ID UBP12_MOUSE Reviewed; 370 AA. AC Q9D9M2; Q790B0; Q7TNV4; Q80Y43; Q8CBN8; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 2. DT 24-JAN-2024, entry version 152. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 12; DE EC=3.4.19.12 {ECO:0000250|UniProtKB:O75317}; DE AltName: Full=Deubiquitinating enzyme 12; DE AltName: Full=Ubiquitin thioesterase 12; DE AltName: Full=Ubiquitin-hydrolyzing enzyme 1; DE AltName: Full=Ubiquitin-specific-processing protease 12; GN Name=Usp12; Synonyms=Ubh1; 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 [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Testis, and Urinary bladder; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Liver; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 16-370 (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Testis; RX PubMed=12391724; DOI=10.1080/10425170290023383; RA Baek K.-H., Park K.-H., Kim Y.-S., Kim M.-S., Choi H.-K.; RT "Molecular cloning and complete cDNA sequence of UBH1 in mouse testis."; RL DNA Seq. 13:145-148(2002). RN [4] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=33941870; DOI=10.1038/s41418-021-00787-y; RA Fu Y., Wang P., Zhao J., Tan Y., Sheng J., He S., Du X., Huang Y., Yang Y., RA Li J., Cai Y., Liu Y., Hu S.; RT "USP12 promotes CD4+ T cell responses through deubiquitinating and RT stabilizing BCL10."; RL Cell Death Differ. 28:2857-2870(2021). RN [5] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=35898171; DOI=10.1111/imm.13552; RA Zhan X., He Q., Sheng J., Jiang X., Lin L., Huang Y., He S., Chen Y., RA Li L., Zeng Z., Hu S., Wang P., Zhang Y.; RT "USP12 positively regulates M-MDSC function to inhibit antitumour immunity RT through deubiquitinating and stabilizing p65."; RL Immunology 167:544-557(2022). CC -!- FUNCTION: Deubiquitinating enzyme that plays various roles in the CC regulation of the immune response and inflammation. In complex with CC WDR48, acts as a potential tumor suppressor by positively regulating CC PHLPP1 stability. During TCR engagement and activation, translocates CC into the cytoplasm and deubiquitinates its substrates LAT and TRAT1 and CC prevents their lysosome-dependent degradation to stabilize the TCR CC signaling complex at the plasma membrane. Plays an essential role in CC the selective LPS-induced macrophage response through the activation of CC NF-kappa-B pathway. In addition, promotes that antiviral immune CC response through targeting DNA sensor IFI16 to inhibit its proteasome- CC dependent degradation. Participates in the interferon signaling pathway CC and antiviral response independently of its deubiquitinase activity by CC maintaining nuclear phosphorylated STAT1 levels via inhibition of its CC CREBBP-mediated acetylation and subsequent dephosphorylation (By CC similarity). Plays an intrinsic role in promoting the differentiation, CC activation and proliferation of CD4(+) T-cell by activating the NF- CC kappa-B signaling pathway through deubiquitinating and stabilizing B- CC cell lymphoma/leukemia 10/BCL10 (PubMed:33941870). In myeloid-derived CC suppressor cells promotes the activation of the NF-kappa-B via CC deubiquitination and stabilization of RELA (PubMed:35898171). Regulates CC the 'Lys-63'-linked polyubiquitin chains of BAX and thereby modulates CC the mitochondrial apoptotic process (By similarity). CC {ECO:0000250|UniProtKB:O75317, ECO:0000269|PubMed:33941870, CC ECO:0000269|PubMed:35898171}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:O75317}; CC -!- ACTIVITY REGULATION: Activated by interaction with WDR20; WDR48 and CC DMWD through different allosteric mechanisms. CC {ECO:0000250|UniProtKB:O75317}. CC -!- SUBUNIT: Interacts with WDR48. Interacts with WDR20; this interaction CC promotes translocation of the USP12 complex to the plasma membrane. CC Component of the USP12/WDR20/WDR48 deubiquitinating complex. Component CC of the USP12/DMWD/WDR48 deubiquitinating complex. Interacts with CC PHLPP1. Interacts with RBPJ. Interacts with CBP; this interaction CC blocks the acetyltransferase activity of CREBBP. CC {ECO:0000250|UniProtKB:O75317}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O75317}. Cytoplasm CC {ECO:0000250|UniProtKB:O75317}. Cell membrane CC {ECO:0000250|UniProtKB:O75317}. Note=Translocates from the nucleus to CC the cytosol on TCR stimulation, while it translocates into the nucleus CC in IFN signaling. USP12/WDR20/WDR48 complex is localized mainly to the CC plasma membrane. {ECO:0000250|UniProtKB:O75317}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9D9M2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9D9M2-2; Sequence=VSP_037617; CC -!