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UniProtKB - Q8R550 (SH3K1_MOUSE)

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Protein

SH3 domain-containing kinase-binding protein 1

Gene

Sh3kbp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 a 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. 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 similarity).By similarity

GO - Molecular functioni

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Biological processApoptosis, Endocytosis

Enzyme and pathway databases

ReactomeiR-MMU-182971. EGFR downregulation.
R-MMU-6807004. Negative regulation of MET activity.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-MMU-8856828. Clathrin-mediated endocytosis.
R-MMU-8866376. Reelin signalling pathway.
R-MMU-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.

Names & Taxonomyi

Protein namesi
Recommended name:
SH3 domain-containing kinase-binding protein 1
Alternative name(s):
Regulator of ubiquitous kinase
Short name:
Ruk
SH3-containing, expressed in tumorigenic astrocytes
Gene namesi
Name:Sh3kbp1
Synonyms:Ruk, Seta
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1889583. Sh3kbp1.

Subcellular locationi

  • Cytoplasm By similarity
  • Cytoplasm › cytoskeleton By similarity
  • Cytoplasmic vesicle membrane By similarity; Peripheral membrane protein By similarity
  • Cell junction › synapse › synaptosome By similarity
  • Cell junction › focal adhesion By similarity

    • Note: Localized in endocytic vesicles containing clustered receptors. Colocalizes with ASAP1 in vesicular structures. Colocalized with actin microfilaments and focal adhesions (By similarity). Colocalized with MAGI2 in synaptosomes (By similarity). Translocation to EGFR containing vesicles upon EGF stimulation is inhibited in the presence of SH3KBP1 (PubMed:21830225). Colocalizes with ZFP36 in the cytoplasm (By similarity).By similarity1 Publication

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • cytoplasm Source: MGI
  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • cytoskeleton Source: UniProtKB-SubCell
  • endocytic vesicle Source: UniProtKB
  • focal adhesion Source: UniProtKB-SubCell
  • neuron projection Source: UniProtKB-SubCell
  • synapse Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000977291 – 709SH3 domain-containing kinase-binding protein 1Add BLAST709

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei156PhosphoserineCombined sources1
Modified residuei159PhosphoserineCombined sources1
Modified residuei227PhosphoserineBy similarity1
Modified residuei274PhosphoserineCombined sources1
Modified residuei298PhosphothreonineBy similarity1
Modified residuei480PhosphoserineCombined sources1
Modified residuei553PhosphoserineCombined sources1
Modified residuei555PhosphoserineCombined sources1
Modified residuei565PhosphoserineCombined sources1
Modified residuei631PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PeptideAtlasiQ8R550.
PRIDEiQ8R550.

PTM databases

iPTMnetiQ8R550.
PhosphoSitePlusiQ8R550.

Expressioni

Gene expression databases

BgeeiENSMUSG00000040990.
CleanExiMM_SH3KBP1.
ExpressionAtlasiQ8R550. baseline and differential.
GenevisibleiQ8R550. MM.

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, CRK, BCAR1, SOS1, ASAP1, ARAP3, HIP1R, SYNJ2, INPP5D and STAP1 (By similarity). Interacts with CBL (PubMed:21830225). Interacts with 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. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3 (By similarity). Interacts (via SH3 domains) with SHKBP1 (via PXXXPR motifs) (PubMed:11152963, PubMed:21830225). Interacts with ATX2 (PubMed:18602463). Interaction with CBL is abolished in the presence of SHKBP1 (PubMed:21830225). Interacts (via SH3 domains) with ZFP36 (via extreme C-terminal region). Interacts with MAP3K4; this interaction enhances the association with ZFP36 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dlg4Q621083EBI-642709,EBI-300895

GO - Molecular functioni

Complete GO annotation...

Protein-protein interaction databases

BioGridi208383. 11 interactors.
IntActiQ8R550. 10 interactors.
MINTiMINT-1591643.

