Target intelligence / Profile preview

KH domain-containing, RNA-binding, signal transduction-associated protein 1 (Sam68)

Target
Sam68
Molecular classification
RNA-binding protein, Adapter protein (SH3/SH2 domain interactions), Signal transduction molecule, STAR (signal transducer and activator of RNA) family protein
01

Overview

KH domain-containing, RNA-binding, signal transduction-associated protein 1 (Sam68) is a multifunctional protein first identified as the 68-kDa substrate for Src family tyrosine kinases during mitosis[4][1][7]. It contains a GSG domain (also called the STAR domain), central KH RNA-binding motif, and several proline- and tyrosine-rich regions that mediate interactions with SH2/SH3 domain-containing signaling proteins[4][5][8]. Sam68 regulates pre-mRNA alternative splicing, RNA metabolism, cell cycle progression, and apoptosis[4][5][2]. It acts as a signaling adaptor and links extracellular signals to RNA processing events. Sam68 is involved in cell proliferation, cytoskeletal dynamics, and viral replication (notably, it is essential for the function of HIV-1 Rev protein)[7]. Overexpression or aberrant activity of Sam68 has been linked to cancer progression in multiple tissue types, making it a potential biomarker and therapeutic target for oncology, though direct inhibitors are not clinically available[4][5].

Other names
Src-associated in mitosis 68 kDaSAM68KHDRBS1Signal transducer and activator of RNA proteinSignal transduction and activation of RNA metabolism protein
02

Mechanism of action

Not applicable for direct drugs, but Sam68 acts as a multifunctional adapter and RNA-binding protein, modulating alternative splicing, RNA localization, and signal relay.

03

Biological functions

Alternative splicing regulationSignal transductionCell cycle regulation and progressionRNA processing, transport, and metabolismCell proliferationApoptosisCytoskeletal remodelingTranscriptional regulation (indirect)
04

Disease associations

Cancer (tumor progression, proliferation, metastasis)Neurodegenerative diseaseImmune response and viral infection (notably HIV-1 replication)Other diseases linked to abnormal RNA metabolism
05

Safety considerations

Targeting Sam68 may disrupt essential RNA metabolism broadly, affecting normal cell cycle, viability, and widespread gene expression due to its central role in mRNA processing and splicing.
06

Interacting drugs

None approved as direct Sam68-targeting drugs. (No clinical Sam68 inhibitors reported, but functions modulated in studies.)
07

Biomarkers

Overexpression is a prognostic biomarker in several cancers (e.g., breast, prostate, ovarian)Expression level may correlate with disease progression in cancer and HIV-1 replication

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