KHDRBS3

KHDRBS3
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	5ELR, 5ELS, 5EMO, 5ELT, 5EL3
識別子
記号	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
外部ID	OMIM: 610421 MGI: 1313312 HomoloGene: 4780 GeneCards: KHDRBS3
遺伝子の位置 (マウス)
染色体	15番染色体 (マウス)
終点	68,973,060 bp
RNA発現パターン
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• SH3 domain binding; • 血漿タンパク結合; • RNA結合; • 核酸結合; • protein domain specific binding; • identical protein binding;
細胞の構成要素	• 細胞核; • 核質;
生物学的プロセス	• regulation of transcription, DNA-templated; • transcription, DNA-templated; • mRNA processing; • regulation of mRNA splicing, via spliceosome; • protein complex oligomerization;
	出典:Amigo / QuickGO
オルソログ
	10656
	13992
	n/a
	ENSMUSG00000022332
	O75525,E5RJZ9
	Q9R226
	NM_006558
	NM_010158
	NP_006549
	NP_034288
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

KHDRBS3（KH domain containing, RNA binding, signal transduction associated 3）またはT-STARは、ヒトではKHDRBS3遺伝子にコードされるタンパク質である^[4]^[5]^[6]。

相互作用

KHDRBS3はSIAH1（英語版）と相互作用することが示されている^[7]^[8]。

またKHDRBS3は前立腺がん細胞において、スプライシングタンパク質Sam68やがんタンパク質メタドヘリンと相互作用している^[9]。

臨床的意義

KHDRBS3（T-STAR）は、前立腺がん組織で周囲の良性組織よりも発現が増加していることが示されている^[9]。KHDRBS3の発現は、Likert scaleによって測定されるマルチパラメトリックMRI（mpMRI）シグナルと相関している。Likert scaleは、PI-RADS（英語版）と類似したシステムである^[9]。いまだ議論はあるものの、mpMRIシグナルはグリソンスコアの高さや腫瘍サイズ、臨床的にアグレッシブな前立腺がんと関係した組織病理学的特徴と相関している^[10]^[11]。KHDRBS3の発現は心不全患者の不全部位の心筋で増加しており、そこでKHDRBS3はACTG1（英語版）、MYL2（英語版）、RYR2（英語版）、TNNI3（英語版）、TNNT2、TPM1（英語版）、TPM2（英語版）、TTNなど、サルコメア（英語版）の構成要素をコードするいくつかの重要なmRNAと相互作用している^[12]。

前立腺がん細胞株ではKHDRBS3はアンドロゲンによって調節されているようであり、合成アンドロゲンR1881（英語版）の投与後にmRNAの発現が低下する^[9]。

機能

KHDRBS3はサルコメアタンパク質であるチチンのmRNAの選択的スプライシングを調節しており、イントロンが保持される。iPS細胞由来心筋細胞におけるKHDRBS3の過剰発現はカルシウムトランジェントを増加させ、F_maxの増加をもたらす^[12]。

出典

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022332 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “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. (June 1999). doi:10.1093/hmg/8.6.959. PMID 10332027.
^ “Salpalpha and Salpbeta, growth-arresting homologs of Sam68”. Gene 240 (1): 133–47. (November 1999). doi:10.1016/S0378-1119(99)00421-7. PMID 10564820.
^ “Entrez Gene: KHDRBS3 KH domain containing, RNA binding, signal transduction associated 3”. 2023年7月1日閲覧。
^ “Towards a proteome-scale map of the human protein-protein interaction network”. Nature 437 (7062): 1173–8. (October 2005). Bibcode: 2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
^ “SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome”. Human Molecular Genetics 13 (14): 1525–34. (July 2004). doi:10.1093/hmg/ddh165. PMID 15163637.
^ ^a ^b ^c ^d “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. (August 2019). doi:10.3390/cancers11091233. PMC 6770463. PMID 31450747.
^ “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. (May 2020). doi:10.1016/j.eururo.2020.04.029. PMC 7397509. PMID 32370911.
^ “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. (April 2020). 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. et al. (2021-07-15). “SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy” (英語). Genomics, Proteomics & Bioinformatics 20 (1): 129–146. doi:10.1016/j.gpb.2021.01.006. ISSN 1672-0229. PMC 9510876. PMID 34273561.

