Reviewed, UniProtKB/Swiss-Prot Q14451 (GRB7_HUMAN)

Names and origin

Protein names

Recommended name:
    Growth factor receptor-bound protein 7
Alternative name(s):
    GRB7 adapter protein
    Epidermal growth factor receptor GRB-7
    B47

Gene names

Name:

GRB7

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	532 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Interacts with the cytoplasmic domain of the epidermal growth factor receptor which is then inhibited. The interaction is mediated by the SH2 domain. Also binds to ERBB2.
Subunit structure	Interacts with RND1.
Post-translational modification	Phosphorylated on tyrosine residues.
Sequence similarities	Belongs to the GRB7/10/14 family. Contains 1 PH domain. Contains 1 Ras-associating domain. Contains 1 SH2 domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	epidermal growth factor receptor signaling pathway Ref.2 Traceable author statement. Source: ProtInc
Molecular function	SH3/SH2 adaptor activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CALM	P62157	1	EBI-970191,EBI-397403	From a different organism.
Calm1	P62161	1	EBI-970191,EBI-397530	From a different organism.
RND1	Q92730	2	EBI-970191,EBI-448618

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Notes: At least 2 isoforms are produced.

Isoform 1 (identifier: Q14451-1)

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: Q14451-2)

Also known as: Grb7V;

The sequence of this isoform differs from the canonical sequence as follows:
     425-447: IHRTQLWFHGRISREESQRLIGQ → CSWSGRVSGTPRALSATCRK
     448-532: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 532

532

Growth factor receptor-bound protein 7

PRO_0000150344

Regions

Domain

100 – 186

87

Ras-associating

Domain

229 – 338

110

PH

Domain

431 – 527

97

SH2

Amino acid modifications

Modified residue

297

1

Phosphothreonine By similarity

Modified residue

361

1

Phosphoserine

Modified residue

366

1

Phosphoserine By similarity

Natural variations

Alternative sequence

425 – 447

23

IHRTQ…RLIGQ → CSWSGRVSGTPRALSATCRK in isoform 2.

VSP_035500

Alternative sequence

448 – 532

85

Missing in isoform 2.

VSP_035501

Experimental info

Sequence conflict

18

1

C → W Ref.1 Ref.2 Ref.3

Secondary structure

1

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532

Helix Strand Turn

Details...

