RBM4_MOUSE
ID RBM4_MOUSE Reviewed; 361 AA.
AC Q8C7Q4; O08752; Q8BN66;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=RNA-binding protein 4;
DE AltName: Full=Lark homolog;
DE Short=mLark;
DE AltName: Full=RNA-binding motif protein 4;
DE AltName: Full=RNA-binding motif protein 4a;
GN Name=Rbm4; Synonyms=Rbm4a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9169144; DOI=10.1006/geno.1997.4704;
RA Jackson F.R., Banfi S., Guffanti A., Rossi E.;
RT "A novel zinc finger-containing RNA-binding protein conserved from
RT fruitflies to humans.";
RL Genomics 41:444-452(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Eye, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP RNA-BINDING.
RX PubMed=16260624; DOI=10.1128/mcb.25.22.10111-10121.2005;
RA Lin J.C., Tarn W.Y.;
RT "Exon selection in alpha-tropomyosin mRNA is regulated by the antagonistic
RT action of RBM4 and PTB.";
RL Mol. Cell. Biol. 25:10111-10121(2005).
RN [4]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=17264215; DOI=10.1073/pnas.0607567104;
RA Kojima S., Matsumoto K., Hirose M., Shimada M., Nagano M., Shigeyoshi Y.,
RA Hoshino S., Ui-Tei K., Saigo K., Green C.B., Sakaki Y., Tei H.;
RT "LARK activates posttranscriptional expression of an essential mammalian
RT clock protein, PERIOD1.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1859-1864(2007).
RN [5]
RP PHOSPHORYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19801630; DOI=10.1074/jbc.m109.032946;
RA Lin J.C., Tarn W.Y.;
RT "RNA-binding motif protein 4 translocates to cytoplasmic granules and
RT suppresses translation via argonaute2 during muscle cell differentiation.";
RL J. Biol. Chem. 284:34658-34665(2009).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=21518792; DOI=10.1083/jcb.201007131;
RA Lin J.C., Tarn W.Y.;
RT "RBM4 down-regulates PTB and antagonizes its activity in muscle cell-
RT specific alternative splicing.";
RL J. Cell Biol. 193:509-520(2011).
CC -!- FUNCTION: RNA-binding factor involved in multiple aspects of cellular
CC processes like alternative splicing of pre-mRNA and translation
CC regulation. Modulates alternative 5'-splice site and exon selection.
CC Acts as a muscle cell differentiation-promoting factor. Activates exon
CC skipping of the PTB pre-mRNA during muscle cell differentiation.
CC Antagonizes the activity of the splicing factor PTBP1 to modulate
CC muscle cell-specific exon selection of alpha tropomyosin. Binds to
CC intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs.
CC Required for the translational activation of PER1 mRNA in response to
CC circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA. Exerts
CC a suppressive activity on Cap-dependent translation via binding to CU-
CC rich responsive elements within the 3'UTR of mRNAs, a process increased
CC under stress conditions or during myocytes differentiation. Recruits
CC EIF4A1 to stimulate IRES-dependent translation initiation in respons to
CC cellular stress. Associates to internal ribosome entry segment (IRES)
CC in target mRNA species under stress conditions. Plays a role for miRNA-
CC guided RNA cleavage and translation suppression by promoting
CC association of AGO2-containing miRNPs with their cognate target mRNAs.
CC Associates with miRNAs during muscle cell differentiation. Binds
CC preferentially to 5'-CGCGCG[GCA]-3' motif in vitro.
CC {ECO:0000269|PubMed:17264215}.
CC -!- SUBUNIT: Interacts with TNPO3; the interaction mediates nuclear import
CC of the protein and is disrupted by nuclear Ran bound to GTP. Interacts
CC with EIF4G1 and WT1. Interacts with EIF4A1; the interaction is
CC modulated under stress-induced conditions. Interacts with AGO1.
