Signal transducing adaptor molecule

Signal transducing adapter molecule 1 is a protein that in humans is encoded by the STAM gene.[4][5]

STAM
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2L0A, 3F1I, 3LDZ
Identifiers
Aliases	STAM, STAM-1, STAM1, Signal transducing adaptor molecule
External IDs	OMIM: 601899 MGI: 1329014 HomoloGene: 37788 GeneCards: STAM
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10p12.33 Start 17,644,151 bp[1] End 17,716,824 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • ubiquitin-like protein ligase binding Cellular component • cytoplasm • cytosol • endosome • early endosome membrane • membrane • ESCRT-0 complex Biological process • negative regulation of epidermal growth factor receptor signaling pathway • regulation of extracellular exosome assembly • multivesicular body assembly • endosomal transport • protein transport • positive regulation of exosomal secretion • intracellular protein transport • signal transduction • positive regulation of signal transduction • macroautophagy • protein deubiquitination • membrane organization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8027	20844
Ensembl	ENSG00000136738	n/a
UniProt	Q92783	P70297
RefSeq (mRNA)	NM_003473 NM_001324282 NM_001324283 NM_001324284 NM_001324285 NM_001324286 NM_001324287 NM_001324288 NM_001324289	NM_011484 NM_001356337
RefSeq (protein)	NP_001311211 NP_001311212 NP_001311213 NP_001311214 NP_001311215 NP_001311216 NP_001311217 NP_001311218 NP_003464	NP_035614 NP_001343266
Location (UCSC)	Chr 10: 17.64 – 17.72 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

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.[5]

Interactions

Signal transducing adaptor molecule has been shown to interact with

• HGS,[6][7][8]
• Janus kinase 2.[9]
• STAMBP,[10][11] and
• TIMM8A.[12]

References

1. GRCh38: Ensembl release 89: ENSG00000136738 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Takeshita T, Arita T, Asao H, Tanaka N, Higuchi M, Kuroda H, Kaneko K, Munakata H, Endo Y, Fujita T, Sugamura K (August 1996). "Cloning of a novel signal-transducing adaptor molecule containing an SH3 domain and ITAM". Biochemical and Biophysical Research Communications. 225 (3): 1035–9. doi:10.1006/bbrc.1996.1290. PMID 8780729.
5. "Entrez Gene: STAM signal transducing adaptor molecule (SH3 domain and ITAM motif) 1".
6. 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
7. 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". The Journal of Biological Chemistry. 272 (52): 32785–91. doi:10.1074/jbc.272.52.32785. PMID 9407053.
8. Bache KG, Raiborg C, Mehlum A, Stenmark H (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". The Journal of Biological Chemistry. 278 (14): 12513–21. doi:10.1074/jbc.M210843200. PMID 12551915.
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. 6 (4): 449–57. doi:10.1016/S1074-7613(00)80288-5. PMID 9133424.
10. 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". The Journal of Biological Chemistry. 275 (48): 37481–7. doi:10.1074/jbc.M007251200. PMID 10982817.
11. 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". The Journal of Biological Chemistry. 274 (27): 19129–35. doi:10.1074/jbc.274.27.19129. PMID 10383417.
12. Blackstone C, Roberts RG, Seeburg DP, Sheng M (May 2003). "Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1". Biochemical and Biophysical Research Communications. 305 (2): 345–52. doi:10.1016/S0006-291X(03)00767-8. PMID 12745081.

Further reading

• 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. 6 (4): 449–57. doi:10.1016/S1074-7613(00)80288-5. PMID 9133424.
• 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". The Journal of Biological Chemistry. 272 (52): 32785–91. doi:10.1074/jbc.272.52.32785. PMID 9407053.
• 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". The Journal of Biological Chemistry. 274 (27): 19129–35. doi:10.1074/jbc.274.27.19129. PMID 10383417.
• Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K (July 2000). "STAM2, a new member of the STAM family, binding to the Janus kinases". FEBS Letters. 477 (1–2): 55–61. doi:10.1016/S0014-5793(00)01760-9. PMID 10899310.
• 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". The Journal of Biological Chemistry. 275 (48): 37481–7. doi:10.1074/jbc.M007251200. PMID 10982817.
• Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, Mann M, Lodish HF (December 2000). "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". The Journal of Biological Chemistry. 275 (49): 38633–9. doi:10.1074/jbc.M007849200. PMID 10993906.
• Steen H, Kuster B, Fernandez M, Pandey A, Mann M (January 2002). "Tyrosine phosphorylation mapping of the epidermal growth factor receptor signaling pathway". The Journal of Biological Chemistry. 277 (2): 1031–9. doi:10.1074/jbc.M109992200. PMID 11687594.
• Bache KG, Raiborg C, Mehlum A, Stenmark H (April 2003). "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". The Journal of Biological Chemistry. 278 (14): 12513–21. doi:10.1074/jbc.M210843200. PMID 12551915.
• Blackstone C, Roberts RG, Seeburg DP, Sheng M (May 2003). "Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1". Biochemical and Biophysical Research Communications. 305 (2): 345–52. doi:10.1016/S0006-291X(03)00767-8. PMID 12745081.
• Mizuno E, Kawahata K, Kato M, Kitamura N, Komada M (September 2003). "STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif". Molecular Biology of the Cell. 14 (9): 3675–89. doi:10.1091/mbc.E02-12-0823. PMC 196559. PMID 12972556.
• Mizuno E, Kawahata K, Okamoto A, Kitamura N, Komada M (March 2004). "Association with Hrs is required for the early endosomal localization, stability, and function of STAM". Journal of Biochemistry. 135 (3): 385–96. doi:10.1093/jb/mvh046. PMID 15113837.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (July 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Kobayashi H, Tanaka N, Asao H, Miura S, Kyuuma M, Semura K, Ishii N, Sugamura K (March 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". The Journal of Biological Chemistry. 280 (11): 10468–77. doi:10.1074/jbc.M409969200. PMID 15640163.
• Row PE, Clague MJ, Urbé S (August 2005). "Growth factors induce differential phosphorylation profiles of the Hrs-STAM complex: a common node in signalling networks with signal-specific properties". The Biochemical Journal. 389 (Pt 3): 629–36. doi:10.1042/BJ20050067. PMC 1180712. PMID 15828871.
• Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM (September 2005). "Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules". Molecular & Cellular Proteomics. 4 (9): 1240–50. doi:10.1074/mcp.M500089-MCP200. PMID 15951569.
• 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.