P63072 (UBD_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin D

Alternative name(s):
Diubiquitin
Ubiquitin-like protein FAT10

Gene names

Name:	Ubd
Synonyms:	Fat10

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	162 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin-like protein modifier which can be covalently attached to target protein and subsequently leads to their degradation by the 26S proteasome, in a NUB1L-dependent manner. Probably functions as a survival factor. Promotes the expression of the proteasome subunit beta type-9 (PSMB9/LMP2). Regulates TNF-alpha-induced and LPS-mediated activation of the central mediator of innate immunity NF-kappa-B by promoting TNF-alpha-mediated proteasomal degradation of ubiquitinated-I-kappa-B-alpha. Required for TNF-alpha-induced p65 nuclear translocation in renal tubular epithelial cells (RTECs). May be involved in dendritic cell (DC) maturation, the process by which immature dendritic cells differentiate into fully competent antigen-presenting cells that initiate T-cell responses. Mediates mitotic non-disjunction and chromosome instability, in long-term in vitro culture and cancers, by abbreviating mitotic phase and impairing the kinetochore localization of MAD2L1 during the prometaphase stage of the cell cycle. May be involved in the formation of aggresomes when proteasome is saturated or impaired. Mediates apoptosis in a caspase-dependent manner, especially in renal epithelium and tubular cells during renal diseases. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12
Subunit structure	Interact directly with the 26S proteasome. The interaction with NUB1L vie the N-terminal ubiquitin domain facilitates the linking of UBD-conjugated target protein to the proteasome complex and accelerates its own degradation and that of its conjugates By similarity. Interacts with the spindle checkpoint protein MAD2L1 during mitosis. Present in aggresomes of proteasome inhibited cells. Interacts with HDAC6 under proteasome impairment conditions. Forms a thioester with UBA6 in cells stimulated with tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg). Ref.10
Subcellular location	Nucleus. Cytoplasm. Note: Accumulates in aggresomes under proteasome inhibition conditions By similarity. Ref.6
Tissue specificity	Mostly expressed in thymus and intestine. Ref.9
Induction	Rapidly degraded by the proteasome. Cell-cycle regulation with highest expression during the S-phase (at protein level). Over expressed in hepatocytes by drug injury (e.g. DDC; diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate). Inducible by the proinflammatory cytokines tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg). Ref.6 Ref.9 Ref.11
Post-translational modification	Can be acetylated By similarity.
Disruption phenotype	Spontaneous sporadic apoptotic death. Higher sensitivity toward endotoxin challenge. Abrogated TNF-alpha-induced NF-kappa-B activation and reduced induction of NF-kappa-B-regulated genes. Impaired TNF-alpha-induced I-kappa-B-alpha degradation and nuclear translocation of p65 in RTECs. Reduced expression of LMP2. Ref.9 Ref.12
Sequence similarities	Contains 2 ubiquitin-like domains.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	Repeat
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aggresome assembly Inferred from sequence or structural similarity. Source: UniProtKB myeloid dendritic cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of mitotic prometaphase Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype Ref.12. Source: UniProtKB positive regulation of apoptotic process Inferred from mutant phenotype Ref.6. Source: UniProtKB protein ubiquitination Inferred from mutant phenotype Ref.6Ref.10. Source: UniProtKB response to interferon-gamma Inferred from expression pattern Ref.9. Source: UniProtKB response to organic nitrogen Inferred from electronic annotation. Source: Compara response to tumor necrosis factor Inferred from expression pattern Ref.9. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.6Ref.10. Source: UniProtKB
Cellular_component	aggresome Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay Ref.6. Source: UniProtKB nucleus Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	proteasome binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 162	162	Ubiquitin D		PRO_0000114894
Regions
	Domain	3 – 78	76	Ubiquitin-like 1
	Domain	87 – 160	74	Ubiquitin-like 2
Sites
	Site	161 – 162	2	Activation by thioester intermediate formation with UBA6
