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FLASH GENE
Symbol SH3KBP1 contributors: mct - updated : 17-01-2017
HGNC name SH3-domain kinase binding protein 1
HGNC id 13867
Location Xp22.12      Physical location : 19.552.083 - 19.905.744
Synonym name
  • migration-inducing gene 18 protein
  • adaptor protein, C-cbl interacting protein
  • human Src family kinase-binding protein 1
  • CD2-binding protein 3
  • Cbl-interacting protein of 85 kDa
  • Synonym symbol(s) CIN85, MIG18, GIG10, RUKL
    DNA
    TYPE functioning gene
    STRUCTURE 353.66 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    FIGF Xp22.1 c-fos induced growth factor (vascular endothelial growth factor D) PIR Xp22.31 c-fos induced growth factor (vascular endothelial growth factor D) BMX Xp22.2 BMX non-receptor tyrosine kinase ACE2 Xp22 angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 NX17 Xp22 kidney-specific membrane protein LOC340591 Xp22.31 similar to carbonic anhydrase VB, mitochondrial precursor; carbonic dehydratase CA5B Xp22.1 carbonic anhydrase VB, mitochondrial U2AF1L2 Xp22.1 U2(RNU2) small nuclear RNA auxiliary factor 1-like 2 AP1S2 Xp36.3-p21.3 adaptor-related protein complex 1, sigma 2 subunit GRPR Xp22.2-p22.13 gastrin-releasing peptide receptor LOC139451 Xp22.22 similar to melanoma antigen, family B, 4; melanoma-associated antigen B4 LOC139452 Xp22.22 similar to 60S ribosomal protein L6 (TAX-responsive enhancer element binding protein 107) (TAXREB107) (Neoplasm-related protein C140) LOC392429 X similar to Hspcb protein CTPS2 Xp22 CTP synthase II CALB3 Xp22.2 calbindin 3, (vitamin D-dependent calcium binding protein) SYAP1 Xp22.31 synapse associated protein 1, SAP47 homolog (Drosophila) CXorf15 Xp22.22 chromosome X open reading frame 15 RBBP7 Xp22.31 retinoblastoma binding protein 7 RNU4P6 Xp22.22 RNA, U4 small nuclear pseudogene 6 REPS2 Xp22.22 RALBP1 associated Eps domain containing 2 PRO0386 Xp22.22 hypothetical protein PRO0386 NHS Xp22.13 Nance-Horan syndrome (congenital cataracts and dental anomalies) SCML1 Xp22 sex comb on midleg-like 1 (Drosophila) LOC392430 X similar to dJ40E16.3 (novel gene similar to D. melanogaster CG5327 ) RAI2 Xp22 retinoic acid induced 2 LOC392431 X similar to Mdm4, transformed 3T3 cell double minute 4, p53 binding protein (mouse) MGC33653 Xp22.22 hypothetical protein MGC33653 SCML2 Xp22 sex comb on midleg-like 2 (Drosophila) CDKL5 Xp22 cyclin-dependent kinase-like 5 RS1 Xp22.2 retinoschisis (X-linked, juvenile) 1 PPEF1 Xp22.2-p22.1 protein phosphatase, EF hand calcium-binding domain 1 PHKA2 Xp22.2-p22.13 phosphorylase kinase, alpha 2 (liver) GPR64 Xp22.22 G protein-coupled receptor 64 PDHA1 Xp22.1 pyruvate dehydrogenase (lipoamide) alpha 1 LOC389840 X similar to MAP/ERK kinase kinase 5; apoptosis signal regulating kinase SH3KBP1 Xp22.3-p11.3 SH3-domain kinase binding protein 1 LOC256643 Xp22.13 hypothetical protein LOC256643 FLJ14503  hypothetical protein FLJ14503 EIF1A Xp22.1 eukaryotic translation initiation factor 1A RPS6KA3 Xp22.13 ribosomal protein S6 kinase, 90kDa, polypeptide 3 CNK2 Xp22.13 ribosomal protein S6 kinase, 90kDa, polypeptide 3 FLJ34960 Xp22.13 hypothetical protein FLJ34960 SMPX Xp22.1 small muscle protein, X-linked MBTPS2 Xp22.1-p22.2 membrane-bound transcription factor protease, site 2 SMS Xp22.1 spermine synthase PHEX Xp22.2-p22.1 phosphate regulating gene with homologies to endopeptidases on the X chromosome (hypophosphatemia, vitamin D resistant rickets) FLJ25735 Xp22.13 hypothetical protein FLJ25735 LOC389841 X LOC389841 DDX53 Xp22 DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 MGC45134 Xp22.13 hypothetical protein MGC45134 LOC392432 X similar to hypothetical protein MGC35083 FLJ30296 Xp22.13 hypothetical protein FLJ30296 PRDX4 Xp22.12-p21.3 peroxiredoxin 4 ACATE2 Xp22.13 likely ortholog of mouse acyl-Coenzyme A thioesterase 2, mitochondrial
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 4766 - 665 - 2009 19268472
  • CIN85A
  • both CIN85A and CIN85B, in isolation or when linked, form heterodimeric complexes with the peptides
  • 18 - 4454 - 628 - 2007 17306257
    CIN85B
    13 - 3864 - 427 - 2009 19268472
  • CIN85C
  • both CIN85A and CIN85B, in isolation or when linked, form heterodimeric complexes with the peptides
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunelymph node   highly
    Nervousbrainbasal nucleistriatum   Homo sapiens
     nervecranial nerve  highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three SH3 domains that specifically bind a unique proline-arginine motif (PxxxPR) found in several SH3KBP1 effectors, and binding to ubiquitin
  • first SH3 domain and the C-terminal region bind to the proline-rich region and the N-terminal region of dendrin, respectively
  • coiled-coil domain, binding nephrin and podocin
  • mono polymer tetramer
    HOMOLOGY
    intraspecies homolog to CMS,CD2AP
    Homologene
    FAMILY
    CATEGORY adaptor , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text synaptic localization
    basic FUNCTION
  • playing a specific role in the receptor-mediated signaling cascade via its interaction with C-CBL
