CPLM-022969

Genbank Nucleotide ID

Poly(U)-binding-splicing factor PUF60

Protein Synonyms/Alias

60 kDa poly(U)-binding-splicing factor; FUSE-binding protein-interacting repressor; FBP-interacting repressor; Ro-binding protein 1; RoBP1; Siah-binding protein 1; Siah-BP1

Homo sapiens (Human)

Position	Peptide	Type	References
80	YAMEQSIKSVLVKQT	ubiquitination	[1, 2, 3]
251	SVFEAFGKIKSCTLA	acetylation	[4]
251	SVFEAFGKIKSCTLA	ubiquitination	[5]
454	ARHMVMQKLLRKQES	acetylation	[4, 6, 7, 8]
454	ARHMVMQKLLRKQES	ubiquitination	[3]

[1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[3] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[6] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330]
[7] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
[8] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
PLoS One. 2012;7(12):e50545. [PMID: 23236377]

Functional Description

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 TROVE2. Binds to poly(U) RNA.

DOMAIN 129 207 RRM 1.
DOMAIN 226 304 RRM 2.
DOMAIN 462 549 RRM 3; atypical.
REGION 1 516 Inhibits homodimerization.
REGION 77 559 Inhibits transcriptional repression,
MOD_RES 60 60 Phosphothreonine.
MOD_RES 112 112 Phosphoserine.
MOD_RES 251 251 N6-acetyllysine.
MOD_RES 314 314 Phosphothreonine.
MOD_RES 454 454 N6-acetyllysine.

3D-structure; Acetylation; Alternative splicing; Apoptosis; Complete proteome; Direct protein sequencing; DNA-binding; mRNA processing; mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor; Ribonucleoprotein; RNA-binding; Transcription; Transcription regulation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005634; C:nucleus; IDA:HPA.
GO:0030529; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
GO:0000166; F:nucleotide binding; IEA:InterPro.
GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.

IPR012677; Nucleotide-bd_a/b_plait.
IPR006532; PolyU-bd.
IPR000504; RRM_dom.
IPR003954; RRM_dom_euk.

SM00360; RRM
SM00361; RRM_1