- DISRUPTION PHENOTYPE: USP12-deficiency attenuates CD4(+) T-cell CC activation (PubMed:33941870). In addition, USP12 mutant mice show CC significantly reduced tumor growth when compared to WT mice. Both the CC frequency and number of CD4(+) or CD8(+) T-cells isolated from the CC tumor are significantly higher in the USP12-deletion mutant mice CC (PubMed:35898171). {ECO:0000269|PubMed:33941870, CC ECO:0000269|PubMed:35898171}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP12/USP46 subfamily. CC {ECO:0000305}. 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; AK006739; BAB24720.2; -; mRNA. DR EMBL; AK035629; BAC29129.1; -; mRNA. DR EMBL; AK167153; BAE39295.1; -; mRNA. DR EMBL; BC049274; AAH49274.1; -; mRNA. DR EMBL; BC055398; AAH55398.1; -; mRNA. DR EMBL; BC068136; AAH68136.1; -; mRNA. DR EMBL; AF441835; AAL86740.1; -; mRNA. DR CCDS; CCDS39395.1; -. [Q9D9M2-1] DR RefSeq; NP_035799.1; NM_011669.3. [Q9D9M2-1] DR RefSeq; XP_006504881.1; XM_006504818.2. DR AlphaFoldDB; Q9D9M2; -. DR SMR; Q9D9M2; -. DR BioGRID; 204419; 7. DR IntAct; Q9D9M2; 1. DR STRING; 10090.ENSMUSP00000082754; -. DR MEROPS; C19.020; -. DR iPTMnet; Q9D9M2; -. DR PhosphoSitePlus; Q9D9M2; -. DR SwissPalm; Q9D9M2; -. DR EPD; Q9D9M2; -. DR MaxQB; Q9D9M2; -. DR PaxDb; 10090-ENSMUSP00000082754; -. DR PeptideAtlas; Q9D9M2; -. DR ProteomicsDB; 298453; -. [Q9D9M2-1] DR ProteomicsDB; 298454; -. [Q9D9M2-2] DR Pumba; Q9D9M2; -. DR Antibodypedia; 22631; 305 antibodies from 27 providers. DR DNASU; 22217; -. DR Ensembl; ENSMUST00000085614.6; ENSMUSP00000082754.6; ENSMUSG00000029640.18. [Q9D9M2-1] DR GeneID; 22217; -. DR KEGG; mmu:22217; -. DR UCSC; uc009anj.1; mouse. [Q9D9M2-1] DR AGR; MGI:1270128; -. DR CTD; 219333; -. DR MGI; MGI:1270128; Usp12. DR VEuPathDB; HostDB:ENSMUSG00000029640; -. DR eggNOG; KOG1864; Eukaryota. DR GeneTree; ENSGT00940000153284; -. DR HOGENOM; CLU_008279_2_0_1; -. DR InParanoid; Q9D9M2; -. DR OMA; KYWVKYL; -. DR OrthoDB; 227085at2759; -. DR PhylomeDB; Q9D9M2; -. DR TreeFam; TF314144; -. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR BioGRID-ORCS; 22217; 1 hit in 77 CRISPR screens. DR ChiTaRS; Usp12; mouse. DR PRO; PR:Q9D9M2; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; Q9D9M2; Protein. DR Bgee; ENSMUSG00000029640; Expressed in retinal neural layer and 241 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB. DR GO; GO:0101005; F:deubiquitinase activity; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISO:MGI. DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd02663; Peptidase_C19G; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR001394; Peptidase_C19_UCH. DR InterPro; IPR018200; USP_CS. DR InterPro; IPR028889; USP_dom. DR PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR24006:SF647; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 12; 1. DR Pfam; PF00443; UCH; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. DR Genevisible; Q9D9M2; MM. PE 2: Evidence at transcript level; KW Alternative splicing; Cell membrane; Cytoplasm; Hydrolase; Membrane; KW Metal-binding; Nucleus; Protease; Reference proteome; Thiol protease; KW Ubl conjugation pathway; Zinc. FT CHAIN 1..370 FT /note="Ubiquitin carboxyl-terminal hydrolase 12" FT /id="PRO_0000260312" FT DOMAIN 39..369 FT /note="USP" FT REGION 146..168 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 1..4 FT /note="Required for plasma membrane localization of FT USP12/WDR20" FT /evidence="ECO:0000250|UniProtKB:O75317" FT COMPBIAS 146..161 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 48 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT ACT_SITE 317 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT BINDING 186 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:O75317" FT BINDING 189 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:O75317" FT BINDING 233 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:O75317" FT BINDING 236 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:O75317" FT VAR_SEQ 1..120 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_037617" SQ SEQUENCE 370 AA; 42914 MW; B11AC16D9B12EBB8 CRC64; MEILMTVSKF ASICTMGANA SALEKEIGPE QFPVNEHYFG LVNFGNTCYC NSVLQALYFC RPFREKVLAY KSQPRKKENL LTCLADLFHS IATQKKKVGV IPPKKFITRL RKENELFDNY MQQDAHEFLN YLLNTIADIL QEERKQEKQN GRLRNGDVDN EDNNSTPDPT WVHEIFQGTL TNETRCLTCE TISSKDEDFL DLSVDVEQNT SITHCLRGFS NTETLCSEYK YYCEECRSKQ EAHKRMKVKK LPLILALHLK RFKYMDQLHR YTKLSYRVVF PLELRLFNTS GDATNPDRMY DLVAVVVHCG SGPNRGHYIA IVKSHDFWLL FDDDIVEKID AQAIEEFYGL TSDISKNSES GYILFYQSRD //