Q8C7Q4 (RBM4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RNA-binding protein 4

Alternative name(s):
Lark homolog
Short name=mLark
RNA-binding motif protein 4
RNA-binding motif protein 4a

Gene names

Name:	Rbm4
Synonyms:	Rbm4a

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	361 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 EIF2C2-containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro. Ref.4
Subunit structure	Interacts with TNPO3; the interaction mediates nuclear import of the protein and is disrupted by nuclear Ran bound to GTP. Interacts with EIF4G1 and WT1. Interacts with EIF4A1; the interaction is modulated under stress-induced conditions. Interacts with EIF2C1. Interacts with EIF2C2; the interaction occurs under both cell proliferation and differentiation conditions and in a RNA- and phosphorylation-independent manner. Interacts with DDX5; the interaction occurs in a RNA-independent manner By similarity.
Subcellular location	Nucleus By similarity. Nucleus › nucleolus By similarity. Nucleus speckle By similarity. Cytoplasm By similarity. Cytoplasmic granule By similarity. Note: Undergoes continuous nucleocytoplasmic shuttling. Upon nuclear import colocalizes with SR proteins in nuclear speckles. Arsenite stress-induced phosphorylation increases its subcellular relocalization from the nucleus to the cytoplasm and to cytoplasmic stress granules (SG) via a p38 MAPK signaling pathway. Primarily localized in nucleus and nucleoli under cell growth conditions and accumulated in the cytoplasm and cytoplasm perinuclear granules upon muscle cell differentiation By similarity. Ref.5
Tissue specificity	Expressed in the suprachiasmatic nucleus (SCN). Expressed in myocytes; expression gradually increases during muscle cell differentiation (at protein level). Expressed in the suprachiasmatic nucleus (SCN). Ref.4 Ref.5 Ref.6
Induction	Accumulates according to a circadian rhythm in the SCN. Ref.4
Post-translational modification	Phosphorylated. Phosphorylated in vitro on Ser-306 by SRPK1. Phosphorylation on Ser-306 is induced upon cell stress signaling, which alters its subcellular localization and may modulate its activity on IRES-mediated mRNA translation By similarity. Phosphorylated. Phosphorylation on Ser-306 is induced upon cell muscle differentiation. Ref.5
Sequence similarities	Contains 1 CCHC-type zinc finger. Contains 2 RRM (RNA recognition motif) domains.
Sequence caution	The sequence AAC53171.1 differs from that shown. Reason: Frameshift at position 239.

Ontologies

Keywords
Biological process	Differentiation RNA-mediated gene silencing mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	IRES-dependent translational initiation Inferred from sequence or structural similarity. Source: UniProtKB RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW circadian regulation of translation Inferred from direct assay Ref.4. Source: UniProtKB entrainment of circadian clock by photoperiod Inferred from direct assay Ref.4. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of translation in response to stress Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translation involved in gene silencing by miRNA Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translational initiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of muscle cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of alternative mRNA splicing, via spliceosome Inferred from sequence or structural similarity. Source: UniProtKB regulation of nucleocytoplasmic transport Inferred from direct assay Ref.5. Source: UniProtKB stress-activated MAPK cascade Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasmic stress granule Inferred from sequence or structural similarity. Source: UniProtKB nuclear speck Inferred from sequence or structural similarity. Source: UniProtKB nucleolus Inferred from direct assay Ref.5. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	mRNA 3'-UTR binding Inferred from direct assay Ref.4. Source: UniProtKB miRNA binding Inferred from sequence or structural similarity. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro pre-mRNA intronic pyrimidine-rich binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8C7Q4-1)

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: Q8C7Q4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     139-168: KRMHVQLSTSRLRTAPGMGDQSGCYRCGKE → ESLFWSAQYKAVRNELVEKRKALGWKDFAG
     169-361: Missing.