CC Interacts with AGO2; the interaction occurs under both cell
CC proliferation and differentiation conditions and in an RNA- and
CC phosphorylation-independent manner. Interacts with DDX5; the
CC interaction occurs in an RNA-independent manner (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus, nucleolus
CC {ECO:0000250}. Nucleus speckle {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Cytoplasmic granule {ECO:0000250}. Note=Undergoes continuous
CC nucleocytoplasmic shuttling. Upon nuclear import colocalizes with SR
CC proteins in nuclear speckles. Arsenite stress-induced phosphorylation
CC increases its subcellular relocalization from the nucleus to the
CC cytoplasm and to cytoplasmic stress granules (SG) via a p38 MAPK
CC signaling pathway. Primarily localized in nucleus and nucleoli under
CC cell growth conditions and accumulated in the cytoplasm and cytoplasm
CC perinuclear granules upon muscle cell differentiation (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C7Q4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C7Q4-2; Sequence=VSP_013417, VSP_013418;
CC -!- TISSUE SPECIFICITY: Expressed in the suprachiasmatic nucleus (SCN).
CC Expressed in myocytes; expression gradually increases during muscle
CC cell differentiation (at protein level). Expressed in the
CC suprachiasmatic nucleus (SCN). {ECO:0000269|PubMed:17264215,
CC ECO:0000269|PubMed:19801630, ECO:0000269|PubMed:21518792}.
CC -!- INDUCTION: Accumulates according to a circadian rhythm in the SCN.
CC {ECO:0000269|PubMed:17264215}.
CC -!- PTM: Phosphorylated. Phosphorylated in vitro on Ser-306 by SRPK1.
CC Phosphorylation on Ser-306 is induced upon cell stress signaling, which
CC alters its subcellular localization and may modulate its activity on
CC IRES-mediated mRNA translation (By similarity). Phosphorylated.
CC Phosphorylation on Ser-306 is induced upon cell muscle differentiation.
CC {ECO:0000250, ECO:0000269|PubMed:19801630}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC53171.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U89506; AAC53171.1; ALT_FRAME; mRNA.
DR EMBL; AK049659; BAC33862.1; -; mRNA.
DR EMBL; AK087488; BAC39895.1; -; mRNA.
DR CCDS; CCDS29436.1; -. [Q8C7Q4-1]
DR RefSeq; NP_001277051.1; NM_001290122.1. [Q8C7Q4-1]
DR RefSeq; NP_001277052.1; NM_001290123.1. [Q8C7Q4-1]
DR RefSeq; NP_001277053.1; NM_001290124.1.
DR RefSeq; NP_001277054.1; NM_001290125.1.
DR RefSeq; NP_033058.2; NM_009032.3. [Q8C7Q4-1]
DR AlphaFoldDB; Q8C7Q4; -.
DR SMR; Q8C7Q4; -.
DR BioGRID; 202822; 2.
DR BioGRID; 207870; 114.
DR IntAct; Q8C7Q4; 1.
DR STRING; 10090.ENSMUSP00000137345; -.
DR iPTMnet; Q8C7Q4; -.
DR PhosphoSitePlus; Q8C7Q4; -.
DR EPD; Q8C7Q4; -.
DR jPOST; Q8C7Q4; -.
DR MaxQB; Q8C7Q4; -.
DR PaxDb; Q8C7Q4; -.
DR PRIDE; Q8C7Q4; -.
DR DNASU; 19653; -.
DR Ensembl; ENSMUST00000179189; ENSMUSP00000137174; ENSMUSG00000094936. [Q8C7Q4-1]
DR Ensembl; ENSMUST00000180248; ENSMUSP00000137345; ENSMUSG00000094936. [Q8C7Q4-1]
DR GeneID; 19653; -.
DR KEGG; mmu:19653; -.
DR UCSC; uc008gau.1; mouse. [Q8C7Q4-1]
DR CTD; 5936; -.
DR MGI; MGI:1100865; Rbm4.
DR VEuPathDB; HostDB:ENSMUSG00000094936; -.
DR eggNOG; KOG0109; Eukaryota.
DR GeneTree; ENSGT00940000154421; -.
DR HOGENOM; CLU_045263_0_0_1; -.
DR InParanoid; Q8C7Q4; -.
DR PhylomeDB; Q8C7Q4; -.
DR TreeFam; TF320661; -.
DR BioGRID-ORCS; 19653; 3 hits in 40 CRISPR screens.
