Function: Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. According to some authors, is not involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species according to (Ref.28). Ref.2 Ref.8 Ref.11 Ref.26 Ref.28Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase. Ref.2 Ref.8 Ref.11 Ref.26 Ref.28
Subunit structure: Self-associates to form homooligomers when bound to RNA, oligomerization appears to be limited when binding to proteins. Interacts with CBL, KHDRBS3, LCK, GRB2, JAK3, PIK3R1, PLCG1, PTPN6, RASA1, RBMY1A1 and STAT3. Interacts with PRMT1. Binds the WW domains of WBP4/FBP21, FNBP4/FBP30 and the SH3 domain of FYN through the Arg/Gly-rich-flanked Pro-rich regions
By similarity. Forms a complex with ILF2, ILF3, YLPM1, RBMX, NCOA5 and PPP1CA. Interacts with PTK6 (via SH3 and SH2 domains). Does not interact with TPR. Ref.1 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.17 Ref.28
Subcellular location: Nucleus. Membrane Ref.1 Ref.10 Ref.12 Ref.15.
Tissue specificity: Ubiquitously expressed in all tissue examined. Isoform 1 is expressed at lower levels in brain, skeletal muscle, and liver whereas isoform 3 is intensified in skeletal muscle and in liver. Ref.2
Developmental stage: Isoform 3 is only expressed in growth-arrested cells. Ref.2
Domain: The KH domain is required for binding to RNA
By similarity.The Pro-rich domains are flanked by Arg/Gly-rich motifs which can be asymmetric dimethylated on arginine residues to give the DMA/Gly-rich regions. Selective methylation on these motifs can modulate protein-protein interactions
By similarity.
Post-translational modification: Tyrosine phosphorylated by several non-receptor tyrosine kinases, LCK, FYN and JAK3. Negatively correlates with ability to bind RNA but required for many interactions with proteins. Phosphorylation by PTK6 negatively regulates its RNA binding ability. Phosphorylation by PTK6 at Tyr-440 dictates the nulear localization of KHDRBS1. Ref.8 Ref.11 Ref.15Acetylated. Positively correlates with ability to bind RNA.Arginine methylation is required for nuclear localization. Also can affect interaction with other proteins. Inhibits interaction with Src-like SH3 domains, but not interaction with WW domains of WBP4/FBP21 AND FNBP4/FBP30.Arg-291, Arg-331 and Arg-346 are found to be also dimethylated, probably to asymmetric dimethylarginine. Ref.1 Ref.7 Ref.12
Sequence similarities: Belongs to the KHDRBS family.Contains 1 KH domain.
Sequence caution: The sequence AAH10132.1 differs from that shown. Reason: Intron retention.
Show more