, EBI-748229; CC Q13049; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-742790, EBI-741158; CC Q13049; O76083: PDE9A; NbExp=10; IntAct=EBI-742790, EBI-742764; CC Q13049; O76083-2: PDE9A; NbExp=10; IntAct=EBI-742790, EBI-11524542; CC Q13049; O76083-4: PDE9A; NbExp=3; IntAct=EBI-742790, EBI-16433425; CC Q13049; Q9HAT8: PELI2; NbExp=3; IntAct=EBI-742790, EBI-448407; CC Q13049; Q8WV60: PTCD2; NbExp=3; IntAct=EBI-742790, EBI-12154567; CC Q13049; Q06124: PTPN11; NbExp=5; IntAct=EBI-742790, EBI-297779; CC Q13049; O14966: RAB29; NbExp=3; IntAct=EBI-742790, EBI-372165; CC Q13049; Q9UI14: RABAC1; NbExp=10; IntAct=EBI-742790, EBI-712367; CC Q13049; P11684: SCGB1A1; NbExp=8; IntAct=EBI-742790, EBI-7797649; CC Q13049; O00560: SDCBP; NbExp=7; IntAct=EBI-742790, EBI-727004; CC Q13049; Q5T7P8-2: SYT6; NbExp=6; IntAct=EBI-742790, EBI-10246152; CC Q13049; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-742790, EBI-11955057; CC Q13049; Q13049: TRIM32; NbExp=5; IntAct=EBI-742790, EBI-742790; CC Q13049; Q9C035: TRIM5; NbExp=2; IntAct=EBI-742790, EBI-924214; CC Q13049; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-742790, EBI-9090990; CC Q13049; P61088: UBE2N; NbExp=3; IntAct=EBI-742790, EBI-1052908; CC Q13049; Q5VVX9: UBE2U; NbExp=4; IntAct=EBI-742790, EBI-2130181; CC Q13049; Q13404: UBE2V1; NbExp=4; IntAct=EBI-742790, EBI-1050671; CC Q13049; Q9UMX0: UBQLN1; NbExp=7; IntAct=EBI-742790, EBI-741480; CC Q13049; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-742790, EBI-10173939; CC Q13049; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-742790, EBI-947187; CC Q13049; Q9NRR5: UBQLN4; NbExp=3; IntAct=EBI-742790, EBI-711226; CC Q13049; B3KPU6; NbExp=3; IntAct=EBI-742790, EBI-10175879; CC Q13049; Q99J34: Irak1; Xeno; NbExp=2; IntAct=EBI-742790, EBI-6117042; CC Q13049; PRO_0000449633 [P0DTD1]: rep; Xeno; NbExp=4; IntAct=EBI-742790, EBI-25492395; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19349376, CC ECO:0000269|PubMed:37543647}. Mitochondrion CC {ECO:0000269|PubMed:22745133, ECO:0000269|PubMed:32918979}. Endoplasmic CC reticulum {ECO:0000269|PubMed:22745133}. Note=Localized in cytoplasmic CC bodies, often located around the nucleus. CC {ECO:0000269|PubMed:19349376}. CC -!- TISSUE SPECIFICITY: Spleen, thymus, prostate, testis, ovary, intestine, CC colon and skeletal muscle. {ECO:0000269|PubMed:11822024}. CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:19349376}. CC -!- DISEASE: Muscular dystrophy, limb-girdle, autosomal recessive 8 CC (LGMDR8) [MIM:254110]: An autosomal recessive degenerative myopathy CC characterized by pelvic girdle, shoulder girdle and quadriceps muscle CC weakness. Clinical phenotype and severity are highly variable. Disease CC progression is slow and most patients remain ambulatory into the sixth CC decade of life. {ECO:0000269|PubMed:11822024, CC ECO:0000269|PubMed:17994549}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Bardet-Biedl syndrome 11 (BBS11) [MIM:615988]: A syndrome CC characterized by usually severe pigmentary retinopathy, early-onset CC obesity, polydactyly, hypogenitalism, renal malformation and CC intellectual disability. Secondary features include diabetes mellitus, CC hypertension and congenital heart disease. Bardet-Biedl syndrome CC inheritance is autosomal recessive, but three mutated alleles (two at CC one locus, and a third at a second locus) may be required for clinical CC manifestation of some forms of the