Structurei

Secondary structure

1709
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi103 – 107Combined sources5
Beta strandi129 – 132Combined sources4
Beta strandi135 – 138Combined sources4
Beta strandi145 – 148Combined sources4
Beta strandi151 – 154Combined sources4
Beta strandi314 – 318Combined sources5
Beta strandi336 – 342Combined sources7
Beta strandi350 – 354Combined sources5
Beta strandi359 – 363Combined sources5
Helixi364 – 366Combined sources3
Beta strandi367 – 369Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WI7NMR-A101-155[»]
2DA9NMR-A314-370[»]
ProteinModelPortaliQ8R550.
SMRiQ8R550.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8R550.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 58SH3 1PROSITE-ProRule annotationAdd BLAST58
Domaini98 – 157SH3 2PROSITE-ProRule annotationAdd BLAST60
Domaini311 – 372SH3 3PROSITE-ProRule annotationAdd BLAST62

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili646 – 708Sequence analysisAdd BLAST63

Keywords - Domaini

Coiled coil, Repeat, SH3 domain, SH3-binding

Phylogenomic databases

GeneTreeiENSGT00530000063594.
HOVERGENiHBG057824.
InParanoidiQ8R550.
KOiK12470.
OMAiEDKEEHV.
OrthoDBiEOG091G041Q.
PhylomeDBiQ8R550.
TreeFamiTF350191.

Family and domain databases

InterProiView protein in InterPro
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 (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8R550-1) [UniParc]FASTAAdd to basket
Also known as: Ruk-xl

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 SVGEVITNIR KEDGGWWEGQ INGRRGLFPD 
        60         70         80         90        100
NFVREIKKDM KKDLLSNKAP EKPMHDVSSG NALLSSETIL RTNKRGERRR 
       110        120        130        140        150
RRCQVAFSYL PQNDDELELK VGDIIEVVGE VEEGWWEGVL NGKTGMFPSN 
       160        170        180        190        200
FIKELSGESD ELGISQDEQL SKSRPEGFLP ASLLPFPAHG AKGKTTFEGT 
       210        220        230        240        250
ILYRAAPGKT EGHRRYYSLR ETTGSESDGG DSSSTKSEGA NGTMATAAIQ 
       260        270        280        290        300
PKKVKGVGFG DIFKDKPIKL RPRSIEVEND FLPVEKTIGK KLPPATSTPD 
       310        320        330        340        350
PSKTEMDSRT KTKDYCKVIF PYEAQNDDEL TIKEGDIVTL INKDCIDVGW 
       360        370        380        390        400
WEGELNGRRG VFPDNFVKLL PSDFDKEGNR PKKPPPPSAP VVKQGAGTTE 
       410        420        430        440        450
RKHEIKKIPP ERPETLPNRT EEKERPEREP KLDLQKPSVP AIPPKKPRPP 
       460        470        480        490        500
KTNSLNRPGA LPPRRPERPV GPLTHTRGDS PKIDLAGSAL SGILDKDLSD 
       510        520        530        540        550
RSNDIDLEGF DSVISSTEKL SHPTTSRPKA TGRRPPSQSL TSSSLSSPDI 
       560        570        580        590        600
FDSPSPEEDK EEHISLAHRG IDVSKKTSKT VTISQVSDNK TSLPPKPGTM 
       610        620        630        640        650
AAASSGPASL SSVASSPMSS SLGTAGQRAS SPSLFSTEGK PKMEPAVSSQ 
       660        670        680        690        700
AAIEELKMQV RELRTIIETM KDQQKREIKQ LLSELDEEKK IRLRLQMEVN 

DIKKALQSK
Length:709
Mass (Da):78,170
Last modified:June 1, 2002 - v1
Checksum:iAC2DDFB3248A458B
GO
Isoform 2 (identifier: Q8R550-2) [UniParc]FASTAAdd to basket
Also known as: Ruk-l

The sequence of this isoform differs from the canonical sequence as follows:
     174-217: Missing.

