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FLASH GENE
Symbol TRIM32 contributors: mct/npt/pgu - updated : 23-05-2014
HGNC name tripartite motif-containing 32
HGNC id 16380
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
    EC.number 6.3.2.-
    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
    Physical map
    AMBP 9q32-q33 alpha-1-microglobulin/bikunin precursor KIF12 9q33.1 kinesin family member 12 COL27A1 9q33.1 collagen, type XXVII, alpha 1 ORM1 9q32 orosomucoid 1 ORM2 9q32 orosomucoid 2 AKNA 9q32 AT-hook transcription factor AKNA CIP98 9q33.1 CASK-interacting protein CIP98 ATP6V1G1 9q33.1 ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G isoform 1 DKFZp547P234 9q33.1 DKFZp547P234 protein LOC389786 9 LOC389786 TNFSF15 9q32 tumor necrosis factor (ligand) superfamily, member 15 LOC392386 9 similar to serine/threonine-protein kinase PRP4K; serine/threonine-protein kinase PRP4 homolog TNFSF8 9q33 tumor necrosis factor (ligand) superfamily, member 8 TNC 9q33.3 tenascin C (hexabrachion) DEC1 9q32 tenascin C (hexabrachion) C9orf27 9q31.3 chromosome 9 open reading frame 27 PAPPA 9q33.1 pregnancy-associated plasma protein A ASTN2 9q33.1 astrotactin 2 TRIM32 9q33.1 tripartite motif-containing 32 TLR4 9q32-q33 toll-like receptor 4 LOC340477 9q33.2 hypothetical LOC340477 LOC389787 9 similar to Translationally controlled tumor protein (TCTP) (p23) (Histamine-releasing factor) (HRF) LOC347165 9q33.3 similar to beta-tubulin 4Q DBC1 9q32-q33 deleted in bladder cancer 1
    RNA
    TRANSCRIPTS type messenger
    text two transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 splicing 3734 71.9 653 - 2001 11331580
    2 splicing 3731 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)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon  
    Lymphoid/Immunespleen    
     thymus    
    Nervousbrain   predominantly Homo sapiensTRIM32 RNA
     braindiencephalonhypothalamus  
    Reproductivefemale systemuterus  highly
     male systemprostate   
     male systemtestis   
    Skin/Tegumentskin   highly
    Visualeye    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal lowly Homo sapiensTRIM32 RNA
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyoblast Homo sapiensTRIM32 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
  • 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
  • is a positive regulator of Asymmetric cell division (ACD) that acts against MYCN and should be considered as a tumor-suppressor candidate
  • 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
  • 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 associates with proteins involved in neurogenesis and RNA-related processes, such as the RNA helicase DDX6, which has been implicated in microRNA regulation
  • TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TICAM1 to TAX1BP1-mediated selective autophagic degradation
  • 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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    potential therapeutic target for developmental disorders and RA-dependent leukemias
    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