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Q13322 (GRB10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length594 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH2 domain
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processinsulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

insulin-like growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of Wnt 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: Ensembl

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: Ensembl

positive regulation of phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from direct assay Ref.19. Source: UniProtKB

response to insulin

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentcytoplasm

Traceable author statement Ref.3. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement Ref.3. Source: ProtInc

   Molecular_functionSH3/SH2 adaptor activity

Traceable author statement Ref.3. Source: ProtInc

insulin receptor binding

Inferred from sequence or structural similarity PubMed 15664450. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.19Ref.20. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EPHB1P547622EBI-80275,EBI-80252
INSRP062133EBI-80275,EBI-475899

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 594594Growth factor receptor-bound protein 10
PRO_0000150346

Regions

Domain166 – 25085Ras-associating
Domain290 – 399110PH
Domain493 – 57482SH2

Amino acid modifications

Modified residue671Phosphotyrosine; by TEC Ref.6
Modified residue1041Phosphoserine Ref.24
Modified residue1501Phosphoserine; by MTOR, MAPK1 and MAPK3 Ref.15 Ref.28
Modified residue4181Phosphoserine; by MAPK1 and MAPK3; in vitro Ref.15 Ref.23 Ref.24
Modified residue4281Phosphoserine; by MTOR and PKB/AKT1 Ref.20 Ref.28
Modified residue4311Phosphoserine By similarity
Modified residue4761Phosphoserine; by MTOR, MAPK1 and MAPK3 Ref.15 Ref.28

Natural variations

Alternative sequence1 – 5858Missing in isoform 2.
VSP_001842
Alternative sequence1 – 1717MALAG…HPYYQ → MQAAGPLFRSK in isoform 4.
VSP_038784
Alternative sequence283 – 32846Missing in isoform 1.
VSP_001843
Natural variant361P → L.
Corresponds to variant rs35647889 [ dbSNP | Ensembl ].
VAR_053112
Natural variant951P → S. Ref.32
Corresponds to variant rs80244589 [ dbSNP | Ensembl ].
VAR_062864
Natural variant5581D → H.
Corresponds to variant rs11768472 [ dbSNP | Ensembl ].
VAR_053113

Experimental info

Mutagenesis1041S → G: No effect on phosphorylation. Ref.15
Mutagenesis1341S → A: No effect on YWHAE-binding. Ref.20
Mutagenesis1361P → A: No effect on NEDD4-binding; when associated with A-139 and A-141. Ref.19
Mutagenesis1391P → A: No effect on NEDD4-binding; when associated with A-136 and A-141. Ref.19
Mutagenesis1411P → S: No effect on NEDD4-binding; when associated with A-136 and A-139. Ref.19
Mutagenesis1501S → I: Loss of phosphorylation. Ref.15
Mutagenesis3001K → A: 2-fold loss of inositide-binding. Ref.30
Mutagenesis3051K → A: 5-fold loss of inositide-binding. Ref.30
Mutagenesis3081K → A: 5-fold loss of inositide-binding. Ref.30
Mutagenesis3551N → G: 5-fold loss of inositide-binding. Ref.30
Mutagenesis4181S → A: No net loss of phosphorylation, this may be due to a compensatory phosphorylation of T-422 in vitro. Ref.15
Mutagenesis4281S → A: Impairs YWHAE-binding. Ref.20
Mutagenesis4761S → A: Loss of phosphorylation. Ref.15
Mutagenesis5201R → 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 conflict1521P → A in BAA13198. Ref.9
Sequence conflict4001G → E in AAB08431. Ref.3
Sequence conflict4281S → F in BAF82200. Ref.10
Sequence conflict4981I → F in AAB08431. Ref.3
Sequence conflict5411N → I in AAC50671. Ref.2

Secondary structure

........................................................... 594
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 3 (Zeta) [UniParc].

Last modified July 15, 1999. Version 2.
Checksum: 53A5F885E17C6C6B

FASTA59467,231
        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 

« Hide

Isoform 1 (Beta) [UniParc].

Checksum: FCAA0792DBEB8AC3
Show »

FASTA54862,026
Isoform 2 (Gamma) (Beta) (SV-1) [UniParc].

Checksum: 626377A169AE6530
Show »

FASTA53660,848
Isoform 4 (Epsilon) [UniParc].

