KHDRBS3

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
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5ELR, 5ELS, 5EMO, 5ELT, 5EL3
Identifiers
Aliases	KHDRBS3, 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 IDs	OMIM: 610421; MGI: 1313312; HomoloGene: 4780; GeneCards: KHDRBS3; OMA:KHDRBS3 - orthologs
Gene location (Mouse) Chr. Chromosome 15 (mouse)[1] Band 15 D3|15 30.36 cM Start 68,800,269 bp[1] End 68,973,060 bp[1]
RNA expression pattern Bgee 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 More reference expression data
Gene ontology Molecular function SH3 domain binding protein binding RNA binding nucleic acid binding protein domain specific binding identical protein binding Cellular component nucleus nucleoplasm Biological process regulation of transcription, DNA-templated transcription, DNA-templated mRNA processing regulation of mRNA splicing, via spliceosome protein complex oligomerization Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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/a Chr 15: 68.8 – 68.97 Mb PubMed search [2] [3]
Wikidata
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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 F_max.^[12]