Signal transducing adaptor molecule

Signal transducing adaptor molecule (SH3 domain and ITAM motif) 1
Rendering based on PDB 2L0A​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2L0A​, 3F1I​, 3LDZ​
Identifiers
Symbols	STAM ; STAM-1; STAM1
External IDs	OMIM: 601899 MGI: 1329014 HomoloGene: 37788 GeneCards: STAM Gene
Gene ontology Molecular function • SH3/SH2 adaptor activity • protein binding Cellular component • cytosol • early endosome membrane Biological process • intracellular protein transport • signal transduction • epidermal growth factor receptor signaling pathway • positive regulation of signal transduction • endosomal transport • negative regulation of epidermal growth factor receptor signaling pathway • membrane organization • positive regulation of exosomal secretion • regulation of extracellular exosome assembly Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8027	20844
Ensembl	ENSG00000136738	ENSMUSG00000026718
UniProt	Q92783	P70297
RefSeq (mRNA)	NM_003473	NM_011484
RefSeq (protein)	NP_003464	NP_035614
Location (UCSC)	Chr 10: 17.64 – 17.72 Mb	Chr 2: 14.07 – 14.15 Mb
PubMed search

Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene.^[1][2]

This gene was identified by the rapid tyrosine-phosphorylation of its product in response to cytokine stimulation. The encoded protein contains an SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). This protein associates with JAK3 and JAK2 kinases via its ITAM region, and is phosphorylated by the JAK kinases upon cytokine stimulation, which suggests the function of this protein is as an adaptor molecule involved in the downstream signaling of cytokine receptors. HGS/HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) has been found to bind and counteract the function of this protein.^[2]

Interactions

Signal transducing adaptor molecule has been shown to interact with STAMBP,^[3][4] HGS,^[5][6][7] TIMM8A^[8] and Janus kinase 2.^[9]

References

1. Takeshita T, Arita T, Asao H, Tanaka N, Higuchi M, Kuroda H, Kaneko K, Munakata H, Endo Y, Fujita T, Sugamura K (October 1996). "Cloning of a novel signal-transducing adaptor molecule containing an SH3 domain and ITAM". Biochem Biophys Res Commun 225 (3): 1035–9. doi:10.1006/bbrc.1996.1290. PMID 8780729.
2. "Entrez Gene: STAM signal transducing adaptor molecule (SH3 domain and ITAM motif) 1".
3. Kato, M; Miyazawa K; Kitamura N (December 2000). "A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP". J. Biol. Chem. (UNITED STATES) 275 (48): 37481–7. doi:10.1074/jbc.M007251200. ISSN 0021-9258. PMID 10982817.
4. Tanaka, N; Kaneko K; Asao H; Kasai H; Endo Y; Fujita T; Takeshita T; Sugamura K (July 1999). "Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines". J. Biol. Chem. (UNITED STATES) 274 (27): 19129–35. doi:10.1074/jbc.274.27.19129. ISSN 0021-9258. PMID 10383417.
5. 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. Cite uses deprecated parameter |coauthors= (help)
6. Asao, H; Sasaki Y; Arita T; Tanaka N; Endo K; Kasai H; Takeshita T; Endo Y; Fujita T; Sugamura K (December 1997). "Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth". J. Biol. Chem. (UNITED STATES) 272 (52): 32785–91. doi:10.1074/jbc.272.52.32785. ISSN 0021-9258. PMID 9407053.
7. Bache, Kristi G; Raiborg Camilla; Mehlum Anja; Stenmark Harald (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". J. Biol. Chem. (United States) 278 (14): 12513–21. doi:10.1074/jbc.M210843200. ISSN 0021-9258. PMID 12551915.
8. Blackstone, Craig; Roberts Roland G; Seeburg Daniel P; Sheng Morgan (May 2003). "Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1". Biochem. Biophys. Res. Commun. (United States) 305 (2): 345–52. doi:10.1016/S0006-291X(03)00767-8. ISSN 0006-291X. PMID 12745081.
9. Takeshita, T; Arita T; Higuchi M; Asao H; Endo K; Kuroda H; Tanaka N; Murata K; Ishii N; Sugamura K (April 1997). "STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction". Immunity (UNITED STATES) 6 (4): 449–57. doi:10.1016/S1074-7613(00)80288-5. ISSN 1074-7613. PMID 9133424.