Show »
Length:665
Mass (Da):73,328
Checksum:i724607807A66B043
GO
Isoform 3 (identifier: Q8R550-3) [UniParc]FASTAAdd to basket
Also known as: Ruk-deltaA

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: MVEAIVEFDYQAQHDDELTISVGEVITNIRKEDGGWWEGQINGRRGLFPDNFVR → MELSAAKAPSPTDLPES
     174-217: Missing.

Show »
Length:628
Mass (Da):68,820
Checksum:i1C4AEC6BE48D5D17
GO
Isoform 4 (identifier: Q8R550-4) [UniParc]FASTAAdd to basket
Also known as: Ruk-m1

The sequence of this isoform differs from the canonical sequence as follows:
     1-286: MVEAIVEFDY...VENDFLPVEK → MGEEVSLGEK...FGVFLVNEET

Show »
Length:464
Mass (Da):50,755
Checksum:i54F018C499D51044
GO
Isoform 5 (identifier: Q8R550-5) [UniParc]FASTAAdd to basket
Also known as: Ruk-m3

The sequence of this isoform differs from the canonical sequence as follows:
     1-286: MVEAIVEFDY...VENDFLPVEK → MGEE

Show »
Length:427
Mass (Da):46,827
Checksum:i460A56431A4FDDCD
GO
Isoform 6 (identifier: Q8R550-6) [UniParc]FASTAAdd to basket
Also known as: Ruk-t

The sequence of this isoform differs from the canonical sequence as follows:
     1-477: MVEAIVEFDY...RPVGPLTHTR → MFPFRKGARPPSMNLFRQTCW

Show »
Length:253
Mass (Da):27,442
Checksum:iD1B221FDDE4C72C7
GO
Isoform 7 (identifier: Q8R550-7) [UniParc]FASTAAdd to basket
Also known as: Ruk-h

The sequence of this isoform differs from the canonical sequence as follows:
     1-599: Missing.

Show »
Length:110
Mass (Da):11,992
Checksum:i6536493B3B3761DE
GO
Isoform 8 (identifier: Q8R550-8) [UniParc]FASTAAdd to basket
Also known as: Ruk-deltaCP

The sequence of this isoform differs from the canonical sequence as follows:
     174-217: Missing.
     320-630: Missing.

Show »
Length:354
Mass (Da):39,765
Checksum:iB580135B37F9B571
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti251 – 259PKKVKGVGF → NDDELTIKE (Ref. 5) Curated9
Sequence conflicti478 – 528GDSPK…TTSRP → YCHVLTKAGGHGMIMKIGEG MRTKLCLKIPATFFSSEKVV ARCWGATWCRL in BAC30033 (PubMed:16141072).CuratedAdd BLAST51
Sequence conflicti529 – 709Missing in BAC30033 (PubMed:16141072).CuratedAdd BLAST181

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0075091 – 599Missing in isoform 7. CuratedAdd BLAST599
Alternative sequenceiVSP_0075081 – 477MVEAI…LTHTR → MFPFRKGARPPSMNLFRQTC W in isoform 6. CuratedAdd BLAST477
Alternative sequenceiVSP_0075071 – 286MVEAI…LPVEK → MGEEVSLGEKNISPEQASCG ALHPRGWGSQTFGVFLVNEE T in isoform 4. CuratedAdd BLAST286
Alternative sequenceiVSP_0075061 – 286MVEAI…LPVEK → MGEE in isoform 5. CuratedAdd BLAST286
Alternative sequenceiVSP_0075051 – 54MVEAI…DNFVR → MELSAAKAPSPTDLPES in isoform 3. 1 PublicationAdd BLAST54
Alternative sequenceiVSP_007510174 – 217Missing in isoform 2, isoform 3 and isoform 8. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_007511320 – 630Missing in isoform 8. 1 PublicationAdd BLAST311

