GRAP2

GRB2-related adaptor protein 2

PDB rendering based on 1h3h.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1h3h, 1oeb, 1r1p, 1r1q, 1r1s, 1uti, 2d0n

Identifiers

Symbols

GRAP2 ; GADS; GRAP-2; GRB2L; GRBLG; GRID; GRPL; GrbX; Grf40; Mona; P38

External IDs

OMIM: 604518 MGI: 1333842 HomoloGene: 21007 GeneCards: GRAP2 Gene

Gene ontology
Molecular function	• SH3/SH2 adaptor activity • protein binding
Cellular component	• nucleus • nucleolus • cytoplasm • endosome • cytosol
Biological process	• Ras protein signal transduction • cell-cell signaling • positive regulation of signal transduction • T cell costimulation • Fc-epsilon receptor signaling pathway • innate immune response • T cell receptor signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 22:
40.3 – 40.37 Mb

Chr 15:
80.62 – 80.65 Mb

PubMed search

GRB2-related adapter protein 2 also known as GRB2-related adaptor downstream of Shc (GADS) is a 37 kDa protein that in humans is encoded by the GRAP2 gene.^[1]^[2]^[3]

This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. Transcript variants utilizing alternative polyA sites exist.^[3]

Interactions

GRAP2 has been shown to interact with CD28,^[4] STAMBP,^[2]^[5] CCNDBP1,^[6] Linker of activated T cells,^[2]^[7] Lymphocyte cytosolic protein 2^[2]^[4]^[5]^[7] and MAP4K1.^[8]

References

↑ Qiu M, Hua S, Agrawal M, Li G, Cai J, Chan E, Zhou H, Luo Y, Liu M (January 1999). "Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1". Biochem Biophys Res Commun 253 (2): 443–7. doi:10.1006/bbrc.1998.9795. PMID 9878555.
↑ 2.0 2.1 2.2 2.3 Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, Takeshita T, Tsuchiya S, Konno T, Sugamura K (June 1999). "Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT". J Exp Med 189 (9): 1383–90. doi:10.1084/jem.189.9.1383. PMC 2193052. PMID 10224278.
↑ 3.0 3.1 "Entrez Gene: GRAP2 GRB2-related adaptor protein 2".
↑ 4.0 4.1 Ellis, J H; Ashman C; Burden M N; Kilpatrick K E; Morse M A; Hamblin P A (June 2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". J. Immunol. (UNITED STATES) 164 (11): 5805–14. doi:10.4049/jimmunol.164.11.5805. ISSN 0022-1767. PMID 10820259.
↑ 5.0 5.1 Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
↑ Xia, C; Bao Z; Tabassam F; Ma W; Qiu M; Hua S; Liu M (July 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity". J. Biol. Chem. (UNITED STATES) 275 (27): 20942–8. doi:10.1074/jbc.M002598200. ISSN 0021-9258. PMID 10801854.
↑ 7.0 7.1 Liu, S K; Fang N; Koretzky G A; McGlade C J (January 1999). "The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors". Curr. Biol. (ENGLAND) 9 (2): 67–75. doi:10.1016/S0960-9822(99)80017-7. ISSN 0960-9822. PMID 10021361.
↑ Ma, W; Xia C; Ling P; Qiu M; Luo Y; Tan T H; Liu M (March 2001). "Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes". Oncogene (England) 20 (14): 1703–14. doi:10.1038/sj.onc.1204224. ISSN 0950-9232. PMID 11313918.