Further reading

• Takeshita T, Arita T, Higuchi M, et al. (1997). "STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction". Immunity 6 (4): 449–57. doi:10.1016/S1074-7613(00)80288-5. PMID 9133424.
• Asao H, Sasaki Y, Arita T, et al. (1998). "Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth". J. Biol. Chem. 272 (52): 32785–91. doi:10.1074/jbc.272.52.32785. PMID 9407053.
• Tanaka N, Kaneko K, Asao H, et al. (1999). "Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines". J. Biol. Chem. 274 (27): 19129–35. doi:10.1074/jbc.274.27.19129. PMID 10383417.
• Endo K, Takeshita T, Kasai H, et al. (2000). "STAM2, a new member of the STAM family, binding to the Janus kinases". FEBS Lett. 477 (1–2): 55–61. doi:10.1016/S0014-5793(00)01760-9. PMID 10899310.
• Kato M, Miyazawa K, Kitamura N (2001). "A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP". J. Biol. Chem. 275 (48): 37481–7. doi:10.1074/jbc.M007251200. PMID 10982817.
• Pandey A, Fernandez MM, Steen H, et al. (2001). "Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways". J. Biol. Chem. 275 (49): 38633–9. doi:10.1074/jbc.M007849200. PMID 10993906.
• Steen H, Kuster B, Fernandez M, et al. (2002). "Tyrosine phosphorylation mapping of the epidermal growth factor receptor signaling pathway". J. Biol. Chem. 277 (2): 1031–9. doi:10.1074/jbc.M109992200. PMID 11687594.
• 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.
• Bache KG, Raiborg C, Mehlum A, Stenmark H (2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". J. Biol. Chem. 278 (14): 12513–21. doi:10.1074/jbc.M210843200. PMID 12551915.
• Blackstone C, Roberts RG, Seeburg DP, Sheng M (2003). "Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1". Biochem. Biophys. Res. Commun. 305 (2): 345–52. doi:10.1016/S0006-291X(03)00767-8. PMID 12745081.
• Mizuno E, Kawahata K, Kato M, et al. (2004). "STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif". Mol. Biol. Cell 14 (9): 3675–89. doi:10.1091/mbc.E02-12-0823. PMC 196559. PMID 12972556.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Mizuno E, Kawahata K, Okamoto A, et al. (2005). "Association with Hrs is required for the early endosomal localization, stability, and function of STAM". J. Biochem. 135 (3): 385–96. doi:10.1093/jb/mvh046. PMID 15113837.
• Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Kobayashi H, Tanaka N, Asao H, et al. (2005). "Hrs, a mammalian master molecule in vesicular transport and protein sorting, suppresses the degradation of ESCRT proteins signal transducing adaptor molecule 1 and 2". J. Biol. Chem. 280 (11): 10468–77. doi:10.1074/jbc.M409969200. PMID 15640163.
• Row PE, Clague MJ, Urbé S (2005). "Growth factors induce differential phosphorylation profiles of the Hrs-STAM complex: a common node in signalling networks with signal-specific properties". Biochem. J. 389 (Pt 3): 629–36. doi:10.1042/BJ20050067. PMC 1180712. PMID 15828871.
• Zhang Y, Wolf-Yadlin A, Ross PL, et al. (2005). "Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules". Mol. Cell Proteomics 4 (9): 1240–50. doi:10.1074/mcp.M500089-MCP200. PMID 15951569.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.