Q14451 (GRB7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth factor receptor-bound protein 7

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

Gene names

Name:

GRB7

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	532 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.12 Ref.14 Ref.15 Ref.22
Subunit structure	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. Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26
Subcellular location	Cytoplasm. Cell junction › focal adhesion. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic granule By similarity. Cell projection. Note: Predominantly cytoplasmic. Detected in stress granules, where mRNA is stored under stress conditions By similarity. Ref.12 Ref.14 Ref.21
Domain	The PH domain mediates interaction with membranes containing phosphoinositides. Ref.14
Post-translational modification	Phosphorylated on serine and threonine residues in response to heregulin. Phosphorylated on tyrosine residues by TEK/TIE2. Phosphorylated on tyrosine residues in response to NTN1 signaling. Phosphorylation promotes stress granule disassembly during recovery after cellular stress By similarity. 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. Ref.10 Ref.12 Ref.15 Ref.20 Ref.21 Ref.22 Ref.23
Sequence similarities	Belongs to the GRB7/10/14 family. Contains 1 PH domain. Contains 1 Ras-associating domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Domain	SH2 domain
Ligand	Lipid-binding RNA-binding
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement Ref.2. Source: ProtInc leukocyte migration Traceable author statement. Source: Reactome negative regulation of translation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from direct assay Ref.12Ref.14. Source: UniProtKB stress granule assembly Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cell projection Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic stress granule Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from direct assay Ref.12Ref.14. Source: UniProtKB focal adhesion Inferred from direct assay Ref.12Ref.14. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW SH3/SH2 adaptor activity Traceable author statement Ref.2. Source: ProtInc phosphatidylinositol binding Inferred from direct assay Ref.14. Source: UniProtKB protein kinase binding Inferred from direct assay Ref.14. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-970191,EBI-970191
CALM	P62157	2	EBI-970191,EBI-397403	From a different organism.
Calm3	P62161	9	EBI-970191,EBI-397530	From a different organism.
EPHB1	P54762	4	EBI-970191,EBI-80252
HAX1	O00165	2	EBI-970191,EBI-357001
RND1	Q92730	4	EBI-970191,EBI-448618

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: 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 → CSWSGRVSGTPRALSSLCATCRK
     448-532: Missing.

Isoform 3 (identifier: Q14451-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGKWRPGQGHTTGSVKPLSCSDAM

Isoform 4 (identifier: Q14451-4)

The sequence of this isoform differs from the canonical sequence as follows:
     48-81: 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

Sites

Site

239

1

Important for lipid binding and for stimulation of cell migration

Site

511

1

Important for dimerization and for HRAS activation

Amino acid modifications

Modified residue

188

1

Phosphotyrosine; by FAK1 Ref.20 Ref.22

Modified residue

297

1

Phosphothreonine By similarity

Modified residue

338

1

Phosphotyrosine; by FAK1 Ref.20 Ref.22

Modified residue

361

1

Phosphoserine Ref.19

Modified residue

366

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1

1

M → MGKWRPGQGHTTGSVKPLSC SDAM in isoform 3.

VSP_041665

Alternative sequence

48 – 81

34

Missing in isoform 4.

VSP_041666

Alternative sequence

425 – 447

23

IHRTQ…RLIGQ → CSWSGRVSGTPRALSSLCAT CRK in isoform 2.

VSP_035500

Alternative sequence

448 – 532

85

Missing in isoform 2.

VSP_035501

Experimental info

Mutagenesis

188

1

Y → F: Abolishes Ras activity increase and ERK1/2 phosphorylation. Ref.22

Mutagenesis

239

1

R → L: Abolishes phosphoinositide binding. Ref.14

Mutagenesis

259

1

Y → F: Global loss of tyrosine phosphorylation. Abolishes interaction with FHL2 and HAX1. Ref.21 Ref.23

Mutagenesis

260

1

Y → F: Global loss of tyrosine phosphorylation. Abolishes interaction with FHL2 and HAX1. Ref.21 Ref.23

Mutagenesis

284

1

Y → F: Global loss of tyrosine phosphorylation. Abolishes interaction with FHL2 and HAX1. Ref.21 Ref.23

Mutagenesis

338

1

Y → F: Abolishes Ras activity increase and ERK1/2 phosphorylation. Ref.22

Mutagenesis

458

1

R → L: Impairs phosphotyrosine binding by SH2 domain.

