KHDRBS1

This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family. The encoded protein appears to have many functions and may be involved in a variety of cellular processes, including alternative splicing, cell cycle regulation, RNA 3'-end formation, tumorigenesis, and regulation of human immunodeficiency virus gene expression. Alternative splicing results in multiple transcript variants.

KHDRBS1

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 (PubMed:22253824).
RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner (By similarity).
In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (PubMed:17371836, PubMed:20186123).
Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (By similarity).
Isoform 3, which is expressed in growth-arrested cells only, inhibits S phase.

G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentTAS:GO_Central
G2/M transition of mitotic cell cycleISS:UniProtKB
mRNA processingManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Negative regulation of transcription, DNA-templatedISS:UniProtKB
Positive regulation of RNA export from nucleusManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of translational initiationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of alternative mRNA splicing, via spliceosomeManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of mRNA splicing, via spliceosomeManual Assertion Based On ExperimentIBA:GO_Central
Regulation of RNA export from nucleusISS:UniProtKB
SpermatogenesisIEA:Ensembl
T cell receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB

Nucleus; Cytoplasm; Membrane. Predominantly located in the nucleus but also located partially in the cytoplasm.

Tyrosine phosphorylated by several non-receptor tyrosine kinases including LCK, FYN and JAK3. Also tyrosine phosphorylated by the non-receptor tyrosine kinase SRMS in an EGF-dependent manner (PubMed:29496907).
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 nuclear localization of KHDRBS1. Phosphorylation at Tyr-387 disrupts interaction with APC. Phosphorylation at tyrosine residues by FYN inverts activity on modulation of BCL2L1 alternative splicing6 Publications
Acetylated. 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.