KHDRBS3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKHDRBS3, Etle, SALP, SLM-2, SLM2, T-STAR, TSTAR, etoile, KH domain containing, RNA binding, signal transduction associated 3, KH RNA binding domain containing, signal transduction associated 3
External IDsOMIM: 610421 MGI: 1313312 HomoloGene: 4780 GeneCards: KHDRBS3
Orthologs
SpeciesHumanMouse
Entrez

10656

13992

Ensembl

n/a

ENSMUSG00000022332

UniProt

O75525

Q9R226

RefSeq (mRNA)

NM_006558

NM_010158

RefSeq (protein)

NP_006549

NP_034288

Location (UCSC)n/aChr 15: 68.8 – 68.97 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

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

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

KHDRBS3 (T-STAR) expression has been shown to be increased in prostate cancer tissue compared to the surrounding benign tissue.[9] Expression of KHDRBS3 correlates with mpMRI signal measured through Likert score a system similar to PI-RADS.[9] While still under debate, mpMRI signal correlates with higher Gleason grade and tumour size, in addition to histopathological features associated with clinically aggressive prostate cancer.[10][11] Expression of KHDRBS3 was increased in the failing human myocardium of heart failure patients, here KHDRBS3 protein interacted with several important mRNAs coding for sarcomere components, such as actin gamma 1 (ACTG1), myosin light chain 2 (MYL2), ryanodine receptor 2 (RYR2), troponin I3 (TNNI3), troponin T2 (TNNT2), tropomyosin 1 (TPM1), tropomyosin 2 (TPM2), and titin (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

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

  1. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022332 – 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. ^ 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.
  5. ^ 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.
  6. ^ "Entrez Gene: KHDRBS3 KH domain containing, RNA binding, signal transduction associated 3".
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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

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