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Protein

SH3 domain-containing kinase-binding protein 1

Gene

SH3KBP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration.By similarity10 Publications

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • axon guidance Source: Reactome
  • cell-cell signaling Source: UniProtKB
  • cell migration Source: UniProtKB
  • cytoskeleton organization Source: UniProtKB
  • endocytosis Source: UniProtKB-KW
  • membrane organization Source: Reactome
  • negative regulation of epidermal growth factor receptor signaling pathway Source: Reactome
  • regulation of cell shape Source: UniProtKB

Keywordsi

Biological processApoptosis, Endocytosis

Enzyme and pathway databases

ReactomeiR-HSA-182971 EGFR downregulation
R-HSA-6807004 Negative regulation of MET activity
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8866376 Reelin signalling pathway
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiQ96B97
SIGNORiQ96B97

Names & Taxonomyi

Protein namesi
Recommended name:
SH3 domain-containing kinase-binding protein 1
Alternative name(s):
CD2-binding protein 3
Short name:
CD2BP3
Cbl-interacting protein of 85 kDa
Human Src family kinase-binding protein 1
Short name:
HSB-1
Gene namesi
Name:SH3KBP1
Synonyms:CIN85
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000147010.17
HGNCiHGNC:13867 SH3KBP1
MIMi300374 gene
neXtProtiNX_Q96B97

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi30011
OpenTargetsiENSG00000147010
PharmGKBiPA37822

Polymorphism and mutation databases

BioMutaiSH3KBP1
DMDMi31077034

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000977281 – 665SH3 domain-containing kinase-binding protein 1Add BLAST665

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei156PhosphoserineBy similarity1
Modified residuei159PhosphoserineBy similarity1
Modified residuei183PhosphoserineCombined sources1
Modified residuei230PhosphoserineCombined sources1
Modified residuei254PhosphothreonineCombined sources1
Modified residuei436PhosphoserineCombined sources1
Modified residuei509PhosphoserineCombined sources1
Modified residuei511PhosphoserineCombined sources1
Modified residuei521PhosphoserineCombined sources1
Modified residuei587PhosphoserineCombined sources1

Post-translational modificationi

Monoubiquitinated by CBL and CBLB after EGF stimulation; probably on its C-terminus.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96B97
MaxQBiQ96B97
PaxDbiQ96B97
PeptideAtlasiQ96B97
PRIDEiQ96B97
ProteomicsDBi76057
76058 [Q96B97-2]

PTM databases

iPTMnetiQ96B97
PhosphoSitePlusiQ96B97

Expressioni

Tissue specificityi

Ubiquitously expressed. Also expressed in some cancer cell lines.

Gene expression databases

BgeeiENSG00000147010
CleanExiHS_SH3KBP1
ExpressionAtlasiQ96B97 baseline and differential
GenevisibleiQ96B97 HS

Organism-specific databases

HPAiCAB021892
HPA003351
HPA003355

Interactioni

Subunit structurei

Can self-associate and form homotetramers. Interacts with CD2, F-actin capping protein, PIK3R3, GRB2, EGFR, MET, BLNK, MAP3K4, PDCD6IP, SPRY2, ARHGAP17, ARHGAP27, MAGI2, CRK, BCAR1, SOS1, ASAP1, ARAP3, HIP1R, SYNJ2, INPP5D and STAP1. Interacts with CBL and CBLB, but does not interact with CBLC. Two molecules of SH3KBP1 seem to bind through their respective SH3 1 domain to one molecule of CBLB. The interaction with CBL or CBLB and EGFR is increased upon EGF stimulation. The interaction with CBL is attenuated by PDCD6IP. Interacts through its proline-rich region with the SH3 domain of endophilins SH3GL1, SH3GL2 and SH3GL3. The SH3KBP1-endophilin complex seems to associate with a complex containing the phosphorylated receptor (EGFR or MET) and phosphorylated CBL. Probably associates with ASAP1 and phosphorylated EGFR. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3. Interacts with focal adhesion kinases PTK2/FAK1 AND PTK2B/PYK2, probably as a dimer. Interacts with DAB2 and probably associates with chathrin through its interaction with DAB2. Part of a complex consisting of SH3KBP1, DAB2, and clathrin heavy chain. DAB2 and clathrin dissociate from SH3KBP1 following growth factor treatment, enabling interaction with CBL. Interacts with DDN and probably associates with MAGI2 through its interaction with DDN. Interacts with the SH3 domains of SRC tyrosine-protein kinases SRC, LCK, LYN, FGR, FYN and HCK. Interacts with TRADD, BIRC2, TRAF1, TRAF2 and TNFR1, and the association with a TNFR1-associated complex upon stimulation with TNF-alpha seems to be mediated by SRC. Interacts (via SH3 domains) with SHKBP1 (via PXXXPR motifs) (By similarity). Interaction with CBL is abolished in the presence of SHKBP1 (By similarity). Interacts (via SH3 domains) with ZFP36 (via extreme C-terminal region) (PubMed:20221403). Interacts with MAP3K4; this interaction enhances the association with ZFP36 (PubMed:20221403).By similarity18 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119029, 274 interactors
CORUMiQ96B97
DIPiDIP-31803N
IntActiQ96B97, 67 interactors
MINTiQ96B97
STRINGi9606.ENSP00000380921