Bourette RP, Arnaud S, Myles GM et al. (1999). "Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development.". EMBO J. 17 (24): 7273–81. doi:10.1093/emboj/17.24.7273. PMC 1171073. PMID 9857184.
Liu SK, McGlade CJ (1999). "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc.". Oncogene 17 (24): 3073–82. doi:10.1038/sj.onc.1202337. PMID 9872323.
Liu SK, Fang N, Koretzky GA, McGlade CJ (1999). "The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors.". Curr. Biol. 9 (2): 67–75. doi:10.1016/S0960-9822(99)80017-7. PMID 10021361.
Law CL, Ewings MK, Chaudhary PM et al. (1999). "GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation.". J. Exp. Med. 189 (8): 1243–53. doi:10.1084/jem.189.8.1243. PMC 2193019. PMID 10209041.
Dunham I, Shimizu N, Roe BA et al. (1999). "The DNA sequence of human chromosome 22.". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
Xia C, Bao Z, Tabassam F et al. (2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity.". J. Biol. Chem. 275 (27): 20942–8. doi:10.1074/jbc.M002598200. PMID 10801854.
Zhang W, Trible RP, Zhu M et al. (2000). "Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling.". J. Biol. Chem. 275 (30): 23355–61. doi:10.1074/jbc.M000404200. PMID 10811803.
Ellis JH, Ashman C, Burden MN et al. (2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28.". J. Immunol. 164 (11): 5805–14. doi:10.4049/jimmunol.164.11.5805. PMID 10820259.
Ma W, Xia C, Ling P et al. (2001). "Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes.". Oncogene 20 (14): 1703–14. doi:10.1038/sj.onc.1204224. PMID 11313918.
Poetsch A, Molday LL, Molday RS (2002). "The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes.". J. Biol. Chem. 276 (51): 48009–16. doi:10.1074/jbc.M108941200. PMID 11641407.
Wenzel J, Sanzenbacher R, Ghadimi M et al. (2002). "Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor.". FEBS Lett. 509 (2): 255–62. doi:10.1016/S0014-5793(01)03174-X. PMID 11741599.
Bourgin C, Bourette RP, Arnaud S et al. (2002). "Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding protein during monocyte/macrophage differentiation.". Mol. Cell. Biol. 22 (11): 3744–56. doi:10.1128/MCB.22.11.3744-3756.2002. PMC 133813. PMID 11997510.
Guyot B, Arnaud S, Phothirath P et al. (2002). "Genomic organization and restricted expression of the human Mona/Gads gene suggests regulation by two specific promoters.". Gene 290 (1–2): 173–9. doi:10.1016/S0378-1119(02)00555-3. PMID 12062812.
Lindholm CK, Henriksson ML, Hallberg B, Welsh M (2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem. 269 (13): 3279–88. doi:10.1046/j.1432-1033.2002.03008.x. PMID 12084069.
Zhu M, Janssen E, Leung K, Zhang W (2003). "Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling". J. Biol. Chem. 277 (48): 46151–8. doi:10.1074/jbc.M208946200. PMID 12359715.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Guyot B, Arnaud S, Phothirath P et al. (2003). "Upstream open reading frames regulate translation of Mona/Gads adapter mRNA in the megakaryocytic lineage". Platelets 13 (8): 459–64. doi:10.1080/0953710021000059431. PMID 12487779.
Yankee TM, Solow SA, Draves KD, Clark EA (2003). "Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways". J. Immunol. 170 (1): 349–55. doi:10.4049/jimmunol.170.1.349. PMID 12496419.

PDB gallery

1h3h: STRUCTURAL BASIS FOR SPECIFIC RECOGNITION OF AN RXXK-CONTAINING SLP-76 PEPTIDE BY THE GADS C-TERMINAL SH3 DOMAIN

1oeb: MONA/GADS SH3C DOMAIN

1r1p: Structural Basis for Differential Recognition of Tyrosine Phosphorylated Sites in the Linker for Activation of T cells (LAT) by the Adaptor Protein Gads

1r1q: Structural Basis for Differential Recognition of Tyrosine Phosphorylated Sites in the Linker for Activation of T cells (LAT) by the Adaptor Protein Gads

1r1s: Structural Basis for Differential Recognition of Tyrosine Phosphorylated Sites in the Linker for Activation of T cells (LAT) by the Adaptor Protein Gads

1uti: MONA/GADS SH3C IN COMPLEX WITH HPK DERIVED PEPTIDE

2d0n: Crystal structure of the C-terminal SH3 domain of the adaptor protein GADS in complex with SLP-76 motif peptide reveals a unique SH3-SH3 interaction

GRAP2

Interactions

References

Further reading