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FLASH GENE

Symbol

TRIM32

contributors: mct/npt/pgu - updated : 27-11-2018

HGNC name	tripartite motif-containing 32
HGNC id	16380

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	BBS11 Bardet-Biedl syndrome 11 LGMD2H limb-girdle muscular dystrophy 2H
Location	9q33.1      Physical location : 119.449.580 - 119.463.579
Synonym name	zinc-finger protein HT2A
	TAT-interactive protein, 72-KD
	muscular dystrophy, Hutterite type
Synonym symbol(s)	HT2A, TATIP, BBS11, LGMD2H
EC.number	6.3.2.-/2.3.2.27

DNA

TYPE	functioning gene
STRUCTURE	14.00 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D9S170 - D9S154 - TRIM32 - D9S1802 - D9S1811 - qter

RNA

TRANSCRIPTS	type	messenger

text	two transcripts encode the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_012210 2 splicing 3734 NP_036342 71.9 653 - 2001 11331580 NM_001099679 2 splicing 3731 NP_001093149 71.9 653 - 2001 11331580 using a different splice site in the 5' UTR compared to variant 1

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 Digestive intestine large intestine colon     Lymphoid/Immune spleen           thymus         Nervous brain       predominantly Homo sapiens TRIM32 RNA   brain diencephalon hypothalamus     Reproductive female system uterus     highly   male system prostate         male system testis       Skin/Tegument skin       highly Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   lowly Homo sapiens TRIM32 RNA Muscular striatum skeletal     Mus musculus Adult

cells

System Cell Pubmed Species Stage Rna symbol Muscular myoblast Homo sapiens TRIM32 RNA

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

Text	TRIM32 mRNA expression is &
	8764;16 times higher in myoblasts than in skeletal muscle tissue

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal RING zinc finger, necessary for the pro-apoptotic function of TRM32 as well as being responsible for its E3 ligase activity
	a type 2 B-box domain
	a coiled-coil domain (RBCC) so called tripartite motif (TRIM)
	five NHL repeats
	C-terminus forms a beta-propeller NHL domain

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to rattus Trim32 (96.9 pc)
	homolog to murine Trim32 (96.2 pc)

Homologene

FAMILY	C-VII TRIM family
	TRIM/RBCC family

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus
text	accumulated in cytoplasmic granules
	localized to the Z-line in skeletal muscle

basic FUNCTION	playing a role in mediating biological activity of the HIV1-TAT protein (lentiviral tat protein)
	having E3-ubiquitin-ligase activity, and playing a role in regulating components of the cytoskeleton
	required for the localization of G protein-coupled receptors to primary cilia on central neurons
	participating in myofibrillar protein turnover, especially during muscle adaptation
	acting as a transcription coactivator
	mediating the ubiquitination of ABI2
	being a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs
	E3 ubiquitin ligase that binds to myosin and ubiquitinates actin
	promotes PIAS4 ubiquitination and degradation, and by controlling PIAS4 stability, regulates UVB-induced keratinocyte apoptosis through induction of NFkappaB
	regulator of dysbindin (the LGMD2H/STM mutations may impair substrate ubiquitination)
	thought to be involved in protein ubiquitination, but its precise physiological role in muscle is unknown
	sensitizes cells to TNF-induced apoptosis
	has specific E3 ligase activity against XIAP and down-regulates XIAP through its RING domain-dependent E3 ligase activity
	may act as a general sensitizer of various pro-apoptotic signals triggering either the intrinsic or the extrinsic pathway
	functions as one of the co-activators for RARA-mediated transcription
	during fasting, desmin phosphorylation increases and enhances TRIM32-mediated degradation of the desmin cytoskeleton, which appears to facilitate the breakdown of Z-bands and thin filaments
	mutual regulation between TP73 and TRIM32 constitutes a novel feedback loop, which might have important implications in central nervous system development as well as relevance in oncogenesis
	function of the cell fate-determinant TRIM32 for a balanced activity of the adult neurogenesis process
	is a positive regulator of Asymmetric cell division (ACD) that acts against MYCN and should be considered as a tumor-suppressor candidate
	regulates fate specification of neural stem cells
	is a novel essential positive factor modulating axonal regeneration and the recovery of motor function following spinal cord injury (SCI), possibly through suppressing proliferation of glial cells
	TRIM32 associates with the deubiquitination enzyme USP7, which previously has been implicated in neural stem cell maintenance, and exhibit a dynamic and partially overlapping expression pattern during neuronal differentiation

CELLULAR PROCESS	cell life, differentiation
	nucleotide, transcription, regulation
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

text	fat cell differentiation

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	maybe involved in protein-protein interaction, noteworthy lentiviral TAT protein through its NHL repeats
	interacting with the head and neck region of myosin
	E3 ubiquitin ligase that acts in conjunction with ubiquitin-conjugating enzymes UBCH5A, UBCH5C, and UBCH6
	binding specifically to the activation domain of HIV-1 Tat
	can also interact with the HIV-2 and EIAV Tat proteins in vivo
	interaction of PIAS4 with TRIM32, an E3-ubiquitin ligase promotes PIAS4 degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB
	binding to ABI2
	binds and ubiquitinates DNBDD1, a protein implicated in the genetic aetiology of schizophrenia, augmenting its degradation)
	binds and ubiquitinates dysbindin, a protein implicated in the genetic aetiology of schizophrenia, augmenting its degradation
	interactions between TRIM32 and UBE2V2, and UBE2V1 (TRIM E3 activity is only manifest with the UBE2 with which they interact)
	colocalizes and directly interacts with XIAP, a well known cancer therapeutic target, through its coiled-coil and NHL domains
	interacts with RARA and enhances its transcriptional activity in the presence of RA
	ubiquitin ligase TRIM32 controls myogenic differentiation process through the regulation of MYC, a similar mechanism to that previously observed in neural progenitors
	interacted with TMEM173A, and was located at the mitochondria and endoplasmic reticulum
	TRIM32, a new direct TP73 transcriptional target in the context of neural progenitor cells, is differentially regulated by TP73
	TRIM32 interacted with MYCN at spindle poles during mitosis, facilitating proteasomal degradation of MYCN at spindle poles and inducing Asymmetric cell division (ACD)
	TRIM32 interacts with TP53 and promotes TP53 degradation through ubiquitination
	NDRG2 is a novel target for TRIM32 and TRIM32 is involved in control of myogenic cells proliferation and differentiation
	TRIM32 associates with proteins involved in neurogenesis and RNA-related processes, such as the RNA helicase DDX6, which has been implicated in microRNA regulation
	is essential for the induction of neuronal differentiation of neural stem cells by poly-ubiquitinating MYC to target it for degradation resulting in inhibition of cell proliferation
	TRIM32 modulates pluripotency entry and exit by directly regulating POU5F1 stability
	TRIM32 binds to the promoter region of SNCA, suggesting a novel mechanism of its transcriptional regulation
	TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TICAM1 to TAX1BP1-mediated selective autophagic degradation
	balanced ubiquitination and deubiquitination of MYC by TRIM32 and USP7 is a novel mechanism for stem cell fate determination

cell & other

REGULATION

induced by

in myogenic differentiation

repressed by

IFN-gamma and LPS

ASSOCIATED DISORDERS

corresponding disease(s)

LGMD2H , BBS11

related resource

Limb-Girdle Muscular Dystrophy pages

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   were detected in gastric cancer tissues       --low   in atopic dermatitis skin compared with healthy control and psoriatic skin suggest a defective TRIM32 pathway in atopic dermatitis pathogenesis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	TRIM32 expression levels may be of potential prognostic value in gastric cancer
Therapy target
	System Type Disorder Pubmed cancer hemopathy   potential therapeutic target for developmental disorders and RA-dependent leukemias neuromuscular myopathy   is a possible therapeutic target to favor skeletal muscle regeneration in DMD patients

ANIMAL & CELL MODELS

	histological analysis of T32KO (Trim32 knock-out model) skeletal muscles revealed mild myopathic changes, electron microscopy showed areas with Z-line streaming and a dilated sarcotubular system with vacuoles -- the latter being a prominent feature of sarcotubular myopathy
	Trim32-null mice showed a decrease in the concentration of neurofilament proteins in the brain and a reduced motoraxon diamete
	Trim32-/- mice produced higher levels of serum inflammatory cytokines and were more sensitive to loss of body weight and inflammatory death upon Salmonella typhimurium infection