Mutagenesis

480

1

Y → F: Global loss of tyrosine phosphorylation. Abolishes interaction with FHL2 and HAX1. Ref.21 Ref.23

Mutagenesis

492

1

Y → F: Global loss of tyrosine phosphorylation. Abolishes interaction with FHL2 and HAX1. Ref.21 Ref.23

Mutagenesis

511

1

F → R: Abolishes dimerization. Abolishes activation of HRAS. Ref.18

Sequence conflict

18

1

C → W in BAA07827. Ref.1

Sequence conflict

18

1

C → W in BAA29059. Ref.2

Sequence conflict

18

1

C → W in BAA29060. Ref.2

Sequence conflict

18

1

C → W in AAG25938. Ref.3

Sequence conflict

118

1

V → A in BAG36998. Ref.5

Sequence conflict

120

1

A → T in BAG54211. Ref.5

Sequence conflict

147

1

E → G in BAG51372. Ref.5

Sequence conflict

164

1

V → L in BAG36998. Ref.5

Sequence conflict

510

1

E → D in BAG36998. Ref.5

Isoform 3:

Sequence conflict

20

1

C → R in BAG54211. Ref.5

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

Helix

421 – 424

4

Helix

425 – 428

4

Helix

429 – 431

3

Beta strand

432 – 436

5

Helix

438 – 447

10

Beta strand

454 – 459

6

Beta strand

461 – 463

3

Beta strand

467 – 473

7

Beta strand

476 – 489

14

Beta strand

491 – 496

6

Beta strand

502 – 504

3

Helix

505 – 512

8

Beta strand

513 – 515

3

Beta strand

519 – 521

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: 2406BFDCBEBB1E49	FASTA	447	49,423
	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 VSGTPRALSS LCATCRK
	Isoform 3 [UniParc]. Checksum: 90E4D15BCBF428A1	FASTA	555	62,064
	10 20 30 40 50 60 MGKWRPGQGH TTGSVKPLSC SDAMELDLSP PHLSSSPEDL CPAPGTPPGT PRPPDTPLPE 70 80 90 100 110 120 EVKRSQPLLI PTTGRKLREE ERRATSLPSI PNPFPELCSP PSQSPILGGP SSARGLLPRD 130 140 150 160 170 180 ASRPHVVKVY SEDGACRSVE VAAGATARHV CEMLVQRAHA LSDETWGLVE CHPHLALERG 190 200 210 220 230 240 LEDHESVVEV QAAWPVGGDS RFVFRKNFAK YELFKSSPHS LFPEKMVSSC LDAHTGISHE 250 260 270 280 290 300 DLIQNFLNAG SFPEIQGFLQ LRGSGRKLWK RFFCFLRRSG LYYSTKGTSK DPRHLQYVAD 310 320 330 340 350 360 VNESNVYVVT QGRKLYGMPT DFGFCVKPNK LRNGHKGLRI FCSEDEQSRT CWLAAFRLFK 370 380 390 400 410 420 YGVQLYKNYQ QAQSRHLHPS CLGSPPLRSA SDNTLVAMDF SGHAGRVIEN PREALSVALE 430 440 450 460 470 480 EAQAWRKKTN HRLSLPMPAS GTSLSAAIHR TQLWFHGRIS REESQRLIGQ QGLVDGLFLV 490 500 510 520 530 540 RESQRNPQGF VLSLCHLQKV KHYLILPSEE EGRLYFSMDD GQTRFTDLLQ LVEFHQLNRG 550 ILPCLLRHCC TRVAL
	Isoform 4 [UniParc]. Checksum: E18D088B19E632C6	FASTA	498	55,920
	10 20 30 40 50 60 MELDLSPPHL SSSPEDLCPA PGTPPGTPRP PDTPLPEEVK RSQPLLIPIL GGPSSARGLL 70 80 90 100 110 120 PRDASRPHVV KVYSEDGACR SVEVAAGATA RHVCEMLVQR AHALSDETWG LVECHPHLAL 130 140 150 160 170 180 ERGLEDHESV VEVQAAWPVG GDSRFVFRKN FAKYELFKSS PHSLFPEKMV SSCLDAHTGI 190 200 210 220 230 240 SHEDLIQNFL NAGSFPEIQG FLQLRGSGRK LWKRFFCFLR RSGLYYSTKG TSKDPRHLQY 250 260 270 280 290 300 VADVNESNVY VVTQGRKLYG MPTDFGFCVK PNKLRNGHKG LRIFCSEDEQ SRTCWLAAFR 310 320 330 340 350 360 LFKYGVQLYK NYQQAQSRHL HPSCLGSPPL RSASDNTLVA MDFSGHAGRV IENPREALSV 370 380 390 400 410 420 ALEEAQAWRK KTNHRLSLPM PASGTSLSAA IHRTQLWFHG RISREESQRL IGQQGLVDGL 430 440 450 460 470 480 FLVRESQRNP QGFVLSLCHL QKVKHYLILP SEEEGRLYFS MDDGQTRFTD LLQLVEFHQL 490 NRGILPCLLR HCCTRVAL