  • multidomain adaptor protein implicated in CBL-mediated down-regulation of receptor tyrosine kinases
  • role in the regulation of cellular stress response via the MAPK pathways
  • adaptor protein linking the ubiquitin ligase CBL and clathrin-binding proteins in clathrin-mediated receptor endocytosis
  • multifunctional protein that plays key roles in endocytic down-regulation of receptor tyrosine kinases, apoptosis, cell adhesion, and cytoskeleton rearrangement
  • important molecule involved in receptor tyrosine kinase endocytosis
  • may function as a scaffold molecule in both the internalization and endocytic cargo sorting processes through its association with the endosomal membrane
  • can act as a linker between Cbl and endophilin and is recruited upon EGF stimulation to the EGF receptor, which leads to receptor endocytosis
  • role in slit diaphragm turnover and proteinuria
  • important function in the regulation of dopamine receptor functions
  • recruits DNM2 to the late endosome, where DNM2 mediates a post-endosomal budding process that helps downregulate EGFR
  • potentially playing a role in endosomal sorting of the ubiquitinated EGFR
  • plays an important role as a negative regulator of signaling pathways induced by receptor tyrosine kinases
  • both BLNK and SH3KBP1 are key components of the BCR-associated primary transducer module required for the onset and progression phases of BCR signal transduction
  • required for CBL-mediated regulation of BCR signaling and for downstream events such as survival, growth, and differentiation of B cells
  • SH3KBP1 phosphorylation is essential for EGFR ubiquitination and sorting into multivesicular bodies
  • promotes recycling of TGFB1 receptors and thereby positively regulates TGFB1 signaling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CIN85-C-CBL and CIN85 - BLNK
  • forms a ternary complex with DDN and MAGI2 and this complex formation facilitates the recruitment of dendrin and MAGI2 to vesicle-like structures where SH3KBP1 is accumulated
  • SH3KBP1–DNM2 complex appears to function predominantly at later stages of EGFR trafficking, namely in the transport of receptors from RAB7-positive late endosomes
  • CBL-SH3KBP1-endophilin complex is not required for efficient internalization of EGFR, a prototype receptor tyrosine kinases (RTKs)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specific interactions of SH3 domains with the PXXXPR motif in CBL play multiple roles in down-regulation of receptor tyrosine kinases
  • competition between CBL and ubiquitin binding to SH3KBP1 regulates CBL function and EGFR endocytosis
  • MAP3K4 is a SH3KBP1-interacting partner (enhances the activation of MKK6 and of the downstream MAPK14 following oxidative stress and growth factor stimulation)
  • endocytic scaffold protein, as a putative dendrin-interactor
  • interacting with ATXN2
  • binding partner of nephrin and podocin and regulates the internalization of the slit diaphragm complex
  • functional competition of CD2AP and SH3KBP1 for binding to nephrin and podocin (when both proteins are coexpressed, nephrin and podocin bind preferentially to CD2AP)
  • interacts with endocytic regulators such as dynamin and endophilins in the striatum
  • induced SERPINE1 mRNA and protein expression both under normoxia and hypoxia (induces SERPINE1 expression via modulation of HIF1A stability)
  • indirectly link the EGFR to the endocytic machinery at the plasma membrane, is also thought to be involved in receptor internalization
  • direct interaction between DNM2 and SH3KBP1 that is induced by EGFR stimulation and, most surprisingly, occurs late in the endocytic process
  • ARAP1 interaction with SH3KBP1 regulates endocytic trafficking of the EGFR and affects ubiquitination of EGFR
  • INPPL1 interacting with SH3KBP1 (this interaction might synergistically facilitate the down-regulation of phosphatidylinositol-3,4,5-trisphosphate levels)
  • novel role for CD2AP in regulating posttranslational modification of SH3KBP1
  • required for CBL-mediated regulation of BCR signaling and for downstream events such as survival, growth, and differentiation of human B cells
  • ubiquitination of EGFR by CBL and its cognate adaptor SH3KBP1 play an essential role in directing this receptor to the lysosome for degradation
  • interaction of SH3KBP1 with MAP3K4 was increased during the late phase of TNFSF10 incubation, suggesting that sustained MAPK14 and HSPB1 phosphorylation protects cells by preventing further cell death
  • DAB1 suppresses SH3KBP1 phosphorylation at Ser587
  • SH3KBP1 participates in RELN signaling through the binding to DAB1
  • interacts with ESCRT components for protein sorting in endosomes
  • SH3KBP1-SEPT9 is localized exclusively to the plasma membrane, where SEPT9 is recruited to EGF-engaged receptors in a SH3KBP1-dependent manner
  • enhanced TGFB1-stimulated SMAD2 phosphorylation, transcriptional responses, and cell migration
  • cell & other
    REGULATION
    Other is postranslationally modified by SUMOylation in wild-type podocytes
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS