UniProtKB - Q8R550 (SH3K1_MOUSE)
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Protein
SH3 domain-containing kinase-binding protein 1
Gene
Sh3kbp1
Organism
Mus musculus (Mouse)
Status
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
- SH3 domain binding Source: UniProtKB-KW
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- cell migration Source: UniProtKB
- cytoskeleton organization Source: UniProtKB
- endocytosis Source: UniProtKB-KW
- regulation of cell shape Source: UniProtKB
Keywordsi
Biological process | Apoptosis, Endocytosis |
Enzyme and pathway databases
Reactomei | R-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 1Alternative name(s): Regulator of ubiquitous kinase Short name: Ruk SH3-containing, expressed in tumorigenic astrocytes |
Gene namesi | Name:Sh3kbp1 Synonyms:Ruk, Seta |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1889583. Sh3kbp1. |
Subcellular locationi
Keywords - Cellular componenti
Cell junction, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Membrane, Synapse, SynaptosomePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000097729 | 1 – 709 | SH3 domain-containing kinase-binding protein 1Add BLAST | 709 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 156 | PhosphoserineCombined sources | 1 | |
Modified residuei | 159 | PhosphoserineCombined sources | 1 | |
Modified residuei | 227 | PhosphoserineBy similarity | 1 | |
Modified residuei | 274 | PhosphoserineCombined sources | 1 | |
Modified residuei | 298 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 480 | PhosphoserineCombined sources | 1 | |
Modified residuei | 553 | PhosphoserineCombined sources | 1 | |
Modified residuei | 555 | PhosphoserineCombined sources | 1 | |
Modified residuei | 565 | PhosphoserineCombined sources | 1 | |
Modified residuei | 631 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Monoubiquitinated by CBL and CBLB after EGF stimulation; probably on its C-terminus.By similarity
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
PeptideAtlasi | Q8R550. |
PRIDEi | Q8R550. |
PTM databases
iPTMneti | Q8R550. |
PhosphoSitePlusi | Q8R550. |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000040990. |
CleanExi | MM_SH3KBP1. |
ExpressionAtlasi | Q8R550. baseline and differential. |
Genevisiblei | Q8R550. 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
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
Dlg4 | Q62108 | 3 | EBI-642709,EBI-300895 |
GO - Molecular functioni
- SH3 domain binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGridi | 208383. 13 interactors. |
CORUMi | Q8R550. |
IntActi | Q8R550. 13 interactors. |
MINTi | Q8R550. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 103 – 107 | Combined sources | 5 | |
Beta strandi | 129 – 132 | Combined sources | 4 | |
Beta strandi | 135 – 138 | Combined sources | 4 | |
Beta strandi | 145 – 148 | Combined sources | 4 | |
Beta strandi | 151 – 154 | Combined sources | 4 | |
Beta strandi | 314 – 318 | Combined sources | 5 | |
Beta strandi | 336 – 342 | Combined sources | 7 | |
Beta strandi | 350 – 354 | Combined sources | 5 | |
Beta strandi | 359 – 363 | Combined sources | 5 | |
Helixi | 364 – 366 | Combined sources | 3 | |
Beta strandi | 367 – 369 | Combined sources | 3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1WI7 | NMR | - | A | 101-155 | [»] | |
2DA9 | NMR | - | A | 314-370 | [»] | |
ProteinModelPortali | Q8R550. | |||||
SMRi | Q8R550. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q8R550. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 58 | SH3 1PROSITE-ProRule annotationAdd BLAST | 58 | |
Domaini | 98 – 157 | SH3 2PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 311 – 372 | SH3 3PROSITE-ProRule annotationAdd BLAST | 62 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 646 – 708 | Sequence analysisAdd BLAST | 63 |
Keywords - Domaini
Coiled coil, Repeat, SH3 domain, SH3-bindingPhylogenomic databases
GeneTreei | ENSGT00530000063594. |
HOVERGENi | HBG057824. |
InParanoidi | Q8R550. |
KOi | K12470. |
OMAi | EDKEEHV. |
OrthoDBi | EOG091G041Q. |
PhylomeDBi | Q8R550. |
TreeFami | TF350191. |
Family and domain databases
CDDi | cd12052. SH3_CIN85_1. 1 hit. cd12055. SH3_CIN85_2. 1 hit. cd12057. SH3_CIN85_3. 1 hit. |
InterProi | View protein in InterPro IPR035770. CIN85_SH3_1. IPR035771. CIN85_SH3_2. IPR035772. CIN85_SH3_3. IPR036028. SH3-like_dom_sf. IPR001452. SH3_domain. |
Pfami | View protein in Pfam PF14604. SH3_9. 3 hits. |
PRINTSi | PR00452. SH3DOMAIN. |
SMARTi | View protein in SMART SM00326. SH3. 3 hits. |
SUPFAMi | SSF50044. SSF50044. 3 hits. |
PROSITEi | View protein in PROSITE PS50002. SH3. 3 hits. |
s (8)i Sequence
Sequence statusi: Complete.
