Protein-coding gene in the species Homo sapiens
KHDRBS3 Identifiers Aliases KHDRBS3 External IDs OMIM : 610421 ; MGI : 1313312 ; HomoloGene : 4780 ; GeneCards : KHDRBS3 ; OMA :KHDRBS3 - orthologs RNA expression patternBgee Human Mouse (ortholog)Top expressed in middle temporal gyrus prefrontal cortex Brodmann area 9 secondary oocyte Brodmann area 23 sperm Brodmann area 46 cingulate gyrus orbitofrontal cortex amygdala
Top expressed in interventricular septum neural layer of retina dentate gyrus of hippocampal formation granule cell visual cortex primary visual cortex superior frontal gyrus hippocampus proper ventricular zone prefrontal cortex primary motor cortex
More reference expression data
BioGPS
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]
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]
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]
^ 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 . 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 . 
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