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FLASH GENE
Symbol KHDRBS1 contributors: shn - updated : 06-06-2014
HGNC name KH domain containing, RNA binding, signal transduction associated 1
HGNC id 18116
Location 1p35.1      Physical location : 32.479.490 - 32.509.471
Synonym name
  • Src-associated in mitosis 68 kDa protein
  • GAP-associated tyrosine phosphoprotein p62 (Sam68)
  • p21 Ras GTPase-activating protein-associated p62
  • Synonym symbol(s) P62, SAM68, FLJ34027, p68
    DNA
    TYPE functioning gene
    STRUCTURE 29.98 kb     9 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D1S2832 - D1S396 - HDRBS1 - D1S2676 - D1S241 - cen
    Physical map
    FABP3 1p33-p32 fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor) TDE2L 1p35.1 tumor differentially expressed 2-like LOC127572 1p35.1 similar to elongation factor 1 alpha LOC149086 1p35.1 hypothetical protein LOC149086 LCN7 1p34.3 lipocalin 7 HCRTR1 1p33 hypocretin (orexin) receptor 1 PEF 1p34 hypocretin (orexin) receptor 1 COL16A1 1p34.3 collagen, type XVI, alpha 1 BAI2 1p35 brain-specific angiogenesis inhibitor 2 FLJ25348 1p35.1 hypothetical protein FLJ25348 PTP4A2 1p36 protein tyrosine phosphatase type IVA, member 2 KHDRBS1 1p32 KH domain containing, RNA binding, signal transduction associated 1 FLJ10315 1p34.3 hypothetical protein FLJ10315 KPNA6 1p35-p34.1 karyopherin alpha 6 (importin alpha 7) DKFZp451J0118 1p34.3 taxilin MGC1203 1p36.11-p34.2 hypothetical protein MGC1203 FLJ10547 1p36.11-p34.2 hypothetical protein FLJ10547 RP4-622L5 1p36.11-p34.2 hypothetical protein RP4-622L5 EIF3S2 1p34.1 eukaryotic translation initiation factor 3, subunit 2 beta, 36kDa LOC339483 1p34.3 hypothetical protein LOC339483 MGC10820 1p34.3 hypothetical protein MGC10820 LCK 1p35.1 lymphocyte-specific protein tyrosine kinase HDAC1 1p34.3 histone deacetylase 1 MLP 1p34 MARCKS-like protein STK22C 1p34-p35 serine/threonine kinase 22C (spermiogenesis associated) FLJ10276 1p34.3 hypothetical protein FLJ10276 LOC343338 1p34.3 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) ZBTB8 1p34.3 zinc finger and BTB domain containing 8
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1416 - 404 highly in brain, heart, skeletale muscle and liver; slightly in kidney and lung 1997 9013542
    9 - 2685 68 443 Highly in heart, kidney and lung ; slightly in brain and skeletal muscle 1997 9013542
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   moderately
    Endocrinepancreas   highly
    Nervousbrain   highly
    Reproductivefemale systemplacenta  lowly
    Respiratorylung    
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • RGG (arginine-glycine repeats) boxes with methylation sites (dimethylarginine)
  • five consensus proline-rich domains SH3 sequences binding sites
  • a KH homology domain interacting with nucleic acids with methylation sites (dimethylarginine)
  • a C terminal Tyr rich domain with phosphorylation sites SH2 sequences binding site
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to Khdrbs1, Mus musculus
    ortholog to Khdrbs1, Rattus norvegicus
    ortholog to KHDRBS1, Pan troglodytes
    ortholog to khdrbs1, Danio rerio
    Homologene
    FAMILY
  • family of GSG (GRP33, Sam68, GLD1) or STAR
  • (signal transduction and activation of RNA) domain proteins
  • KHDRBS family
  • CATEGORY adaptor , RNA associated , protooncogene , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nuclear envelope,int
    basic FUNCTION
  • involved in linking signal transduction to RNA metabolism
  • involved, through its KH domain signaling, in cell proliferation, and more precisely in G1/S transition
  • acting as a regulator of alternative splicing in a signal dependant manner,RNA processing
  • involved in HIV1 replication
  • involved in insulin signaling pathway as a docking protein
  • involved in leptin pathway
  • Sam68 controls neurogenesis through its effects on a specific set of RNA targets
  • Sam68 may be acting as a modulator of neuronal differentiation
  • contributes to transformation by oncogenic VAV1
