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Protein-coding gene in the species Homo sapiens
KHDRBS3 Identifiers Aliases KHDRBS3 External IDs OMIM : 610421 MGI : 1313312 HomoloGene : 4780 GeneCards : KHDRBS3 Wikidata
KH domain-containing, RNA-binding, signal transduction-associated protein 3 is a protein that in humans is encoded by the KHDRBS3 gene .[4] [5] [6]
Interactions [ edit ] KHDRBS3 has been shown to interact with SIAH1 .[7] [8]
KHDRBS3 interacts with splicing protein Sam68 and oncogene metadherin in prostate cancer cells.[9]
Clinical significance [ edit ] KHDRBS3 (T-STAR) expression has been shown to be increased in prostate cancer tissue compared to the surrounding benign tissue.[9] mpMRI signal measured through Likert score a system similar to PI-RADS .[9] Gleason grade and tumour size, in addition to histopathological features associated with clinically aggressive prostate cancer.[10] [11] heart failure patients, here KHDRBS3 protein interacted with several important mRNAs coding for sarcomere components, such as actin gamma 1 (ACTG1 MYL2 RYR2 TNNI3 TNNT2 TPM1 TPM2 TTN )[12]
In prostate cancer cell lines KHDRBS3 appears to be androgen regulated, with a reduction in mRNA expression occurring following addition of synthetic androgen R1881 to cells.[9]
Function [ edit ] KHDRBS3 regulates the alternative mRNA splicing of the sacromere protein titin (TTN ), leading to intron retention. Overexpression of KHDRBS3 in induced pluripotent stem cell -derived cardiomyocytes (iPSC-CMs) increased Ca2+ transient amplitude and resulted in an increase of Fmax .[12]
References [ edit ]
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022332 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Venables JP, Vernet C, Chew SL, Elliott DJ, Cowmeadow RB, Wu J, et al. (June 1999). "T-STAR/ETOILE: a novel relative of SAM68 that interacts with an RNA-binding protein implicated in spermatogenesis" . Human Molecular Genetics . 8 (6): 959–69. doi :10.1093/hmg/8.6.959 PMID 10332027 . ^ Lee J, Burr JG (November 1999). "Salpalpha and Salpbeta, growth-arresting homologs of Sam68". Gene . 240 (1): 133–47. doi :10.1016/S0378-1119(99)00421-7 . PMID 10564820 . ^ "Entrez Gene: KHDRBS3 KH domain containing, RNA binding, signal transduction associated 3" .^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173–8. Bibcode :2005Natur.437.1173R . doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 . ^ Venables JP, Dalgliesh C, Paronetto MP, Skitt L, Thornton JK, Saunders PT, et al. (July 2004). "SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome". Human Molecular Genetics . 13 (14): 1525–34. doi :10.1093/hmg/ddh165 . PMID 15163637 . ^ a b c d Luxton HJ, Simpson BS, Mills IG, Brindle NR, Ahmed Z, Stavrinides V, et al. (August 2019). "The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing" . Cancers . 11 (9): 1233. doi :10.3390/cancers11091233 PMC 6770463 PMID 31450747 . ^ Norris JM, Carmona Echeverria LM, Bott SR, Brown LC, Burns-Cox N, Dudderidge T, et al. (May 2020). "What Type of Prostate Cancer Is Systematically Overlooked by Multiparametric Magnetic Resonance Imaging? An Analysis from the PROMIS Cohort" . European Urology . 78 (2): 163–170. doi :10.1016/j.eururo.2020.04.029 PMC 7397509 PMID 32370911 . ^ Norris JM, Carmona Echeverria LM, Simpson BS, Allen C, Ball R, Freeman A, et al. (April 2020). "Prostate cancer visibility on multiparametric magnetic resonance imaging: high Gleason grade and increased tumour volume are not the only important histopathological features" . BJU International . 126 (2): 237–239. doi :10.1111/bju.15085 PMID 32319152 . ^ a b Boeckel, Jes-Niels; Möbius-Winkler, Maximilian; Müller, Marion; Rebs, Sabine; Eger, Nicole; Schoppe, Laura; Tappu, Rewati; Kokot, Karoline E.; Kneuer, Jasmin M.; Gaul, Susanne; Bordalo, Diana M. (2021-07-15). "SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy" . Genomics, Proteomics & Bioinformatics . 20 (1): 129–146. doi :10.1016/j.gpb.2021.01.006 ISSN 1672-0229 . PMC 9510876 PMID 34273561 .
