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Protein

Ubiquitin D

Gene

UBD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ubiquitin-like protein modifier which can be covalently attached to target protein and subsequently leads to their degradation by the 26S proteasome, in a NUB1-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).10 Publications

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei164 – 165Activation by thioester intermediate formation with UBA62

GO - Molecular functioni

  • proteasome binding Source: UniProtKB

GO - Biological processi

  • aggresome assembly Source: UniProtKB
  • myeloid dendritic cell differentiation Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • post-translational protein modification Source: Reactome
  • protein modification by small protein conjugation Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • proteolysis Source: UniProtKB
  • regulation of mitotic cell cycle phase transition Source: UniProtKB
  • response to interferon-gamma Source: UniProtKB
  • response to tumor necrosis factor Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-8951664. Neddylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin D
Alternative name(s):
Diubiquitin
Ubiquitin-like protein FAT10
Gene namesi
Name:UBD
Synonyms:FAT10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000213886.3.
HGNCiHGNC:18795. UBD.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi11H → D: Decreases interaction with MAD2L1, no effect on the interaction with HDAC6, UBA6, NUB1 and SQSTM1 and moderately attenuates UBD-induced tumor formation in vivo; when associated with Q-13. Complete loss of interaction with MAD2L1, no effect on the interaction with TP53/p53, HDAC6, UBA6, NUB1 and SQSTM1 and significantly attenuates UBD-induced tumor formation in vivo; when associated with Q-13; D-75; D-77 and Q-79. 1 Publication1
Mutagenesisi13R → Q: Decreases interaction with MAD2L1, no effect on the interaction with HDAC6, UBA6, NUB1 and SQSTM1 and moderately attenuates UBD-induced tumor formation in vivo; when associated with D-11. Complete loss of interaction with MAD2L1, no effect on the interaction with TP53/p53, HDAC6, UBA6, NUB1 and SQSTM1 and significantly attenuates UBD-induced tumor formation in vivo; when associated with D-11; D-75; D-77 and Q-79. 1 Publication1
Mutagenesisi75H → D: Decreases interaction with MAD2L1, no effect on the interaction with HDAC6, UBA6, NUB1 and SQSTM1 and moderately attenuates UBD-induced tumor formation in vivo; when associated with D-77 and Q-79. Complete loss of interaction with MAD2L1, no effect on the interaction with TP53/p53, HDAC6, UBA6, NUB1 and SQSTM1 and significantly attenuates UBD-induced tumor formation in vivo; when associated with D-11; Q-13; D-77 and Q-79. 1 Publication1
Mutagenesisi77T → D: Decreases interaction with MAD2L1, no effect on the interaction with HDAC6, UBA6, NUB1 and SQSTM1 and moderately attenuates UBD-induced tumor formation in vivo; when associated with D-75 and Q-79. Complete loss of interaction with MAD2L1, no effect on the interaction with TP53/p53, HDAC6, UBA6, NUB1 and SQSTM1 and significantly attenuates UBD-induced tumor formation in vivo; when associated with D-11; Q-13; D-75 and Q-79. 1 Publication1
Mutagenesisi79K → Q: Decreases interaction with MAD2L1, no effect on the interaction with HDAC6, UBA6, NUB1 and SQSTM1 and moderately attenuates UBD-induced tumor formation in vivo; when associated with D-75 and D-77. Complete loss of interaction with MAD2L1, no effect on the interaction with TP53/p53, HDAC6, UBA6, NUB1 and SQSTM1 and significantly attenuates UBD-induced tumor formation in vivo; when associated with D-11; Q-13; D-75 and D-77. 1 Publication1
Mutagenesisi164 – 165GG → AA: Impaired thioester formation-mediated activation by UBA6. Loss of interaction with UBA6 and SQSTM1. No effect on its interaction with MAD2L1, HDAC6 and NUB1. 2 Publications2

Organism-specific databases

DisGeNETi10537.
OpenTargetsiENSG00000213886.
PharmGKBiPA38682.

Polymorphism and mutation databases

BioMutaiUBD.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001148931 – 165Ubiquitin DAdd BLAST165

Post-translational modificationi

Can be acetylated.1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiO15205.
PaxDbiO15205.
PeptideAtlasiO15205.
PRIDEiO15205.

