O15205 (UBD_HUMAN) 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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	165 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. Conjugation ability activated by UBA6. 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 such as polycystic kidney disease and Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). Ref.8 Ref.10 Ref.11 Ref.14 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22
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. 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.2 Ref.7 Ref.11 Ref.12 Ref.14 Ref.16
Subcellular location	Nucleus. Cytoplasm By similarity. Note: Accumulates in aggresomes under proteasome inhibition conditions. Ref.6 Ref.16
Tissue specificity	Constitutively expressed in mature dendritic cells and B cells. Mostly expressed in the reticuloendothelial system (e.g. thymus, spleen), the gastrointestinal system, kidney, lung and prostate gland. Ref.1 Ref.6
Induction	Rapidly degraded by the proteasome. Cell-cycle regulation with highest expression during the S-phase (at protein level). Induced during dendritic cell maturation. Negatively regulated by p53/TP53. High levels in various gastrointestinal and gynecological cancer cells. Induced in RTECs in common renal diseases including diabetic nephropathy (DN), IgA nephropathy (IgAN), and hypertensive nephrosclerosis (HN), as well as in hepatocellular carcinoma (HCC) and during HIVAN. Inducible by the proinflammatory cytokines IFNG/IFN-gamma and TNF in cancers of liver and colon. Repressed by NUB1L (at protein level). Ref.6 Ref.7 Ref.9 Ref.10 Ref.13 Ref.14 Ref.17 Ref.19 Ref.20 Ref.21 Ref.22
Post-translational modification	Can be acetylated.
Miscellaneous	Common types of chronic kidney disease are associated with tubulointerstitial up-regulation of FAT10. FAT10 may mediate NF-kappa-B activation and may promote tubulointerstitial inflammation in chronic kidney diseases.
Sequence similarities	Contains 2 ubiquitin-like domains.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	aggresome assembly Inferred from direct assay Ref.16. Source: UniProtKB myeloid dendritic cell differentiation Inferred from mutant phenotype Ref.19. Source: UniProtKB negative regulation of mitotic prometaphase Inferred from mutant phenotype Ref.11. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype Ref.22. Source: UniProtKB positive regulation of apoptotic process Inferred from mutant phenotype Ref.10. Source: UniProtKB protein ubiquitination Inferred from direct assay Ref.8Ref.14. Source: UniProtKB response to interferon-gamma Inferred from expression pattern Ref.14. Source: UniProtKB response to tumor necrosis factor Inferred from expression pattern Ref.14. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.14. Source: UniProtKB
Cellular component	aggresome Inferred from direct assay Ref.16. Source: UniProtKB cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from direct assay Ref.6. Source: UniProtKB
Molecular function	proteasome binding Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 165	165	Ubiquitin D		PRO_0000114893
Regions
	Region	6 – 81	76	Ubiquitin 1
	Region	90 – 163	74	Ubiquitin 2
Sites
	Site	164 – 165	2	Activation by thioester intermediate formation with UBA6
Amino acid modifications
	Modified residue	109	1	Phosphoserine Ref.15
	Modified residue	110	1	Phosphoserine Ref.15
	Modified residue	111	1	Phosphoserine Ref.15
Natural variations
	Natural variant	51	1	L → S. Corresponds to variant rs2076484 [ dbSNP | Ensembl ].		VAR_024273
	Natural variant	68	1	I → T. Corresponds to variant rs2076485 [ dbSNP | Ensembl ].		VAR_024274
	Natural variant	95	1	S → P. Corresponds to variant rs2076486 [ dbSNP | Ensembl ].		VAR_024275
	Natural variant	99	1	A → G. Corresponds to variant rs2076487 [ dbSNP | Ensembl ].		VAR_025401
	Natural variant	120	1	E → K. Corresponds to variant rs17184290 [ dbSNP | Ensembl ].		VAR_052693
	Natural variant	160	1	C → S. Ref.1 Ref.2 Ref.3 Ref.4 Corresponds to variant rs8337 [ dbSNP | Ensembl ].		VAR_025402
	Natural variant	162	1	C → F. Corresponds to variant rs7757931 [ dbSNP | Ensembl ].		VAR_024276
Experimental info
	Mutagenesis	164 – 165	2	GG → AA: Impaired thioester formation-mediated activation by UBA6. Ref.14

Sequences

	Sequence		Length	Mass (Da)
	O15205 [UniParc]. Last modified November 24, 2009. Version 2. Checksum: 40BE415049920CC6	FASTA	165	18,473
	10 20 30 40 50 60 MAPNASCLCV HVRSEEWDLM TFDANPYDSV KKIKEHVRSK TKVPVQDQVL LLGSKILKPR 70 80 90 100 110 120 RSLSSYGIDK EKTIHLTLKV VKPSDEELPL FLVESGDEAK RHLLQVRRSS SVAQVKAMIE 130 140 150 160 TKTGIIPETQ IVTCNGKRLE DGKMMADYGI RKGNLLFLAC YCIGG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells." Bates E.E.M., Ravel O., Dieu M.-C., Ho S., Guret C., Bridon J.-M., Ait-Yahia S., Briere F., Caux C., Banchereau J., Lebecque S. Eur. J. Immunol. 27:2471-2477(1997) [PubMed: 9368598] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-160, TISSUE SPECIFICITY.
[2]	"A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2." Liu Y.-C., Pan J., Zhang C., Fan W., Collinge M., Bender J.R., Weissman S.M. Proc. Natl. Acad. Sci. U.S.A. 96:4313-4318(1999) [PubMed: 10200259] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MAD2L1, VARIANT SER-160. Tissue: Spleen.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-160.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-160.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[6]	"Expression of the FAT10 gene is highly upregulated in hepatocellular carcinoma and other gastrointestinal and gynecological cancers." Lee C.G.L., Ren J., Cheong I.S.Y., Ban K.H.K., Ooi L.L.P.J., Yong Tan S., Kan A., Nuchprayoon I., Jin R., Lee K.-H., Choti M., Lee L.A. Oncogene 22:2592-2603(2003) [PubMed: 12730673] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION IN HEPATOCELLULAR CARCINOMA.
[7]	"NEDD8 ultimate buster-1L interacts with the ubiquitin-like protein FAT10 and accelerates its degradation." Hipp M.S., Raasi S., Groettrup M., Schmidtke G. J. Biol. Chem. 279:16503-16510(2004) [PubMed: 14757770] [Abstract] Cited for: INTERACTION WITH NUB1L, INDUCTION BY NUB1L.
[8]	"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: 15831455] [Abstract] Cited for: FUNCTION.
[9]	"FAT10, a gene up-regulated in various cancers, is cell-cycle regulated." Lim C.-B., Zhang D., Lee C.G. Cell Div. 1:20-20(2006) [PubMed: 16959044] [Abstract] Cited for: INDUCTION BY CELL CYCLE.
[10]	"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: 16495380] [Abstract] Cited for: FUNCTION, INDUCTION IN HIVAN.
[11]	"FAT10 plays a role in the regulation of chromosomal stability." Ren J., Kan A., Leong S.H., Ooi L.L.P.J., Jeang K.-T., Chong S.S., Kon O.L., Lee C.G.L. J. Biol. Chem. 281:11413-11421(2006) [PubMed: 16495226] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAD2L1.
[12]	"The UBA domains of NUB1L are required for binding but not for accelerated degradation of the ubiquitin-like modifier FAT10." Schmidtke G., Kalveram B., Weber E., Bochtler P., Lukasiak S., Hipp M.S., Groettrup M. J. Biol. Chem. 281:20045-20054(2006) [PubMed: 16707496] [Abstract] Cited for: INTERACTION WITH NUB1L AND PROTEASOME.
[13]	"p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers." Zhang D.W., Jeang K.-T., Lee C.G. Oncogene 25:2318-2327(2006) [PubMed: 16501612] [Abstract] Cited for: INDUCTION BY TP53.
[14]	"E1-L2 activates both ubiquitin and FAT10." Chiu Y.-H., Sun Q., Chen Z.J. Mol. Cell 27:1014-1023(2007) [PubMed: 17889673] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBA6, THIOESTER FORMATION, INDUCTION BY TNF AND IFNG, MUTAGENESIS OF 164-GLY-GLY-165.
[15]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-109; SER-110 AND SER-111, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition." Kalveram B., Schmidtke G., Groettrup M. J. Cell Sci. 121:4079-4088(2008) [PubMed: 19033385] [Abstract] Cited for: FUNCTION, INTERACTION WITH HDAC6, SUBCELLULAR LOCATION, ACETYLATION.