DR PRO; PR:Q8C7Q4; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8C7Q4; protein.
DR Bgee; ENSMUSG00000094936; Expressed in cortical plate and 212 other tissues.
DR ExpressionAtlas; Q8C7Q4; baseline and differential.
DR Genevisible; Q8C7Q4; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; ISO:MGI.
DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; ISO:MGI.
DR GO; GO:0036002; F:pre-mRNA binding; IDA:UniProtKB.
DR GO; GO:0097157; F:pre-mRNA intronic binding; ISS:UniProtKB.
DR GO; GO:0097158; F:pre-mRNA intronic pyrimidine-rich binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002190; P:cap-independent translational initiation; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:MGI.
DR GO; GO:0097167; P:circadian regulation of translation; IDA:UniProtKB.
DR GO; GO:0035883; P:enteroendocrine cell differentiation; IMP:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
DR GO; GO:0002192; P:IRES-dependent translational initiation of linear mRNA; ISS:UniProtKB.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; ISS:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:0032055; P:negative regulation of translation in response to stress; ISS:UniProtKB.
DR GO; GO:0045947; P:negative regulation of translational initiation; ISS:UniProtKB.
DR GO; GO:0031016; P:pancreas development; IMP:MGI.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IDA:MGI.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IDA:MGI.
DR GO; GO:0046822; P:regulation of nucleocytoplasmic transport; IDA:UniProtKB.
DR GO; GO:0046685; P:response to arsenic-containing substance; ISS:UniProtKB.
DR CDD; cd12606; RRM1_RBM4; 1.
DR CDD; cd12607; RRM2_RBM4; 1.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR034897; RBM4_RRM1.
DR InterPro; IPR034898; RBM4_RRM2.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR001878; Znf_CCHC.
DR Pfam; PF00076; RRM_1; 2.
DR Pfam; PF00098; zf-CCHC; 1.
DR SMART; SM00360; RRM; 2.
DR SMART; SM00343; ZnF_C2HC; 1.
DR SUPFAM; SSF54928; SSF54928; 2.
DR PROSITE; PS50102; RRM; 2.
DR PROSITE; PS50158; ZF_CCHC; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; Differentiation;
KW Isopeptide bond; Metal-binding; mRNA processing; mRNA splicing; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW RNA-mediated gene silencing; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..361
FT /note="RNA-binding protein 4"
FT /id="PRO_0000081755"
FT DOMAIN 2..72
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 78..148
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT ZN_FING 160..177
FT /note="CCHC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 196..361
FT /note="Interaction with TNPO3"
FT /evidence="ECO:0000250"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BWF3"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BWF3"
FT CROSSLNK 79
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9BWF3"
FT VAR_SEQ 139..168
FT /note="KRMHVQLSTSRLRTAPGMGDQSGCYRCGKE -> ESLFWSAQYKAVRNELVE
FT KRKALGWKDFAG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013417"
FT VAR_SEQ 169..361
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013418"
FT CONFLICT 243
FT /note="S -> N (in Ref. 1; AAC53171)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="A -> AAAAA (in Ref. 1; AAC53171)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="S -> P (in Ref. 1; AAC53171)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="L -> P (in Ref. 1; AAC53171)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 361 AA; 40046 MW; D50BB51553AFA4E0 CRC64;
MVKLFIGNLP REATEQEIRS LFEQYGKVLE CDIIKNYGFV HIEDKTAAED AIRNLHHYKL
HGVNINVEAS KNKSKASTKL HVGNISPTCT NQELRAKFEE YGPVIECDIV KDYAFVHMER
AEDAVEAIRG LDNTEFQGKR MHVQLSTSRL RTAPGMGDQS GCYRCGKEGH WSKECPIDRS
GRVADLTEQY NEQYGAVRTP YTMSYGDSLY YNNTYGALDA YYKRCRAARS YEAVAAAAAS
AYSNYAEQTL SQLPQVQNTA MASHLTSTSL DPYNRHLLPP SGAAAAAAAA AACTAASTSY
YGRDRSPLRR ATGPVLTVGE GYGYGHDSEL SQASAAARNS LYDMARYERE QYADRARYSA
F