  • substrate of numerous tyrosine kinases, and often referred to as a STAR (signal transduction activator of RNA) protein
  • may be a modulator of tyrosine kinase activity and a signaling requirement for mammary tumorigenesis and metastasis
  • recruited into SG (stress granules) through complexing with TIA1 in response to oxidative stress and suggest that cytoplasmic stress granules recruitment of KHDRBS1 and ensuing changes in KHDRBS1 physiological functions are part of the host response to external stressful conditions
  • crucial regulator of SMN2 splicing, that might affect disease severity, suggesting that interference with its function offers a potential therapeutic approach for SMA
  • has reduced nuclear spatial mobility and splicing regulatory function in CGG-expressing cell
  • potential crucial function in the regulation of female fertility and may be required to insure proper expression of the gonadotropin receptor transcripts in pre-ovulatory follicles in adult ovary
  • may potentially mediate some of the leptin effects in placenta
  • acts as a convergence point for ERK signaling to cell migration
  • implicated in various cellular processes including RNA metabolism, apoptosis, and signal transduction
  • role in the TNF signaling pathway, where it acts as a signaling adaptor both in the membrane-associated complex I and in the cytoplasmic complex II, regulating both NFKB activation and apoptosis
  • RNA binding protein that links cellular signaling to RNA processing
  • key regulator of dynamic control of NRXN1 molecular diversity and activity-dependent alternative splicing in the central nervous system
  • regulates MTOR alternative splicing during adipogenesis
  • functions as a classical scaffold protein in this context, assembling components of an osteoclast-specific signalling pathway
  • modulates the promoter specificity of NFKB1 and mediates expression of IL2RA in activated T cells
  • CELLULAR PROCESS cell cycle, checkpoint
    cell life, proliferation/growth
    nucleotide, RNA splicing
    protein, post translation, targeting
    PHYSIOLOGICAL PROCESS
    text Sam68 is a nuclear RNA binding protein implicated in various
    aspects of mRNA metabolism, including splicing, nuclear
    export, somatodendritic transport, and translation
    PATHWAY
    metabolism nucleic
    signaling signal transduction
    a component
    INTERACTION
    DNA Sam68 protein binds to exonic regulatory elements of v5 and cooperates with the splicing coactivator SRm160
    RNA Sam68 protein binds to a variety of A- and U-rich sequences, often including the motifs UAAA and UUUAregulatory elements in mRNAs
    Sorbs1, Kifap3/Kap3, Numa1, Chl1
    small molecule
    protein
  • binding to GAP, Fyn, HNRNPK, Rev(HIV1 protein), RHA, Tap, p85, PI3K, IRS-1, IR, Src, Grb-2, PLC-1, STAT3, Jak3, BRK, CBP
  • VAV1 SH3C-associating protein
  • ligand whose proline-rich motifs interact with the WW domains of FNBP4 and WBP4
  • binds to the UUUUA consensus site in SMN2 exon-7
  • interacts with IRS1 in basal conditions, and insulin increases the affinity between these two partners
  • KHDRBS1 has an essential role in the induction and maintenance of IL2RA in T cells
  • interaction of KHDRBS1 with SND1
  • cell & other
    REGULATION
    activated by insulin by phosphorylation
    leptin by phosphorylation
    induced by insulin
    inhibited by HNRNPK,Sik/BRK
    repressed by Salpalpha
    KHDRBS3
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    likely can strongly reduce follicle maturation and ovulation, thereby limiting the female fertility potential
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancermetastases 
    blockade of phospho-KHDRBS1 may provide a new avenue for therapeutic inhibition of metastatic cancers
    ANIMAL & CELL MODELS
  • Sam68-/- females were severely subfertile, and they showed a delay in the age of first pregnancy, increased breeding time for successful pregnancy and yielded smaller litters
  • Sam68(-/-) mice were protected from obesity, insulin resistance, and glucose intolerance induced with a high-fat diet