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B5KFD7

- GRB10_PIG

UniProt

B5KFD7 - GRB10_PIG

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Protein

Growth factor receptor-bound protein 10

Gene

Grb10

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at transcript leveli

Functioni

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).By similarity

Enzyme regulationi

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

GO - Biological processi

  1. insulin-like growth factor receptor signaling pathway Source: Ensembl
  2. negative regulation of glucose import Source: Ensembl
  3. negative regulation of insulin receptor signaling pathway Source: Ensembl
  4. negative regulation of phosphorylation Source: Ensembl
  5. negative regulation of Wnt signaling pathway Source: UniProtKB
  6. positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_192916. Signaling by SCF-KIT.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth factor receptor-bound protein 10
Alternative name(s):
GRB10 adapter protein
Gene namesi
Name:Grb10
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: Chromosome 9

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 589589Growth factor receptor-bound protein 10PRO_0000392073Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei99 – 991PhosphoserineBy similarity
Modified residuei145 – 1451Phosphoserine; by MTOR, MAPK1 and MAPK3By similarity
Modified residuei413 – 4131Phosphoserine; by MAPK1 and MAPK3; in vitroBy similarity
Modified residuei423 – 4231Phosphoserine; by MTOR and PKB/AKT1By similarity
Modified residuei426 – 4261PhosphoserineBy similarity
Modified residuei471 – 4711Phosphoserine; by MTOR, MAPK1 and MAPK3By similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000016570.

Structurei

3D structure databases

ProteinModelPortaliB5KFD7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini161 – 24585Ras-associatingPROSITE-ProRule annotationAdd
BLAST
Domaini285 – 394110PHPROSITE-ProRule annotationAdd
BLAST
Domaini488 – 58497SH2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the GRB7/10/14 family.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 Ras-associating domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG307156.
GeneTreeiENSGT00550000074537.
HOGENOMiHOG000231904.
HOVERGENiHBG000468.
InParanoidiB5KFD7.
OMAiESTMGSE.
OrthoDBiEOG7SFHW7.
TreeFamiTF317511.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR015042. BPS-dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000159. Ras-assoc.
IPR000980. SH2.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF08947. BPS. 1 hit.
PF00169. PH. 1 hit.
PF00788. RA. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00233. PH. 1 hit.
SM00314. RA. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: B5KFD7-1) [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
MALAGGPDSF LHHPYYQDQV EQTSPHHPRD LAGPGFPAQP DRLAPHQEDD
60 70 80 90 100
VDLEALVNDM DASLESLCSA SETAPLLHNG QHARGPPPPG ARPLRPQASP
110 120 130 140 150
RHRVPRSQPL HILAARRLQE EDQQFRTSSL PAIPNPFPEL CGPGSPPVLS
160 170 180 190 200
PGSLPPGQAA AKQDVKVFSE DGTCKVVEIL ADMTARDLCQ LLVYRSHCVD
210 220 230 240 250
DNSWTLVEHH PHLGLERGLE DHERVTQVQH TLASESKFLF RKNYAKYEFF
260 270 280 290 300
KNPTNFFPEQ MVTWCQQSNG SQTQLLQNFL NSSSCPEIQG FLHVKELGRK
310 320 330 340 350
SWKKLYVCLR RSGLYCSTKG ASKEPRHLQL LADLEDSSIF SLIAGRKQYG
360 370 380 390 400
APTDYGFCIK PNRVRTEAKE LRLLCAEDEQ SRTCWMTAFR LLKYGMLLYQ
410 420 430 440 450
NYRVPQQRKA VLSPFSAPVR SVSENSLVAM DFSGQTGRVI ENPAEAQSAA
460 470 480 490 500
LEEGHAWRKR STRMNILGSQ SPLHPSTLST VIHRTQHWFH GRISREESHR
510 520 530 540 550
IIKQQGLVDG LFLLRDSQSN PKAFVLTLCH HQKIKNFQIL PCEDDGQTFF
560 570 580
SLDDGNTKFS DLIQLVDFYQ LNKGVLPCKL KHHCIRVAL
Length:589
Mass (Da):66,386
Last modified:October 14, 2008 - v1
Checksum:i7F7F32CC84042B4D
GO
Isoform 2 (identifier: B5KFD7-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.

Note: No experimental confirmation available.

Show »
Length:530
Mass (Da):59,890
Checksum:i638E6F5F222D713D
GO
Isoform 3 (identifier: B5KFD7-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:489
Mass (Da):54,924
Checksum:i624A5272DA396169
GO
Isoform 4 (identifier: B5KFD7-4) [UniParc]FASTAAdd to Basket

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.

Show »
Length:548
Mass (Da):61,420
Checksum:i0BE86E93396C4F3B
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5959Missing in isoform 2 and isoform 3. 1 PublicationVSP_038785Add
BLAST
Alternative sequencei511 – 54838LFLLR…DDGQT → RCTRLQWPSSKSLQTISAGE GVEKKEPYDPVGGIAYSI in isoform 3 and isoform 4. 1 PublicationVSP_038786Add
BLAST
Alternative sequencei549 – 58941Missing in isoform 3 and isoform 4. 1 PublicationVSP_038787Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_001128437.1. NM_001134965.1. [B5KFD7-1]
UniGeneiSsc.21857.
Ssc.95889.

Genome annotation databases

EnsembliENSSSCT00000017025; ENSSSCP00000016570; ENSSSCG00000015631. [B5KFD7-4]
ENSSSCT00000031836; ENSSSCP00000020573; ENSSSCG00000015631. [B5KFD7-1]
GeneIDi100188977.
KEGGissc:100188977.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
RefSeqi NP_001128437.1. NM_001134965.1. [B5KFD7-1 ]
UniGenei Ssc.21857.
Ssc.95889.

3D structure databases

ProteinModelPortali B5KFD7.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9823.ENSSSCP00000016570.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSSSCT00000017025 ; ENSSSCP00000016570 ; ENSSSCG00000015631 . [B5KFD7-4 ]
ENSSSCT00000031836 ; ENSSSCP00000020573 ; ENSSSCG00000015631 . [B5KFD7-1 ]
GeneIDi 100188977.
KEGGi ssc:100188977.

Organism-specific databases

CTDi 2887.

Phylogenomic databases

eggNOGi NOG307156.
GeneTreei ENSGT00550000074537.
HOGENOMi HOG000231904.
HOVERGENi HBG000468.
InParanoidi B5KFD7.
OMAi ESTMGSE.
OrthoDBi EOG7SFHW7.
TreeFami TF317511.

Enzyme and pathway databases

Reactomei REACT_192916. Signaling by SCF-KIT.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProi IPR015042. BPS-dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR000159. Ras-assoc.
IPR000980. SH2.
IPR029071. Ubiquitin-rel_dom.
[Graphical view ]
Pfami PF08947. BPS. 1 hit.
PF00169. PH. 1 hit.
PF00788. RA. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
SMARTi SM00233. PH. 1 hit.
SM00314. RA. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view ]
SUPFAMi SSF54236. SSF54236. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEi PS50003. PH_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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).

Entry informationi

Entry nameiGRB10_PIG
AccessioniPrimary (citable) accession number: B5KFD7
Secondary accession number(s): B5KFD3, B5KFD4, B5KFD6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 2, 2010
Last sequence update: October 14, 2008
Last modified: October 29, 2014
This is version 42 of the entry and version 1 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

External Data

Dasty 3