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Protein

Growth factor receptor-bound protein 7

Gene

Grb7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 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 (By similarity). 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 similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • negative regulation of translation Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of signal transduction Source: GOC
  • signal transduction Source: MGI
  • stress granule assembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Ligandi

Lipid-binding, RNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-1306955. GRB7 events in ERBB2 signaling.
R-MMU-1433557. Signaling by SCF-KIT.
R-MMU-186763. Downstream signal transduction.
R-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:102683. Grb7.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Cell projection By similarity
  • Cell junctionfocal adhesion By similarity
  • Cell membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
  • Cytoplasmic granule 1 Publication

  • Note: Predominantly cytoplasmic. Detected in stress granules where mRNA is stored under stress conditions.1 Publication

GO - Cellular componenti

  • cell projection Source: UniProtKB-SubCell
  • cytoplasmic stress granule Source: UniProtKB
  • cytosol Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi262 – 2621Y → F: Abolishes interaction with FHL2.
Mutagenesisi263 – 2631Y → F: Abolishes interaction with FHL2.
Mutagenesisi287 – 2871Y → F: Abolishes interaction with FHL2.
Mutagenesisi483 – 4831Y → F: Strongly reduced tyrosine phosphorylation. Abolishes interaction with FHL2. 1 Publication
Mutagenesisi495 – 4951Y → F: Strongly reduced tyrosine phosphorylation. Abolishes interaction with FHL2. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 535535Growth factor receptor-bound protein 7PRO_0000150345Add
BLAST

Amino acid modifications

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

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. Tyrosine phosphorylation is essential for activation of down-stream protein kinases (By similarity). Phosphorylated on tyrosine residues in response to NTN1 signaling. Phosphorylation promotes stress granule disassembly during recovery after cellular stress.By similarity3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ03160.
PaxDbiQ03160.
PRIDEiQ03160.

PTM databases

iPTMnetiQ03160.
PhosphoSiteiQ03160.

Expressioni

Gene expression databases

BgeeiQ03160.
CleanExiMM_GRB7.
ExpressionAtlasiQ03160. baseline and differential.
GenevisibleiQ03160. MM.

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 similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CAV1Q031353EBI-7100053,EBI-603614From a different organism.
Elavl1P703727EBI-7100053,EBI-6877056
TekQ028583EBI-7100053,EBI-7099626
Tia1Q80ZW74EBI-7100053,EBI-7809240

GO - Molecular functioni

  • identical protein binding Source: MGI
  • protein kinase binding Source: MGI
  • SH3/SH2 adaptor activity Source: MGI

Protein-protein interaction databases

BioGridi200047. 1 interaction.
DIPiDIP-43965N.
IntActiQ03160. 6 interactions.
MINTiMINT-4544456.
STRINGi10090.ENSMUSP00000019456.

Structurei

3D structure databases

ProteinModelPortaliQ03160.
SMRiQ03160. Positions 85-350, 372-408, 423-535.
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.
InParanoidiQ03160.
OMAiVQAAWPI.
PhylomeDBiQ03160.
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.

Q03160-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELDLSPTHL SSSPEDVCPT PATPPETPPP PDNPPPGDVK RSQPLPIPSS
60 70 80 90 100
RKLREEEFQA TSLPSIPNPF PELCSPPSQK PILGGSSGAR GLLPRDSSRL
110 120 130 140 150
CVVKVYSEDG ACRSVEVAAG ATARHVCEML VQRAHALSDE SWGLVESHPY
160 170 180 190 200
LALERGLEDH EFVVEVQEAW PVGGDSRFIF RKNFAKYELF KSPPHTLFPE
210 220 230 240 250
KMVSSCLDAQ TGISHEDLIQ NFLNAGSFPE IQGFLQLRGS GRGSGRKLWK
260 270 280 290 300
RFFCFLRRSG LYYSTKGTSK DPRHLQYVAD VNESNVYVVT QGRKLYGMPT
310 320 330 340 350
DFGFCVKPNK LRNGHKGLHI FCSEDEQSRT CWLAAFRLFK YGVQLYKNYQ
360 370 380 390 400
QAQSRHLRLS YLGSPPLRSV SDNTLVAMDF SGHAGRVIDN PREALSAAME
410 420 430 440 450
EAQAWRKKTN HRLSLPTTCS GSSLSAAIHR TQPWFHGRIS REESQRLIGQ
460 470 480 490 500
QGLVDGVFLV RESQRNPQGF VLSLCHLQKV KHYLILPSED EGCLYFSMDE
510 520 530
GQTRFTDLLQ LVEFHQLNRG ILPCLLRHCC ARVAL
Length:535
Mass (Da):59,959
Last modified:November 1, 1996 - v1
Checksum:iCD8C307864703645
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94450 mRNA. Translation: AAA37733.1.
AK145996 mRNA. Translation: BAE26817.1.
AK168438 mRNA. Translation: BAE40343.1.
AL591390 Genomic DNA. Translation: CAM22007.1.
CH466556 Genomic DNA. Translation: EDL16144.1.
BC003295 mRNA. Translation: AAH03295.1.
CCDSiCCDS25351.1.
PIRiC46243.
RefSeqiNP_034476.1. NM_010346.2.
XP_006532296.1. XM_006532233.1.
UniGeneiMm.276702.