disease. CC {ECO:0000269|PubMed:16606853}. Note=The disease is caused by variants CC affecting the gene represented in this entry. It has been suggested CC that TRIM32 might be the E3 ubiquitin ligase for BBS2, a component of CC the BBSome complex involved in ciliogenesis, that is ubiquitinated and CC degraded by the proteasome (PubMed:22500027). CC {ECO:0000269|PubMed:22500027}. CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Leiden Muscular Dystrophy pages; Note=TRIM32; CC URL="https://www.dmd.nl/trim32_home.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U18543; AAA86474.1; -; mRNA. DR EMBL; AL133284; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003154; AAH03154.1; -; mRNA. DR CCDS; CCDS6817.1; -. DR RefSeq; NP_001093149.1; NM_001099679.1. DR RefSeq; NP_036342.2; NM_012210.3. DR RefSeq; XP_005251870.1; XM_005251813.3. DR RefSeq; XP_011516700.1; XM_011518398.2. DR RefSeq; XP_016869975.1; XM_017014486.1. DR PDB; 2CT2; NMR; -; A=10-84. DR PDB; 5FEY; X-ray; 2.23 A; A/B=7-93. DR PDBsum; 2CT2; -. DR PDBsum; 5FEY; -. DR AlphaFoldDB; Q13049; -. DR SMR; Q13049; -. DR BioGRID; 116608; 207. DR CORUM; Q13049; -. DR IntAct; Q13049; 73. DR MINT; Q13049; -. DR STRING; 9606.ENSP00000408292; -. DR iPTMnet; Q13049; -. DR PhosphoSitePlus; Q13049; -. DR SwissPalm; Q13049; -. DR BioMuta; TRIM32; -. DR DMDM; 20178303; -. DR EPD; Q13049; -. DR jPOST; Q13049; -. DR MassIVE; Q13049; -. DR MaxQB; Q13049; -. DR PaxDb; 9606-ENSP00000408292; -. DR PeptideAtlas; Q13049; -. DR ProteomicsDB; 59123; -. DR Pumba; Q13049; -. DR Antibodypedia; 15684; 254 antibodies from 32 providers. DR DNASU; 22954; -. DR Ensembl; ENST00000373983.2; ENSP00000363095.1; ENSG00000119401.11. DR Ensembl; ENST00000450136.2; ENSP00000408292.1; ENSG00000119401.11. DR GeneID; 22954; -. DR KEGG; hsa:22954; -. DR MANE-Select; ENST00000450136.2; ENSP00000408292.1; NM_012210.4; NP_036342.2. DR UCSC; uc004bjw.3; human. DR AGR; HGNC:16380; -. DR CTD; 22954; -. DR DisGeNET; 22954; -. DR GeneCards; TRIM32; -. DR GeneReviews; TRIM32; -. DR HGNC; HGNC:16380; TRIM32. DR HPA; ENSG00000119401; Low tissue specificity. DR MalaCards; TRIM32; -. DR MIM; 254110; phenotype. DR MIM; 602290; gene. DR MIM; 615988; phenotype. DR neXtProt; NX_Q13049; -. DR OpenTargets; ENSG00000119401; -. DR Orphanet; 110; Bardet-Biedl syndrome. DR Orphanet; 1878; TRIM32-related limb-girdle muscular dystrophy R8. DR PharmGKB; PA38130; -. DR VEuPathDB; HostDB:ENSG00000119401; -. DR eggNOG; KOG2177; Eukaryota. DR GeneTree; ENSGT00940000160949; -. DR HOGENOM; CLU_423860_0_0_1; -. DR InParanoid; Q13049; -. DR OMA; YTTDGHC; -. DR OrthoDB; 5295945at2759; -. DR PhylomeDB; Q13049; -. DR TreeFam; TF331018; -. DR PathwayCommons; Q13049; -. DR Reactome; R-HSA-3134975; Regulation of innate immune responses to cytosolic DNA. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q13049; -. DR SIGNOR; Q13049; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 22954; 14 hits in 1194 CRISPR screens. DR ChiTaRS; TRIM32; human. DR EvolutionaryTrace; Q13049; -. DR GeneWiki; TRIM32; -. DR GenomeRNAi; 22954; -. DR Pharos; Q13049; Tbio. DR PRO; PR:Q13049; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q13049; Protein. DR Bgee; ENSG00000119401; Expressed in stromal cell of endometrium and 177 other cell types or tissues. DR ExpressionAtlas; Q13049; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProt. