Gene Symbol: Khdrbs1
Description: KH RNA binding domain containing, signal transduction associated 1
Alias: P62, Sam68, KH domain-containing, RNA-binding, signal transduction-associated protein 1, GAP-associated tyrosine phosphoprotein p62, KH domain containing, RNA binding, signal transduction associated 1, KH domain-containing, RNA-binding, signal transduction-associated protein 1-like, p21 Ras GTPase-activating protein-associated p62, p68, src associated in mitosis, 68 kDa, src-associated in mitosis 68 kDa protein
Species: rat
Products:     Khdrbs1

Top Publications

  1. Venables J, Vernet C, Chew S, Elliott D, Cowmeadow R, Wu J, et al. T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis. Hum Mol Genet. 1999;8:959-69 pubmed
    ..cDNA, the most frequent isolates encoded a novel RNA-binding protein, termed T-STAR, that is closely related to SAM68, an Src-associated protein of unknown function. The mouse homologue was also cloned and designated étoile...
  2. Pedrotti S, Bielli P, Paronetto M, Ciccosanti F, Fimia G, Stamm S, et al. The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy. EMBO J. 2010;29:1235-47 pubmed publisher
    ..We observed that the C-to-T transition in SMN2 creates a putative binding site for the RNA-binding protein Sam68. RNA pull-down assays and UV-crosslink experiments showed that Sam68 binds to this sequence...
  3. Ben Fredj N, Grange J, Sadoul R, Richard S, Goldberg Y, Boyer V. Depolarization-induced translocation of the RNA-binding protein Sam68 to the dendrites of hippocampal neurons. J Cell Sci. 2004;117:1079-90 pubmed
    ..The regulation of neuronal RNA-binding proteins is therefore currently receiving attention. Sam68 is a ubiquitous nuclear RNA-binding protein implicated in post-transcriptional processes such as signal-dependent ..
  4. Chen Q, Zhou Y, Richards A, Wang P. Up-regulation of miRNA-221 inhibits hypoxia/reoxygenation-induced autophagy through the DDIT4/mTORC1 and Tp53inp1/p62 pathways. Biochem Biophys Res Commun. 2016;474:168-174 pubmed publisher
    ..Autophagy was assessed by GFP-LC3 labeling of autophagosome formation, LC3 and p62 measurements...
  5. Fusaki N, Iwamatsu A, Iwashima M, Fujisawa J. Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling. J Biol Chem. 1997;272:6214-9 pubmed
    ..Purification and microsequencing of this protein revealed that it was the RNA-binding protein, Sam68 (Src associated in mitosis, 68 kDa)...
  6. Chen X, Liu L, Qian R, Liu J, Yao Y, Jiang Z, et al. Expression of Sam68 Associates with Neuronal Apoptosis and Reactive Astrocytes After Spinal Cord Injury. Cell Mol Neurobiol. 2017;37:487-498 pubmed publisher
    Src-associated in mitosis (Sam68; 68 kDa) is a novel RNA-binding protein that belongs to the signal transduction and activation of RNA family involved in various biological processes...
  7. Wu W, Liu Y, Wang Y. Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush. Biochem Biophys Res Commun. 2016;473:1045-1051 pubmed publisher
    b>Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes...
  8. Xu L, Sun C, Zhang S, Xu X, Zhai L, Wang Y, et al. Sam68 Promotes NF-κB Activation and Apoptosis Signaling in Articular Chondrocytes during Osteoarthritis. Inflamm Res. 2015;64:895-902 pubmed publisher
    To investigate the expression of Sam68 in articular cartilage of knee osteoarthritis (OA) and the relationship between Sam68 and NF-κB activation and apoptosis signaling in OA articular chondrocytes...
  9. Moran M, Polakis P, McCormick F, Pawson T, Ellis C. Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein. Mol Cell Biol. 1991;11:1804-12 pubmed
    ..phosphorylated on tyrosine and serine and forms distinct complexes with two phosphoproteins of 62 and 190 kDa (p62 and p190)...

More Information


  1. Lukong K, Larocque D, Tyner A, Richard S. Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression. J Biol Chem. 2005;280:38639-47 pubmed
    ..Although BRK is known to phosphorylate the RNA-binding protein Sam68, the specific tyrosines phosphorylated and the exact role of this phosphorylation remains unknown...
  2. El Mabrouk M, Diep Q, Benkirane K, Touyz R, Schiffrin E. SAM68: a downstream target of angiotensin II signaling in vascular smooth muscle cells in genetic hypertension. Am J Physiol Heart Circ Physiol. 2004;286:H1954-62 pubmed
    We investigated whether phosphatidylinositol 3-kinase (PI3K) and 68-kDa Src associated during mitosis (SAM68) are involved in angiotensin II (ANG II) growth signaling in vascular smooth muscle cells (VSMCs) from spontaneously ..
