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FLASH GENE

Symbol

HERC2

contributors: mct/pgu - updated : 30-10-2014

HGNC name	hect domain and RLD 2
HGNC id	4868

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004667 93 - 15334 NP_004658 527.5 4834 - 2007 17952075

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         Endocrine adrenal gland       highly   parathyroid       highly Nervous nerve       highly Reproductive female system ovary     highly   male system testis     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac     Muscular striatum skeletal     Nervous central

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	highly in fetal tissues

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	19 RCC1-like domains (RLD)
	a ZZ type putative zinc finger motif
	a cytochrome b5 heme-binding domain
	a DOC domain
	a MIB/HERC2 domain
	six WD repeats
	a C terminal HECT domain characteristic of (E6-AP) E3 ubiquitin ligases, homologous to the UBE3A carboxy terminus

HOMOLOGY

interspecies

homolog to murine Herc2

Homologene

FAMILY

HERC family

CATEGORY

enzyme , regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
text	centriole
	HERC2 and NEURL4 localize to the centrosome

basic FUNCTION	guanyl-nucleotide exchange factor
	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates
	factor that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes
	function for HERC2 in regulating BRCA1 stability in opposition to BARD1, suggesting that this mechanism may play a role in breast carcinogenesis
	stimulates the ubiquitin-protein ligase activity of UBE3A within cells and this stimulatory effect does not depend on the ubiquitin-protein ligase activity of HERC2
	regulates DNA replication progression and origin firing by facilitating MCM2 phosphorylation
	having a critical function in DNA repair, checkpoint activation, and DNA replication
	HERC2 and RNF168 are novel DNA damage-dependent SUMOylation targets in human cells
	modulates the ubiquitin ligase activity of UBE3A
	regulates the basal turnover of FBXL5, and this ubiquitin-dependent degradation pathway contributes to the control of mammalian iron metabolism

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

cellular trafficking transport

text	vesicular transport

PATHWAY

metabolism

signaling

a component	forming a complex with RNF8, complex involved in DNA damage response
	component of the DNA replication fork complex that plays a critical role in DNA elongation and origin firing
	NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture

INTERACTION

DNA

RNA

small molecule

protein	HERC2-RNF8 interaction requires ionising radiation-inducible phosphorylation of HERC2 at Thr 4827, which in turn binds to the forkhead-associated (FHA) domain of RNF8
	targets BARD1-uncoupled BRCA1 for degradation
	UBE3A interaction with HERC2 is mediated by the RCC1-like domain 2 of HERC2 and a region spanning amino acid residues 150-200 of UBE3A
	interaction between HERC2 and SLC24A4 affecting determination of blue eye colour
	significant interactions of a redundant character between the HERC2 and OCA2 genes affecting determination of hazel eye colour
	E3 ubiquitin ligase that targets breast cancer suppressor BRCA1 for degradation
	in the presence of BRCA1, interacts with CLSPN, a protein essential for G(2)-M checkpoint activation and replication fork stability
	HERC2 and the neuralized homologue NEURL4 are novel interaction partners of the centrosomal protein CCP110, and association between CCP110 and HERC2 depends on nonoverlapping regions of NEURL4
	both HERC2 and RNF168 were specifically modified with SUMO1 at DSB sites in a manner dependent on the SUMO E3 ligase PIAS4
	thought to be a key regulator of E6AP
	is an FBXL5-associated protein
	HERC2, a HECT domain-containing E3 ligase, as being responsible for polyubiquitination of USP33
	HERC2 interacts with the coiled-coil domain of USP16 through its C-terminal HECT domain
	function of HERC2/USP20 in coordinating CHEK1 activation by modulating CLSPN stability, which ultimately promotes genome stability and suppresses tumor growth
	USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HECD , MRAGI

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     mapped within the commonly deleted PWS/AS region, with multiple duplications at the common breapoints

Susceptibility

to blue or brown eye colors

Variant & Polymorphism SNP	two SNPs perfectly associated with the blue and brown eye colors

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS