PUF60
Domain
The third RNA recognition motif, called PUMP domain, is atypical and may rather mediate homodimerization and/or protein-protein interactions.
Function
DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with RO60. Binds to poly(U) RNA.
Involvement in disease
Verheij syndrome
VRJS
A syndrome characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the RRM half pint family.
Tissue Specificity
Isoform 2 is expressed in colonic epithelium and colorectal epithelium cancer (at protein level). Isoform 6 is expressed in colorectal epithelial cancer but below detection level in colonic epithelium. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.
Cellular localization
- Nucleus
- Colocalizes partially with RO60.
Alternative names
FIR, ROBPI, SIAHBP1, PUF60, Poly(U)-binding-splicing factor PUF60, 60 kDa poly(U)-binding-splicing factor, FUSE-binding protein-interacting repressor, Ro-binding protein 1, Siah-binding protein 1, FBP-interacting repressor, RoBP1, Siah-BP1