CPLM-020275

Genbank Nucleotide ID

RNA-binding protein 4

Protein Synonyms/Alias

Lark homolog; hLark; RNA-binding motif protein 4; RNA-binding motif protein 4a

Homo sapiens (Human)

Position	Peptide	Type	References
3	*****MVKLFIGNLP	ubiquitination	[1, 2]
27	SLFEQYGKVLECDII	ubiquitination	[3, 4, 5]
45	GFVHIEDKTAAEDAI	ubiquitination	[4]
79	NKSKTSTKLHVGNIS	ubiquitination	[6]
92	ISPTCTNKELRAKFE	ubiquitination	[3, 4, 5, 6]
139	DNTEFQGKRMHVQLS	ubiquitination	[4]
173	GKEGHWSKECPIDRS	ubiquitination	[4, 6]
223	GALDAYYKRCRAARS	ubiquitination	[4]

[1] 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]
[2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[4] 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]
[5] 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]
[6] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]

Functional Description

RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation. Modulates alternative 5'-splice site and exon selection. Acts as a muscle cell differentiation-promoting factor. Activates exon skipping of the PTB pre-mRNA during muscle cell differentiation. Antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. Binds to intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA. Exerts a suppressive activity on Cap-dependent translation via binding to CU-rich responsive elements within the 3'UTR of mRNAs, a process increased under stress conditions or during myocytes differentiation. Recruits EIF4A1 to stimulate IRES-dependent translation initiation in respons to cellular stress. Associates to internal ribosome entry segment (IRES) in target mRNA species under stress conditions. Plays a role for miRNA-guided RNA cleavage and translation suppression by promoting association of AGO2- containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro.

DOMAIN 2 72 RRM 1.
DOMAIN 78 148 RRM 2.
ZN_FING 160 177 CCHC-type.
REGION 196 364 Interaction with TNPO3.
MOD_RES 309 309 Phosphoserine.

3D-structure; Activator; Alternative splicing; Complete proteome; Cytoplasm; Differentiation; Metal-binding; mRNA processing; mRNA splicing; Nucleus; Phosphoprotein; Reference proteome; Repeat; RNA-binding; RNA-mediated gene silencing; Zinc; Zinc-finger.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
GO:0016607; C:nuclear speck; IDA:UniProtKB.
GO:0005730; C:nucleolus; IDA:UniProtKB.
GO:0035198; F:miRNA binding; IDA:UniProtKB.
GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
GO:0000166; F:nucleotide binding; IEA:InterPro.
GO:0097158; F:pre-mRNA intronic pyrimidine-rich binding; IDA:UniProtKB.
GO:0008270; F:zinc ion binding; IEA:InterPro.
GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO:0097167; P:circadian regulation of translation; ISS:UniProtKB.
GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
GO:0002192; P:IRES-dependent translational initiation; IDA:UniProtKB.
GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
GO:0032055; P:negative regulation of translation in response to stress; IDA:UniProtKB.
GO:0035278; P:negative regulation of translation involved in gene silencing by miRNA; IDA:UniProtKB.
GO:0045947; P:negative regulation of translational initiation; IDA:UniProtKB.
GO:0051149; P:positive regulation of muscle cell differentiation; IDA:UniProtKB.
GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
GO:0046822; P:regulation of nucleocytoplasmic transport; IDA:UniProtKB.
GO:0006396; P:RNA processing; TAS:ProtInc.
GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB.

IPR012677; Nucleotide-bd_a/b_plait.
IPR000504; RRM_dom.
IPR001878; Znf_CCHC.

PF00076; RRM_1
PF00098; zf-CCHC

SM00360; RRM
SM00343; ZnF_C2HC

PS50102; RRM
PS50158; ZF_CCHC