poly(U)-binding-splicing factor PUF60 (60 kD poly(U)-binding-splicing factor, FUSE-binding protein-interacting repressor, FBP-interacting repressor, siah-binding protein 1, Siah-BP1, Ro-binding protein 1, RoBP1, PUF60, FIR, ROBPI, SIAHBP1)

Function: - DNA- & RNA-binding protein - involved in several nuclear processes including pre-mRNA splicing, apoptosis & 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 facto - 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 - role in pre-mRNA splicing - promotes splicing of an intron with weak 3'-splice site & pyrimidine tract in a cooperative manner with U2AF2 - role in apoptosis induction when overexpressed in HeLa cells - isoform 6 failed to repress MYC transcription & inhibited FIR-induced apoptosis in colorectal cancer - isoform 6 may contribute to tumor progression by enabling increased MYC expression & 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 & 3'-splice site regions of pre-mRNA - binding is enhanced in presence of U2AF2 - binds to Y5 RNA in association with TROVE2 - binds to poly(U) RNA - associates with the spliceosome - found in a complex with TROVE2 & Y5 RNA - found in a complex with FUBP1 & far upstream element (FUSE) DNA segment - interacts directly with ERCC3 - interacts with CDK7, GTF2H1 & SFRS11 Structure: - homodimer - the third RNA recognition motif, called PUMP domain, is atypical & may rather mediate homodimerization &/or protein- protein interactions - belongs to the RRM half pint family - contains 3 RRM (RNA recognition motif) domains Compartment: - nucleus - colocalizes partially with TROVE2 Alternative splicing: named isoforms=6 Expression: - isoform 2 is expressed in colonic epithelium & colorectal epithelium cancer (at protein level) - expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon & peripheral blood leukocytes Pathology: - does not interact with ERCC3 or repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells - isoform 6 is expressed in colorectal epithelial cancer but below detection level in colonic epithelium

General

DNA-binding protein splicing factor; snRNP-associated protein transcriptional silencer (transcriptional repressor)

Properties

SIZE: entity length = 559 aa MW = 60 kD COMPARTMENT: cell nucleus MOTIF: Inhibits homodimerization {1-516} MOTIF: Thr phosphorylation site {T60} DNA-binding motif silencer element SITE: 77-559 MOTIF: RNP motif NAME: RNP motif SITE: 129-207 FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif NAME: ribonucleoprotein-1 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif ribonucleoprotein-2 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif RNP motif NAME: RNP motif SITE: 226-304 FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif NAME: ribonucleoprotein-1 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif ribonucleoprotein-2 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif alanine-rich region {321-343} MOTIF: alanine residue (SEVERAL) RNP motif NAME: RNP motif SITE: 462-549 FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif NAME: ribonucleoprotein-1 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif ribonucleoprotein-2 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif

Database Correlations

OMIM 604819 UniProt Q9UHX1 Pfam PF00076

References

UniProt :accession Q9UHX1