UBD_MOUSE
ID UBD_MOUSE Reviewed; 162 AA.
AC P63072; Q4FJZ5; Q9WV10;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Ubiquitin D;
DE AltName: Full=Diubiquitin;
DE AltName: Full=Ubiquitin-like protein FAT10;
GN Name=Ubd; Synonyms=Fat10;
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 [GENOMIC DNA].
RA Yu X., Liu Y., Weissman S.M.;
RT "Disruption of the mouse Fat10 gene by gene targeting in the mouse
RT embryonic stem cells.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Small intestine;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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, SUBCELLULAR LOCATION, INDUCTION, AND MUTAGENESIS OF
RP 161-GLY-GLY-162.
RX PubMed=11445583; DOI=10.1074/jbc.m105139200;
RA Raasi S., Schmidtke G., Groettrup M.;
RT "The ubiquitin-like protein FAT10 forms covalent conjugates and induces
RT apoptosis.";
RL J. Biol. Chem. 276:35334-35343(2001).
RN [7]
RP FUNCTION.
RX PubMed=15831455; DOI=10.1128/mcb.25.9.3483-3491.2005;
RA Hipp M.S., Kalveram B., Raasi S., Groettrup M., Schmidtke G.;
RT "FAT10, a ubiquitin-independent signal for proteasomal degradation.";
RL Mol. Cell. Biol. 25:3483-3491(2005).
RN [8]
RP FUNCTION.
RX PubMed=16495380; DOI=10.1681/asn.2005070692;
RA Ross M.J., Wosnitzer M.S., Ross M.D., Granelli B., Gusella G.L., Husain M.,
RA Kaufman L., Vasievich M., D'Agati V.D., Wilson P.D., Klotman M.E.,
RA Klotman P.E.;
RT "Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal
RT disease.";
RL J. Am. Soc. Nephrol. 17:996-1004(2006).
RN [9]
RP FUNCTION, INDUCTION BY TNFA AND IFNG, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=16782901; DOI=10.1128/mcb.00966-05;
RA Canaan A., Yu X., Booth C.J., Lian J., Lazar I., Gamfi S.L., Castille K.,
RA Kohya N., Nakayama Y., Liu Y.-C., Eynon E., Flavell R., Weissman S.M.;
RT "FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic
RT differences.";
RL Mol. Cell. Biol. 26:5180-5189(2006).
RN [10]
RP FUNCTION, AND INTERACTION WITH UBA6.
RX PubMed=17889673; DOI=10.1016/j.molcel.2007.08.020;
RA Chiu Y.-H., Sun Q., Chen Z.J.;
RT "E1-L2 activates both ubiquitin and FAT10.";
RL Mol. Cell 27:1014-1023(2007).
RN [11]
RP INDUCTION BY DRUG INJURY.
RX PubMed=18280469; DOI=10.1016/j.yexmp.2007.12.003;
RA Oliva J., Bardag-Gorce F., French B.A., Li J., McPhaul L., Amidi F.,
RA Dedes J., Habibi A., Nguyen S., French S.W.;
RT "Fat10 is an epigenetic marker for liver preneoplasia in a drug-primed
RT mouse model of tumorigenesis.";
RL Exp. Mol. Pathol. 84:102-112(2008).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19959714; DOI=10.1681/asn.2009050479;
RA Gong P., Canaan A., Wang B., Leventhal J., Snyder A., Nair V., Cohen C.D.,
RA Kretzler M., D'Agati V., Weissman S., Ross M.J.;
RT "The ubiquitin-like protein FAT10 mediates NF-kappa-B activation.";
RL J. Am. Soc. Nephrol. 21:316-326(2010).
CC -!- FUNCTION: Ubiquitin-like protein modifier which can be covalently
CC attached to target protein and subsequently leads to their degradation
CC by the 26S proteasome, in a NUB1-dependent manner. Probably functions
CC as a survival factor. Promotes the expression of the proteasome subunit
CC beta type-9 (PSMB9/LMP2). Regulates TNF-alpha-induced and LPS-mediated
CC activation of the central mediator of innate immunity NF-kappa-B by
CC promoting TNF-alpha-mediated proteasomal degradation of ubiquitinated-
CC I-kappa-B-alpha. Required for TNF-alpha-induced p65 nuclear
CC translocation in renal tubular epithelial cells (RTECs). May be
CC involved in dendritic cell (DC) maturation, the process by which
CC immature dendritic cells differentiate into fully competent antigen-
CC presenting cells that initiate T-cell responses. Mediates mitotic non-
CC disjunction and chromosome instability, in long-term in vitro culture
CC and cancers, by abbreviating mitotic phase and impairing the
CC kinetochore localization of MAD2L1 during the prometaphase stage of the
CC cell cycle. May be involved in the formation of aggresomes when
CC proteasome is saturated or impaired. Mediates apoptosis in a caspase-
CC dependent manner, especially in renal epithelium and tubular cells
CC during renal diseases. {ECO:0000269|PubMed:11445583,
CC ECO:0000269|PubMed:15831455, ECO:0000269|PubMed:16495380,
CC ECO:0000269|PubMed:16782901, ECO:0000269|PubMed:17889673,
CC ECO:0000269|PubMed:19959714}.
CC -!- SUBUNIT: Interacts directly with the 26S proteasome. The interaction
CC with NUB1 via the N-terminal ubiquitin domain facilitates the linking
CC of UBD-conjugated target protein to the proteasome complex and
CC accelerates its own degradation and that of its conjugates. Interacts
CC (via ubiquitin-like 1 domain) with the spindle checkpoint protein
CC MAD2L1 during mitosis. Present in aggresomes of proteasome inhibited
CC cells. Interacts with HDAC6 under proteasome impairment conditions (By
CC similarity). Forms a thioester with UBA6 in cells stimulated with tumor
CC necrosis factor-alpha (TNFa) and interferon-gamma (IFNg)
CC (PubMed:17889673). Interacts with SQSTM1 and TP53/p53 (By similarity).