Beta strand

102 – 108

7

Beta strand

113 – 118

6

Helix

124 – 132

9

Beta strand

134 – 136

3

Beta strand

145 – 148

4

Turn

150 – 152

3

Beta strand

155 – 158

4

Beta strand

160 – 162

3

Helix

164 – 168

5

Beta strand

173 – 175

3

Beta strand

178 – 181

4

Beta strand

427 – 429

3

Beta strand

432 – 434

3

Helix

438 – 444

7

Helix

445 – 447

3

Beta strand

456 – 459

4

Beta strand

461 – 463

3

Beta strand

467 – 472

6

Beta strand

477 – 483

7

Helix

505 – 511

7

Beta strand

513 – 515

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: A6867C20AFD46F74	FASTA	532	59,681
	10 20 30 40 50 60 MELDLSPPHL SSSPEDLCPA PGTPPGTPRP PDTPLPEEVK RSQPLLIPTT GRKLREEERR 70 80 90 100 110 120 ATSLPSIPNP FPELCSPPSQ SPILGGPSSA RGLLPRDASR PHVVKVYSED GACRSVEVAA 130 140 150 160 170 180 GATARHVCEM LVQRAHALSD ETWGLVECHP HLALERGLED HESVVEVQAA WPVGGDSRFV 190 200 210 220 230 240 FRKNFAKYEL FKSSPHSLFP EKMVSSCLDA HTGISHEDLI QNFLNAGSFP EIQGFLQLRG 250 260 270 280 290 300 SGRKLWKRFF CFLRRSGLYY STKGTSKDPR HLQYVADVNE SNVYVVTQGR KLYGMPTDFG 310 320 330 340 350 360 FCVKPNKLRN GHKGLRIFCS EDEQSRTCWL AAFRLFKYGV QLYKNYQQAQ SRHLHPSCLG 370 380 390 400 410 420 SPPLRSASDN TLVAMDFSGH AGRVIENPRE ALSVALEEAQ AWRKKTNHRL SLPMPASGTS 430 440 450 460 470 480 LSAAIHRTQL WFHGRISREE SQRLIGQQGL VDGLFLVRES QRNPQGFVLS LCHLQKVKHY 490 500 510 520 530 LILPSEEEGR LYFSMDDGQT RFTDLLQLVE FHQLNRGILP CLLRHCCTRV AL
	Isoform 2 (Grb7V) [UniParc]. Checksum: 7E376B08D114A9E2		444	49,120
	10 20 30 40 50 60 MELDLSPPHL SSSPEDLCPA PGTPPGTPRP PDTPLPEEVK RSQPLLIPTT GRKLREEERR 70 80 90 100 110 120 ATSLPSIPNP FPELCSPPSQ SPILGGPSSA RGLLPRDASR PHVVKVYSED GACRSVEVAA 130 140 150 160 170 180 GATARHVCEM LVQRAHALSD ETWGLVECHP HLALERGLED HESVVEVQAA WPVGGDSRFV 190 200 210 220 230 240 FRKNFAKYEL FKSSPHSLFP EKMVSSCLDA HTGISHEDLI QNFLNAGSFP EIQGFLQLRG 250 260 270 280 290 300 SGRKLWKRFF CFLRRSGLYY STKGTSKDPR HLQYVADVNE SNVYVVTQGR KLYGMPTDFG 310 320 330 340 350 360 FCVKPNKLRN GHKGLRIFCS EDEQSRTCWL AAFRLFKYGV QLYKNYQQAQ SRHLHPSCLG 370 380 390 400 410 420 SPPLRSASDN TLVAMDFSGH AGRVIENPRE ALSVALEEAQ AWRKKTNHRL SLPMPASGTS 430 440 LSAACSWSGR VSGTPRALSA TCRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer." Kishi T., Sasaki H., Akiyama N., Ishizuka T., Sakamoto H., Aizawa S., Sugimura T., Terada M. Biochem. Biophys. Res. Commun. 232:5-9(1997) [PubMed: 9125150] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Oesophageal carcinoma.
[2]	"A novel variant of human Grb7 is associated with invasive esophageal carcinoma." Tanaka S., Mori M., Akiyoshi T., Tanaka Y., Mafune K., Wands J.R., Sugimachi K. J. Clin. Invest. 102:821-827(1998) [PubMed: 9710451] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Genomic organization and amplification of the human GRB7 gene." Whittock N.V., Eady R.A.J., McGrath J.A. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	"Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma." Tanaka S., Mori M., Akiyoshi T., Tanaka Y., Mafune K., Wands J.R., Sugimachi K. Cancer Res. 57:28-31(1997) [PubMed: 8988034] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 130-343.
[6]	"Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family." Vayssiere B., Zalcman G., Mahe Y., Mirey G., Ligensa T., Weidner K.M., Chardin P., Camonis J. FEBS Lett. 467:91-96(2000) [PubMed: 10664463] [Abstract] Cited for: INTERACTION WITH RND1.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, MASS SPECTROMETRY.
[8]	"Solution structure of the RA domain of human GRB7 protein." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 100-186.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D43772 mRNA. Translation: BAA07827.1.
AB008789 mRNA. Translation: BAA29059.1.
AB008790 mRNA. Translation: BAA29060.1.
AF274875 Genomic DNA. Translation: AAG25938.1.
BC006535 mRNA. Translation: AAH06535.1.
D87513 mRNA. Translation: BAA13412.1.

PIR

JC5412.

RefSeq

NP_001025173.1.
NP_005301.2.

UniGene

Hs.86859

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MW4	NMR	-	A	415-532	[»]
1WGR	NMR	-	A	100-186	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:502N.

IntAct

Q14451.

PTM databases

PhosphoSite

Q14451.

Genome annotation databases

Ensembl

ENSG00000141738. Homo sapiens. [Contig view]

GeneID

2886.

KEGG

hsa:2886.

Organism-specific databases

H-InvDB

HIX0013788.

HGNC

HGNC:4567. GRB7.

HPA

CAB005226.

MIM

601522. gene.

PharmGKB

PA28963.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q14451.

HOVERGEN

Q14451.

Gene expression databases

ArrayExpress

Q14451.

CleanEx

HS_GRB7.

GermOnline

ENSG00000141738. Homo sapiens.

Family and domain databases

InterPro

IPR015042. BPS.
IPR001849. PH.
IPR011993. PH_type.
IPR000159. Ras-assoc.
IPR000980. SH2.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF08947. BPS. 1 hit.
PF00169. PH. 1 hit.
PF00788. RA. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.

ProDom

PD000093. SH2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00233. PH. 1 hit.
SM00314. RA. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

11395.

SOURCE

Search...

Entry information

Entry name

GRB7_HUMAN

Accession

Primary (citable) accession number: Q14451
Secondary accession number(s): Q92568, Q96DF9, Q9Y220

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	October 17, 2006
Last modified:	November 25, 2008
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)