This entry describes 8 produced by isoformsialternative 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.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 251 – 259 | PKKVKGVGF → NDDELTIKE (Ref. 5) Curated | 9 | |
Sequence conflicti | 478 – 528 | GDSPK…TTSRP → YCHVLTKAGGHGMIMKIGEG MRTKLCLKIPATFFSSEKVV ARCWGATWCRL in BAC30033 (PubMed:16141072).CuratedAdd BLAST | 51 | |
Sequence conflicti | 529 – 709 | Missing in BAC30033 (PubMed:16141072).CuratedAdd BLAST | 181 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_007509 | 1 – 599 | Missing in isoform 7. CuratedAdd BLAST | 599 | |
Alternative sequenceiVSP_007508 | 1 – 477 | MVEAI…LTHTR → MFPFRKGARPPSMNLFRQTC W in isoform 6. CuratedAdd BLAST | 477 | |
Alternative sequenceiVSP_007507 | 1 – 286 | MVEAI…LPVEK → MGEEVSLGEKNISPEQASCG ALHPRGWGSQTFGVFLVNEE T in isoform 4. CuratedAdd BLAST | 286 | |
Alternative sequenceiVSP_007506 | 1 – 286 | MVEAI…LPVEK → MGEE in isoform 5. CuratedAdd BLAST | 286 | |
Alternative sequenceiVSP_007505 | 1 – 54 | MVEAI…DNFVR → MELSAAKAPSPTDLPES in isoform 3. 1 PublicationAdd BLAST | 54 | |
Alternative sequenceiVSP_007510 | 174 – 217 | Missing in isoform 2, isoform 3 and isoform 8. 2 PublicationsAdd BLAST | 44 | |
Alternative sequenceiVSP_007511 | 320 – 630 | Missing in isoform 8. 1 PublicationAdd BLAST | 311 |
Sequence databases
Genome annotation databases
Ensembli | ENSMUST00000073094; ENSMUSP00000072840; ENSMUSG00000040990. [Q8R550-1] ENSMUST00000080394; ENSMUSP00000079257; ENSMUSG00000040990. [Q8R550-3] ENSMUST00000112451; ENSMUSP00000108070; ENSMUSG00000040990. [Q8R550-5] ENSMUST00000112453; ENSMUSP00000108072; ENSMUSG00000040990. [Q8R550-4] ENSMUST00000112456; ENSMUSP00000108075; ENSMUSG00000040990. [Q8R550-2] |
GeneIDi | 58194. |
KEGGi | mmu:58194. |
UCSCi | uc009uss.3. mouse. [Q8R550-1] uc009usv.3. mouse. [Q8R550-3] uc009usx.3. mouse. [Q8R550-5] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | SH3K1_MOUSE | |
Accessioni | Q8R550Primary (citable) accession number: Q8R550 Secondary accession number(s): B1AZ86 Q9JKC3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 23, 2003 |
Last sequence update: | June 1, 2002 | |
Last modified: | March 28, 2018 | |
This is version 147 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |