Q13322 (GRB10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth factor receptor-bound protein 10

Alternative name(s):
GRB10 adapter protein
Insulin receptor-binding protein Grb-IR

Gene names

Name:	GRB10
Synonyms:	GRBIR, KIAA0207

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	594 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. May play a role in mediating insulin-stimulated ubiquitination of INSR, leading to proteasomal degradation. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2. Ref.17 Ref.19 Ref.21 Ref.22
Enzyme regulation	Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling. Ref.28
Subunit structure	Interacts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain By similarity. Poorly binds to the EGFR By similarity. Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex. Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15 By similarity. When unphosphorylated, interacts with AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus interfering with the binding of AXIN1 to LRP6 By similarity. Binds to activated NRAS. Ref.17 Ref.18 Ref.19 Ref.20 Ref.30
Subcellular location	Cytoplasm By similarity. Note: When complexed with NEDD4 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment By similarity.
Tissue specificity	Widely expressed in fetal and adult tissues, including fetal and postnatal liver, lung, kidney, skeletal muscle, heart, spleen, skin and brain. Ref.16
Domain	The PH domain binds relatively non-specifically to several phosphoinositides, including PI5P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities.
Post-translational modification	Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation By similarity. Phosphorylated at Tyr-67 by TEC. Ref.6 Ref.15 Ref.20 Ref.28
Miscellaneous	The GRB10 locus is imprinted. During embryonic development, the expression in the brain and spinal cord is from the paternal allele, while in placental villous trophoblasts and skeletal muscle, it is from the maternal one. Expression is biallelic in most other tissues. Paternal expression in the brain is maintained throughout adulthood. Imprinting often is isoform-specific. GRB10 is unlikely to be responsible for Silver-Russell syndrome (SRS).
Sequence similarities	Belongs to the GRB7/10/14 family. Contains 1 PH domain. Contains 1 Ras-associating domain. Contains 1 SH2 domain.
Sequence caution	The sequence BAA13198.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL insulin-like growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of Wnt receptor signaling pathway Inferred from direct assay Ref.22. Source: UniProtKB negative regulation of glucose import Inferred from sequence or structural similarity PubMed 15664450. Source: BHF-UCL negative regulation of glycogen biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of insulin receptor signaling pathway Inferred from sequence or structural similarity PubMed 15664450. Source: BHF-UCL negative regulation of phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of vascular endothelial growth factor receptor signaling pathway Inferred from direct assay Ref.19. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Traceable author statement Ref.3. Source: ProtInc
Molecular_function	SH3/SH2 adaptor activity Traceable author statement Ref.3. Source: ProtInc insulin receptor binding Inferred from sequence or structural similarity PubMed 15664450. Source: BHF-UCL phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EPHB1	P54762	2	EBI-80275,EBI-80252

Alternative products

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

Note: Additional isoforms seem to exist, many of which involve splicing of 5' non-coding exons.

Isoform 3 (identifier: Q13322-1)

Also known as: Zeta;

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 1 (identifier: Q13322-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     283-328: Missing.

Isoform 2 (identifier: Q13322-3)

Also known as: Gamma; Beta; SV-1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.

Isoform 4 (identifier: Q13322-4)

Also known as: Epsilon;

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MALAGCPDSFLHHPYYQ → MQAAGPLFRSK

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 594

594

Growth factor receptor-bound protein 10

PRO_0000150346

Regions

Domain

166 – 250

85

Ras-associating

Domain

290 – 399

110

PH

Domain

493 – 574

82

SH2

Amino acid modifications

Modified residue

67

1

Phosphotyrosine; by TEC Ref.6

Modified residue

104

1

Phosphoserine Ref.24

Modified residue

150

1

Phosphoserine; by MTOR, MAPK1 and MAPK3 Ref.15 Ref.28

Modified residue

418

1

Phosphoserine; by MAPK1 and MAPK3; in vitro Ref.15 Ref.23 Ref.24

Modified residue

428

1

Phosphoserine; by MTOR and PKB/AKT1 Ref.20 Ref.28

Modified residue

431

1

Phosphoserine By similarity

Modified residue

476

1

Phosphoserine; by MTOR, MAPK1 and MAPK3 Ref.15 Ref.28

Natural variations

Alternative sequence

1 – 58

58

Missing in isoform 2.

VSP_001842

Alternative sequence

1 – 17

17

MALAG…HPYYQ → MQAAGPLFRSK in isoform 4.

VSP_038784

Alternative sequence

283 – 328

46

Missing in isoform 1.

VSP_001843

Natural variant

36

1

P → L.
Corresponds to variant rs35647889 [ dbSNP | Ensembl ].

VAR_053112

Natural variant

95

1

P → S. Ref.32
Corresponds to variant rs80244589 [ dbSNP | Ensembl ].

VAR_062864

Natural variant

558

1

D → H.
Corresponds to variant rs11768472 [ dbSNP | Ensembl ].

VAR_053113

Experimental info

Mutagenesis

104

1

S → G: No effect on phosphorylation. Ref.15

Mutagenesis

134

1

S → A: No effect on YWHAE-binding. Ref.20

Mutagenesis

136

1

P → A: No effect on NEDD4-binding; when associated with A-139 and A-141. Ref.19

Mutagenesis

139

1

P → A: No effect on NEDD4-binding; when associated with A-136 and A-141. Ref.19

Mutagenesis

141

1

P → S: No effect on NEDD4-binding; when associated with A-136 and A-139. Ref.19

Mutagenesis

150

1

S → I: Loss of phosphorylation. Ref.15

Mutagenesis

300

1

K → A: 2-fold loss of inositide-binding. Ref.30

Mutagenesis

305

1

K → A: 5-fold loss of inositide-binding. Ref.30

Mutagenesis

308

1

K → A: 5-fold loss of inositide-binding. Ref.30

Mutagenesis

355

1

N → G: 5-fold loss of inositide-binding. Ref.30

Mutagenesis

418

1

S → A: No net loss of phosphorylation, this may be due to a compensatory phosphorylation of T-422 in vitro. Ref.15

Mutagenesis

428

1

S → A: Impairs YWHAE-binding. Ref.20

Mutagenesis

476

1

S → A: Loss of phosphorylation. Ref.15

Mutagenesis

520

1

R → K: No effect on NEDD4-binding. No effect on the disruption of the interaction between INSR and IRS1 and IRS2. Ref.17 Ref.19

Sequence conflict

152

1

P → A in BAA13198. Ref.9

Sequence conflict

400

1

G → E in AAB08431. Ref.3

Sequence conflict

428

1

S → F in BAF82200. Ref.10

Sequence conflict

498

1

I → F in AAB08431. Ref.3

Sequence conflict

541

1

N → I in AAC50671. Ref.2

Secondary structure

1

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594

Helix Strand Turn

Details...