[17]	"Proinflammatory cytokines cause FAT10 upregulation in cancers of liver and colon." Lukasiak S., Schiller C., Oehlschlaeger P., Schmidtke G., Krause P., Legler D.F., Autschbach F., Schirmacher P., Breuhahn K., Groettrup M. Oncogene 27:6068-6074(2008) [PubMed: 18574467] [Abstract] Cited for: FUNCTION, INDUCTION BY CYTOKINES.
[18]	"Degradation of FAT10 by the 26S proteasome is independent of ubiquitylation but relies on NUB1L." Schmidtke G., Kalveram B., Groettrup M. FEBS Lett. 583:591-594(2009) [PubMed: 19166848] [Abstract] Cited for: FUNCTION.
[19]	"Maturation of human dendritic cells is accompanied by functional remodelling of the ubiquitin-proteasome system." Ebstein F., Lange N., Urban S., Seifert U., Krueger E., Kloetzel P.-M. Int. J. Biochem. Cell Biol. 41:1205-1215(2009) [PubMed: 19028597] [Abstract] Cited for: FUNCTION, INDUCTION.
[20]	"FAT10: a novel mediator of Vpr-induced apoptosis in human immunodeficiency virus-associated nephropathy." Snyder A., Alsauskas Z., Gong P., Rosenstiel P.E., Klotman M.E., Klotman P.E., Ross M.J. J. Virol. 83:11983-11988(2009) [PubMed: 19726511] [Abstract] Cited for: FUNCTION, INDUCTION.
[21]	"FAT10 level in human gastric cancer and its relation with mutant p53 level, lymph node metastasis and TNM staging." Ji F., Jin X., Jiao C.-H., Xu Q.-W., Wang Z.-W., Chen Y.-L. World J. Gastroenterol. 15:2228-2233(2009) [PubMed: 19437562] [Abstract] Cited for: INDUCTION.
[22]	"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: 19959714] [Abstract] Cited for: FUNCTION, INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y12653 mRNA. Translation: CAA73200.1. AF123050 mRNA. Translation: AAD52982.1. AL031983 Genomic DNA. Translation: CAA21458.1. AL662826 Genomic DNA. Translation: CAI17384.1. AL645936 Genomic DNA. Translation: CAI18010.1. CR759766, CR942274 Genomic DNA. Translation: CAQ06603.1. CR759770 Genomic DNA. Translation: CAQ10041.1. CR942274, CR759766 Genomic DNA. Translation: CAQ10316.1. CH471081 Genomic DNA. Translation: EAX03201.1. BC012472 mRNA. Translation: AAH12472.1.
IPI	IPI00007405.
RefSeq	NP_006389.2. NM_006398.3.
UniGene	Hs.728313.
3D structure databases
ProteinModelPortal	O15205.
SMR	O15205. Positions 7-165.
ModBase	Search...
Protein-protein interaction databases
STRING	O15205.
PTM databases
PhosphoSite	O15205.
Proteomic databases
PRIDE	O15205.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000383547; ENSP00000373039; ENSG00000206468. ENST00000432676; ENSP00000410416; ENSG00000228913.
GeneID	10537.
KEGG	hsa:10537.
UCSC	uc003nmo.1. human.
Organism-specific databases
CTD	10537.
GeneCards	GC06M029525.
HGNC	HGNC:18795. UBD.
MIM	606050. gene.
neXtProt	NX_O15205.
PharmGKB	PA38682.
GenAtlas	Search...
Phylogenomic databases
eggNOG	maNOG20522.
HOVERGEN	HBG101094.
InParanoid	O15205.
OMA	ETQIVTC.
OrthoDB	EOG4QRH5C.
PhylomeDB	O15205.
Gene expression databases
CleanEx	HS_UBD.
Genevestigator	O15205.
Family and domain databases
InterPro	IPR000626. Ubiquitin. IPR019956. Ubiquitin_subgr. IPR019955. Ubiquitin_supergroup. [Graphical view]
KO	K12157.
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
NextBio	39977.
SOURCE	Search...

Entry information

Entry name

UBD_HUMAN

Accession

Primary (citable) accession number: O15205
Secondary accession number(s): B0UZT6 , Q5STL2, Q5SUK2, Q96EC7

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	November 24, 2009
Last modified:	January 25, 2012
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.