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF472327
, AF472306, AF472307, AF472308, AF472309, AF472312, AF472315, AF472316, AF472317, AF472318, AF472319, AF472320, AF472322, AF472323, AF472324, AF472325, AF472326 Genomic DNA. Translation: AAL82456.1.
AF472327, AF472325, AF472326 Genomic DNA. Translation: AAL82457.1.
AF472327
, AF472304, AF472305, AF472307, AF472308, AF472309, AF472312, AF472315, AF472316, AF472317, AF472318, AF472319, AF472320, AF472322, AF472323, AF472324, AF472325, AF472326 Genomic DNA. Translation: AAL82458.1.
AF472327
, AF472313, AF472314, AF472315, AF472316, AF472317, AF472318, AF472319, AF472320, AF472322, AF472323, AF472324, AF472325, AF472326 Genomic DNA. Translation: AAL82459.1.
AF472327
, AF472313, AF472315, AF472316, AF472317, AF472318, AF472319, AF472320, AF472322, AF472323, AF472324, AF472325, AF472326 Genomic DNA. Translation: AAL82460.1.
AF472327
, AF472321, AF472322, AF472323, AF472324, AF472325, AF472326 Genomic DNA. Translation: AAL82461.1.
AF472327
, AF472304, AF472305, AF472307, AF472308, AF472309, AF472310, AF472311, AF472312, AF472315, AF472316, AF472317, AF472318, AF472319, AF472320, AF472322, AF472323, AF472324, AF472325, AF472326 Genomic DNA. Translation: AAL82462.1.
AK004636 mRNA. Translation: BAB23427.2.
AK020782 mRNA. Translation: BAB32209.2.
AK038540 mRNA. Translation: BAC30033.1.
AK049182 mRNA. Translation: BAC33592.1.
AL929452 Genomic DNA. Translation: CAM21669.1.
AL929452 Genomic DNA. Translation: CAM21670.1.
AF243508 Genomic DNA. Translation: AAF68439.1.
AI428677 mRNA. No translation available.
CCDSiCCDS41194.1. [Q8R550-3]
CCDS53234.1. [Q8R550-2]
CCDS53235.1. [Q8R550-5]
RefSeqiNP_001129199.1. NM_001135727.2. [Q8R550-2]
NP_001129200.1. NM_001135728.2. [Q8R550-5]
NP_001277590.1. NM_001290661.1. [Q8R550-7]
NP_001277593.1. NM_001290664.1. [Q8R550-7]
NP_067364.2. NM_021389.6. [Q8R550-3]
XP_006528987.1. XM_006528924.3. [Q8R550-1]
XP_011246151.1. XM_011247849.2. [Q8R550-1]
XP_011246153.1. XM_011247851.2. [Q8R550-6]
UniGeneiMm.286495.

Genome annotation databases

EnsembliENSMUST00000073094; ENSMUSP00000072840; ENSMUSG00000040990. [Q8R550-1]
ENSMUST00000080394; ENSMUSP00000079257; ENSMUSG00000040990. [Q8R550-3]
ENSMUST00000112451; ENSMUSP00000108070; ENSMUSG00000040990. [Q8R550-5]
ENSMUST00000112453; ENSMUSP00000108072; ENSMUSG00000040990. [Q8R550-4]
ENSMUST00000112456; ENSMUSP00000108075; ENSMUSG00000040990. [Q8R550-2]
GeneIDi58194.
KEGGimmu:58194.
UCSCiuc009uss.3. mouse. [Q8R550-1]
uc009usv.3. mouse. [Q8R550-3]
uc009usx.3. mouse. [Q8R550-5]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSH3K1_MOUSE
AccessioniPrimary (citable) accession number: Q8R550
Secondary accession number(s): B1AZ86
, B1AZ87, Q8CAL8, Q8CEF6, Q8R545, Q8R546, Q8R547, Q8R548, Q8R549, Q8R551, Q9CTQ9, Q9DC14, Q9JKC3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: June 1, 2002
Last modified: May 10, 2017
This is version 141 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references