Experimental info
	Mutagenesis	161 – 162	2	Missing: Impaired conjugation of target proteins. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P63072 [UniParc]. Last modified September 13, 2004. Version 1. Checksum: 6107D8604F96455F	FASTA	162	18,376
	10 20 30 40 50 60 MASVRTCVVR SDQWRLMTFE TTENDKVKKI NEHIRSQTKV SVQDQILLLD SKILKPHRKL 70 80 90 100 110 120 SSYGIDKETT IHLTLKVVKP SDEELPLFLV ESKNEGQRHL LRVRRSSSVA QVKEMIESVT 130 140 150 160 SVIPKKQVVN CNGKKLEDGK IMADYNIKSG SLLFLTTHCT GG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Disruption of the mouse Fat10 gene by gene targeting in the mouse embryonic stem cells." Yu X., Liu Y., Weissman S.M. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Small intestine.
[3]	"Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)." Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Mammary gland.
[6]	"The ubiquitin-like protein FAT10 forms covalent conjugates and induces apoptosis." Raasi S., Schmidtke G., Groettrup M. J. Biol. Chem. 276:35334-35343(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, MUTAGENESIS OF 161-GLY-GLY-162.
[7]	"FAT10, a ubiquitin-independent signal for proteasomal degradation." Hipp M.S., Kalveram B., Raasi S., Groettrup M., Schmidtke G. Mol. Cell. Biol. 25:3483-3491(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease." Ross M.J., Wosnitzer M.S., Ross M.D., Granelli B., Gusella G.L., Husain M., Kaufman L., Vasievich M., D'Agati V.D., Wilson P.D., Klotman M.E., Klotman P.E. J. Am. Soc. Nephrol. 17:996-1004(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences." Canaan A., Yu X., Booth C.J., Lian J., Lazar I., Gamfi S.L., Castille K., Kohya N., Nakayama Y., Liu Y.-C., Eynon E., Flavell R., Weissman S.M. Mol. Cell. Biol. 26:5180-5189(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION BY TNFA AND IFNG, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[10]	"E1-L2 activates both ubiquitin and FAT10." Chiu Y.-H., Sun Q., Chen Z.J. Mol. Cell 27:1014-1023(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBA6.
[11]	"Fat10 is an epigenetic marker for liver preneoplasia in a drug-primed mouse model of tumorigenesis." Oliva J., Bardag-Gorce F., French B.A., Li J., McPhaul L., Amidi F., Dedes J., Habibi A., Nguyen S., French S.W. Exp. Mol. Pathol. 84:102-112(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY DRUG INJURY.
[12]	"The ubiquitin-like protein FAT10 mediates NF-kappa-B activation." Gong P., Canaan A., Wang B., Leventhal J., Snyder A., Nair V., Cohen C.D., Kretzler M., D'Agati V., Weissman S., Ross M.J. J. Am. Soc. Nephrol. 21:316-326(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF314088 Genomic DNA. Translation: AAG27477.1. AK008116 mRNA. Translation: BAB25471.1. AK008552 mRNA. Translation: BAB25738.1. CT010257 mRNA. Translation: CAJ18465.1. AL078630 Genomic DNA. No translation available. BC027627 mRNA. Translation: AAH27627.2. BC036383 mRNA. Translation: AAH36383.1.
IPI	IPI00387566.
RefSeq	NP_075626.1. NM_023137.3.
UniGene	Mm.140210.
3D structure databases
ProteinModelPortal	P63072.
SMR	P63072. Positions 9-162.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1341042.
STRING	10090.ENSMUSP00000035808.
PTM databases
PhosphoSite	P63072.
Proteomic databases
PRIDE	P63072.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000038844; ENSMUSP00000035808; ENSMUSG00000035186.
GeneID	24108.
KEGG	mmu:24108.
UCSC	uc008cmi.2. mouse.
Organism-specific databases
CTD	10537.
MGI	MGI:1344410. Ubd.
Phylogenomic databases
eggNOG	NOG259502.
GeneTree	ENSGT00550000074658.
HOGENOM	HOG000134446.
HOVERGEN	HBG101094.
InParanoid	Q4FJZ5.
KO	K12157.
OMA	TQIVTCN.
OrthoDB	EOG4QRH5C.
Gene expression databases
Bgee	P63072.
CleanEx	MM_UBD.
Genevestigator	P63072.
GermOnline	ENSMUSG00000035186. Mus musculus.
Family and domain databases
InterPro	IPR000626. Ubiquitin. IPR019956. Ubiquitin_subgr. IPR019955. Ubiquitin_supergroup. [Graphical view]
Pfam	PF00240. ubiquitin. 2 hits. [Graphical view]
PRINTS	PR00348. UBIQUITIN.
SMART	SM00213. UBQ. 2 hits. [Graphical view]
PROSITE	PS50053. UBIQUITIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	UBD. mouse.
NextBio	304123.
SOURCE	Search...

Entry information

Entry name

UBD_MOUSE

Accession

Primary (citable) accession number: P63072
Secondary accession number(s): Q4FJZ5, Q9WV10

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	September 13, 2004
Last modified:	May 1, 2013
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program