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL. DR GO; GO:0005863; C:striated muscle myosin thick filament; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0017022; F:myosin binding; ISS:BHF-UCL. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProt. DR GO; GO:0003723; F:RNA binding; ISS:BHF-UCL. DR GO; GO:0030957; F:Tat protein binding; TAS:BHF-UCL. DR GO; GO:0003713; F:transcription coactivator activity; IDA:ARUK-UCL. DR GO; GO:0031369; F:translation initiation factor binding; ISS:BHF-UCL. DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0007014; P:actin ubiquitination; IEA:Ensembl. DR GO; GO:0061564; P:axon development; IEA:Ensembl. DR GO; GO:0045444; P:fat cell differentiation; ISS:BHF-UCL. DR GO; GO:0010994; P:free ubiquitin chain polymerization; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl. DR GO; GO:1902018; P:negative regulation of cilium assembly; IDA:UniProt. DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISS:BHF-UCL. DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IDA:BHF-UCL. DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IDA:UniProt. DR GO; GO:0032897; P:negative regulation of viral transcription; IDA:UniProtKB. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0045787; P:positive regulation of cell cycle; IDA:BHF-UCL. DR GO; GO:0030307; P:positive regulation of cell growth; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:2000147; P:positive regulation of cell motility; ISS:BHF-UCL. DR GO; GO:1903886; P:positive regulation of chemokine (C-C motif) ligand 20 production; IEA:Ensembl. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:1903883; P:positive regulation of interleukin-17-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:BHF-UCL. DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:BHF-UCL. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:BHF-UCL. DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:BHF-UCL. DR GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; IEA:Ensembl. DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IBA:GO_Central. DR GO; GO:0000209; P:protein polyubiquitination; IDA:BHF-UCL. DR GO; GO:0016567; P:protein ubiquitination; IDA:BHF-UCL. DR GO; GO:0034612; P:response to tumor necrosis factor; ISS:BHF-UCL. DR GO; GO:0009411; P:response to UV; ISS:BHF-UCL. DR GO; GO:0044790; P:suppression of viral release by host; IDA:UniProtKB. DR GO; GO:0001894; P:tissue homeostasis; IEA:Ensembl. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR CDD; cd19806; Bbox1_TRIM32_C-VII; 1. DR CDD; cd14961; NHL_TRIM32_like; 1. DR CDD; cd16587; RING-HC_TRIM32_C-VII; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR001258; NHL_repeat. DR InterPro; IPR047051; TRIM32_Bbox1_Znf. DR InterPro; IPR027370; Znf-RING_euk. 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 PANTHER; PTHR25464:SF3; E3 UBIQUITIN-PROTEIN LIGASE TRIM32; 1. DR PANTHER; PTHR25464; TRIPARTITE MOTIF-CONTAINING PROTEIN 2-LIKE PROTEIN; 1. DR Pfam; PF01436; NHL; 3. DR Pfam; PF13445; zf-RING_UBOX; 1. DR SMART; SM00336; BBOX; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57845; B-box zinc-binding domain; 1. DR SUPFAM; SSF101898; NHL repeat; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS51125; NHL; 5. DR PROSITE; PS50119; ZF_BBOX; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; Q13049; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Bardet-Biedl syndrome; Ciliopathy; Coiled coil; KW Cytoplasm; Direct protein sequencing; Disease variant; KW Endoplasmic