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Esophageal 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[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]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). Tissue: Ovary, Prostate and Thalamus.
[6]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] (ISOFORM 1). Tissue: Lung.
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 130-343.
[10]	"Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3." Fiddes R.J., Campbell D.H., Janes P.W., Sivertsen S.P., Sasaki H., Wallasch C., Daly R.J. J. Biol. Chem. 273:7717-7724(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ERBB3 AND ERBB4, SERINE AND THREONINE PHOSPHORYLATION.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RND1.
[12]	"Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration." Han D.C., Shen T.L., Guan J.L. J. Biol. Chem. 275:28911-28917(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[13]	"Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2." Kasus-Jacobi A., Bereziat V., Perdereau D., Girard J., Burnol A.F. Oncogene 19:2052-2059(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INSR.
[14]	"Association of Grb7 with phosphoinositides and its role in the regulation of cell migration." Shen T.L., Han D.C., Guan J.L. J. Biol. Chem. 277:29069-29077(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PTK2/FAK1, MUTAGENESIS OF ARG-239, DOMAIN.
[15]	"EphB1 associates with Grb7 and regulates cell migration." Han D.C., Shen T.L., Miao H., Wang B., Guan J.L. J. Biol. Chem. 277:45655-45661(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH EPHB1.
[16]	"Signal transduction via the stem cell factor receptor/c-Kit." Ronnstrand L. Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
[17]	"Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor." Roskoski R. Jr. Biochem. Biophys. Res. Commun. 337:1-13(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[18]	"Grb7-SH2 domain dimerisation is affected by a single point mutation." Porter C.J., Wilce M.C., Mackay J.P., Leedman P., Wilce J.A. Eur. Biophys. J. 34:454-460(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF PHE-511.
[19]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Tyrosine phosphorylation of growth factor receptor-bound protein-7 by focal adhesion kinase in the regulation of cell migration, proliferation, and tumorigenesis." Chu P.Y., Huang L.Y., Hsu C.H., Liang C.C., Guan J.L., Hung T.H., Shen T.L. J. Biol. Chem. 284:20215-20226(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-188 AND TYR-338, INTERACTION WITH PTK2/FAK1.
[21]	"The cell migration protein Grb7 associates with transcriptional regulator FHL2 in a Grb7 phosphorylation-dependent manner." Siamakpour-Reihani S., Argiros H.J., Wilmeth L.J., Haas L.L., Peterson T.A., Johnson D.L., Shuster C.B., Lyons B.A. J. Mol. Recognit. 22:9-17(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FHL2, NMR, MUTAGENESIS OF TYR-259; TYR-260; TYR-284; TYR-480 AND TYR-492, SUBCELLULAR LOCATION, TYROSINE PHOSPHORYLATION.
[22]	"EGF-induced Grb7 recruits and promotes Ras activity essential for the tumorigenicity of Sk-Br3 breast cancer cells." Chu P.Y., Li T.K., Ding S.T., Lai I.R., Shen T.L. J. Biol. Chem. 285:29279-29285(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, PHOSPHORYLATION AT TYR-188 AND TYR-338, MUTAGENESIS OF TYR-188 AND TYR-338.
[23]	"Grb7 binds to Hax-1 and undergoes an intramolecular domain association that offers a model for Grb7 regulation." Siamakpour-Reihani S., Peterson T.A., Bradford A.M., Argiros H.J., Haas L.L., Lor S.N., Haulsee Z.M., Spuches A.M., Johnson D.L., Rohrschneider L.R., Shuster C.B., Lyons B.A. J. Mol. Recognit. 24:314-321(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HAX1, MUTAGENESIS OF TYR-259; TYR-260; TYR-284; TYR-480 AND TYR-492, CIRCULAR DICHROISM, TYROSINE PHOSPHORYLATION.
[24]	"Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2." Ivancic M., Daly R.J., Lyons B.A. J. Biomol. NMR 27:205-219(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 415-532 IN COMPLEX WITH ERBB2, INTERACTION WITH ERBB2.
[25]	"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.
[26]	"Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation." Porter C.J., Matthews J.M., Mackay J.P., Pursglove S.E., Schmidberger J.W., Leedman P.J., Pero S.C., Krag D.N., Wilce M.C., Wilce J.A. BMC Struct. Biol. 7:58-58(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 415-532, INTERACTION WITH THE SYNTHETIC INHIBITOR G7-18NATE, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D43772 mRNA. Translation: BAA07827.1.
AB008789 mRNA. Translation: BAA29059.1.
AB008790 mRNA. Translation: BAA29060.1.
AF274875 Genomic DNA. Translation: AAG25938.1.
BT006686 mRNA. Translation: AAP35332.1.
AK222849 mRNA. Translation: BAD96569.1.
AK222870 mRNA. Translation: BAD96590.1.
AK290115 mRNA. Translation: BAF82804.1.
AK314368 mRNA. Translation: BAG36998.1.
AK027729 mRNA. Translation: BAG51372.1.
AK125544 mRNA. Translation: BAG54211.1.
AC079199 Genomic DNA. No translation available.
CH471152 Genomic DNA. Translation: EAW60600.1.
CH471152 Genomic DNA. Translation: EAW60601.1.
BC006535 mRNA. Translation: AAH06535.1.
D87513 mRNA. Translation: BAA13412.1.