関連文献

“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. (March 1999). Bibcode: 1999PNAS...96.2710D. doi:10.1073/pnas.96.6.2710. PMC 15834. PMID 10077576.
“RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2beta and affect splicing”. Human Molecular Genetics 9 (5): 685–94. (March 2000). doi:10.1093/hmg/9.5.685. PMID 10749975.
“The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites”. The Journal of Biological Chemistry 276 (12): 8665–73. (March 2001). doi:10.1074/jbc.M006851200. PMID 11118435.
“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. (August 2001). doi:10.1016/S0920-1211(01)00274-1. PMID 11463515.
“Down-regulation of T-STAR, a growth inhibitory protein, after SV40-mediated immortalization”. Cell Growth & Differentiation 12 (11): 535–41. (November 2001). PMID 11714634.
“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. (February 2002). doi:10.1074/jbc.M106836200. PMID 11741900.
“Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1”. Molecular Biology of the Cell 14 (1): 274–87. (January 2003). doi:10.1091/mbc.E02-08-0484. PMC 140244. PMID 12529443.
“SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome”. Human Molecular Genetics 13 (14): 1525–34. (July 2004). doi:10.1093/hmg/ddh165. PMID 15163637.
“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. (July 2005). doi:10.1681/ASN.2005020204. PMID 15901763.
“Towards a proteome-scale map of the human protein-protein interaction network”. Nature 437 (7062): 1173–8. (October 2005). Bibcode: 2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
“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. (July 2006). doi:10.3748/wjg.v12.i25.4056. PMC 4087721. PMID 16810759.
“Global, in vivo, and site-specific phosphorylation dynamics in signaling networks”. Cell 127 (3): 635–48. (November 2006). doi:10.1016/j.cell.2006.09.026. PMID 17081983.

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000022332 - Ensembl, May 2017

[2] Human PubMed Reference:

[3] Mouse PubMed Reference:

[pmid10332027-4] “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. (June 1999). doi:10.1093/hmg/8.6.959. PMID 10332027.

[pmid10564820-5] “Salpalpha and Salpbeta, growth-arresting homologs of Sam68”. Gene 240 (1): 133–47. (November 1999). doi:10.1016/S0378-1119(99)00421-7. PMID 10564820.

[entrez-6] “Entrez Gene: KHDRBS3 KH domain containing, RNA binding, signal transduction associated 3”. 2023年7月1日閲覧。

[pmid16189514-7] “Towards a proteome-scale map of the human protein-protein interaction network”. Nature 437 (7062): 1173–8. (October 2005). Bibcode: 2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.

[pmid15163637-8] “SIAH1 targets the alternative splicing factor T-STAR for degradation by the proteasome”. Human Molecular Genetics 13 (14): 1525–34. (July 2004). doi:10.1093/hmg/ddh165. PMID 15163637.

[:0-9] “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. (August 2019). doi:10.3390/cancers11091233. PMC 6770463. PMID 31450747.

[:2-10] “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. (May 2020). doi:10.1016/j.eururo.2020.04.029. PMC 7397509. PMID 32370911.

[:3-11] “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. (April 2020). doi:10.1111/bju.15085. PMID 32319152.

[:1-12] Boeckel, Jes-Niels; Möbius-Winkler, Maximilian; Müller, Marion; Rebs, Sabine; Eger, Nicole; Schoppe, Laura; Tappu, Rewati; Kokot, Karoline E. et al. (2021-07-15). “SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy” (英語). Genomics, Proteomics & Bioinformatics 20 (1): 129–146. doi:10.1016/j.gpb.2021.01.006. ISSN 1672-0229. PMC 9510876. PMID 34273561.

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