PTM databases

iPTMnetiO15205.
PhosphoSitePlusiO15205.

Expressioni

Tissue specificityi

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.2 Publications

Inductioni

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 NUB1 (at protein level).11 Publications

Gene expression databases

BgeeiENSG00000213886.
CleanExiHS_UBD.
GenevisibleiO15205. HS.

Organism-specific databases

HPAiHPA043710.

Interactioni

Subunit structurei

Interact directly with the 26S proteasome. The interaction with NUB1 via 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 (via ubiquitin-like 1 domain) 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). Interacts with SQSTM1 and TP53/p53 (PubMed:25422469).7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • proteasome binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115791. 24 interactors.
IntActiO15205. 6 interactors.
STRINGi9606.ENSP00000366249.

Structurei

Secondary structure

1165
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 15Combined sources7
Helixi30 – 35Combined sources6
Beta strandi38 – 44Combined sources7
Beta strandi47 – 60Combined sources14
Beta strandi74 – 79Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MBENMR-A8-82[»]
ProteinModelPortaliO15205.
SMRiO15205.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini6 – 81Ubiquitin-like 1PROSITE-ProRule annotationAdd BLAST76
Domaini90 – 163Ubiquitin-like 2PROSITE-ProRule annotationAdd BLAST74

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0001. Eukaryota.
COG5272. LUCA.
GeneTreeiENSGT00810000125435.
HOVERGENiHBG101094.
InParanoidiO15205.
KOiK12157.
OMAiETQIVTC.
OrthoDBiEOG091G178I.
PhylomeDBiO15205.

Family and domain databases

InterProiView protein in InterPro
IPR019956. Ubiquitin.
IPR029071. Ubiquitin-rel_dom.
IPR000626. Ubiquitin_dom.
PfamiView protein in Pfam
PF00240. ubiquitin. 2 hits.
PRINTSiPR00348. UBIQUITIN.
SMARTiView protein in SMART
SM00213. UBQ. 2 hits.
SUPFAMiSSF54236. SSF54236. 2 hits.
PROSITEiView protein in PROSITE
PS50053. UBIQUITIN_2. 2 hits.

Sequencei

Sequence statusi: Complete.

O15205-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPNASCLCV HVRSEEWDLM TFDANPYDSV KKIKEHVRSK TKVPVQDQVL
60 70 80 90 100
LLGSKILKPR RSLSSYGIDK EKTIHLTLKV VKPSDEELPL FLVESGDEAK
110 120 130 140 150
RHLLQVRRSS SVAQVKAMIE TKTGIIPETQ IVTCNGKRLE DGKMMADYGI
160
RKGNLLFLAC YCIGG
Length:165
Mass (Da):18,473
Last modified:November 24, 2009 - v2
Checksum:i40BE415049920CC6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02427351L → S. Corresponds to variant dbSNP:rs2076484Ensembl.1
Natural variantiVAR_02427468I → T. Corresponds to variant dbSNP:rs2076485Ensembl.1
Natural variantiVAR_02427595S → P. Corresponds to variant dbSNP:rs2076486Ensembl.1
Natural variantiVAR_02540199A → G. Corresponds to variant dbSNP:rs2076487Ensembl.1
Natural variantiVAR_052693120E → K. Corresponds to variant dbSNP:rs17184290Ensembl.1
Natural variantiVAR_025402160C → S4 PublicationsCorresponds to variant dbSNP:rs8337Ensembl.1
Natural variantiVAR_024276162C → F. Corresponds to variant dbSNP:rs7757931Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4662.1.
RefSeqiNP_006389.2. NM_006398.3.
UniGeneiHs.44532.

Genome annotation databases

EnsembliENST00000377050; ENSP00000366249; ENSG00000213886.
ENST00000383547; ENSP00000373039; ENSG00000206468.
ENST00000421519; ENSP00000396152; ENSG00000231968.
ENST00000432676; ENSP00000410416; ENSG00000228913.
GeneIDi10537.
KEGGihsa:10537.
UCSCiuc003nmo.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUBD_HUMAN
AccessioniPrimary (citable) accession number: O15205
Secondary accession number(s): B0UZT6
, Q5STL2, Q5SUK2, Q96EC7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: November 24, 2009
Last modified: September 27, 2017
This is version 147 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references