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FLASH GENE

Symbol

TRIP12

contributors: mct - updated : 28-02-2015

HGNC name	thyroid hormone receptor interactor 12
HGNC id	12306

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MRD49 mental retardation, autosomal dominant 49
Location	2q36.3      Physical location : 230.631.929 - 230.786.655
Synonym symbol(s)	KIAA0045, H4, MGC138849, MGC138850, TRIP-12, ULF
EC.number	6.3.2.-

DNA

TYPE	functioning gene
STRUCTURE	158.20 kb     41 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001284214 42 - 10035 NM_001284214 - 2040 - 2009 19028681 NM_001284216 39 - 9082 NP_001271145 - 1722 - 2009 19028681 NM_004238 41 - 9892 NP_004229 - 1992 - 2009 19028681 NM_001284215 40 - 9861 NP_001271144 - 2025 - 2009 19028681

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 Digestive liver           mouth gingiva       Endocrine thyroid       highly Lymphoid/Immune lymph node       highly Nervous brain       lowly Homo sapiens   spinal cord         Reproductive male system testis       Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Muscular striatum     highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal region containing armadillo repeats and a WWE domain, both of which are presumed to mediate protein-protein interactions (Park 2009)
	one HECT-type E3 ubiquitin-protein ligase domain, that possesses a noncovalent ubiquitin-binding site, unique in that the HECT domain can conjugate ubiquitin to noncovalently bound ubiquitin (Park 2009)
	7 RCC1 domains
	an ARM domain (armadillo/CTNNB1-like repeats)

HOMOLOGY

Homologene

FAMILY

HECT family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	HECT domain-containing E3 ubiquitin–protein ligase
	activating the proteolytic activities of the multifunctional proteinase (20s proteasome) of the 26s complex and specifically interacting with the ligand binding domain of the thyroid hormone receptor
	functions as an E3 enzyme of NAE1 and additionally requires an E4 activity for polyubiquitination of NAE1
	promotes degradation of NAE1 by catalyzing its ubiquitination, which in turn modulates the neddylation pathway
	can recognize UFD substrates and catalyze their ubiquitination, through its HECT domain (Park 2009)
	is potentially involved in global gene expression and plays an important role in embryonic development
	TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage
	HUWE1 and TRIP12 function likely in parallel during ubiquitin fusion degradation (UFD)
	PTF1A/TRIP12 functional interaction may regulate pancreatic epithelial cell homeostasis
	E3 ubiquitin ligase TRIP12 plays an important role in nervous system development and function

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

ubiquitin fusion degradation (UFD) pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	interaction with NAE1 (ubiquitinates NAE1)
	is a bona fide E3 ligase for CDKN2A, suggesting that TRIP12 is an important target for activating the CDKN2A-TP53 axis in acute myeloid leukaemia (AML) cells
	TRADD shuttles dynamically from the cytoplasm into the nucleus to modulate the interaction between CDKN2A and its E3 ubiquitin ligase TRIP12, thereby promoting CDKN2A stability and tumour suppression
	interaction with CUL1 (regulates neddylation of CUL1)
	recognizes and polyubiquitinates SOX6
	GNL3 stabilizes CDKN2A by inhibiting the ubiquitin ligase TRIP12
	TRIP12 is an E3 ubiquitin-protein ligase as a new partner of PTF1A (protein stability of PTF1A is significantly increased upon decreased expression of TRIP12)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MRD49

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

homozygous mutation in Trip12 (Trip12(mt/mt)) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development