CUG-BP- and ETR-3-like factor 2 - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
    CUG-BP- and ETR-3-like factor 2
      Short name=CELF-2
Alternative name(s):
    Bruno-like protein 3
    RNA-binding protein BRUNOL-3
    CUG triplet repeat RNA-binding protein 2
      Short name=CUG-BP2
    ELAV-type RNA-binding protein 3
      Short name=ETR-3
    Neuroblastoma apoptosis-related RNA-binding protein
      Short name=hNAPOR

Gene names

Name:	CUGBP2
Synonyms:	BRUNOL3, CELF2, ETR3, NAPOR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of TNNT2 in embryonic, but not adult, skeletal muscle. Activates TNNT2 exon 5 inclusion by antagonizing the repressive effect of PTB. Acts as both an activator and repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Promotes inclusion of exonS 21 and exclusion of exon 5 of the NMDA receptor R1 pre-mRNA. Involved in the apoB RNA editing activity. Increases COX2 mRNA stability and inhibits COX2 mRNA translation in epithelial cells after radiation injury By similarity. Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression By similarity. Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK. Binds to the muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5. Binds preferentially to UG-rich sequences, in particular UG repeat and UGUU motifs. Binds to apoB mRNA, specifically to AU-rich sequences located immediatly upstream of the edited cytidine. Binds AU-rich sequences in the 3'-UTR of COX2 mRNA By similarity. Binds to an intronic RNA element responsible for the silencing of exon 21 splicing By similarity. Binds to (CUG)n repeats By similarity.
Subunit structure	Found in a complex with APOBEC1 and A1CF.
Subcellular location	Nucleus. Cytoplasm. Note= Accumulates in the cytoplasm after ionizing radiation By similarity. Colocalizes with APOBEC1 and A1CF. RNA-binding activity is detected in both nuclear and cytoplasmic compartments.
Tissue specificity	Expressed in frontal cortex. Isoform 1 is expressed in brain and lung. Isoform 2 is expressed in heart, brain, placenta, lung, liver, kidney, skeletal muscle and pancreas. Isoform 4 is expressed in heart, lung, skeletal muscle, kidney and pancreas.
Developmental stage	Isoform 1 is expressed in fetal brain. Isoform 2 is expressed in fetal heart, brain, thymus, lung, liver, skeletal muscle, kidney and spleen. Isoform 4 is expressed in fetal heart, brain, thymus, lung and skeletal muscle.
Sequence similarities	Belongs to the CELF/BRUNOL family. Contains 3 RRM (RNA recognition motif) domains.

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Ontologies

Keywords
Biological process	mRNA processing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Ligand	RNA-binding
Molecular function	Repressor
Gene Ontology (GO)
Biological process	mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW regulation of heart contraction Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	RNA binding Traceable author statement. Source: ProtInc nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	1	EBI-949790,EBI-401755

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Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95319-1) Also known as: NAPOR-3; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O95319-2) Also known as: NAPOR-1; The sequence of this isoform differs from the canonical sequence as follows: 1-24: Missing. 358-358: A → AVAQMLS

Isoform 3 (identifier: O95319-3) The sequence of this isoform differs from the canonical sequence as follows: 1-18: MRCPKSAVTMRNEELLLS → MMVEGRLLVPDRI 358-358: A → AGTINTPRSKRLLLPKDNN

Isoform 4 (identifier: O95319-4) Also known as: NAPOR-2; The sequence of this isoform differs from the canonical sequence as follows: 1-18: MRCPKSAVTMRNEELLLS → MMVEGRLLVPDRI 358-358: A → AVAQMLS

Isoform 5 (identifier: O95319-5) The sequence of this isoform differs from the canonical sequence as follows: 1-24: Missing. 359-359: G → GTINS

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 508

508

CUG-BP- and ETR-3-like factor 2

PRO_0000295189

Regions

Domain

40 – 123

84

RRM 1

Domain

132 – 212

81

RRM 2

Domain

423 – 501

79

RRM 3

Region

1 – 283

283

Necessary for RNA-binding, TNNT2 exon 5 and NMDA R1 exon 21 inclusion

Region

357 – 508

152

Necessary for RNA-binding, TNNT2 exon 5 and NMDA R1 exon 21 inclusion

Compositional bias

284 – 397

114

Ala-rich

Natural variations

Alternative sequence

1 – 24

24

Missing in isoform 2 and isoform 5.

