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FLASH GENE

Symbol

UBE2I

contributors: mct/npt/pgu - updated : 08-04-2016

HGNC name	ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast)
HGNC id	12485

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	16p13.3      Physical location : 1.359.179 - 1.375.390
Synonym name	SUMO-1-protein ligase
	ubiquitin carrier protein
	ubiquitin conjugating enzyme 9
	ubiquitin-like protein SUMO-1 conjugating enzyme
Synonym symbol(s)	UBC9, UBCI, C358B7.1, P18, UBCE9
EC.number	6.3.2.19

DNA

TYPE	functioning gene
STRUCTURE	17.87 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003345 7 - 2871 NP_003336 18 158 - 1996 8668529 NM_194259 8 - 3128 NP_919235 18 158 - 1996 8668529 NM_194260 7 - 2991 NP_919236 18 158 - 1996 8668529 NM_194261 7 - 2843 NP_919237 18 158 - 1996 8668529

EXPRESSION

Type	ubiquitous

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         Digestive liver           stomach       highly Endocrine thyroid       highly Lymphoid/Immune lymph node       highly Nervous brain         Reproductive female system ovary     highly Respiratory lung         Visual eye         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Homo sapiens Adult

cells

System Cell Pubmed Species Stage Rna symbol not specific adipocyte Homo sapiens Adult

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	conserved UBC domain of 150 AA harboring the cysteine residue required for enzyme-ubiquitin thioester formation
	C-terminus involved in both the protein-protein interaction and its sumoylation-modifying activity provide the mechanism for regulating nuclear receptor functions

HOMOLOGY

interspecies	homolog to yeast UBC9
	homolog to S.Cerevisiae Scubc9

Homologene

FAMILY

ubiquitin-conjugating enzyme family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
text	strikingly colocalized with SFRS2, which is a component of nuclear speckles and critical for mRNA processing
	expressed predominantly in the nucleus of preadipocytes but shifted to cytoplasmic compartments
	SAE1, UBE2I and PIAS1 are distributed in both nucleus and cytoplasm of ocular cell lines

basic FUNCTION	involved in ubiquitin conjugation,second step of ubiquitin-dependent proteolysis
	SUMO-E2 enzyme, sufficient for substrate recognition and lysine modifications of SUMO targets
	promoting nuclear accumulation and metabolic stability of tumor suppressor SMAD4
	can function as a co-factor of PLAGL2, uncoupling from its enzymatic activity, to mediate PLAGL2 interactive surfactant protein-C promoter activity
	essential gene which is required for cell cycle progression and is involved in the degradation of S phase and M phase cyclins
	sufficient for substrate recognition and lysine modification of known SUMO targets
	essential protein in mammalian cells with a predominantly nuclear localization
	critical for mRNA processing, and having a possible function of sumoylation in gene expression
	E2-conjugating enzyme that transfers the activated small ubiquitin-like modifier (SUMO) to protein substrates, and thus it has an important function in sumoylation-mediated cellular pathways
	involved in protein modification through covalent attachment of small ubiquitin-like modifier and, has emerged as a key regulator of cell proliferation and differentiation
	appears to play an important role in adipogenesis
	negatively regulates osteoblastic differentiation induced by BMP via, at least in part, SUMOylation of SMAD4
	UBE2I acts as a functional binding partner of FYB1 and plays a selective role in integrin-mediated T cell adhesion via modulation of RAP1A-RASSF5 membrane recruitment and RAC1 activation

CELLULAR PROCESS	cell cycle
	nucleotide, repair
	protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	UBE2I associated to FHIT
	RANBP2 forms a stable complex with SUMO-modified RANGAP1 and UBE2I at the nuclear pore complex
	member of the surfactant protein-C promoter complex
	IPO13–UBE2I9 complex forms in the cytosol and translocates into the nucleus
	non-covalent ternary complex formed by PIAS1, SUMO1, and UBE2I proteins involved in transcriptional regulation

INTERACTION

DNA

RNA

small molecule

protein	associating with RAD51, RAD52 proteins in the double strand RAD51/RAD52 repair pathway
	associating with UBL1 and TP53, involved in DNA recombination and essential for cell-cycle progression
	associating with FHIT for cell-cycle control
	interacting with ETV6 leading to sumoylation of ETV6 (TEL) by UBL (SUMO-1)
	interacted with the DNA-binding and ligand-binding domains of ESR1
	protein interacting with UIMC1
	interacted with SOX4 through HMG-box domain of SOX4 and represses its transcriptional activity independent of its SUMO-1-conjugating activity
	interacting with STAR and FOXL2 (UBE2I-mediated sumoylation at lysine 25 of FOXL2 is required for transcriptional repression of the STAR gene and may be responsible for controlling the development of ovarian follicles)
	ZMYND11 interacts with PIAS1 (a well-characterized SUMO E3 enzyme) and UBE2I (the only SUMO E2 enzyme so far identified) through its distinct regions
	molecular link between UBE2I and the metastasis genes such as CDC42 and CXCR4, and thus provide new insight into the mechanism by which UBE2I9 promotes tumor invasion and metastasis
	binding of BRCA1 proteins to nuclear chaperone UE2I provides a novel mechanism for nuclear import and control of tumor growth
	is an interaction partner of the transcription factor EGR2, a key regulator of hindbrain development
	SETD8 interacts with the UBE2I E2 SUMO conjugating enzyme (directly binds SETD8 proximal to the catalytic SET domain)
	RANBP2 forms a stable complex with SUMO-modified RANGAP1 and UBE2I at the nuclear pore complex
	SKI can enhance UBE2I-mediated cellular sumoylation, possibly through direct interaction with UBE2I
	interaction between the CANX cytoplasmic domain and UBE2I, a SUMOylation E2 ligase, which modified the calnexin cytoplasmic domain by the addition of SUMO
	UBE2I interacted directly with FYB1 and the association was increased in response to anti-CD3 stimulation

cell & other

REGULATION

Other

autosumoylation of the mammalian E2-conjugating enzyme UBE2I at Lys14 regulates target discrimination

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in advanced melanomas

Susceptibility

to late-onset Alzheimer disease (AD)

Variant & Polymorphism other	UBE2I polymorphisms might be associated with a risk of AD

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer skin   blocking expression of UBE2I sensitizes melanomas to the cytotoxic effects of chemotherapeutic drugs

ANIMAL & CELL MODELS