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FLASH GENE

Symbol

UBD

contributors: mct/pgu - updated : 09-07-2016

HGNC name	ubiquitin D
HGNC id	18795

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	4.31 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

Map

see MHC1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006398 2 - 1006 NP_006389 18 165 - 2005 15831455

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Homo sapiens Digestive liver       highly   stomach       highly Lymphoid/Immune thymus       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune B cell

cell lineage	some lymphoblastoid lineages
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two ubiquitin-like domains UBL) that share 29 and 36 p100 sequence identity with ubiquitin, respectively , two tandem, head-to-tail, ubiquitin domains
	C-terminal diglycine motif required for the formation of UBD conjugates, mediating its covalent binding to target proteins

HOMOLOGY

Homologene

FAMILY

ubiquitin-like modifier family of proteins

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus,nucleolus

basic FUNCTION	potential modulator of cell growth during B cell or dendritic cell development and activation
	small ubiquitin-like modifier encoded in the major histocompatibility complex and ubiquitin-independent signal for proteasomal degradation
	playing a role in epithelial apoptosis, which is an important component of the pathogenesis of many renal diseases
	plays a role in the regulation of chromosomal stability
	acting as a ubiquitin-independent but NUB1-dependent targeting signal for proteasomal degradation
	mediates NF-kappaB activation and may promote tubulointerstitial inflammation in chronic kidney diseases
	implicated in the regulation of diverse cellular processes, including mitosis, immune response, and apoptosis
	ubiquitin-like that accelerate protein degradation through a ubiquitin-independent manner
	new role in the pathogenesis of polyglutamine diseases
	plays an important role in mediating the function of TNF during tumorigenesis by inducing cell cycle deregulation and chromosomal instability, and by inhibiting apoptosis
	ubiquitin-like protein modifier that is induced in vertebrates following certain inflammatory stimuli
	implicated in retinal cell biology and LCA (Leber congenital amaurosis) pathogenesis
	by promoting the translocation of LRRFIP2 into cytoplasmic aggregates, UBD might block its recruitment to the membrane and its subsequent role in NFKB1 activation through TLR4 stimulation
	is a cardioprotective protein
	plays an important role in cell proliferation
	cytokine-inducible ubiquitin-like modifier that directly targets UBD-conjugated proteins for degradation by the proteasome
	is a novel modifier of thymic Ag presentation and epitope-dependent elimination of self-reactive T cells
	attenuates DDX58 mediated antiviral signaling by segregating activated DDX58 from its signaling platform
	only ubiquitin-like protein that can directly target substrates for degradation by proteasomes, but it can also stabilize the expression of certain substrates by antagonizing ubiquitination
	stabilizes EEF1A1 expression to promote tumor proliferation in a complex manner
	is involved in proteasomal degradation and antigen processing
	unlike ISG15, ubiquitin and UBD are conjugated to a similar degree to newly translated and pre-existing proteins
	UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation

CELLULAR PROCESS	cell cycle, division, mitosis
	protein, degradation

PHYSIOLOGICAL PROCESS

immunity/defense

text	antimicrobial tumoral response

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	non covalently binding to MAD2L1, a spindle checkpoint protein, during mitosis
	binding partner of HDAC6, UBD serves as a signal for proteasomal degradation
	USE1 is an interaction partner of UBD
	in the nucleus was found co-localized with TP53 and altered its subcellular compartmentalization
	binds preferably to huntingtin with a short pQ chain and completely aggregated huntingtin was UBD-negative
	AIPL1 may have a role in directly regulating the UBD conjugation machinery
	potential role of cytokine-induced UBD expression in regulating UBA6 pathways
	UBA6 bound UBD with significantly higher affinity than ubiquitin
	UBD and NUB1 both interact with PSMD4 via the VWA domain
	inflammatory mediator LRRFIP2 is covalently modified by UBD
	STAT3 binding stabilizes NFKB1 on the UBD promoter and leads to maximum induction of UBD gene expression
	UBD play a role in mitotic regulation through its interaction with mitotic arrest-deficient 2 (MAD2L1)
	UBA1 and UBD form a stable non-reducible conjugate under overexpression as well as under endogenous conditions after induction of endogenous UBD expression with proinflammatory cytokines
	UBD conjugation, a post-translational modification analogous to ubiquitination, specifically requires UBA6 and UBE2Z as its activating (E1) and conjugating (E2) enzymes
	UBD is a novel negative regulator of DDX58-mediated inflammatory response
	UBD stabilizes the translation elongation factor EEF1A1 which contributes to cancer cell proliferation
	novel function of LMO2 involving in the regulatory hierarchy of UBA6-USE1-FAT10ylation pathway by targeting the E1 enzyme UBA6
	UBD appears to mitigate APOL1-mediated toxicity by targeting it for destruction

cell & other

REGULATION

activated by

UBA6 (is exclusively activated by UBA6)

induced by	IFNG
		inducible by tumor necrosis factor alpha

Other

its degradation is accelerated after induction of apoptosis, suggesting that it plays a role in prosurvival pathways

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in hepatocellular carcinoma and in several gastrointestinal and gynecological cancers constitutional     --over   in cells lead to increased mitotic nondisjunction and chromosome instability, and this effect is mediated by an abbreviated mitotic phase and the reduction in the kinetochore localization during the prometaphase stage of the cell cycle constitutional     --over   led to chromosomal instability that is mediated by an abbreviated mitotic phase constitutional     --over   in the heart at the border zone of myocardial infarction tumoral     --over   significantly correlated with poor survival in pancreatic ductal adenocarcinoma (PDAC) patients

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	may be involved in gastric carcinogenesis, and is a potential marker for the prognosis of gastric cancer patients
Therapy target
	System Type Disorder Pubmed cancer     interaction of FAT10 with MAD2L1 is a key mechanism underlying the promalignant property of UBD and offer prospects for the development of anticancer strategies

ANIMAL & CELL MODELS