VSP_026796

Alternative sequence

1 – 18

18

MRCPK…ELLLS → MMVEGRLLVPDRI in isoform 3 and isoform 4.

VSP_026797

Alternative sequence

358

1

A → AVAQMLS in isoform 2 and isoform 4.

VSP_026798

Alternative sequence

358

1

A → AGTINTPRSKRLLLPKDNN in isoform 3.

VSP_026799

Alternative sequence

359

1

G → GTINS in isoform 5.

VSP_026800

Experimental info

Sequence conflict

438

1

D → H in AAD13761. Ref.1

Sequence conflict

438

1

D → H in AAB09040. Ref.3

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (NAPOR-3) [UniParc]. Last modified May 1, 1999. Version 1. Checksum: C65F337D462717F2 Show »	FASTA	508	54,285
10 20 30 40 50 60 MRCPKSAVTM RNEELLLSNG TANKMNGALD HSDQPDPDAI KMFVGQIPRS WSEKELKELF 70 80 90 100 110 120 EPYGAVYQIN VLRDRSQNPP QSKGCCFVTF YTRKAALEAQ NALHNIKTLP GMHHPIQMKP 130 140 150 160 170 180 ADSEKSNAVE DRKLFIGMVS KKCNENDIRV MFSPFGQIEE CRILRGPDGL SRGCAFVTFS 190 200 210 220 230 240 TRAMAQNAIK AMHQSQTMEG CSSPIVVKFA DTQKDKEQRR LQQQLAQQMQ QLNTATWGNL 250 260 270 280 290 300 TGLGGLTPQY LALLQQATSS SNLGAFSGIQ QMAGMNALQL QNLATLAAAA AAAQTSATST 310 320 330 340 350 360 NANPLSTTSS ALGALTSPVA ASTPNSTAGA AMNSLTSLGT LQGLAGATVG LNNINALAGM 370 380 390 400 410 420 AALNGGLGAT GLTNGTAGTM DALTQAYSGI QQYAAAALPT LYSQSLLQQQ SAAGSQKEGP 430 440 450 460 470 480 EGANLFIYHL PQEFGDQDIL QMFMPFGNVI SAKVFIDKQT NLSKCFGFVS YDNPVSAQAA 490 500 IQAMNGFQIG MKRLKVQLKR SKNDSKPY « Hide
Isoform 2 (NAPOR-1) [UniParc]. Checksum: 3A17B1F5F31AC5BD Show »		490	52,268
10 20 30 40 50 60 MNGALDHSDQ PDPDAIKMFV GQIPRSWSEK ELKELFEPYG AVYQINVLRD RSQNPPQSKG 70 80 90 100 110 120 CCFVTFYTRK AALEAQNALH NIKTLPGMHH PIQMKPADSE KSNAVEDRKL FIGMVSKKCN 130 140 150 160 170 180 ENDIRVMFSP FGQIEECRIL RGPDGLSRGC AFVTFSTRAM AQNAIKAMHQ SQTMEGCSSP 190 200 210 220 230 240 IVVKFADTQK DKEQRRLQQQ LAQQMQQLNT ATWGNLTGLG GLTPQYLALL QQATSSSNLG 250 260 270 280 290 300 AFSGIQQMAG MNALQLQNLA TLAAAAAAAQ TSATSTNANP LSTTSSALGA LTSPVAASTP 310 320 330 340 350 360 NSTAGAAMNS LTSLGTLQGL AGATVGLNNI NALAVAQMLS GMAALNGGLG ATGLTNGTAG 370 380 390 400 410 420 TMDALTQAYS GIQQYAAAAL PTLYSQSLLQ QQSAAGSQKE GPEGANLFIY HLPQEFGDQD 430 440 450 460 470 480 ILQMFMPFGN VISAKVFIDK QTNLSKCFGF VSYDNPVSAQ AAIQAMNGFQ IGMKRLKVQL 490 KRSKNDSKPY « Hide
Isoform 3 [UniParc]. Checksum: DD6E4F77FE6B4073 Show »		521	55,754