reticulum; Intellectual disability; KW Limb-girdle muscular dystrophy; Metal-binding; Mitochondrion; Obesity; KW Phosphoprotein; Reference proteome; Repeat; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.4" FT CHAIN 2..653 FT /note="E3 ubiquitin-protein ligase TRIM32" FT /id="PRO_0000056246" FT REPEAT 358..401 FT /note="NHL 1" FT REPEAT 415..458 FT /note="NHL 2" FT REPEAT 459..499 FT /note="NHL 3" FT REPEAT 562..605 FT /note="NHL 4" FT REPEAT 606..646 FT /note="NHL 5" FT ZN_FING 20..65 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 103..133 FT /note="B box-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT COILED 138..197 FT /evidence="ECO:0000255" FT BINDING 100 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 103 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 123 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 128 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.4" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CH72" FT MOD_RES 335 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 130 FT /note="P -> S (in BBS11; dbSNP:rs111033571)" FT /evidence="ECO:0000269|PubMed:16606853" FT /id="VAR_038807" FT VARIANT 257 FT /note="T -> R (in dbSNP:rs3747834)" FT /id="VAR_038808" FT VARIANT 299 FT /note="R -> Q (in a patient with Bardet-Biedl syndrome; FT uncertain significance; dbSNP:rs766439806)" FT /evidence="ECO:0000269|PubMed:21344540" FT /id="VAR_066295" FT VARIANT 394 FT /note="R -> H (in LGMDR8; dbSNP:rs121434447)" FT /evidence="ECO:0000269|PubMed:17994549" FT /id="VAR_042939" FT VARIANT 408 FT /note="R -> C (in dbSNP:rs3747835)" FT /id="VAR_038809" FT VARIANT 487 FT /note="D -> N (in LGMDR8; dbSNP:rs111033570)" FT /evidence="ECO:0000269|PubMed:11822024" FT /id="VAR_018725" FT VARIANT 588 FT /note="Missing (in LGMDR8)" FT /evidence="ECO:0000269|PubMed:17994549" FT /id="VAR_042940" FT MUTAGEN 39 FT /note="C->S: Abolished E3 ubiquitin ligase activity and FT ability to activate ULK1." FT /evidence="ECO:0000269|PubMed:31123703, FT ECO:0000269|PubMed:37543647" FT CONFLICT 27 FT /note="F -> I (in Ref. 1; AAA86474)" FT /evidence="ECO:0000305" FT HELIX 11..16 FT /evidence="ECO:0007829|PDB:5FEY" FT TURN 21..23 FT /evidence="ECO:0007829|PDB:5FEY" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:5FEY" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:2CT2" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:5FEY" FT HELIX 45..51 FT /evidence="ECO:0007829|PDB:5FEY" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:5FEY" FT TURN 73..75 FT /evidence="ECO:0007829|PDB:2CT2" FT STRAND 76..78 FT /evidence="ECO:0007829|PDB:2CT2" FT HELIX 80..85 FT /evidence="ECO:0007829|PDB:5FEY" SQ SEQUENCE 653 AA; 71989 MW; D83B1595CA8378FD CRC64; MAAAAASHLN LDALREVLEC PICMESFTEE QLRPKLLHCG HTICRQCLEK LLASSINGVR CPFCSKITRI TSLTQLTDNL TVLKIIDTAG LSEAVGLLMC RSCGRRLPRQ FCRSCGLVLC EPCREADHQP PGHCTLPVKE AAEERRRDFG EKLTRLRELM GELQRRKAAL EGVSKDLQAR YKAVLQEYGH EERRVQDELA RSRKFFTGSL AEVEKSNSQV VEEQSYLLNI AEVQAVSRCD YFLAKIKQAD VALLEETADE EEPELTASLP RELTLQDVEL LKVGHVGPLQ IGQAVKKPRT VNVEDSWAME ATASAASTSV TFREMDMSPE EVVASPRASP AKQRGPEAAS NIQQCLFLKK MGAKGSTPGM FNLPVSLYVT SQGEVLVADR GNYRIQVFTR KGFLKEIRRS PSGIDSFVLS FLGADLPNLT PLSVAMNCQG LIGVTDSYDN SLKVYTLDGH CVACHRSQLS KPWGITALPS GQFVVTDVEG GKLWCFTVDR GSGVVKYSCL CSAVRPKFVT CDAEGTVYFT QGLGLNLENR QNEHHLEGGF SIGSVGPDGQ LGRQISHFFS ENEDFRCIAG MCVDARGDLI VADSSRKEIL HFPKGGGYSV LIREGLTCPV GIALTPKGQL LVLDCWDHCI KIYSYHLRRY STP //