IPI

IPI00293948.
IPI00448767.
IPI00902705.
IPI00939546.

PIR

JC5412.

RefSeq

NP_001025173.1. NM_001030002.2.
NP_001229371.1. NM_001242442.1.
NP_001229372.1. NM_001242443.1.
NP_005301.2. NM_005310.3.

UniGene

Hs.86859.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MW4	NMR	-	A	415-532	[»]
1WGR	NMR	-	A	100-186	[»]
2L4K	NMR	-	A	415-532	[»]
2QMS	X-ray	2.10	A/B/C/D	415-532	[»]
3PQZ	X-ray	2.41	A/B/C/D	416-532	[»]

ProteinModelPortal

Q14451.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-502N.

IntAct

Q14451. 9 interactions.

MINT

MINT-1492212.

STRING

9606.ENSP00000310771.

PTM databases

PhosphoSite

Q14451.

Polymorphism databases

DMDM

116242503.

Proteomic databases

PaxDb

Q14451.

PRIDE

Q14451.

Protocols and materials databases

DNASU

2886.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309156; ENSP00000310771; ENSG00000141738.
ENST00000309185; ENSP00000311752; ENSG00000141738.
ENST00000394204; ENSP00000377754; ENSG00000141738.
ENST00000394209; ENSP00000377759; ENSG00000141738.
ENST00000394211; ENSP00000377761; ENSG00000141738.
ENST00000445327; ENSP00000403459; ENSG00000141738.

GeneID

2886.

KEGG

hsa:2886.

UCSC

uc002hsr.3. human.
uc002hst.3. human.
uc021twu.1. human.

Organism-specific databases

CTD

2886.

GeneCards

GC17P037894.

HGNC

HGNC:4567. GRB7.

HPA

CAB005226.

MIM

601522. gene.

neXtProt

NX_Q14451.

PharmGKB

PA28963.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG307156.

HOVERGEN

HBG000468.

InParanoid

Q14451.

OMA

QRNPQGF.

OrthoDB

EOG4C2H97.

PhylomeDB

Q14451.

Enzyme and pathway databases

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
ephbfwdpathway. EPHB forward signaling.
pdgfrbpathway. PDGFR-beta signaling pathway.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

Bgee

Q14451.

CleanEx

HS_GRB7.

Genevestigator

Q14451.

GermOnline

ENSG00000141738. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.
3.30.505.10. 1 hit.

InterPro

IPR015042. BPS-dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000159. Ras-assoc.
IPR000980. SH2.
[Graphical view]

Pfam

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

PRINTS

PR00401. SH2DOMAIN.

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

BindingDB

Q14451.

ChEMBL

CHEMBL1649051.

EvolutionaryTrace

Q14451.

GenomeRNAi

2886.

NextBio

11395.

SOURCE

Search...

Entry information

Entry name

GRB7_HUMAN

Accession

Primary (citable) accession number: Q14451
Secondary accession number(s): B2RAV1 , B3KNL0, B3KWP9, B7WP75, J3KQM4, Q53YD3, Q92568, Q96DF9, Q9Y220

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.