  3. Wooten M, Geetha T, Seibenhener M, Babu J, Diaz Meco M, Moscat J. The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination. J Biol Chem. 2005;280:35625-9 pubmed
    Sequestosome 1/p62 is a scaffolding protein with several interaction modules that include a PB1 dimerization domain, a TRAF6 (tumor necrosis factor receptor-associated factor 6) binding site, and a ubiquitin-associating (UBA) domain...
  4. Najib S, Sanchez Margalet V. Sam68 associates with the SH3 domains of Grb2 recruiting GAP to the Grb2-SOS complex in insulin receptor signaling. J Cell Biochem. 2002;86:99-106 pubmed
    The 68 kDa Src substrate associated during mitosis (Sam68) is an RNA binding protein with Src homology (SH) 2 and 3 domain binding sites...
  5. Venables J, Elliott D, Makarova O, Makarov E, Cooke H, Eperon I. RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2beta and affect splicing. Hum Mol Genet. 2000;9:685-94 pubmed
    ..The RNA-binding domain of RBM affected 5' splice site selection. We conclude that the hnRNP G family of proteins is involved in pre-mRNA splicing and infer that RBM may be involved in Tra2beta-dependent splicing in spermatocytes. ..
  6. Hong W, Resnick R, Rakowski C, Shalloway D, Taylor S, Blobel G. Physical and functional interaction between the transcriptional cofactor CBP and the KH domain protein Sam68. Mol Cancer Res. 2002;1:48-55 pubmed
    ..We identified the Src substrate and RNA-binding protein Sam68 as novel CH3-binding protein...
  7. Iijima T, Wu K, Witte H, Hanno Iijima Y, Glatter T, Richard S, et al. SAM68 regulates neuronal activity-dependent alternative splicing of neurexin-1. Cell. 2011;147:1601-14 pubmed publisher
    ..Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA-binding protein SAM68 that associates with RNA response elements in the Nrxn1 pre-mRNA...
  8. Coyle J, Bor Y, Rekosh D, Hammarskjold M. The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA. 2011;17:1344-56 pubmed publisher
    ..Also, no effects were observed on export of a completely spliced mRNA. Taken together, our results indicate that Tpr plays an important role in quality control of mRNA trafficked on the Nxf1 pathway. ..
  9. Ishizuka A, Hasegawa Y, Ishida K, Yanaka K, Nakagawa S. Formation of nuclear bodies by the lncRNA Gomafu-associating proteins Celf3 and SF1. Genes Cells. 2014;19:704-21 pubmed publisher
    ..These observations suggest that Gomafu indirectly modulates the function of the splicing factors SF1 and Celf3 by sequestering these proteins into separate nuclear bodies. ..
  10. Stoss O, Olbrich M, Hartmann A, Konig H, Memmott J, Andreadis A, et al. The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites. J Biol Chem. 2001;276:8665-73 pubmed
    We identified the rat Sam68-like mammalian protein (rSLM-2), a member of the STAR (signal transduction and activation of RNA) protein family as a novel splicing regulatory protein...
  11. Derry J, Prins G, Ray V, Tyner A. Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. Oncogene. 2003;22:4212-20 pubmed
    ..However localization of Sam68, a nuclear substrate of BRK/Sik, was unaltered in all prostate tumors examined...
  12. Bielli P, Bus R, Di Stasi S, Munoz M, Botti F, Kornblihtt A, et al. The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis. EMBO Rep. 2014;15:419-27 pubmed publisher
    ..FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA...
  13. Chen T, Damaj B, Herrera C, Lasko P, Richard S. Self-association of the single-KH-domain family members Sam68, GRP33, GLD-1, and Qk1: role of the KH domain. Mol Cell Biol. 1997;17:5707-18 pubmed
    b>Sam68 is a member of a growing family of proteins that contain a single KH domain embedded in a larger conserved domain of approximately 170 amino acids...
  14. Pedrotti S, Busà R, Compagnucci C, Sette C. The RNA recognition motif protein RBM11 is a novel tissue-specific splicing regulator. Nucleic Acids Res. 2012;40:1021-32 pubmed publisher
    ..Thus, our findings identify RBM11 as a novel tissue-specific splicing factor with potential implication in the regulation of alternative splicing during neuron and germ cell differentiation. ..
  15. Chen Z, Fu Q, Shen B, Huang X, Wang K, He P, et al. Enhanced p62 expression triggers concomitant autophagy and apoptosis in a rat chronic spinal cord compression model. Mol Med Rep. 2014;9:2091-6 pubmed publisher
    ..b>p62 is a multidomain adapter protein, which is involved in apoptosis and cell survival as well as autophagy, and is a ..
  16. Hartmann A, Nayler O, Schwaiger F, Obermeier A, Stamm S. The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn). Mol Biol Cell. 1999;10:3909-26 pubmed
    ..transcriptosomal component scaffold attachment factor B, and the 68-kDa Src substrate associated during mitosis, Sam68. Northern blot analysis demonstrated ubiquitous expression, but detailed RNA in situ analysis revealed cell type ..
  17. Garner T, Strachan J, Shedden E, Long J, Cavey J, Shaw B, et al. Independent interactions of ubiquitin-binding domains in a ubiquitin-mediated ternary complex. Biochemistry. 2011;50:9076-87 pubmed publisher
    ..We subsequently demonstrate by NMR that the A20 Znf domain of ZNF216 and the UBA domain of the p62 protein (an Ile44-binding UBD), which function in the same biological pathways, are able to form such a Ub-mediated ..
  18. Wang W, Kang J, Li H, Su J, Wu J, Xu Y, et al. Regulation of endoplasmic reticulum stress in rat cortex by p62/ZIP through the Keap1-Nrf2-ARE signalling pathway after transient focal cerebral ischaemia. Brain Inj. 2013;27:924-33 pubmed publisher
    b>p62/ZIP as the autophagy receptor can transport the misfolded proteins to a macroautophagy-lysosome system for degradation and also create a positive feedback loop between p62/ZIP and Nrf2...
  19. Grange J, Boyer V, Fabian Fine R, Fredj N, Sadoul R, Goldberg Y. Somatodendritic localization and mRNA association of the splicing regulatory protein Sam68 in the hippocampus and cortex. J Neurosci Res. 2004;75:654-66 pubmed
    The RNA-binding protein Sam68 has been implicated in the signal-dependent processing of pre-mRNA and in the utilization of intron-containing retroviral mRNAs...
  20. Wong G, Muller O, Clark R, Conroy L, Moran M, Polakis P, et al. Molecular cloning and nucleic acid binding properties of the GAP-associated tyrosine phosphoprotein p62. Cell. 1992;69:551-8 pubmed
    b>p62 is a tyrosine phosphoprotein that associates with p21ras GTPase-activating protein (GAP). Purification and cDNA cloning of p62 reveal extensive sequence similarity to a putative hnRNP protein, GRP33...
  21. Richard S, Yu D, Blumer K, Hausladen D, Olszowy M, Connelly P, et al. Association of p62, a multifunctional SH2- and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1. Mol Cell Biol. 1995;15:186-97 pubmed
    ..By using the yeast two-hybrid system, we identified p62, a tyrosine-phosphorylated protein that associates with p21ras GTPase-activating protein, as a src family kinase ..
  22. Stoss O, Novoyatleva T, Gencheva M, Olbrich M, Benderska N, Stamm S. p59(fyn)-mediated phosphorylation regulates the activity of the tissue-specific splicing factor rSLM-1. Mol Cell Neurosci. 2004;27:8-21 pubmed
    The Sam68-like mammalian protein SLM-1 is a member of the STAR protein family and is related to SAM68 and SLM-2...
  23. Heinrich B, Zhang Z, Raitskin O, Hiller M, Benderska N, Hartmann A, et al. Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA. J Biol Chem. 2009;284:14303-15 pubmed publisher
  24. Kim Y, Uhm D, Shin J, Chung S. Modulation of delayed rectifier potassium channel by protein kinase C zeta-containing signaling complex in pheochromocytoma cells. Neuroscience. 2004;125:359-68 pubmed
    ..Since NGF treatment of PC12 cells is known to increase the expression of p62 protein, which binds both to Kv beta and to PKC zeta, our results are consistent with the model in which p62 ..
  25. Sanchez Margalet V, Najib S. p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K. FEBS Lett. 1999;455:307-10 pubmed
    ..This association may be important for the link of the signaling with RNA metabolism. ..
  26. Kim Y, Inoue T, Nakajima R, Shirai Morishita Y, Tokuyama K, Suzuki M. Effect of long-term exercise on gene expression of insulin signaling pathway intermediates in skeletal muscle. Biochem Biophys Res Commun. 1999;254:720-7 pubmed
    ..mRNA levels of SHP-2, Grb2, Sos, Shc, GAP, p62 and p90 S6 kinase were unaltered by running training...