Further reading [ edit ]
Di Fruscio M, Chen T, Richard S (March 1999). "Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src substrate during mitosis" . Proceedings of the National Academy of Sciences of the United States of America . 96 (6): 2710–5. Bibcode :1999PNAS...96.2710D . doi :10.1073/pnas.96.6.2710 PMC 15834 PMID 10077576 . Venables JP, Elliott DJ, Makarova OV, Makarov EM, Cooke HJ, Eperon IC (March 2000). "RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2beta and affect splicing" . Human Molecular Genetics . 9 (5): 685–94. doi :10.1093/hmg/9.5.685 PMID 10749975 . Stoss O, Olbrich M, Hartmann AM, Konig H, Memmott J, Andreadis A, Stamm S (March 2001). "The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites" . The Journal of Biological Chemistry . 276 (12): 8665–73. doi :10.1074/jbc.M006851200 PMID 11118435 . Sugimoto Y, Morita R, Amano K, Shah PU, Pascual-Castroviejo I, Khan S, et al. (August 2001). "T-STAR gene: fine mapping in the candidate region for childhood absence epilepsy on 8q24 and mutational analysis in patients". Epilepsy Research . 46 (2): 139–44. doi :10.1016/S0920-1211(01)00274-1 . PMID 11463515 . S2CID 28713407 . Kool J, van Zaane W, van der Eb AJ, Terleth C (November 2001). "Down-regulation of T-STAR, a growth inhibitory protein, after SV40-mediated immortalization". Cell Growth & Differentiation . 12 (11): 535–41. PMID 11714634 . Reddy TR, Suhasini M, Xu W, Yeh LY, Yang JP, Wu J, et al. (February 2002). "A role for KH domain proteins (Sam68-like mammalian proteins and quaking proteins) in the post-transcriptional regulation of HIV replication" . The Journal of Biological Chemistry . 277 (8): 5778–84. doi :10.1074/jbc.M106836200 PMID 11741900 . Côté J, Boisvert FM, Boulanger MC, Bedford MT, Richard S (January 2003). "Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1" . Molecular Biology of the Cell . 14 (1): 274–87. doi :10.1091/mbc.E02-08-0484 . PMC 140244 PMID 12529443 . Venables JP, Dalgliesh C, Paronetto MP, Skitt L, Thornton JK, Saunders PT, et al. (July 2004). "SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome". Human Molecular Genetics . 13 (14): 1525–34. doi :10.1093/hmg/ddh165 . PMID 15163637 . Cohen CD, Doran PP, Blattner SM, Merkle M, Wang GQ, Schmid H, et al. (July 2005). "Sam68-like mammalian protein 2, identified by digital differential display as expressed by podocytes, is induced in proteinuria and involved in splice site selection of vascular endothelial growth factor" . Journal of the American Society of Nephrology . 16 (7): 1958–65. doi :10.1681/ASN.2005020204 PMID 15901763 . Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173–8. Bibcode :2005Natur.437.1173R . doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 . Zhang L, Guo L, Peng Y, Chen B (July 2006). "Expression of T-STAR gene is associated with regulation of telomerase activity in human colon cancer cell line HCT-116" . World Journal of Gastroenterology . 12 (25): 4056–60. doi :10.3748/wjg.v12.i25.4056 PMC 4087721 PMID 16810759 . Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks" . Cell . 127 (3): 635–48. doi :10.1016/j.cell.2006.09.026 PMID 17081983 . S2CID 7827573 .