Structurei

Secondary structure

1665
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 8Combined sources5
Beta strandi25 – 30Combined sources6
Turni33 – 35Combined sources3
Beta strandi36 – 41Combined sources6
Beta strandi44 – 49Combined sources6
Helixi50 – 52Combined sources3
Beta strandi53 – 55Combined sources3
Beta strandi102 – 105Combined sources4
Beta strandi113 – 115Combined sources3
Beta strandi124 – 126Combined sources3
Helixi130 – 132Combined sources3
Beta strandi149 – 153Combined sources5
Turni161 – 164Combined sources4
Beta strandi270 – 276Combined sources7
Beta strandi283 – 285Combined sources3
Beta strandi293 – 299Combined sources7
Beta strandi301 – 303Combined sources3
Beta strandi306 – 311Combined sources6
Beta strandi314 – 319Combined sources6
Helixi320 – 322Combined sources3
Beta strandi323 – 325Combined sources3
Helixi605 – 661Combined sources57

3D structure databases

ProteinModelPortaliQ96B97
SMRiQ96B97
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96B97

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 58SH3 1PROSITE-ProRule annotationAdd BLAST58
Domaini98 – 157SH3 2PROSITE-ProRule annotationAdd BLAST60
Domaini267 – 328SH3 3PROSITE-ProRule annotationAdd BLAST62

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili602 – 664Sequence analysisAdd BLAST63

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi327 – 428Pro-richAdd BLAST102

Keywords - Domaini

Coiled coil, Repeat, SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG4348 Eukaryota
ENOG410XQBY LUCA
GeneTreeiENSGT00530000063594
HOGENOMiHOG000231405
HOVERGENiHBG057824
InParanoidiQ96B97
KOiK12470
OMAiEDKEEHV
OrthoDBiEOG091G041Q
PhylomeDBiQ96B97
TreeFamiTF350191

Family and domain databases

CDDicd12052 SH3_CIN85_1, 1 hit
cd12055 SH3_CIN85_2, 1 hit
cd12057 SH3_CIN85_3, 1 hit
InterProiView protein in InterPro
IPR035770 CIN85_SH3_1
IPR035771 CIN85_SH3_2
IPR035772 CIN85_SH3_3
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF14604 SH3_9, 3 hits
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00326 SH3, 3 hits
SUPFAMiSSF50044 SSF50044, 3 hits
PROSITEiView protein in PROSITE
PS50002 SH3, 3 hits