Note: May be due to an intron retention. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 361	361	RNA-binding protein 4		PRO_0000081755
Regions
	Domain	2 – 72	71	RRM 1
	Domain	78 – 148	71	RRM 2
	Zinc finger	160 – 177	18	CCHC-type
	Region	196 – 361	166	Interaction with TNPO3 By similarity
	Compositional bias	233 – 241	9	Poly-Ala
	Compositional bias	283 – 292	10	Poly-Ala
Amino acid modifications
	Modified residue	306	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	139 – 168	30	KRMHV…RCGKE → ESLFWSAQYKAVRNELVEKR KALGWKDFAG in isoform 2.		VSP_013417
	Alternative sequence	169 – 361	193	Missing in isoform 2.		VSP_013418
Experimental info
	Sequence conflict	243	1	S → N in AAC53171. Ref.1
	Sequence conflict	292	1	A → AAAAA in AAC53171. Ref.1
	Sequence conflict	299	1	S → P in AAC53171. Ref.1
	Sequence conflict	316	1	L → P in AAC53171. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: D50BB51553AFA4E0	FASTA	361	40,046
	10 20 30 40 50 60 MVKLFIGNLP REATEQEIRS LFEQYGKVLE CDIIKNYGFV HIEDKTAAED AIRNLHHYKL 70 80 90 100 110 120 HGVNINVEAS KNKSKASTKL HVGNISPTCT NQELRAKFEE YGPVIECDIV KDYAFVHMER 130 140 150 160 170 180 AEDAVEAIRG LDNTEFQGKR MHVQLSTSRL RTAPGMGDQS GCYRCGKEGH WSKECPIDRS 190 200 210 220 230 240 GRVADLTEQY NEQYGAVRTP YTMSYGDSLY YNNTYGALDA YYKRCRAARS YEAVAAAAAS 250 260 270 280 290 300 AYSNYAEQTL SQLPQVQNTA MASHLTSTSL DPYNRHLLPP SGAAAAAAAA AACTAASTSY 310 320 330 340 350 360 YGRDRSPLRR ATGPVLTVGE GYGYGHDSEL SQASAAARNS LYDMARYERE QYADRARYSA F
	Isoform 2 [UniParc]. Checksum: 5E2CD35CB4E4FEFB	FASTA	168	19,206
	10 20 30 40 50 60 MVKLFIGNLP REATEQEIRS LFEQYGKVLE CDIIKNYGFV HIEDKTAAED AIRNLHHYKL 70 80 90 100 110 120 HGVNINVEAS KNKSKASTKL HVGNISPTCT NQELRAKFEE YGPVIECDIV KDYAFVHMER 130 140 150 160 AEDAVEAIRG LDNTEFQGES LFWSAQYKAV RNELVEKRKA LGWKDFAG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel zinc finger-containing RNA-binding protein conserved from fruitflies to humans." Jackson F.R., Banfi S., Guffanti A., Rossi E. Genomics 41:444-452(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Eye and Spinal cord.
[3]	"Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic action of RBM4 and PTB." Lin J.C., Tarn W.Y. Mol. Cell. Biol. 25:10111-10121(2005) [PubMed] [Europe PMC] [Abstract] Cited for: RNA-BINDING.
[4]	"LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1." Kojima S., Matsumoto K., Hirose M., Shimada M., Nagano M., Shigeyoshi Y., Hoshino S., Ui-Tei K., Saigo K., Green C.B., Sakaki Y., Tei H. Proc. Natl. Acad. Sci. U.S.A. 104:1859-1864(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[5]	"RNA-binding motif protein 4 translocates to cytoplasmic granules and suppresses translation via argonaute2 during muscle cell differentiation." Lin J.C., Tarn W.Y. J. Biol. Chem. 284:34658-34665(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"RBM4 down-regulates PTB and antagonizes its activity in muscle cell-specific alternative splicing." Lin J.C., Tarn W.Y. J. Cell Biol. 193:509-520(2011) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U89506 mRNA. Translation: AAC53171.1. Frameshift. AK049659 mRNA. Translation: BAC33862.1. AK087488 mRNA. Translation: BAC39895.1.
IPI	IPI00309195. IPI00403780.
RefSeq	NP_033058.2. NM_009032.2.
UniGene	Mm.426069.
3D structure databases
ProteinModelPortal	Q8C7Q4.
SMR	Q8C7Q4. Positions 1-155.
ModBase	Search...
PTM databases
PhosphoSite	Q8C7Q4.
Proteomic databases
PaxDb	Q8C7Q4.
PRIDE	Q8C7Q4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000006628; ENSMUSP00000006628; ENSMUSG00000096370. ENSMUST00000180248; ENSMUSP00000137345; ENSMUSG00000094936.
GeneID	19653.
KEGG	mmu:19653.
Organism-specific databases
CTD	5936.
MGI	MGI:1100865. Rbm4.
Phylogenomic databases
eggNOG	NOG294108.
GeneTree	ENSGT00390000020883.
HOGENOM	HOG000026790.
HOVERGEN	HBG062217.
InParanoid	Q8C7Q4.
KO	K13187.
OrthoDB	EOG4NP74W.
Gene expression databases
ArrayExpress	Q8C7Q4.
Bgee	Q8C7Q4.
CleanEx	MM_RBM4.
Genevestigator	Q8C7Q4.
GermOnline	ENSMUSG00000056951. Mus musculus.
Family and domain databases
Gene3D	3.30.70.330. 2 hits. 4.10.60.10. 1 hit.
InterPro	IPR012677. Nucleotide-bd_a/b_plait. IPR000504. RRM_dom. IPR001878. Znf_CCHC. [Graphical view]
Pfam	PF00076. RRM_1. 2 hits. PF00098. zf-CCHC. 1 hit. [Graphical view]
SMART	SM00360. RRM. 2 hits. SM00343. ZnF_C2HC. 1 hit. [Graphical view]
PROSITE	PS50102. RRM. 2 hits. PS50158. ZF_CCHC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	296920.
SOURCE	Search...

Entry information

Entry name

RBM4_MOUSE

Accession

Primary (citable) accession number: Q8C7Q4
Secondary accession number(s): O08752, Q8BN66

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	March 1, 2003
Last modified:	April 3, 2013
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program