Genome annotation databases

EnsembliENSMUST00000019456; ENSMUSP00000019456; ENSMUSG00000019312.
GeneIDi14786.
KEGGimmu:14786.
UCSCiuc007lgk.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94450 mRNA. Translation: AAA37733.1.
AK145996 mRNA. Translation: BAE26817.1.
AK168438 mRNA. Translation: BAE40343.1.
AL591390 Genomic DNA. Translation: CAM22007.1.
CH466556 Genomic DNA. Translation: EDL16144.1.
BC003295 mRNA. Translation: AAH03295.1.
CCDSiCCDS25351.1.
PIRiC46243.
RefSeqiNP_034476.1. NM_010346.2.
XP_006532296.1. XM_006532233.1.
UniGeneiMm.276702.

3D structure databases

ProteinModelPortaliQ03160.
SMRiQ03160. Positions 85-350, 372-408, 423-535.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200047. 1 interaction.
DIPiDIP-43965N.
IntActiQ03160. 6 interactions.
MINTiMINT-4544456.
STRINGi10090.ENSMUSP00000019456.

PTM databases

iPTMnetiQ03160.
PhosphoSiteiQ03160.

Proteomic databases

MaxQBiQ03160.
PaxDbiQ03160.
PRIDEiQ03160.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019456; ENSMUSP00000019456; ENSMUSG00000019312.
GeneIDi14786.
KEGGimmu:14786.
UCSCiuc007lgk.1. mouse.

Organism-specific databases

CTDi2886.
MGIiMGI:102683. Grb7.

Phylogenomic databases

eggNOGiKOG3751. Eukaryota.
ENOG410XXC8. LUCA.
GeneTreeiENSGT00550000074537.
HOGENOMiHOG000231904.
HOVERGENiHBG000468.
InParanoidiQ03160.
OMAiVQAAWPI.
PhylomeDBiQ03160.
TreeFamiTF317511.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ03160.
SOURCEiSearch...

Gene expression databases

BgeeiQ03160.
CleanExiMM_GRB7.
ExpressionAtlasiQ03160. baseline and differential.
GenevisibleiQ03160. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains."
    Margolis B., Silvennoinen O., Comoglio F., Roonprapunt C., Skolnik E.Y., Ullrich A., Schlessinger J.
    Proc. Natl. Acad. Sci. U.S.A. 89:8894-8898(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryo.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Kidney and Placenta.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  6. "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7."
    Pandey A., Liu X., Dixon J.E., Di Fiore P.P., Dixit V.M.
    J. Biol. Chem. 271:10607-10610(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RET, TYROSINE PHOSPHORYLATION.
  7. "Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors."
    Yokote K., Margolis B., Heldin C.H., Claesson-Welsh L.
    J. Biol. Chem. 271:30942-30949(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PDGFRA; PDGFRB AND SHC1.
  8. "Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor."
    Thommes K., Lennartsson J., Carlberg M., Ronnstrand L.
    Biochem. J. 341:211-216(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KIT.
  9. "Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration."
    Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R., Alitalo K., Dumont D.J.
    J. Biol. Chem. 274:30896-30905(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TEK/TIE2, PHOSPHORYLATION.
  10. "The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation."
    Tsai N.P., Bi J., Wei L.N.
    EMBO J. 26:1522-1531(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PTK2/FAK1, PHOSPHORYLATION, RNA-BINDING, MUTAGENESIS OF TYR-483 AND TYR-495.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  12. "Regulation of stress granule dynamics by Grb7 and FAK signalling pathway."
    Tsai N.P., Ho P.C., Wei L.N.
    EMBO J. 27:715-726(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH ELAVL1, IDENTIFICATION IN A COMPLEX WITH PTK2/FAK1; ELAVL1 AND TIA1.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney and Liver.

Entry informationi

Entry nameiGRB7_MOUSE
AccessioniPrimary (citable) accession number: Q03160
Secondary accession number(s): Q3TH55
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 131 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.