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Protein

SH3 domain-containing kinase-binding protein 1

Gene

Sh3kbp1

Organism
Rattus norvegicus (Rat)
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 (By similarity). 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 - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Endocytosis

Enzyme and pathway databases

ReactomeiR-RNO-182971. EGFR downregulation.
R-RNO-6807004. Negative regulation of MET activity.
R-RNO-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-RNO-8856828. Clathrin-mediated endocytosis.
R-RNO-8866376. Reelin signalling pathway.
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome X

Organism-specific databases

RGDi620904. Sh3kbp1.

Subcellular locationi

GO - Cellular componenti

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_00000977301 – 709SH3 domain-containing kinase-binding protein 1Add BLAST709

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei156PhosphoserineBy similarity1
Modified residuei159PhosphoserineBy similarity1
Modified residuei227PhosphoserineBy similarity1
Modified residuei274PhosphoserineBy similarity1
Modified residuei298PhosphothreonineBy similarity1
Modified residuei480PhosphoserineBy similarity1
Modified residuei553PhosphoserineCombined sources1
Modified residuei555PhosphoserineCombined sources1
Modified residuei565PhosphoserineBy similarity1
Modified residuei631PhosphoserineCombined sources1
Isoform 7 (identifier: Q925Q9-7)
Modified residuei110PhosphoserineCombined sources1
Isoform 2 (identifier: Q925Q9-2)
Modified residuei183PhosphoserineCombined sources1

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

PaxDbiQ925Q9.
PRIDEiQ925Q9.

PTM databases

iPTMnetiQ925Q9.
PhosphoSitePlusiQ925Q9.

Expressioni

Tissue specificityi

Highly expressed in spinal cord.

Gene expression databases

BgeeiENSRNOG00000004322.
ExpressionAtlasiQ925Q9. baseline and differential.
GenevisibleiQ925Q9. RN.

Interactioni

Subunit structurei

Can self-associate and form homotetramers (By similarity). Interacts with MAGI2, PDCD6IP, CBL, GRB2 and PI3KR3. Interacts with CD2, F-actin capping protein, EGFR, MET, BLNK, MAP3K4, SPRY2, ARHGAP17, 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. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3 (By similarity). Interacts with ARHGAP27. Interacts (via SH3 domains) with SHKBP1 (via PXXXPR motifs) (PubMed:11152963). Interaction with CBL is abolished in the presence of SHKBP1 (By similarity). Interacts (via SH3 domains) with ZFP36 (via extreme C-terminal region). Interacts with MAP3K4; this interaction enhances the association with ZFP36 (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ITSN1Q15811-24EBI-8020091,EBI-8052395From a different organism.

Protein-protein interaction databases

IntActiQ925Q9. 5 interactors.
MINTiMINT-4611781.
STRINGi10116.ENSRNOP00000006741.

Structurei

3D structure databases

ProteinModelPortaliQ925Q9.
ModBaseiSearch...
MobiDBiSearch...

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 coili643 – 708Sequence analysisAdd BLAST66

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi381 – 472Pro-richAdd BLAST92
Compositional biasi537 – 649Ser-richAdd BLAST113

Sequence similaritiesi

Contains 3 SH3 domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, SH3 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG4348. Eukaryota.
ENOG410XQBY. LUCA.
GeneTreeiENSGT00530000063594.
HOVERGENiHBG057824.
InParanoidiQ925Q9.
KOiK12470.
OrthoDBiEOG091G041Q.
PhylomeDBiQ925Q9.
TreeFamiTF350191.