CC {ECO:0000250|UniProtKB:O15205, ECO:0000269|PubMed:17889673}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11445583}. Cytoplasm
CC {ECO:0000269|PubMed:11445583}. Note=Accumulates in aggresomes under
CC proteasome inhibition conditions. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Mostly expressed in thymus and intestine.
CC {ECO:0000269|PubMed:16782901}.
CC -!- INDUCTION: Rapidly degraded by the proteasome. Cell-cycle regulation
CC with highest expression during the S-phase (at protein level). Over
CC expressed in hepatocytes by drug injury (e.g. DDC; diethyl 1,4-dihydro-
CC 2,4,6-trimethyl-3,5-pyridinedicarboxylate). Inducible by the pro-
CC inflammatory cytokines tumor necrosis factor-alpha (TNFa) and
CC interferon-gamma (IFNg). {ECO:0000269|PubMed:11445583,
CC ECO:0000269|PubMed:16782901, ECO:0000269|PubMed:18280469}.
CC -!- PTM: Can be acetylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Spontaneous sporadic apoptotic death. Higher
CC sensitivity toward endotoxin challenge. Abrogated TNF-alpha-induced NF-
CC kappa-B activation and reduced induction of NF-kappa-B-regulated genes.
CC Impaired TNF-alpha-induced I-kappa-B-alpha degradation and nuclear
CC translocation of p65 in RTECs. Reduced expression of LMP2.
CC {ECO:0000269|PubMed:16782901, ECO:0000269|PubMed:19959714}.
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DR EMBL; AF314088; AAG27477.1; -; Genomic_DNA.
DR EMBL; AK008116; BAB25471.1; -; mRNA.
DR EMBL; AK008552; BAB25738.1; -; mRNA.
DR EMBL; CT010257; CAJ18465.1; -; mRNA.
DR EMBL; AL078630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027627; AAH27627.2; -; mRNA.
DR EMBL; BC036383; AAH36383.1; -; mRNA.
DR CCDS; CCDS28737.1; -.
DR RefSeq; NP_075626.1; NM_023137.3.
DR AlphaFoldDB; P63072; -.
DR SMR; P63072; -.
DR BioGRID; 204900; 1.
DR MINT; P63072; -.
DR STRING; 10090.ENSMUSP00000035808; -.
DR iPTMnet; P63072; -.
DR PhosphoSitePlus; P63072; -.
DR PaxDb; P63072; -.
DR PRIDE; P63072; -.
DR Antibodypedia; 25984; 318 antibodies from 37 providers.
DR DNASU; 24108; -.
DR Ensembl; ENSMUST00000038844; ENSMUSP00000035808; ENSMUSG00000035186.
DR GeneID; 24108; -.
DR KEGG; mmu:24108; -.
DR UCSC; uc008cmi.2; mouse.
DR CTD; 10537; -.
DR MGI; MGI:1344410; Ubd.
DR VEuPathDB; HostDB:ENSMUSG00000035186; -.
DR eggNOG; KOG0001; Eukaryota.
DR GeneTree; ENSGT00910000144359; -.
DR HOGENOM; CLU_139252_0_0_1; -.
DR InParanoid; P63072; -.
DR OMA; ETQIVTC; -.
DR OrthoDB; 1377739at2759; -.
DR PhylomeDB; P63072; -.
DR Reactome; R-MMU-8951664; Neddylation.
DR BioGRID-ORCS; 24108; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Ubd; mouse.
DR PRO; PR:P63072; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P63072; protein.
DR Bgee; ENSMUSG00000035186; Expressed in thymus and 53 other tissues.
DR Genevisible; P63072; MM.
DR GO; GO:0016235; C:aggresome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0070628; F:proteasome binding; ISS:UniProtKB.
DR GO; GO:0070842; P:aggresome assembly; ISS:UniProtKB.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IC:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; ISS:UniProtKB.
DR GO; GO:0034341; P:response to interferon-gamma; IEP:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR042969; Ubiquitin_D.
DR InterPro; IPR019956; Ubiquitin_dom.
DR PANTHER; PTHR47731; PTHR47731; 1.
DR Pfam; PF00240; ubiquitin; 2.
DR PRINTS; PR00348; UBIQUITIN.
DR SMART; SM00213; UBQ; 2.
DR SUPFAM; SSF54236; SSF54236; 2.
DR PROSITE; PS50053; UBIQUITIN_2; 2.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Nucleus; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..162
FT /note="Ubiquitin D"
FT /id="PRO_0000114894"
FT DOMAIN 3..78
FT /note="Ubiquitin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 87..160
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT SITE 161..162
FT /note="Activation by thioester intermediate formation with
FT UBA6"
FT MUTAGEN 161..162
FT /note="Missing: Impaired conjugation of target proteins."
FT /evidence="ECO:0000269|PubMed:11445583"
SQ SEQUENCE 162 AA; 18376 MW; 6107D8604F96455F CRC64;
MASVRTCVVR SDQWRLMTFE TTENDKVKKI NEHIRSQTKV SVQDQILLLD SKILKPHRKL
SSYGIDKETT IHLTLKVVKP SDEELPLFLV ESKNEGQRHL LRVRRSSSVA QVKEMIESVT
SVIPKKQVVN CNGKKLEDGK IMADYNIKSG SLLFLTTHCT GG