10 20 30 40 50 60 MMVEGRLLVP DRINGTANKM NGALDHSDQP DPDAIKMFVG QIPRSWSEKE LKELFEPYGA 70 80 90 100 110 120 VYQINVLRDR SQNPPQSKGC CFVTFYTRKA ALEAQNALHN IKTLPGMHHP IQMKPADSEK 130 140 150 160 170 180 SNAVEDRKLF IGMVSKKCNE NDIRVMFSPF GQIEECRILR GPDGLSRGCA FVTFSTRAMA 190 200 210 220 230 240 QNAIKAMHQS QTMEGCSSPI VVKFADTQKD KEQRRLQQQL AQQMQQLNTA TWGNLTGLGG 250 260 270 280 290 300 LTPQYLALLQ QATSSSNLGA FSGIQQMAGM NALQLQNLAT LAAAAAAAQT SATSTNANPL 310 320 330 340 350 360 STTSSALGAL TSPVAASTPN STAGAAMNSL TSLGTLQGLA GATVGLNNIN ALAGTINTPR 370 380 390 400 410 420 SKRLLLPKDN NGMAALNGGL GATGLTNGTA GTMDALTQAY SGIQQYAAAA LPTLYSQSLL 430 440 450 460 470 480 QQQSAAGSQK EGPEGANLFI YHLPQEFGDQ DILQMFMPFG NVISAKVFID KQTNLSKCFG 490 500 510 520 FVSYDNPVSA QAAIQAMNGF QIGMKRLKVQ LKRSKNDSKP Y « Hide
Isoform 4 (NAPOR-2) [UniParc]. Checksum: 4A0DB5E2372193ED Show »		509	54,365
10 20 30 40 50 60 MMVEGRLLVP DRINGTANKM NGALDHSDQP DPDAIKMFVG QIPRSWSEKE LKELFEPYGA 70 80 90 100 110 120 VYQINVLRDR SQNPPQSKGC CFVTFYTRKA ALEAQNALHN IKTLPGMHHP IQMKPADSEK 130 140 150 160 170 180 SNAVEDRKLF IGMVSKKCNE NDIRVMFSPF GQIEECRILR GPDGLSRGCA FVTFSTRAMA 190 200 210 220 230 240 QNAIKAMHQS QTMEGCSSPI VVKFADTQKD KEQRRLQQQL AQQMQQLNTA TWGNLTGLGG 250 260 270 280 290 300 LTPQYLALLQ QATSSSNLGA FSGIQQMAGM NALQLQNLAT LAAAAAAAQT SATSTNANPL 310 320 330 340 350 360 STTSSALGAL TSPVAASTPN STAGAAMNSL TSLGTLQGLA GATVGLNNIN ALAVAQMLSG 370 380 390 400 410 420 MAALNGGLGA TGLTNGTAGT MDALTQAYSG IQQYAAAALP TLYSQSLLQQ QSAAGSQKEG 430 440 450 460 470 480 PEGANLFIYH LPQEFGDQDI LQMFMPFGNV ISAKVFIDKQ TNLSKCFGFV SYDNPVSAQA 490 500 AIQAMNGFQI GMKRLKVQLK RSKNDSKPY « Hide
Isoform 5 [UniParc]. Checksum: CBB835681201C245 Show »		488	52,054
10 20 30 40 50 60 MNGALDHSDQ PDPDAIKMFV GQIPRSWSEK ELKELFEPYG AVYQINVLRD RSQNPPQSKG 70 80 90 100 110 120 CCFVTFYTRK AALEAQNALH NIKTLPGMHH PIQMKPADSE KSNAVEDRKL FIGMVSKKCN 130 140 150 160 170 180 ENDIRVMFSP FGQIEECRIL RGPDGLSRGC AFVTFSTRAM AQNAIKAMHQ SQTMEGCSSP 190 200 210 220 230 240 IVVKFADTQK DKEQRRLQQQ LAQQMQQLNT ATWGNLTGLG GLTPQYLALL QQATSSSNLG 250 260 270 280 290 300 AFSGIQQMAG MNALQLQNLA TLAAAAAAAQ TSATSTNANP LSTTSSALGA LTSPVAASTP 310 320 330 340 350 360 NSTAGAAMNS LTSLGTLQGL AGATVGLNNI NALAGTINSM AALNGGLGAT GLTNGTAGTM 370 380 390 400 410 420 DALTQAYSGI QQYAAAALPT LYSQSLLQQQ SAAGSQKEGP EGANLFIYHL PQEFGDQDIL 430 440 450 460 470 480 QMFMPFGNVI SAKVFIDKQT NLSKCFGFVS YDNPVSAQAA IQAMNGFQIG MKRLKVQLKR SKNDSKPY « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Fluorescent differential display analysis of gene expression in apoptotic neuroblastoma cells." Choi D.-K., Ito T., Mitsui Y., Sakaki Y. Gene 223:21-31(1998) [PubMed: 9858671] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). Tissue: Brain.
[2]	"Developmentally-regulated expression of mNapor encoding an apoptosis-induced ELAV-type RNA binding protein." Choi D.-K., Ito T., Tsukahara F., Hirai M., Sakaki Y. Gene 237:135-142(1999) [PubMed: 10524244] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Brain.
[3]	"A family of human RNA-binding proteins related to the Drosophila Bruno translational regulator." Good P.J., Chen Q., Warner S.J., Herring D.C. J. Biol. Chem. 275:28583-28592(2000) [PubMed: 10893231] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Heart.
[4]	"Genomic organization and isoform-specific tissue expression of human NAPOR (CUGBP2) as a candidate gene for familial arrhythmogenic right ventricular dysplasia." Li D., Bachinski L.L., Roberts R. Genomics 74:396-401(2001) [PubMed: 11414768] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[5]	"Mutation screening of the NAPOR gene: a candidate for adult-onset primary open angle glaucoma (GLC1E) on 10p14." Sarfarazi M., Rezaie T. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[8]	"Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy." Timchenko L.T., Miller J.W., Timchenko N.A., DeVore D.R., Datar K.V., Lin L., Roberts R., Caskey C.T., Swanson M.S. Nucleic Acids Res. 24:4407-4414(1996) [PubMed: 8948631] [Abstract] Cited for: SUBCELLULAR LOCATION, RNA-BINDING.
[9]	"Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor." Anant S., Henderson J.O., Mukhopadhyay D., Navaratnam N., Kennedy S., Min J., Davidson N.O. J. Biol. Chem. 276:47338-47351(2001) [PubMed: 11577082] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH APOBEC1 AND A1CF, RNA-BINDING, SUBCELLULAR LOCATION.
[10]	"The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing." Ladd A.N., Charlet-B N., Cooper T.A. Mol. Cell. Biol. 21:1285-1296(2001) [PubMed: 11158314] [Abstract] Cited for: FUNCTION, RNA-BINDING, TISSUE SPECIFICITY.
[11]	"Dynamic antagonism between ETR-3 and PTB regulates cell type-specific alternative splicing." Charlet-B N., Logan P., Singh G., Cooper T.A. Mol. Cell 9:649-658(2002) [PubMed: 11931771] [Abstract] Cited for: FUNCTION, RNA-BINDING.
[12]	"Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein." Gromak N., Matlin A.J., Cooper T.A., Smith C.W. RNA 9:443-456(2003) [PubMed: 12649496] [Abstract] Cited for: FUNCTION, RNA-BINDING.
[13]	"ETR-3 and CELF4 protein domains required for RNA binding and splicing activity in vivo." Singh G., Charlet-B N., Han J., Cooper T.A. Nucleic Acids Res. 32:1232-1241(2004) [PubMed: 14973222] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING.
[14]	"Identification of putative new splicing targets for ETR-3 using sequences identified by systematic evolution of ligands by exponential enrichment." Faustino N.A., Cooper T.A. Mol. Cell. Biol. 25:879-887(2005) [PubMed: 15657417] [Abstract] Cited for: FUNCTION, RNA-BINDING.
[15]	"Identification of CELF splicing activation and repression domains in vivo." Han J., Cooper T.A. Nucleic Acids Res. 33:2769-2780(2005) [PubMed: 15894795] [Abstract] Cited for: FUNCTION.
[16]	"ETR-3 represses Tau exons 2/3 inclusion, a splicing event abnormally enhanced in myotonic dystrophy type I." Leroy O., Dhaenens C.-M., Schraen-Maschke S., Belarbi K., Delacourte A., Andreadis A., Sablonniere B., Buee L., Sergeant N., Caillet-Boudin M.-L. J. Neurosci. Res. 84:852-859(2006) [PubMed: 16862542] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AF090694 mRNA. Translation: AAD13761.1. AF090693 mRNA. Translation: AAD13760.1. AF036956 mRNA. Translation: AAD02074.1. U69546 mRNA. Translation: AAB09040.1. AF295068 AF295067 Genomic DNA. Translation: AAK72223.1. AF295068 AF314199 Genomic DNA. Translation: AAK72224.1. AF295068 AF295067 Genomic DNA. Translation: AAK92699.1. AF432906 mRNA. Translation: AAL27627.1. AL157704, AC026887, AL136320 Genomic DNA. Translation: CAH70230.1. AL136320, AC026887, AL157704 Genomic DNA. Translation: CAI20169.1. BC036391 mRNA. Translation: AAH36391.1.
RefSeq	NP_001020247.1. NP_001020248.1. NP_001077060.1. NP_006552.3.
UniGene	Hs.309288
3D structure databases
HSSP	HSSP built from PDB template 1UAW based on UniProtKB Q61474.
SMR	O95319. Positions 25-211, 405-506.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95319.
PTM databases
PhosphoSite	O95319.
Genome annotation databases
Ensembl	ENSG00000048740. Homo sapiens. [Contig view]
GeneID	10659.
KEGG	hsa:10659.
Organism-specific databases
HGNC	HGNC:2550. CUGBP2.
MIM	602538. gene.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	O95319.
Gene expression databases
ArrayExpress	O95319.
CleanEx	HS_CUGBP2.
Family and domain databases
InterPro	IPR012677. a_b_plait_nuc_bd. IPR002343. Hud_Sxl_RNA. IPR015903. RNP_BRUNO-like. IPR000504. RRM_RNP1. [Graphical view]
Gene3D	G3DSA:3.30.70.330. a_b_plait_nuc_bd. 3 hits.
PANTHER	PTHR10432:SF35. RNP_BRUNO-like. 1 hit.
Pfam	PF00076. RRM_1. 3 hits. [Graphical view]
PRINTS	PR00961. HUDSXLRNA.
SMART	SM00360. RRM. 3 hits. [Graphical view]
PROSITE	PS50102. RRM. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	40529.
SOURCE	Search...

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Entry information

Entry name

CELF2_HUMAN

Accession

Primary (citable) accession number: O95319
Secondary accession number(s): Q7KYU4

Q9UL67

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 10, 2007
Last sequence update:	May 1, 1999
Last modified:	November 25, 2008
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information