Family and domain databases

InterProiIPR001452. SH3_domain.
[Graphical view]
PfamiPF14604. SH3_9. 3 hits.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 3 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
PROSITEiPS50002. SH3. 3 hits.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q925Q9-1) [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 SVGEVITNIR KEDGGWWEGQ INGRRGLFPD
60 70 80 90 100
NFVREIKKDV KKDLLSNKAP EKPMHDVSSG NSLLSSETIL 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 NGTVATAAIQ
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 VIKQGAGTTE
410 420 430 440 450
RKHEIKKIPP ERPETLPNRT EEKERPEREP KLDLQKPSVP AIPPKKPRPP
460 470 480 490 500
KTNSLNRPGV LPPRRPERPV GPLTHTRGDS SKIDLAGSTL SGILDKDLSD
510 520 530 540 550
RSNDIDLEGF DSVISSTEKL SHPTTSRPKA TGRRPPSQSL TSSSLSSPDI
560 570 580 590 600
FDSPSPEEDK EEHISLAHRG IDVSKKTSRT VTISQVSDNK ASLPPKPGTM
610 620 630 640 650
AAASSGPASL SSVASSPMSS SLGTAGQRAS SPSLFSAEGK AKTESAVSSQ
660 670 680 690 700
AAIEELKMQV RELRTIIETM KDQQKREIKQ LLSELDEEKK IRLRLQMEVN

DIKKALQSK
Length:709
Mass (Da):78,086
Last modified:May 23, 2003 - v2
Checksum:iB995308497072064
GO
Isoform 2 (identifier: Q925Q9-2) [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):73,243
Checksum:i7F3E5A61CA707919
GO
Isoform 3 (identifier: Q925Q9-3) [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):46,791
Checksum:iDA810FE869CE57EC
GO
Isoform 4 (identifier: Q925Q9-4) [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):11,896
Checksum:i97E08F0ED25BF6F4
GO
Isoform 5 (identifier: Q925Q9-5) [UniParc]FASTAAdd to basket
Also known as: Ruk-s

The sequence of this isoform differs from the canonical sequence as follows:
     1-652: MVEAIVEFDY...TESAVSSQAA → MGEEVSSGGK...VTSSYINPRP

Show »
Length:111
Mass (Da):12,999
Checksum:i2F9F5B56AC061602
GO
Isoform 6 (identifier: Q925Q9-6) [UniParc]FASTAAdd to basket
Also known as: Ruk-m1

The sequence of this isoform differs from the canonical sequence as follows:
     1-305: Missing.

Show »
Length:404
Mass (Da):44,394
Checksum:i39283E253F5894BF
GO
Isoform 7 (identifier: Q925Q9-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: Missing.
     174-217: Missing.

Show »
Length:592
Mass (Da):64,847
Checksum:iD70CEF26DE231C4F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti99R → Q (PubMed:11302255).Curated1
Sequence conflicti99R → Q (PubMed:11152963).Curated1
Sequence conflicti333K → Q in AAF43035 (PubMed:11152963).Curated1
Sequence conflicti333K → Q in AAF43036 (PubMed:11152963).Curated1
Sequence conflicti507L → V (PubMed:11302255).Curated1
Sequence conflicti507L → V (PubMed:11152963).Curated1
Sequence conflicti517T → S (PubMed:11302255).Curated1
Sequence conflicti517T → S (PubMed:11152963).Curated1
Sequence conflicti645S → F (PubMed:11302255).Curated1
Sequence conflicti645S → F (PubMed:11152963).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0075171 – 652MVEAI…SSQAA → MGEEVSSGGKNISTEQASCG ASQPRGSQTLWSFPLEWRNY NWEEVTSSYINPRP in isoform 5. 1 PublicationAdd BLAST652
Alternative sequenceiVSP_0075151 – 599Missing in isoform 4. 1 PublicationAdd BLAST599
Alternative sequenceiVSP_0075141 – 305Missing in isoform 6. 1 PublicationAdd BLAST305
Alternative sequenceiVSP_0075161 – 286MVEAI…LPVEK → MGEE in isoform 3. 1 PublicationAdd BLAST286
Alternative sequenceiVSP_0075131 – 73Missing in isoform 7. 1 PublicationAdd BLAST73
Alternative sequenceiVSP_007512174 – 217Missing in isoform 2 and isoform 7. 3 PublicationsAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF255884 mRNA. Translation: AAK51625.1.
AF255885 mRNA. Translation: AAK51626.1.
AF255886 mRNA. Translation: AAK51627.1.
AF255887 mRNA. Translation: AAK51628.1.
AF255888 mRNA. Translation: AAK51629.1.
AF131867 mRNA. Translation: AAF36522.1.
AF230519 mRNA. Translation: AAF43035.1.
AF230520 mRNA. Translation: AAF43036.1.
RefSeqiNP_445812.1. NM_053360.2. [Q925Q9-2]
XP_006256992.1. XM_006256930.3. [Q925Q9-3]
XP_006256993.1. XM_006256931.1. [Q925Q9-1]
XP_008771422.1. XM_008773200.2. [Q925Q9-4]
XP_008771423.1. XM_008773201.2. [Q925Q9-4]
XP_008771424.1. XM_008773202.2. [Q925Q9-4]
XP_017457655.1. XM_017602166.1. [Q925Q9-6]
UniGeneiRn.107226.

