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Protein

Growth factor receptor-bound protein 7

Gene

Grb7

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein that interacts with the cytoplasmic domain of numerous receptor kinases and modulates down-stream signaling. Promotes activation of down-stream protein kinases, including STAT3, AKT1, MAPK1 and/or MAPK3. Promotes activation of HRAS. Plays a role in signal transduction in response to EGF. Plays a role in the regulation of cell proliferation and cell migration. Plays a role in the assembly and stability of RNA stress granules. Binds to the 5'UTR of target mRNA molecules and represses translation of target mRNA species, when not phosphorylated. Phosphorylation impairs RNA binding and promotes stress granule disassembly during recovery after cellular stress (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei238 – 2381Important for lipid binding and for stimulation of cell migrationBy similarity
Sitei514 – 5141Important for dimerization and for HRAS activationBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Ligandi

Lipid-binding, RNA-binding

Enzyme and pathway databases

ReactomeiR-RNO-1306955. GRB7 events in ERBB2 signaling.
R-RNO-1433557. Signaling by SCF-KIT.
R-RNO-186763. Downstream signal transduction.
R-RNO-210993. Tie2 Signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth factor receptor-bound protein 7
Alternative name(s):
Epidermal growth factor receptor GRB-7
GRB7 adapter protein
Gene namesi
Name:Grb7
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi619759. Grb7.

Subcellular locationi

  • Cytoplasm By similarity
  • Cell projection By similarity
  • Cell junctionfocal adhesion By similarity
  • Cell membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
  • Cytoplasmic granule By similarity

  • Note: Predominantly cytoplasmic. Detected in stress granules where mRNA is stored under stress conditions.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi461 – 4611R → K: Reduces interaction with INSR. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 535535Growth factor receptor-bound protein 7PRO_0000412210Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei187 – 1871Phosphotyrosine; by FAK1By similarity
Modified residuei341 – 3411Phosphotyrosine; by FAK1By similarity
Modified residuei364 – 3641PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated on serine and threonine residues in response to activation of receptor kinases. Phosphorylated on tyrosine residues by TEK/TIE2. Phosphorylated on tyrosine residues by PTK2/FAK1, and possibly also other kinases. Phosphorylation is enhanced by activation of receptor kinases by a cognate ligand. Tyrosine phosphorylation is essential for activation of down-stream protein kinases. Phosphorylation decreases affinity for target mRNA molecules (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9QZC5.

PTM databases

iPTMnetiQ9QZC5.
PhosphoSiteiQ9QZC5.

Expressioni

Tissue specificityi

Detected in liver, kidney and placenta, and at lower levels in lung.1 Publication

Gene expression databases

BgeeiENSRNOG00000006990.
GenevisibleiQ9QZC5. RN.

Interactioni

Subunit structurei

Homodimer. Interacts (via SH2 domain) with EGFR, ERBB2, ERBB3 (when phosphorylated), ERBB4 (when phosphorylated), EPHB1, INSR, FGFR1, PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts with SHC1. Interacts with RND1. Interacts (when tyrosine phosphorylated) with FHL2 and HAX1 (By similarity). Interacts (via SH2 domain) with RET and PTK2/FAK1. Interacts (when not phosphorylated) with ELAVL1. In stressed cells, but not in normal cells, part of a complex that contains at least GRB7, PTK2/FAK1, STAU1, ELAVL1 and TIA1. Interacts (via SH2 domain) with KIT (phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009299.

Structurei

3D structure databases

ProteinModelPortaliQ9QZC5.
SMRiQ9QZC5. Positions 85-185, 372-408, 417-535.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini99 – 18587Ras-associatingPROSITE-ProRule annotationAdd
BLAST
Domaini228 – 341114PHPROSITE-ProRule annotationAdd
BLAST
Domaini434 – 53097SH2PROSITE-ProRule annotationAdd
BLAST

Domaini

The PH domain mediates interaction with membranes containing phosphoinositides.By similarity

