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B5KFD7 (GRB10_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 39. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth factor receptor-bound protein 10
Alternative name(s):
GRB10 adapter protein
Gene names
Name:Grb10
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length589 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. A similar role in the mediation of ubiquitination has also been suggested with INSR. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2 By similarity.

Enzyme regulation

Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling By similarity.

Subunit structure

Interacts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain. Poorly binds to the EGFR. Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex. Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15. When unphosphorylated, interacts with AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus interfering with the binding of AXIN1 to LRP6. Binds relatively non-specifically to several phosphoinositides, including PI5P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities through the PH domain. Binds to activated NRAS By similarity.

Subcellular location

Cytoplasm By similarity.

Post-translational modification

Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation By similarity.

Sequence similarities

Belongs to the GRB7/10/14 family.

Contains 1 PH domain.

Contains 1 Ras-associating domain.

Contains 1 SH2 domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: B5KFD7-1)

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.
Isoform 2 (identifier: B5KFD7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: B5KFD7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.
     511-548: LFLLRDSQSN...ILPCEDDGQT → RCTRLQWPSS...DPVGGIAYSI
     549-589: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: B5KFD7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     511-548: LFLLRDSQSN...ILPCEDDGQT → RCTRLQWPSS...DPVGGIAYSI
     549-589: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 589589Growth factor receptor-bound protein 10
PRO_0000392073

Regions

Domain161 – 24585Ras-associating
Domain285 – 394110PH
Domain488 – 58497SH2

Amino acid modifications

Modified residue991Phosphoserine By similarity
Modified residue1451Phosphoserine; by MTOR, MAPK1 and MAPK3 By similarity
Modified residue4131Phosphoserine; by MAPK1 and MAPK3; in vitro By similarity
Modified residue4231Phosphoserine; by MTOR and PKB/AKT1 By similarity
Modified residue4261Phosphoserine By similarity
Modified residue4711Phosphoserine; by MTOR, MAPK1 and MAPK3 By similarity

Natural variations

Alternative sequence1 – 5959Missing in isoform 2 and isoform 3.
VSP_038785
Alternative sequence511 – 54838LFLLR…DDGQT → RCTRLQWPSSKSLQTISAGE GVEKKEPYDPVGGIAYSI in isoform 3 and isoform 4.
VSP_038786
Alternative sequence549 – 58941Missing in isoform 3 and isoform 4.
VSP_038787

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 14, 2008. Version 1.
Checksum: 7F7F32CC84042B4D

FASTA58966,386
        10         20         30         40         50         60 
MALAGGPDSF LHHPYYQDQV EQTSPHHPRD LAGPGFPAQP DRLAPHQEDD VDLEALVNDM 

        70         80         90        100        110        120 
DASLESLCSA SETAPLLHNG QHARGPPPPG ARPLRPQASP RHRVPRSQPL HILAARRLQE 

       130        140        150        160        170        180 
EDQQFRTSSL PAIPNPFPEL CGPGSPPVLS PGSLPPGQAA AKQDVKVFSE DGTCKVVEIL 

       190        200        210        220        230        240 
ADMTARDLCQ LLVYRSHCVD DNSWTLVEHH PHLGLERGLE DHERVTQVQH TLASESKFLF 

       250        260        270        280        290        300 
RKNYAKYEFF KNPTNFFPEQ MVTWCQQSNG SQTQLLQNFL NSSSCPEIQG FLHVKELGRK 

       310        320        330        340        350        360 
SWKKLYVCLR RSGLYCSTKG ASKEPRHLQL LADLEDSSIF SLIAGRKQYG APTDYGFCIK 

       370        380        390        400        410        420 
PNRVRTEAKE LRLLCAEDEQ SRTCWMTAFR LLKYGMLLYQ NYRVPQQRKA VLSPFSAPVR 

       430        440        450        460        470        480 
SVSENSLVAM DFSGQTGRVI ENPAEAQSAA LEEGHAWRKR STRMNILGSQ SPLHPSTLST 

       490        500        510        520        530        540 
VIHRTQHWFH GRISREESHR IIKQQGLVDG LFLLRDSQSN PKAFVLTLCH HQKIKNFQIL 

       550        560        570        580 
PCEDDGQTFF SLDDGNTKFS DLIQLVDFYQ LNKGVLPCKL KHHCIRVAL 

« Hide

Isoform 2 [UniParc].

Checksum: 638E6F5F222D713D
Show »

FASTA53059,890
Isoform 3 [UniParc].

Checksum: 624A5272DA396169
Show »

FASTA48954,924
Isoform 4 [UniParc].

Checksum: 0BE86E93396C4F3B
Show »

FASTA54861,420

References

[1]"Pig Grb10 is bi-alleic expressed."
Nielsen A.L.
Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
EF174191 mRNA. Translation: ABO93312.1.
EF174192 mRNA. Translation: ABO93313.1.
EF174193 mRNA. Translation: ABO93314.1.
EF174194 mRNA. Translation: ABO93315.1.
EF174195 mRNA. Translation: ABO93316.1.
EF174196 mRNA. Translation: ABO93317.1.
EF174197 mRNA. Translation: ABO93318.1.
EF174198 mRNA. Translation: ABO93319.1.
EF174199 mRNA. Translation: ABO93320.1.
RefSeqNP_001128437.1. NM_001134965.1. [B5KFD7-1]
UniGeneSsc.21857.
Ssc.95889.

3D structure databases

ProteinModelPortalB5KFD7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9823.ENSSSCP00000016570.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSSSCT00000017025; ENSSSCP00000016570; ENSSSCG00000015631. [B5KFD7-4]
ENSSSCT00000031836; ENSSSCP00000020573; ENSSSCG00000015631. [B5KFD7-1]
GeneID100188977.
KEGGssc:100188977.

Organism-specific databases

CTD2887.

Phylogenomic databases

eggNOGNOG307156.
GeneTreeENSGT00550000074537.
HOGENOMHOG000231904.
HOVERGENHBG000468.
OMAESTMGSE.
OrthoDBEOG7SFHW7.
TreeFamTF317511.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProIPR015042. BPS-dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000159. Ras-assoc.
IPR000980. SH2.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamPF08947. BPS. 1 hit.
PF00169. PH. 1 hit.
PF00788. RA. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00233. PH. 1 hit.
SM00314. RA. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameGRB10_PIG
AccessionPrimary (citable) accession number: B5KFD7
Secondary accession number(s): B5KFD3, B5KFD4, B5KFD6
Entry history
Integrated into UniProtKB/Swiss-Prot: March 2, 2010
Last sequence update: October 14, 2008
Last modified: June 11, 2014
This is version 39 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families