Reviewed, UniProtKB/Swiss-Prot Q9BZC1 (CELF4_HUMAN)

Names and origin

Protein names

Recommended name:
    CUG-BP- and ETR-3-like factor 4
      Short name=CELF-4
Alternative name(s):
    Bruno-like protein 4
    RNA-binding protein BRUNOL-4

Gene names

Name:	BRUNOL4
Synonyms:	CELF4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	486 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing. 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 cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Promotes exclusion of both the smooth muscle (SM) and non-muscle (NM) exons in actinin pre-mRNAs. Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA. Ref.1 Ref.7 Ref.8 Ref.9
Subcellular location	Nucleus. Cytoplasm.
Tissue specificity	Ubiquitous. Strongly expressed in the cerebellum, hippocampus, amygdala, temporal and frontal cortex and frontal lobes. Ref.1 Ref.6 Ref.10
Sequence similarities	Belongs to the CELF/BRUNOL family. Contains 3 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	RNA-binding
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	embryonic development Ref.5 Non-traceable author statement. Source: UniProtKB germ cell development Ref.5 Non-traceable author statement. Source: UniProtKB regulation of alternative nuclear mRNA splicing, via spliceosome Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	BRE binding Inferred from sequence or structural similarity. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro translation repressor activity, nucleic acid binding Ref.5 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9BZC1-1)

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: Q9BZC1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     150-151: QD → H
     388-389: GP → A

Isoform 3 (identifier: Q9BZC1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     150-151: QD → H
     268-268: Missing.

Isoform 4 (identifier: Q9BZC1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     268-268: Missing.

Isoform 5 (identifier: Q9BZC1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     140-150: GSSCLRQPPSQ → E
     417-444: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 486

486

CUG-BP- and ETR-3-like factor 4

PRO_0000295221

Regions

Domain

54 – 135

82

RRM 1

Domain

152 – 232

81

RRM 2

Domain

404 – 479

76

RRM 3

Region

1 – 298

298

Sufficient for RNA-binding and MSE-dependent splicing activity

Region

239 – 258

20

Necessary for TNNT2 exon 5 inclusion

Compositional bias

260 – 310

51

Ala-rich

Natural variations

Alternative sequence

140 – 150

11

GSSCLRQPPSQ → E in isoform 5.

VSP_026828

Alternative sequence

150 – 151

2

QD → H in isoform 2 and isoform 3.

VSP_026829

Alternative sequence

268

1

Missing in isoform 3 and isoform 4.

VSP_026830

Alternative sequence

388 – 389

2

GP → A in isoform 2.

VSP_026831

Alternative sequence

417 – 444

28

Missing in isoform 5.

VSP_026832

Natural variant

388

1

G → S: dbSNP rs12458669.

VAR_052203

Experimental info

Sequence conflict

60

1

Q → R in BAC11082. Ref.2

Sequence conflict

166

1

D → E in BAC11082. Ref.2

Sequence conflict

215

1

S → G in BAC11082. Ref.2

Sequence conflict

237

1

T → M in BAC11082. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

486

Helix Strand Turn

Details...

Beta strand

153 – 158

6

Helix

165 – 173

9

Beta strand

178 – 185

8

Beta strand

189 – 201

13

Helix

202 – 212

11

Turn

213 – 215

3

Beta strand

226 – 229

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 17EA8A6A6752C565	FASTA	486	51,966
	10 20 30 40 50 60 MYIKMATLAN GQADNASLST NGLGSSPGSA GHMNGLSHSP GNPSTIPMKD HDAIKLFIGQ 70 80 90 100 110 120 IPRNLDEKDL KPLFEEFGKI YELTVLKDRF TGMHKGCAFL TYCERESALK AQSALHEQKT 130 140 150 160 170 180 LPGMNRPIQV KPADSESRGG SSCLRQPPSQ DRKLFVGMLN KQQSEDDVRR LFEAFGNIEE 190 200 210 220 230 240 CTILRGPDGN SKGCAFVKYS SHAEAQAAIN ALHGSQTMPG ASSSLVVKFA DTDKERTMRR 250 260 270 280 290 300 MQQMAGQMGM FNPMAIPFGA YGAYAQALMQ QQAALMASVA QGGYLNPMAA FAAAQMQQMA 310 320 330 340 350 360 ALNMNGLAAA PMTPTSGGST PPGITAPAVP SIPSPIGVNG FTGLPPQANG QPAAEAVFAN 370 380 390 400 410 420 GIHPYPAQSP TAADPLQQAY AGVQQYAGPA AYPAAYGQIS QAFPQPPPMI PQQQREGPEG 430 440 450 460 470 480 CNLFIYHLPQ EFGDAELMQM FLPFGFVSFD NPASAQTAIQ AMNGFQIGMK RLKVQLKRPK DANRPY
	Isoform 2. Checksum: EAB4512456ED8FAA	FASTA	484	51,777
	10 20 30 40 50 60 MYIKMATLAN GQADNASLST NGLGSSPGSA GHMNGLSHSP GNPSTIPMKD HDAIKLFIGQ 70 80 90 100 110 120 IPRNLDEKDL KPLFEEFGKI YELTVLKDRF TGMHKGCAFL TYCERESALK AQSALHEQKT 130 140 150 160 170 180 LPGMNRPIQV KPADSESRGG SSCLRQPPSH RKLFVGMLNK QQSEDDVRRL FEAFGNIEEC 190 200 210 220 230 240 TILRGPDGNS KGCAFVKYSS HAEAQAAINA LHGSQTMPGA SSSLVVKFAD TDKERTMRRM 250 260 270 280 290 300 QQMAGQMGMF NPMAIPFGAY GAYAQALMQQ QAALMASVAQ GGYLNPMAAF AAAQMQQMAA 310 320 330 340 350 360 LNMNGLAAAP MTPTSGGSTP PGITAPAVPS IPSPIGVNGF TGLPPQANGQ PAAEAVFANG 370 380 390 400 410 420 IHPYPAQSPT AADPLQQAYA GVQQYAAAAY PAAYGQISQA FPQPPPMIPQ QQREGPEGCN 430 440 450 460 470 480 LFIYHLPQEF GDAELMQMFL PFGFVSFDNP ASAQTAIQAM NGFQIGMKRL KVQLKRPKDA NRPY
	Isoform 3. Checksum: 090258D14ECB73FC	FASTA	484	51,747
	10 20 30 40 50 60 MYIKMATLAN GQADNASLST NGLGSSPGSA GHMNGLSHSP GNPSTIPMKD HDAIKLFIGQ 70 80 90 100 110 120 IPRNLDEKDL KPLFEEFGKI YELTVLKDRF TGMHKGCAFL TYCERESALK AQSALHEQKT 130 140 150 160 170 180 LPGMNRPIQV KPADSESRGG SSCLRQPPSH RKLFVGMLNK QQSEDDVRRL FEAFGNIEEC 190 200 210 220 230 240 TILRGPDGNS KGCAFVKYSS HAEAQAAINA LHGSQTMPGA SSSLVVKFAD TDKERTMRRM 250 260 270 280 290 300 QQMAGQMGMF NPMAIPFGAY GAYAQAMQQQ AALMASVAQG GYLNPMAAFA AAQMQQMAAL 310 320 330 340 350 360 NMNGLAAAPM TPTSGGSTPP GITAPAVPSI PSPIGVNGFT GLPPQANGQP AAEAVFANGI 370 380 390 400 410 420 HPYPAQSPTA ADPLQQAYAG VQQYAGPAAY PAAYGQISQA FPQPPPMIPQ QQREGPEGCN 430 440 450 460 470 480 LFIYHLPQEF GDAELMQMFL PFGFVSFDNP ASAQTAIQAM NGFQIGMKRL KVQLKRPKDA NRPY
	Isoform 4. Checksum: 430142CAE54F71BB	FASTA	485	51,853
	10 20 30 40 50 60 MYIKMATLAN GQADNASLST NGLGSSPGSA GHMNGLSHSP GNPSTIPMKD HDAIKLFIGQ 70 80 90 100 110 120 IPRNLDEKDL KPLFEEFGKI YELTVLKDRF TGMHKGCAFL TYCERESALK AQSALHEQKT 130 140 150 160 170 180 LPGMNRPIQV KPADSESRGG SSCLRQPPSQ DRKLFVGMLN KQQSEDDVRR LFEAFGNIEE 190 200 210 220 230 240 CTILRGPDGN SKGCAFVKYS SHAEAQAAIN ALHGSQTMPG ASSSLVVKFA DTDKERTMRR 250 260 270 280 290 300 MQQMAGQMGM FNPMAIPFGA YGAYAQAMQQ QAALMASVAQ GGYLNPMAAF AAAQMQQMAA 310 320 330 340 350 360 LNMNGLAAAP MTPTSGGSTP PGITAPAVPS IPSPIGVNGF TGLPPQANGQ PAAEAVFANG 370 380 390 400 410 420 IHPYPAQSPT AADPLQQAYA GVQQYAGPAA YPAAYGQISQ AFPQPPPMIP QQQREGPEGC 430 440 450 460 470 480 NLFIYHLPQE FGDAELMQMF LPFGFVSFDN PASAQTAIQA MNGFQIGMKR LKVQLKRPKD ANRPY
	Isoform 5. Checksum: F518F3D37DA1386C	FASTA	448	47,727
	10 20 30 40 50 60 MYIKMATLAN GQADNASLST NGLGSSPGSA GHMNGLSHSP GNPSTIPMKD HDAIKLFIGQ 70 80 90 100 110 120 IPRNLDEKDL KPLFEEFGKI YELTVLKDRF TGMHKGCAFL TYCERESALK AQSALHEQKT 130 140 150 160 170 180 LPGMNRPIQV KPADSESRGE DRKLFVGMLN KQQSEDDVRR LFEAFGNIEE CTILRGPDGN 190 200 210 220 230 240 SKGCAFVKYS SHAEAQAAIN ALHGSQTMPG ASSSLVVKFA DTDKERTMRR MQQMAGQMGM 250 260 270 280 290 300 FNPMAIPFGA YGAYAQALMQ QQAALMASVA QGGYLNPMAA FAAAQMQQMA ALNMNGLAAA 310 320 330 340 350 360 PMTPTSGGST PPGITAPAVP SIPSPIGVNG FTGLPPQANG QPAAEAVFAN GIHPYPAQSP 370 380 390 400 410 420 TAADPLQQAY AGVQQYAGPA AYPAAYGQIS QAFPQPPPMI PQQQREGFVS FDNPASAQTA 430 440 IQAMNGFQIG MKRLKVQLKR PKDANRPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, RNA-BINDING, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Embryo.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Brain.
[4]	"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] (ISOFORMS 2 AND 5). Tissue: Brain and Lung.
[5]	"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] OF 1-304 (ISOFORM 5), NUCLEOTIDE SEQUENCE [MRNA] OF 324-486 (ISOFORMS 1/3/4).
[6]	"Identification and characterization of murine Brunol4, a new member of the elav/bruno family." Meins M., Schlickum S., Wilhelm C., Missbach J., Yadav S., Glaeser B., Grzmil M., Burfeind P., Laccone F. Cytogenet. Genome Res. 97:254-260(2002) [PubMed: 12438720] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"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.
[8]	"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.
[9]	"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, RNA-BINDING.
[10]	"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.
[11]	"Solution structure of RNA-binding domain in Bruno-like 4 RNA-binding protein." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 143-235.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF329265 mRNA. Translation: AAK07475.1.
AK074596 mRNA. Translation: BAC11082.1.
AB209774 mRNA. Translation: BAD93011.1. Different initiation.
BC001946 mRNA. Translation: AAH01946.2.
BC004167 mRNA. Translation: AAH04167.2.
BC045711 mRNA. Translation: AAH45711.1.
AF248650 mRNA. Translation: AAF86232.1.
AF248651 mRNA. Translation: AAF86233.1.

IPI

IPI00024603.
IPI00384535.
IPI00853216.
IPI00853277.
IPI00853444.

RefSeq

NP_001020258.1.
NP_001020259.1.
NP_001020260.1.
NP_064565.1.

UniGene

Hs.435976
Hs.600908

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DGP	NMR	-	A	48-141	[»]
2DNK	NMR	-	A	152-235	[»]

SMR

Q9BZC1. Positions 414-484.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9BZC1.

Proteomic databases

PRIDE

Q9BZC1.

Genome annotation databases

Ensembl

ENST00000361795; ENSP00000355089; ENSG00000101489; Homo sapiens. [Genome view]

GeneID

56853.

KEGG

hsa:56853.

UCSC

uc002lae.2. human.
uc002laf.2. human.
uc002lag.2. human.
uc010dnd.1. human.

Organism-specific databases

CTD

56853.

GeneCards

GC18M033078.

HGNC

HGNC:14015. BRUNOL4.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9BZC1.

OMA

ATLTNGQ

OrthoDB

EOG9V19KN

Gene expression databases

ArrayExpress

Q9BZC1.

Bgee

Q9BZC1.

CleanEx

HS_BRUNOL4.

Genevestigator

Q9BZC1.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
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]

SMART

SM00360. RRM. 3 hits.
[Graphical view]

PROSITE

PS50102. RRM. 3 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

62266.

Entry information

Entry name

CELF4_HUMAN

Accession

Primary (citable) accession number: Q9BZC1
Secondary accession number(s): Q59EN7 , Q86XB9, Q8N2M6, Q9BQ96, Q9NR84, Q9NR85

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 10, 2007
Last sequence update:	June 1, 2001
Last modified:	November 24, 2009
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.