Genome annotation databases

EnsembliENSRNOT00000006438; ENSRNOP00000006438; ENSRNOG00000004322. [Q925Q9-2]
GeneIDi84357.
KEGGirno:84357.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF255884 mRNA. Translation: AAK51625.1.
AF255885 mRNA. Translation: AAK51626.1.
AF255886 mRNA. Translation: AAK51627.1.
AF255887 mRNA. Translation: AAK51628.1.
AF255888 mRNA. Translation: AAK51629.1.
AF131867 mRNA. Translation: AAF36522.1.
AF230519 mRNA. Translation: AAF43035.1.
AF230520 mRNA. Translation: AAF43036.1.
RefSeqiNP_445812.1. NM_053360.2. [Q925Q9-2]
XP_006256992.1. XM_006256930.3. [Q925Q9-3]
XP_006256993.1. XM_006256931.1. [Q925Q9-1]
XP_008771422.1. XM_008773200.2. [Q925Q9-4]
XP_008771423.1. XM_008773201.2. [Q925Q9-4]
XP_008771424.1. XM_008773202.2. [Q925Q9-4]
XP_017457655.1. XM_017602166.1. [Q925Q9-6]
UniGeneiRn.107226.

3D structure databases

ProteinModelPortaliQ925Q9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ925Q9. 5 interactors.
MINTiMINT-4611781.
STRINGi10116.ENSRNOP00000006741.

PTM databases

iPTMnetiQ925Q9.
PhosphoSitePlusiQ925Q9.

Proteomic databases

PaxDbiQ925Q9.
PRIDEiQ925Q9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006438; ENSRNOP00000006438; ENSRNOG00000004322. [Q925Q9-2]
GeneIDi84357.
KEGGirno:84357.

Organism-specific databases

CTDi30011.
RGDi620904. Sh3kbp1.

Phylogenomic databases

eggNOGiKOG4348. Eukaryota.
ENOG410XQBY. LUCA.
GeneTreeiENSGT00530000063594.
HOVERGENiHBG057824.
InParanoidiQ925Q9.
KOiK12470.
OrthoDBiEOG091G041Q.
PhylomeDBiQ925Q9.
TreeFamiTF350191.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ925Q9.

Gene expression databases

BgeeiENSRNOG00000004322.
ExpressionAtlasiQ925Q9. baseline and differential.
GenevisibleiQ925Q9. RN.

Family and domain databases

InterProiIPR001452. SH3_domain.
[Graphical view]
PfamiPF14604. SH3_9. 3 hits.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 3 hits.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 3 hits.
PROSITEiPS50002. SH3. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSH3K1_RAT
AccessioniPrimary (citable) accession number: Q925Q9
Secondary accession number(s): Q925R0
, Q925R1, Q925R2, Q925R3, Q9JKQ0, Q9JKQ1, Q9JLU9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: May 23, 2003
Last modified: November 30, 2016
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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.