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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
    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
    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
    13 - 3864 - 427 - 2009 19268472
  • CIN85C
  • both CIN85A and CIN85B, in isolation or when linked, form heterodimeric complexes with the peptides
    Type widely
       expressed in (based on citations)
    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
    at STAGE
  • 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
    intraspecies homolog to CMS,CD2AP
    CATEGORY adaptor , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
    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
    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)
    small molecule
  • 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
    Other is postranslationally modified by SUMOylation in wild-type podocytes