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FLASH GENE
Symbol PRMT5 contributors: mctpgu/shn - updated : 06-10-2015
HGNC name protein arginine methyltransferase 5
HGNC id 10894
Location 14q11.2      Physical location : 23.389.732 - 23.398.661
Synonym name
  • SKB1 homolog (S. pombe)
  • SHK1 kinase-binding protein 1
  • histone-arginine N-methyltransferase PRMT5
  • 72 kDa ICln-binding protein
  • JAK-binding protein 1
  • HMT1 hnRNP methyltransferase-like 5
  • skb1 (S. pombe) homolog
  • SKB1 homolog (S. pombe)
  • 72 kDa ICln-binding protein
  • HMT1 hnRNP methyltransferase-like
  • Synonym symbol(s) SKB1HS, JBP1, IBP72, SKB1, HRMT1L5
    EC.number 2.1.1.125
    DNA
    TYPE functioning gene
    STRUCTURE 8.93 kb     17 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - D14S1003 - D14S283 - PRMT5 - D14S990 - D14S581 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 2385 72 637 - 2008 18219319
    isoform a
    17 - 2470 72 620 - 2008 18404153
  • isoform b
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately Homo sapiens
    Endocrinepancreas   moderately Homo sapiens
    Nervousbrain   moderately Homo sapiens
    Respiratorylung   moderately Homo sapiens
    Urinarykidney   lowly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    Nervousneuron Homo sapiens
    Nervousoligodendrocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal part of PRMT5 (AA 1291) interacts with RIOK1 , and has a TIM-barrel fold, important for homodimerization, and for the assembly of PRMT5 complexes and their substrate selectivities
  • conserved motif of s-adenosyl-1 methionine-dependent protein-arginine methyltransferase
  • a shorter oligomerization domain, but extensive conservation of AAs involved in intermolecular interactions implies that it also forms a dimer, consistent with the report of dimeric and higher oligomeric forms of PRMT5
  • mono polymer homomer , oligo
    HOMOLOGY
    interspecies ortholog to Prmt5, Mus musculus
    ortholog to Prmt5, Rattus norvegicus
    ortholog to prmt5, Danio rerio
    ortholog to PRMT5, Pan troglodytes
    Homologene
    FAMILY
  • protein arginine methyltransferase family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • translocated into the nucleus in a SNAI1- and JUB-dependent manner
  • predominantly nuclear in the bone marrow progenitors, whereas it was primarily localized in the cytoplasm in the cord blood progenitors
  • PRMT5 and WDR77 were evenly distributed between cytoplasm and nucleus
  • exists in the cytoplasm and nucleus, and acts as a multiplayer that regulates gene expression and signal transduction
  • basic FUNCTION
  • playing a role in cellular signaling (mitotic inhibitor)
  • methylating specific arginine residues in the small nuclear ribonucleoproteins Sm D1 and Sm D3
  • involved in the control of transcription and proliferation
  • may play a role in cytokine-activated transduction pathways
  • negatively regulating cyclin E1 promoter activity and cellular proliferation
  • may regulate the SUPT5H transcriptional elongation properties
  • methylating histone H2A/H4 Arg-3 during germ cell development
  • involved in an early stage of U7 snRNP assembly and hence may have a second snRNP assembly function unrelated to sDMA modification
  • involved in cyclin E repression
  • required for skeletal muscle differentiation at the early stages of myogenesis
  • effector recruited to SNAI1 through an interaction with JUB that functions to repress the SNAI1 target gene, CDH1
  • effector of SNAI1-dependent gene repression
  • playing a role in developmental globin gene silencing
  • may play a developmentally specific role in regulating gene expression at the gamma-globin locus
  • distinct functions of the nuclear and the WDR77/PRMT5 complexes in the developing fetal testis and in the oncogenesis of testicular tumors
  • required for Sm protein sDMA modification
  • binds to the non-LIM region of JUB and is translocated into the nucleus in a SNAI1- and JUB-dependent manner
  • required for early-gene expression but dispensable for late-gene expression of myogenesis
  • major pro-survival factor regulating eIF4E expression and TP53 translation
  • participates in the assembly of the transcriptional repressor complex on different eukaryotic promoters
  • involved in the formation of the complex that negatively regulates aldolase A gene transcription during the cell cycle