Checksum: B5EE8FA86A240D21
Show »

FASTA58866,487

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.

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 expand/collapse EMBL AC list , AF073363, AF073364, AF073365, AF073366, AF073367, AF073368, AF073369, AF073370, AF073371, AF073372, AF073373, AF073374, AF073375, AF073376, AF073377 Genomic DNA. Translation: AAC83655.1.
AF073378 expand/collapse EMBL AC list , 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.
CCDSCCDS43582.1. [Q13322-1]
CCDS43583.1. [Q13322-3]
CCDS47586.1. [Q13322-2]
PIRI39175.
RefSeqNP_001001549.1. NM_001001549.2. [Q13322-2]
NP_001001550.1. NM_001001550.2. [Q13322-3]
NP_001001555.1. NM_001001555.2. [Q13322-3]
NP_005302.3. NM_005311.4. [Q13322-1]
XP_005271817.1. XM_005271760.1. [Q13322-1]
XP_005271818.1. XM_005271761.2. [Q13322-1]
XP_005271822.1. XM_005271765.1. [Q13322-3]
XP_005271823.1. XM_005271766.2. [Q13322-3]
XP_006715766.1. XM_006715703.1. [Q13322-1]
XP_006715767.1. XM_006715704.1. [Q13322-4]
XP_006715768.1. XM_006715705.1. [Q13322-3]
UniGeneHs.164060.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NRVX-ray1.65A/B487-591[»]
3HK0X-ray2.60A/B164-415[»]
ProteinModelPortalQ13322.
SMRQ13322. Positions 167-409, 429-465, 487-593.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109144. 29 interactions.
DIPDIP-31657N.
IntActQ13322. 11 interactions.
MINTMINT-1534184.
STRING9606.ENSP00000381793.

PTM databases

PhosphoSiteQ13322.

Polymorphism databases

DMDM6166186.

Proteomic databases

MaxQBQ13322.
PaxDbQ13322.
PRIDEQ13322.

Protocols and materials databases

DNASU2887.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335866; ENSP00000338543; ENSG00000106070. [Q13322-3]
ENST00000357271; ENSP00000349818; ENSG00000106070. [Q13322-2]
ENST00000398810; ENSP00000381790; ENSG00000106070. [Q13322-3]
ENST00000398812; ENSP00000381793; ENSG00000106070. [Q13322-1]
ENST00000401949; ENSP00000385770; ENSG00000106070. [Q13322-1]
ENST00000402497; ENSP00000385748; ENSG00000106070. [Q13322-3]
ENST00000402578; ENSP00000385189; ENSG00000106070. [Q13322-3]
ENST00000403097; ENSP00000385544; ENSG00000106070. [Q13322-4]
ENST00000406641; ENSP00000385366; ENSG00000106070. [Q13322-3]
ENST00000407526; ENSP00000385046; ENSG00000106070. [Q13322-3]
ENST00000439599; ENSP00000406716; ENSG00000106070. [Q13322-4]
GeneID2887.
KEGGhsa:2887.
UCSCuc003tph.3. human. [Q13322-1]
uc003tpj.2. human. [Q13322-2]
uc003tpl.2. human. [Q13322-4]

Organism-specific databases

CTD2887.
GeneCardsGC07M050625.
HGNCHGNC:4564. GRB10.
HPACAB019423.
HPA027502.
MIM601523. gene.
neXtProtNX_Q13322.
PharmGKBPA28960.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307156.
HOVERGENHBG000468.
InParanoidQ13322.
OMAESTMGSE.
OrthoDBEOG7SFHW7.
PhylomeDBQ13322.
TreeFamTF317511.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ13322.

Gene expression databases

ArrayExpressQ13322.
BgeeQ13322.
CleanExHS_GRB10.
GenevestigatorQ13322.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProIPR015042. BPS-dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000159. Ras-assoc.
IPR000980. SH2.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamPF08947. BPS. 1 hit.
PF00169. PH. 1 hit.
PF00788. RA. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00233. PH. 1 hit.
SM00314. RA. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS50200. RA. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13322.
GeneWikiGRB10.
GenomeRNAi2887.
NextBio11401.
PROQ13322.
SOURCESearch...

Entry information

Entry nameGRB10_HUMAN
AccessionPrimary (citable) accession number: Q13322
Secondary accession number(s): A4D258 expand/collapse secondary AC list , 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: July 9, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM