GRAP2

GRB2-related adaptor protein 2
PDB rendering based on 1h3h.
Available structures PDB 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 • nucleoplasm • 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
Entrez	9402	17444
Ensembl	ENSG00000100351	ENSMUSG00000042351
UniProt	O75791	O89100
RefSeq (mRNA)	NM_001291824	NM_001289442
RefSeq (protein)	NP_001278753	NP_001276371
Location (UCSC)	Chr 22: 39.9 – 39.97 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]

Function

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:

• CCNDBP1,^[4]
• CD28,^[5]
• Linker of activated T cells,^[2][6]
• Lymphocyte cytosolic protein 2^[2][5][7][6]
• MAP4K1,^[8] and
• STAMBP.^[2][7]

References

1. Qiu M, Hua S, Agrawal M, Li G, Cai J, Chan E, Zhou H, Luo Y, Liu M (Dec 1998). "Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1". Biochemical and Biophysical Research Communications 253 (2): 443–7. doi:10.1006/bbrc.1998.9795. PMID 9878555.
2. Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, Takeshita T, Tsuchiya S, Konno T, Sugamura K (May 1999). "Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT". The Journal of Experimental Medicine 189 (9): 1383–90. doi:10.1084/jem.189.9.1383. PMC 2193052. PMID 10224278.
3. "Entrez Gene: GRAP2 GRB2-related adaptor protein 2".
4. Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M (Jul 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity". The Journal of Biological Chemistry 275 (27): 20942–8. doi:10.1074/jbc.M002598200. PMID 10801854.
5. Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA (Jun 2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". Journal of Immunology 164 (11): 5805–14. doi:10.4049/jimmunol.164.11.5805. PMID 10820259.
6. Liu SK, Fang N, Koretzky GA, McGlade CJ (Jan 1999). "The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors". Current Biology 9 (2): 67–75. doi:10.1016/s0960-9822(99)80017-7. PMID 10021361.
7. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
8. Ma W, Xia C, Ling P, Qiu M, Luo Y, Tan TH, Liu M (Mar 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.

Further reading

• Bourette RP, Arnaud S, Myles GM, Blanchet JP, Rohrschneider LR, Mouchiroud G (Dec 1998). "Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development". The EMBO Journal 17 (24): 7273–81. doi:10.1093/emboj/17.24.7273. PMC 1171073. PMID 9857184.
• Liu SK, McGlade CJ (Dec 1998). "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 (Jan 1999). "The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors". Current Biology 9 (2): 67–75. doi:10.1016/S0960-9822(99)80017-7. PMID 10021361.
• Law CL, Ewings MK, Chaudhary PM, Solow SA, Yun TJ, Marshall AJ, Hood L, Clark EA (Apr 1999). "GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation". The Journal of Experimental Medicine 189 (8): 1243–53. doi:10.1084/jem.189.8.1243. PMC 2193019. PMID 10209041.
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 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, Ma W, Qiu M, Hua S, Liu M (Jul 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity". The Journal of Biological Chemistry 275 (27): 20942–8. doi:10.1074/jbc.M002598200. PMID 10801854.
• Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE (Jul 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". The Journal of Biological Chemistry 275 (30): 23355–61. doi:10.1074/jbc.M000404200. PMID 10811803.
• Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA (Jun 2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". Journal of Immunology 164 (11): 5805–14. doi:10.4049/jimmunol.164.11.5805. PMID 10820259.
• Ma W, Xia C, Ling P, Qiu M, Luo Y, Tan TH, Liu M (Mar 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 (Dec 2001). "The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes". The Journal of Biological Chemistry 276 (51): 48009–16. doi:10.1074/jbc.M108941200. PMID 11641407.
• Wenzel J, Sanzenbacher R, Ghadimi M, Lewitzky M, Zhou Q, Kaplan DR, Kabelitz D, Feller SM, Janssen O (Dec 2001). "Multiple interactions of the cytosolic polyproline region of the CD95 ligand: hints for the reverse signal transduction capacity of a death factor". FEBS Letters 509 (2): 255–62. doi:10.1016/S0014-5793(01)03174-X. PMID 11741599.
• Bourgin C, Bourette RP, Arnaud S, Liu Y, Rohrschneider LR, Mouchiroud G (Jun 2002). "Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding protein during monocyte/macrophage differentiation". Molecular and Cellular Biology 22 (11): 3744–56. doi:10.1128/MCB.22.11.3744-3756.2002. PMC 133813. PMID 11997510.
• Guyot B, Arnaud S, Phothirath P, Bourette RP, Grasset MF, Rigal D, Mouchiroud G (May 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 (Jul 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". European Journal of Biochemistry / FEBS 269 (13): 3279–88. doi:10.1046/j.1432-1033.2002.03008.x. PMID 12084069.
• Zhu M, Janssen E, Leung K, Zhang W (Nov 2002). "Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling". The Journal of Biological Chemistry 277 (48): 46151–8. doi:10.1074/jbc.M208946200. PMID 12359715.
• Guyot B, Arnaud S, Phothirath P, Rigal D, Mouchiroud G (Dec 2002). "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 (Jan 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". Journal of Immunology 170 (1): 349–55. doi:10.4049/jimmunol.170.1.349. PMID 12496419.