Beta strand

168 – 174

7

Beta strand

179 – 184

6

Helix

190 – 198

9

Beta strand

209 – 215

7

Turn

216 – 219

4

Beta strand

220 – 223

4

Helix

230 – 235

6

Beta strand

242 – 247

6

Turn

249 – 252

4

Helix

253 – 256

4

Helix

258 – 260

3

Beta strand

266 – 269

4

Helix

281 – 285

5

Beta strand

291 – 300

10

Beta strand

307 – 315

9

Beta strand

318 – 324

7

Helix

330 – 332

3

Beta strand

333 – 337

5

Beta strand

342 – 349

8

Helix

351 – 354

4

Beta strand

357 – 366

10

Beta strand

377 – 383

7

Helix

384 – 399

16

Helix

401 – 407

7

Helix

500 – 509

10

Beta strand

516 – 521

6

Beta strand

529 – 535

7

Beta strand

538 – 546

9

Beta strand

555 – 558

4

Beta strand

564 – 566

3

Helix

567 – 574

8

Beta strand

581 – 583

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 (Zeta) [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 53A5F885E17C6C6B	FASTA	594	67,231
	10 20 30 40 50 60 MALAGCPDSF LHHPYYQDKV EQTPRSQQDP AGPGLPAQSD RLANHQEDDV DLEALVNDMN 70 80 90 100 110 120 ASLESLYSAC SMQSDTVPLL QNGQHARSQP RASGPPRSIQ PQVSPRQRVQ RSQPVHILAV 130 140 150 160 170 180 RRLQEEDQQF RTSSLPAIPN PFPELCGPGS PPVLTPGSLP PSQAAAKQDV KVFSEDGTSK 190 200 210 220 230 240 VVEILADMTA RDLCQLLVYK SHCVDDNSWT LVEHHPHLGL ERCLEDHELV VQVESTMASE 250 260 270 280 290 300 SKFLFRKNYA KYEFFKNPMN FFPEQMVTWC QQSNGSQTQL LQNFLNSSSC PEIQGFLHVK 310 320 330 340 350 360 ELGKKSWKKL YVCLRRSGLY CSTKGTSKEP RHLQLLADLE DSNIFSLIAG RKQYNAPTDH 370 380 390 400 410 420 GLCIKPNKVR NETKELRLLC AEDEQTRTCW MTAFRLLKYG MLLYQNYRIP QQRKALLSPF 430 440 450 460 470 480 STPVRSVSEN SLVAMDFSGQ TGRVIENPAE AQSAALEEGH AWRKRSTRMN ILGSQSPLHP 490 500 510 520 530 540 STLSTVIHRT QHWFHGRISR EESHRIIKQQ GLVDGLFLLR DSQSNPKAFV LTLCHHQKIK 550 560 570 580 590 NFQILPCEDD GQTFFSLDDG NTKFSDLIQL VDFYQLNKGV LPCKLKHHCI RVAL
	Isoform 1 (Beta) [UniParc]. Checksum: FCAA0792DBEB8AC3	FASTA	548	62,026
	10 20 30 40 50 60 MALAGCPDSF LHHPYYQDKV EQTPRSQQDP AGPGLPAQSD RLANHQEDDV DLEALVNDMN 70 80 90 100 110 120 ASLESLYSAC SMQSDTVPLL QNGQHARSQP RASGPPRSIQ PQVSPRQRVQ RSQPVHILAV 130 140 150 160 170 180 RRLQEEDQQF RTSSLPAIPN PFPELCGPGS PPVLTPGSLP PSQAAAKQDV KVFSEDGTSK 190 200 210 220 230 240 VVEILADMTA RDLCQLLVYK SHCVDDNSWT LVEHHPHLGL ERCLEDHELV VQVESTMASE 250 260 270 280 290 300 SKFLFRKNYA KYEFFKNPMN FFPEQMVTWC QQSNGSQTQL LQEPRHLQLL ADLEDSNIFS 310 320 330 340 350 360 LIAGRKQYNA PTDHGLCIKP NKVRNETKEL RLLCAEDEQT RTCWMTAFRL LKYGMLLYQN 370 380 390 400 410 420 YRIPQQRKAL LSPFSTPVRS VSENSLVAMD FSGQTGRVIE NPAEAQSAAL EEGHAWRKRS 430 440 450 460 470 480 TRMNILGSQS PLHPSTLSTV IHRTQHWFHG RISREESHRI IKQQGLVDGL FLLRDSQSNP 490 500 510 520 530 540 KAFVLTLCHH QKIKNFQILP CEDDGQTFFS LDDGNTKFSD LIQLVDFYQL NKGVLPCKLK HHCIRVAL
	Isoform 2 (Gamma) (Beta) (SV-1) [UniParc]. Checksum: 626377A169AE6530	FASTA	536	60,848
	10 20 30 40 50 60 MNASLESLYS ACSMQSDTVP LLQNGQHARS QPRASGPPRS IQPQVSPRQR VQRSQPVHIL 70 80 90 100 110 120 AVRRLQEEDQ QFRTSSLPAI PNPFPELCGP GSPPVLTPGS LPPSQAAAKQ DVKVFSEDGT 130 140 150 160 170 180 SKVVEILADM TARDLCQLLV YKSHCVDDNS WTLVEHHPHL GLERCLEDHE LVVQVESTMA 190 200 210 220 230 240 SESKFLFRKN YAKYEFFKNP MNFFPEQMVT WCQQSNGSQT QLLQNFLNSS SCPEIQGFLH 250 260 270 280 290 300 VKELGKKSWK KLYVCLRRSG LYCSTKGTSK EPRHLQLLAD LEDSNIFSLI AGRKQYNAPT 310 320 330 340 350 360 DHGLCIKPNK VRNETKELRL LCAEDEQTRT CWMTAFRLLK YGMLLYQNYR IPQQRKALLS 370 380 390 400 410 420 PFSTPVRSVS ENSLVAMDFS GQTGRVIENP AEAQSAALEE GHAWRKRSTR MNILGSQSPL 430 440 450 460 470 480 HPSTLSTVIH RTQHWFHGRI SREESHRIIK QQGLVDGLFL LRDSQSNPKA FVLTLCHHQK 490 500 510 520 530 IKNFQILPCE DDGQTFFSLD DGNTKFSDLI QLVDFYQLNK GVLPCKLKHH CIRVAL
	Isoform 4 (Epsilon) [UniParc]. Checksum: B5EE8FA86A240D21	FASTA	588	66,487
	10 20 30 40 50 60 MQAAGPLFRS KDKVEQTPRS QQDPAGPGLP AQSDRLANHQ EDDVDLEALV NDMNASLESL 70 80 90 100 110 120 YSACSMQSDT VPLLQNGQHA RSQPRASGPP RSIQPQVSPR QRVQRSQPVH ILAVRRLQEE 130 140 150 160 170 180 DQQFRTSSLP AIPNPFPELC GPGSPPVLTP GSLPPSQAAA KQDVKVFSED GTSKVVEILA 190 200 210 220 230 240 DMTARDLCQL LVYKSHCVDD NSWTLVEHHP HLGLERCLED HELVVQVEST MASESKFLFR 250 260 270 280 290 300 KNYAKYEFFK NPMNFFPEQM VTWCQQSNGS QTQLLQNFLN SSSCPEIQGF LHVKELGKKS 310 320 330 340 350 360 WKKLYVCLRR SGLYCSTKGT SKEPRHLQLL ADLEDSNIFS LIAGRKQYNA PTDHGLCIKP 370 380 390 400 410 420 NKVRNETKEL RLLCAEDEQT RTCWMTAFRL LKYGMLLYQN YRIPQQRKAL LSPFSTPVRS 430 440 450 460 470 480 VSENSLVAMD FSGQTGRVIE NPAEAQSAAL EEGHAWRKRS TRMNILGSQS PLHPSTLSTV 490 500 510 520 530 540 IHRTQHWFHG RISREESHRI IKQQGLVDGL FLLRDSQSNP KAFVLTLCHH QKIKNFQILP 550 560 570 580 CEDDGQTFFS LDDGNTKFSD LIQLVDFYQL NKGVLPCKLK HHCIRVAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function." Liu F., Roth R.A. Proc. Natl. Acad. Sci. U.S.A. 92:10287-10291(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Skeletal muscle.
[2]	"Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling." O'Neill T.J., Rose D.W., Pillay T.S., Hotta K., Olefsky J.M., Gustafson T.A. J. Biol. Chem. 271:22506-22513(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Skeletal muscle.
[3]	"Human GRB-IR-beta/GRB10: splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains." Frantz J.D., Giorgetti-Peraldi S., Ottinger E.A., Shoelson S.E. J. Biol. Chem. 272:2659-2667(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Cerebellum and Skeletal muscle.
[4]	"Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma." Dong L.Q., Du H., Porter S.G., Kolakowski L.F. Jr., Lee A.V., Mandarino L.J., Fan J., Yee D., Liu F. J. Biol. Chem. 272:29104-29112(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]	"Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases." Nantel A., Mohammad-Ali K., Sherk J., Posner B.I., Thomas D.Y. J. Biol. Chem. 273:10475-10484(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Brain.
[6]	"Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase." Mano H., Ohya K., Miyazato A., Yamashita Y., Ogawa W., Inazawa J., Ikeda U., Shimada K., Hatake K., Kasuga M., Ozawa K., Kajigaya S. Genes Cells 3:431-441(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION AT TYR-67.
[7]	"Genomic structure of the gene for the SH2 and pleckstrin homology domain-containing protein GRB10 and evaluation of its role in Hirschsprung disease." Angrist M., Bolk S., Bentley K., Nallasamy S., Halushka M.K., Chakravarti A. Oncogene 17:3065-3070(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 3).
[8]	"Human GRB10 is imprinted and expressed from the paternal and maternal allele in a highly tissue- and isoform-specific fashion." Blagitko N., Mergenthaler S., Schulz U., Wollmann H.A., Craigen W., Eggermann T., Ropers H.-H., Kalscheuer V.M. Hum. Mol. Genet. 9:1587-1595(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING, IMPRINTING. Tissue: Testis.
[9]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Bone marrow.
[10]	"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] (ISOFORM 2). Tissue: Cerebellum.
[11]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]	"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 2). Tissue: Kidney.
[15]	"Phosphorylation of Grb10 by mitogen-activated protein kinase: identification of Ser150 and Ser476 of human Grb10zeta as major phosphorylation sites." Langlais P., Wang C., Dong L.Q., Carroll C.A., Weintraub S.T., Liu F. Biochemistry 44:8890-8897(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 415-425, PHOSPHORYLATION AT SER-150; SER-418 AND SER-476, MUTAGENESIS OF SER-104; SER-150; SER-418 AND SER-476.
[16]	"Evidence against GRB10 as the gene responsible for Silver-Russell syndrome." McCann J.A., Zheng H., Islam A., Goodyer C.G., Polychronakos C. Biochem. Biophys. Res. Commun. 286:943-948(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, IMPRINTING.
[17]	"Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor." Wick K.R., Werner E.D., Langlais P., Ramos F.J., Dong L.Q., Shoelson S.E., Liu F. J. Biol. Chem. 278:8460-8467(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH INSR, MUTAGENESIS OF ARG-520.
[18]	"NIK is a component of the EGF/heregulin receptor signaling complexes." Chen D., Xu L.G., Chen L., Li L., Zhai Z., Shu H.B. Oncogene 22:4348-4355(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAP3K14, IDENTIFICATION IN A COMPLEX WITH EGFR AND ERBB2.
[19]	"Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation." Murdaca J., Treins C., Monthouel-Kartmann M.N., Pontier-Bres R., Kumar S., Van Obberghen E., Giorgetti-Peraldi S. J. Biol. Chem. 279:26754-26761(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NEDD4, MUTAGENESIS OF PRO-136; PRO-139; PRO-141 AND ARG-520.
[20]	"Phosphorylation of grb10 regulates its interaction with 14-3-3." Urschel S., Bassermann F., Bai R.Y., Munch S., Peschel C., Duyster J. J. Biol. Chem. 280:16987-16993(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH YWHAE, PHOSPHORYLATION AT SER-428, MUTAGENESIS OF SER-134 AND SER-428.
[21]	"Grb10 mediates insulin-stimulated degradation of the insulin receptor: a mechanism of negative regulation." Ramos F.J., Langlais P.R., Hu D., Dong L.Q., Liu F. Am. J. Physiol. 290:E1262-E1266(2006) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN THE UBIQUITINATION OF INSR.
[22]	"GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt signaling pathway." Tezuka N., Brown A.M., Yanagawa S. Biochem. Biophys. Res. Commun. 356:648-654(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[23]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[24]	"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-104 AND SER-418, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"Reciprocal imprinting of human GRB10 in placental trophoblast and brain: evolutionary conservation of reversed allelic expression." Monk D., Arnaud P., Frost J., Hills F.A., Stanier P., Feil R., Moore G.E. Hum. Mol. Genet. 18:3066-3074(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IMPRINTING.
[26]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[27]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[28]	"The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling." Hsu P.P., Kang S.A., Rameseder J., Zhang Y., Ottina K.A., Lim D., Peterson T.R., Choi Y., Gray N.S., Yaffe M.B., Marto J.A., Sabatini D.M. Science 332:1317-1322(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-150; SER-428 AND SER-476 BY MTOR, ENZYME REGULATION.
[29]	"Structural basis for dimerization of the Grb10 Src homology 2 domain. Implications for ligand specificity." Stein E.G., Ghirlando R., Hubbard S.R. J. Biol. Chem. 278:13257-13264(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 487-591.
[30]	"Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14." Depetris R.S., Wu J., Hubbard S.R. Nat. Struct. Mol. Biol. 16:833-839(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 164-415, INTERACTION WITH NRAS AND PHOSPHOINOSITIDES, MUTAGENESIS OF LYS-300; LYS-305; LYS-308 AND ASN-355.
[31]	Erratum Depetris R.S., Wu J., Hubbard S.R. Nat. Struct. Mol. Biol. 16:1331-1331(2009)
[32]	"Imprinting of human GRB10 and its mutations in two patients with Russell-Silver syndrome." Yoshihashi H., Maeyama K., Kosaki R., Ogata T., Tsukahara M., Goto Y., Hata J., Matsuo N., Smith R.J., Kosaki K. Am. J. Hum. Genet. 67:476-482(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-95, IMPRINTING.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U34355 mRNA. Translation: AAA88819.1.
U66065 mRNA. Translation: AAC50671.1.
U69276 mRNA. Translation: AAB08431.1.
AF001534 mRNA. Translation: AAB81134.1.
AF000017 mRNA. Translation: AAC19748.1.
AB000731 mRNA. Translation: BAF76353.1.
AJ271366 mRNA. Translation: CAB96542.1.
D86962 mRNA. Translation: BAA13198.2. Different initiation.
AK289511 mRNA. Translation: BAF82200.1.
AF073378 , AF073363, AF073364, AF073365, AF073366, AF073367, AF073368, AF073369, AF073370, AF073371, AF073372, AF073373, AF073374, AF073375, AF073376, AF073377 Genomic DNA. Translation: AAC83655.1.
AF073378 , AF073363, AF073364, AF073365, AF073366, AF073367, AF073368, AF073369, AF073371, AF073372, AF073373, AF073374, AF073375, AF073376, AF073377 Genomic DNA. Translation: AAC83654.1.
AC005153 Genomic DNA. No translation available.
CH236955 Genomic DNA. Translation: EAL23897.1.
CH471128 Genomic DNA. Translation: EAW60964.1.
CH471128 Genomic DNA. Translation: EAW60965.1.
CH471128 Genomic DNA. Translation: EAW60967.1.
BC024285 mRNA. Translation: AAH24285.1.

IPI

IPI00012752.
IPI00218909.
IPI00218910.
IPI00790216.

PIR

I39175.

RefSeq

NP_001001549.1. NM_001001549.2.
NP_001001550.1. NM_001001550.2.
NP_001001555.1. NM_001001555.2.
NP_005302.3. NM_005311.4.

UniGene

Hs.164060.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NRV	X-ray	1.65	A/B	487-591	[»]
3HK0	X-ray	2.60	A/B	164-415	[»]

ProteinModelPortal

Q13322.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31657N.

IntAct

Q13322. 4 interactions.

STRING

9606.ENSP00000381793.

PTM databases

PhosphoSite

Q13322.

Polymorphism databases

DMDM

6166186.

Proteomic databases

PaxDb

Q13322.

PRIDE

Q13322.

Protocols and materials databases

DNASU

2887.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000335866; ENSP00000338543; ENSG00000106070.
ENST00000357271; ENSP00000349818; ENSG00000106070.
ENST00000398810; ENSP00000381790; ENSG00000106070.
ENST00000398812; ENSP00000381793; ENSG00000106070.
ENST00000401949; ENSP00000385770; ENSG00000106070.
ENST00000402497; ENSP00000385748; ENSG00000106070.
ENST00000402578; ENSP00000385189; ENSG00000106070.
ENST00000403097; ENSP00000385544; ENSG00000106070.
ENST00000406641; ENSP00000385366; ENSG00000106070.
ENST00000407526; ENSP00000385046; ENSG00000106070.
ENST00000439599; ENSP00000406716; ENSG00000106070.

GeneID

2887.

KEGG

hsa:2887.

UCSC

uc003tph.3. human.
uc003tpj.2. human.
uc003tpl.2. human.

Organism-specific databases

CTD

2887.

GeneCards

GC07M050625.

HGNC

HGNC:4564. GRB10.

HPA

CAB019423.
HPA027502.

MIM

601523. gene.

neXtProt

NX_Q13322.

PharmGKB

PA28960.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG307156.

HOVERGEN

HBG000468.

InParanoid

Q13322.

OMA

ESTMGSE.

Enzyme and pathway databases

Pathway_Interaction_DB

igf1_pathway. IGF1 pathway.
insulin_pathway. Insulin Pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q13322.

Bgee

Q13322.

CleanEx

HS_GRB10.

Genevestigator

Q13322.

GermOnline

ENSG00000106070. 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

EvolutionaryTrace

Q13322.

GenomeRNAi

2887.

NextBio

11401.

SOURCE

Search...

Entry information

Entry name

GRB10_HUMAN

Accession

Primary (citable) accession number: Q13322
Secondary accession number(s): A4D258 , A7VJ95, A8K0E6, D3DVM9, O00427, O00701, O75222, Q92606, Q92907, Q92948

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 15, 1999
Last modified:	May 1, 2013
This is version 140 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.