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96B97-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVEAIVEFDY QAQHDDELTI SVGEIITNIR KEDGGWWEGQ INGRRGLFPD
60 70 80 90 100
NFVREIKKEM KKDPLTNKAP EKPLHEVPSG NSLLSSETIL RTNKRGERRR
110 120 130 140 150
RRCQVAFSYL PQNDDELELK VGDIIEVVGE VEEGWWEGVL NGKTGMFPSN
160 170 180 190 200
FIKELSGESD ELGISQDEQL SKSSLRETTG SESDGGDSSS TKSEGANGTV
210 220 230 240 250
ATAAIQPKKV KGVGFGDIFK DKPIKLRPRS IEVENDFLPV EKTIGKKLPA
260 270 280 290 300
TTATPDSSKT EMDSRTKSKD YCKVIFPYEA QNDDELTIKE GDIVTLINKD
310 320 330 340 350
CIDVGWWEGE LNGRRGVFPD NFVKLLPPDF EKEGNRPKKP PPPSAPVIKQ
360 370 380 390 400
GAGTTERKHE IKKIPPERPE MLPNRTEEKE RPEREPKLDL QKPSVPAIPP
410 420 430 440 450
KKPRPPKTNS LSRPGALPPR RPERPVGPLT HTRGDSPKID LAGSSLSGIL
460 470 480 490 500
DKDLSDRSND IDLEGFDSVV SSTEKLSHPT TSRPKATGRR PPSQSLTSSS
510 520 530 540 550
LSSPDIFDSP SPEEDKEEHI SLAHRGVDAS KKTSKTVTIS QVSDNKASLP
560 570 580 590 600
PKPGTMAAGG GGPAPLSSAA PSPLSSSLGT AGHRANSPSL FGTEGKPKME
610 620 630 640 650
PAASSQAAVE ELRTQVRELR SIIETMKDQQ KREIKQLLSE LDEEKKIRLR
660
LQMEVNDIKK ALQSK
Note: Interacts with CBL.
Length:665
Mass (Da):73,126
Last modified:May 23, 2003 - v2
Checksum:i3BD350FCDB14BD4C
GO
Isoform 2 (identifier: Q96B97-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MVEAIVEFDYQAQHDDELTISVGEIITNIRKEDGGWWEGQINGRRGLFPDNFVR → MEVSAAKAPSAADLSEI

Note: Interacts with CD2 cytoplasmic tail and does not interact with F-actin.
Show »
Length:628
Mass (Da):68,550
Checksum:i8AD93481480879D6
GO
Isoform 3 (identifier: Q96B97-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MVEA → MGEE
     5-242: Missing.

Note: No experimental confirmation available.
Show »
Length:427
Mass (Da):46,610
Checksum:iCDD6AC2770E695F4
GO

Sequence cautioni

The sequence AAH50663 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti288I → T in BAH11471 (PubMed:14702039).Curated1
Sequence conflicti426V → A in BAH11471 (PubMed:14702039).Curated1
Sequence conflicti570A → V in AAH15806 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015667382P → L1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0075041 – 54MVEAI…DNFVR → MEVSAAKAPSAADLSEI in isoform 2. 2 PublicationsAdd BLAST54
Alternative sequenceiVSP_0446551 – 4MVEA → MGEE in isoform 3. 1 Publication4
Alternative sequenceiVSP_0446565 – 242Missing in isoform 3. 1 PublicationAdd BLAST238

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF230904 mRNA Translation: AAF37854.1
AF542051 mRNA Translation: AAN77231.1
AK293234 mRNA Translation: BAH11470.1
AK293237 mRNA Translation: BAH11471.1
AL732423 Genomic DNA No translation available.
AL732327 Genomic DNA No translation available.
AL732325 Genomic DNA No translation available.
AL732409 Genomic DNA No translation available.
AL772197 Genomic DNA No translation available.
BC015806 mRNA Translation: AAH15806.1
BC050663 mRNA Translation: AAH50663.1 Sequence problems.
AF329267 mRNA Translation: AAK95587.1
AF329268 mRNA Translation: AAO13348.1
CCDSiCCDS14193.1 [Q96B97-1]
CCDS35213.1 [Q96B97-2]
CCDS55383.1 [Q96B97-3]
PIRiJC7191
RefSeqiNP_001019837.1, NM_001024666.2 [Q96B97-2]
NP_001171889.1, NM_001184960.1 [Q96B97-3]
NP_114098.1, NM_031892.2 [Q96B97-1]
XP_016884958.1, XM_017029469.1
UniGeneiHs.726365

Genome annotation databases

EnsembliENST00000379698; ENSP00000369020; ENSG00000147010 [Q96B97-2]
ENST00000379716; ENSP00000369039; ENSG00000147010 [Q96B97-3]
ENST00000397821; ENSP00000380921; ENSG00000147010 [Q96B97-1]
GeneIDi30011
KEGGihsa:30011
UCSCiuc004czl.4 human [Q96B97-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSH3K1_HUMAN
AccessioniPrimary (citable) accession number: Q96B97
Secondary accession number(s): B7Z1D5
, Q5JPT4, Q5JPT5, Q8IWX6, Q8IX98, Q96RN4, Q9NYR0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: July 18, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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