  • links the circadian clock to the control of alternative splicing in plants
  • PRMT1 and PRMT5 methylate Arg-296 within ASH2L
  • catalyzes monomethylation and symmetric dimethylation of arginine residues
  • role of PRMT5 in glial cell differentiation and PRMT5 is linked to epigenetic changes during oligodendrocyte differentiation
  • plays a role in gene silencing during oligodendrocyte differentiation
  • plays critical roles in cellular processes as diverse as receptor signaling and gene expression
  • probably promotes tumor growth by stimulating cell proliferation and by participating in the construction of a tumor-favorable microenvironment via HIF1 activation
  • critical coactivator component in HOXA9-containing transcription complex
  • is a master regulator of splicing in mammals
  • WDR77 can transform cells independent of AR and ESR, and PRMT5 has partial contribution to that process
  • likely WDR77 and PRMT5 simultaneously engage the protein substrate, orienting its targeted arginine to the catalytic site
  • is a potential vulnerability across multiple cancer lineages augmented by a common "passenger" genomic alteration
  • CELLULAR PROCESS cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS
    text
  • transfers methyl groups to arginine residues present in histones and Sm spliceosomal proteins
  • PATHWAY
    metabolism
    signaling
  • may be part of a pathway that is connected to a chloride current, possibly through cytoskeletal rearrangement
  • a component
  • component of the methylosome
  • PRMT5/WDR77 complex for pluripotency, may occur in conjunction with the leukemia inhibitory factor (LIF)/STAT3 pathway
  • PRMT5/WDR77-dependent methylation is an epigenetic mechanism that assists in silencing of IVL expression, and PRKCD signaling activates gene expression by directly activating transcription and by suppressing PRMT5/WDR77-dependent arginine dimethylation of promoter-associated histones
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • chloride channel, nucleotide-sensitive, 1A, ICln
  • Janus kinase 2, JAK2
  • somatostatin receptor subtype 1, SSTR1
  • SmD1 and SmD3
  • member of the 20 S protein arginine methyltransferase complex
  • suppressor of Ty 5, SPT5
  • Fibrillarin, FIB
  • Brg1 and hBrm-based hSWI/SNF complexes
  • F-cell production 1, FCP1
  • U7-specific Lsm proteins
  • stably and specifically associates with and methylates the RG-rich N terminus of MBD2
  • B-lymphocyte-induced maturation protein 1, BLIMP1
  • protein AJUBA
  • cooperator of PRMT5, COPR5
  • Ski co-repressor complexes
  • interacts directly with DNMT3A and establishes the histone modification
  • Kruppel-like associated box-zinc finger protein ZNF224
  • SRGAP2 physically interacts with protein arginine methyltransferase 5 (PRMT5)
  • RIOK1 and CLNS1A might bind to the same site in PRMT5 and thus compete for binding
  • PRMT5 was demonstrated to play a crucial role in the transcriptional ZNF224 repressor complex
  • BRD7 interacts with PRMT5, and is involved in transcriptional repression of its target genes
  • required for maintaining the methylation status of CpG islands of ID2 and ID4 leading to gene silencing during glial cell differentiation
  • PRMT5 is essential for recruiting Polycomb proteins, in a PAX2/TLE4 dependent manner, which results in H3K27 methylation
  • essential for the HIF1A translation initiated by the 5prime UTR of HIF1A mRNA
  • HOXA9
  • CDK8 and CDK19, individually interact with PRMT5 and WDR77, and their interactions with PRMT5 cause transcriptional repression of CEBPB target genes by regulating symmetric dimethylation of histone H4 arginine 3 (H4R3me2s) in the promoter regions of those genes
  • PRMT5 dimethylates R30 of RELA
  • LYAR directly interacted with the methyltransferase PRMT5 which triggers the histone H4 Arg3 symmetric dimethylation (H4R3me2s) mark
  • RASSF1-dependent microtubule recruitment of PRMT5, suggesting a novel role for RASSF1 in the anchoring of cytosolic PRMT5 to microtubules
  • MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
  • potent stress granules (SG)-nucleating protein G3BP1 is methylated by protein arginine methyltransferase 1 and 5 (PRMT1 and PRMT5)
  • cell & other
    REGULATION
    repressed by MEP50
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS