Reviewed, UniProtKB/Swiss-Prot Q13480 (GAB1_HUMAN)

Names and origin

Protein names

Recommended name:
    GRB2-associated-binding protein 1
Alternative name(s):
    Growth factor receptor bound protein 2-associated protein 1
    GRB2-associated binder 1

Gene names

Name:

GAB1

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

General annotation (Comments)

Function	Probably involved in EGF and insulin receptor signaling.
Subunit structure	Interacts with GRB2 and with other SH2-containing proteins. Interacts with phosphorylated LAT2.
Post-translational modification	Phosphorylated on tyrosine residue(s) by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Tyrosine phosphorylation of GAB1 mediates interaction with several proteins that contain SH2 domains.
Sequence similarities	Belongs to the GAB family. Contains 1 PH domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell proliferation Ref.1 Traceable author statement. Source: ProtInc epidermal growth factor receptor signaling pathway Ref.1 Traceable author statement. Source: ProtInc insulin receptor signaling pathway Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	SH3/SH2 adaptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PTPN11	Q06124	1	EBI-517684,EBI-297779

Alternative products

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

Isoform 1 (identifier: Q13480-1)

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: Q13480-2)

The sequence of this isoform differs from the canonical sequence as follows:
     528-528: K → KGQSPKILRLKPHGLERTDSQTIGDFATRRK

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 694	694	GRB2-associated-binding protein 1		PRO_0000050282
Regions
	Domain	5 – 116	112	PH
	Compositional bias	449 – 540	92	Pro-rich
Amino acid modifications
	Modified residue	259	1	Phosphotyrosine
	Modified residue	266	1	Phosphoserine
	Modified residue	406	1	Phosphotyrosine
	Modified residue	503	1	Phosphothreonine By similarity
	Modified residue	627	1	Phosphotyrosine
	Modified residue	659	1	Phosphotyrosine
Natural variations
	Alternative sequence	528	1	K → KGQSPKILRLKPHGLERTDS QTIGDFATRRK in isoform 2.		VSP_017137
	Natural variant	83	1	Y → C in a breast cancer sample; somatic mutation.		VAR_036132
	Natural variant	311	1	P → L: dbSNP rs28925904.		VAR_025261
	Natural variant	387	1	T → N in a breast cancer sample; somatic mutation.		VAR_036133
Experimental info
	Sequence conflict	204	1	A → G in AAC50380. Ref.1
	Sequence conflict	213	1	C → S in AAC50380. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 7, 2006. Version 2. Checksum: E0FAC78772B6677B	FASTA	694	76,616
	10 20 30 40 50 60 MSGGEVVCSG WLRKSPPEKK LKRYAWKRRW FVLRSGRLTG DPDVLEYYKN DHAKKPIRII 70 80 90 100 110 120 DLNLCQQVDA GLTFNKKEFE NSYIFDINTI DRIFYLVADS EEEMNKWVRC ICDICGFNPT 130 140 150 160 170 180 EEDPVKPPGS SLQAPADLPL AINTAPPSTQ ADSSSATLPP PYQLINVPPH LETLGIQEDP 190 200 210 220 230 240 QDYLLLINCQ SKKPEPTRTH ADSAKSTSSE TDCNDNVPSH KNPASSQSKH GMNGFFQQQM 250 260 270 280 290 300 IYDSPPSRAP SASVDSSLYN LPRSYSHDVL PKVSPSSTEA DGELYVFNTP SGTSSVETQM 310 320 330 340 350 360 RHVSISYDIP PTPGNTYQIP RTFPEGTLGQ TSKLDTIPDI PPPRPPKPHP AHDRSPVETC 370 380 390 400 410 420 SIPRTASDTD SSYCIPTAGM SPSRSNTIST VDLNKLRKDA SSQDCYDIPR AFPSDRSSSL 430 440 450 460 470 480 EGFHNHFKVK NVLTVGSVSS EELDENYVPM NPNSPPRQHS SSFTEPIQEA NYVPMTPGTF 490 500 510 520 530 540 DFSSFGMQVP PPAHMGFRSS PKTPPRRPVP VADCEPPPVD RNLKPDRKVK PAPLEIKPLP 550 560 570 580 590 600 EWEELQAPVR SPITRSFARD SSRFPMSPRP DSVHSTTSSS DSHDSEENYV PMNPNLSSED 610 620 630 640 650 660 PNLFGSNSLD GGSSPMIKPK GDKQVEYLDL DLDSGKSTPP RKQKSSGSGS SVADERVDYV 670 680 690 VVDQQKTLAL KSTREAWTDG RQSTESETPA KSVK
	Isoform 2 [UniParc]. Checksum: EAA4573B9E5A25B9		724	80,005
	10 20 30 40 50 60 MSGGEVVCSG WLRKSPPEKK LKRYAWKRRW FVLRSGRLTG DPDVLEYYKN DHAKKPIRII 70 80 90 100 110 120 DLNLCQQVDA GLTFNKKEFE NSYIFDINTI DRIFYLVADS EEEMNKWVRC ICDICGFNPT 130 140 150 160 170 180 EEDPVKPPGS SLQAPADLPL AINTAPPSTQ ADSSSATLPP PYQLINVPPH LETLGIQEDP 190 200 210 220 230 240 QDYLLLINCQ SKKPEPTRTH ADSAKSTSSE TDCNDNVPSH KNPASSQSKH GMNGFFQQQM 250 260 270 280 290 300 IYDSPPSRAP SASVDSSLYN LPRSYSHDVL PKVSPSSTEA DGELYVFNTP SGTSSVETQM 310 320 330 340 350 360 RHVSISYDIP PTPGNTYQIP RTFPEGTLGQ TSKLDTIPDI PPPRPPKPHP AHDRSPVETC 370 380 390 400 410 420 SIPRTASDTD SSYCIPTAGM SPSRSNTIST VDLNKLRKDA SSQDCYDIPR AFPSDRSSSL 430 440 450 460 470 480 EGFHNHFKVK NVLTVGSVSS EELDENYVPM NPNSPPRQHS SSFTEPIQEA NYVPMTPGTF 490 500 510 520 530 540 DFSSFGMQVP PPAHMGFRSS PKTPPRRPVP VADCEPPPVD RNLKPDRKGQ SPKILRLKPH 550 560 570 580 590 600 GLERTDSQTI GDFATRRKVK PAPLEIKPLP EWEELQAPVR SPITRSFARD SSRFPMSPRP 610 620 630 640 650 660 DSVHSTTSSS DSHDSEENYV PMNPNLSSED PNLFGSNSLD GGSSPMIKPK GDKQVEYLDL 670 680 690 700 710 720 DLDSGKSTPP RKQKSSGSGS SVADERVDYV VVDQQKTLAL KSTREAWTDG RQSTESETPA KSVK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A Grb2-associated docking protein in EGF- and insulin-receptor signalling." Holgado-Madruga M., Emlet D.R., Moscatello D.K., Godwin A.K., Wong A.J. Nature 379:560-564(1996) [PubMed: 8596638] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-311.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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] (ISOFORM 2). Tissue: Testis.
[5]	"Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling." Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O., Spicka J., Hilgert I., Luskova P., Draber P., Novak P., Engels N., Wienands J., Simeoni L., Oesterreicher J., Aguado E., Malissen M., Schraven B., Horejsi V. J. Exp. Med. 196:1617-1626(2002) [PubMed: 12486104] [Abstract] Cited for: INTERACTION WITH LAT2.
[6]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed: 12522270] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-259 AND SER-266, MASS SPECTROMETRY.
[7]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-406; TYR-627 AND TYR-659, MASS SPECTROMETRY.
[8]	"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 TYR-659, MASS SPECTROMETRY.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-83 AND ASN-387.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U43885 mRNA. Translation: AAC50380.1. DQ021880 Genomic DNA. Translation: AAY26398.1. AC097658 Genomic DNA. No translation available. AC104685 Genomic DNA. Translation: AAY40964.1. BC064848 mRNA. Translation: AAH64848.1.
PIR	S68442.
RefSeq	NP_002030.2. NP_997006.1.
UniGene	Hs.618456 Hs.80720
3D structure databases
HSSP	HSSP built from PDB template 1EAZ based on UniProtKB Q9HB21.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13480.
PTM databases
PhosphoSite	Q13480.
Polymorphism databases
NIEHS-SNPs	Search...
Genome annotation databases
Ensembl	ENSG00000109458. Homo sapiens. [Contig view]
GeneID	2549.
KEGG	hsa:2549.
Organism-specific databases
H-InvDB	HIX0004530.
HGNC	HGNC:4066. GAB1.
HPA	CAB002605.
MIM	604439. gene.
PharmGKB	PA28477.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q13480.
Gene expression databases
ArrayExpress	Q13480.
CleanEx	HS_GAB1.
GermOnline	ENSG00000109458. Homo sapiens.
Family and domain databases
InterPro	IPR001849. PH. IPR011993. PH_type. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
Pfam	PF00169. PH. 1 hit. [Graphical view]
SMART	SM00233. PH. 1 hit. [Graphical view]
PROSITE	PS50003. PH_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	10055.
SOURCE	Search...

Entry information

Entry name

GAB1_HUMAN

Accession

Primary (citable) accession number: Q13480
Secondary accession number(s): Q4W5G2, Q6P1W2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	February 7, 2006
Last modified:	November 25, 2008
This is version 66 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)