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

eggNOGiKOG3751. Eukaryota.
ENOG410XXC8. LUCA.
GeneTreeiENSGT00550000074537.
HOGENOMiHOG000231904.
HOVERGENiHBG000468.
InParanoidiQ9QZC5.
OMAiVQAAWPI.
OrthoDBiEOG091G135G.
PhylomeDBiQ9QZC5.
TreeFamiTF317511.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR015042. BPS-dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000159. RA_dom.
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]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9QZC5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELDLSPSHL SSSPEDVCPT PGTPPETPPP PDNPPPGDVK RSQPLPIPSS
60 70 80 90 100
RKLREEEFQA TSLPSIPNPF PELCSPPSQK PILGGSSGAR GLLPRDSSRL
110 120 130 140 150
CVVKVYSEDG ACRSVEVAAG ATARHVCEML VQRAHALSDE NWGLVECHPY
160 170 180 190 200
LALERGLEDH ESVVEVQEAW PVGGDSRFIF RKNFAKYELF KSPPHTLFPE
210 220 230 240 250
KMVSSCLDTP TGISHEDLIQ NFLNAGSFPE IQGFLQLRGS GRGSGRKLWK
260 270 280 290 300
RFFCFLRRSG LYYSTKGTSK DPRHLQYVAD INESNVYVVT QGRKLYGIPT
310 320 330 340 350
DFGFCVKPNK LRNGHKGLHI FCSEDEQSRT CWLSAFRLFK YGVQLYKNYQ
360 370 380 390 400
QAQSRHLRLS YLGSPPLRSV SDNTLVAMDF SGHAGRVIEN PQEALSAATE
410 420 430 440 450
EAQAWRKKTN HRLSLPTPCS GLSLSAAIHR TQPWFHGRIS REESQRLIGQ
460 470 480 490 500
QGLVDGVFLV RESQRNPQGF VLSLCHLQKV KHYLILPSED EGCLYFSMDD
510 520 530
GQTRFTDLLQ LVEFHQLNRG ILPCLLRHCC ARVAL
Length:535
Mass (Da):59,889
Last modified:May 1, 2000 - v1
Checksum:i15DB67C4D19B89E4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190121 mRNA. Translation: AAF01776.1.
CH473948 Genomic DNA. Translation: EDM05933.1.
BC081757 mRNA. Translation: AAH81757.1.
RefSeqiNP_445855.1. NM_053403.2.
XP_006247494.1. XM_006247432.2.
XP_006247495.1. XM_006247433.2.
XP_008766347.1. XM_008768125.1.
UniGeneiRn.28109.

Genome annotation databases

EnsembliENSRNOT00000009299; ENSRNOP00000009299; ENSRNOG00000006990.
GeneIDi84427.
KEGGirno:84427.
UCSCiRGD:619759. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190121 mRNA. Translation: AAF01776.1.
CH473948 Genomic DNA. Translation: EDM05933.1.
BC081757 mRNA. Translation: AAH81757.1.
RefSeqiNP_445855.1. NM_053403.2.
XP_006247494.1. XM_006247432.2.
XP_006247495.1. XM_006247433.2.
XP_008766347.1. XM_008768125.1.
UniGeneiRn.28109.

3D structure databases

ProteinModelPortaliQ9QZC5.
SMRiQ9QZC5. Positions 85-185, 372-408, 417-535.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009299.

PTM databases

iPTMnetiQ9QZC5.
PhosphoSiteiQ9QZC5.

Proteomic databases

PaxDbiQ9QZC5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000009299; ENSRNOP00000009299; ENSRNOG00000006990.
GeneIDi84427.
KEGGirno:84427.
UCSCiRGD:619759. rat.

Organism-specific databases

CTDi2886.
RGDi619759. Grb7.

Phylogenomic databases

eggNOGiKOG3751. Eukaryota.
ENOG410XXC8. LUCA.
GeneTreeiENSGT00550000074537.
HOGENOMiHOG000231904.
HOVERGENiHBG000468.
InParanoidiQ9QZC5.
OMAiVQAAWPI.
OrthoDBiEOG091G135G.
PhylomeDBiQ9QZC5.
TreeFamiTF317511.

Enzyme and pathway databases

ReactomeiR-RNO-1306955. GRB7 events in ERBB2 signaling.
R-RNO-1433557. Signaling by SCF-KIT.
R-RNO-186763. Downstream signal transduction.
R-RNO-210993. Tie2 Signaling.

Miscellaneous databases

PROiQ9QZC5.

Gene expression databases

BgeeiENSRNOG00000006990.
GenevisibleiQ9QZC5. RN.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR015042. BPS-dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000159. RA_dom.
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]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGRB7_RAT
AccessioniPrimary (citable) accession number: Q9QZC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 21, 2011
Last sequence update: May 1, 2000
Last modified: September 7, 2016
This is version 107 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

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.