RBM4_HUMAN
ID RBM4_HUMAN Reviewed; 364 AA.
AC Q9BWF3; B3KUN0; B4E1U0; E7EQS3; O02916; Q4VC48; Q6P1P2; Q8WU85;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=RNA-binding protein 4;
DE AltName: Full=Lark homolog;
DE Short=hLark;
DE AltName: Full=RNA-binding motif protein 4;
DE AltName: Full=RNA-binding motif protein 4a;
GN Name=RBM4; Synonyms=RBM4A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
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 4).
RC TISSUE=Testis, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Lung, Pancreas, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=12469345;
RX DOI=10.1002/1615-9861(200212)2:12<1752::aid-prot1752>3.0.co;2-y;
RA Bernert G., Fountoulakis M., Lubec G.;
RT "Manifold decreased protein levels of matrin 3, reduced motor protein HMP
RT and hlark in fetal Down's syndrome brain.";
RL Proteomics 2:1752-1757(2002).
RN [7]
RP FUNCTION, INTERACTION WITH TNPO3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF TYR-37; PHE-39; TYR-113 AND PHE-115.
RX PubMed=12628928; DOI=10.1093/emboj/cdg126;
RA Lai M.-C., Kuo H.-W., Chang W.-C., Tarn W.-Y.;
RT "A novel splicing regulator shares a nuclear import pathway with SR
RT proteins.";
RL EMBO J. 22:1359-1369(2003).
RN [8]
RP FUNCTION, RNA-BINDING, AND TISSUE SPECIFICITY.
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 [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=16907643; DOI=10.1089/dna.2006.25.457;
RA Markus M.A., Morris B.J.;
RT "Lark is the splicing factor RBM4 and exhibits unique subnuclear
RT localization properties.";
RL DNA Cell Biol. 25:457-464(2006).
RN [11]
RP FUNCTION, INTERACTION WITH WT1, AND SUBCELLULAR LOCATION.
RX PubMed=16934801; DOI=10.1016/j.yexcr.2006.07.008;
RA Markus M.A., Heinrich B., Raitskin O., Adams D.J., Mangs H., Goy C.,
RA Ladomery M., Sperling R., Stamm S., Morris B.J.;
RT "WT1 interacts with the splicing protein RBM4 and regulates its ability to
RT modulate alternative splicing in vivo.";
RL Exp. Cell Res. 312:3379-3388(2006).
RN [12]
RP FUNCTION, RNA-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=16777844; DOI=10.1074/jbc.m603971200;
RA Kar A., Havlioglu N., Tarn W.Y., Wu J.Y.;
RT "RBM4 interacts with an intronic element and stimulates tau exon 10
RT inclusion.";
RL J. Biol. Chem. 281:24479-24488(2006).
RN [13]
RP FUNCTION, INTERACTION WITH EIF4A1 AND EIF4G1, PHOSPHORYLATION AT SER-309,
RP ASSOCIATION WITH IRES OF MRNAS, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-309.
RX PubMed=17284590; DOI=10.1073/pnas.0611015104;
RA Lin J.C., Hsu M., Tarn W.Y.;
RT "Cell stress modulates the function of splicing regulatory protein RBM4 in
RT translation control.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2235-2240(2007).
RN [14]
RP FUNCTION, AND INTERACTION WITH AGO1 AND AGO2.
RX PubMed=17932509; DOI=10.1038/sj.embor.7401088;
RA Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M.,
RA Urlaub H., Meister G.;
RT "Proteomic and functional analysis of Argonaute-containing mRNA-protein
RT complexes in human cells.";
RL EMBO Rep. 8:1052-1060(2007).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [16]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18708123; DOI=10.1016/j.neulet.2008.08.017;
RA Pfuhl T., Mamiani A., Durr M., Welter S., Stieber J., Ankara J., Liss M.,
RA Dobner T., Schmitt A., Falkai P., Kremmer E., Jung V., Barth S.,
RA Grasser F.A.;
RT "The LARK/RBM4a protein is highly expressed in cerebellum as compared to
RT cerebrum.";
RL Neurosci. Lett. 444:11-15(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP FUNCTION, INTERACTION WITH AGO2, MUTAGENESIS OF SER-309, AND SUBCELLULAR
RP LOCATION.
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 [19]
RP RNA-BINDING.
RX PubMed=19561594; DOI=10.1038/nbt.1550;
RA Ray D., Kazan H., Chan E.T., Pena Castillo L., Chaudhry S., Talukder S.,
RA Blencowe B.J., Morris Q., Hughes T.R.;
RT "Rapid and systematic analysis of the RNA recognition specificities of RNA-
RT binding proteins.";
RL Nat. Biotechnol. 27:667-670(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP FUNCTION, AND MUTAGENESIS OF SER-309.
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).
RN [23]
RP FUNCTION, INTERACTION WITH DDX5, AND RNA-BINDING.
RX PubMed=21343338; DOI=10.1128/mcb.01149-10;
RA Kar A., Fushimi K., Zhou X., Ray P., Shi C., Chen X., Liu Z., Chen S.,
RA Wu J.Y.;
RT "RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a
RT stem-loop structure at the 5' splice site.";
RL Mol. Cell. Biol. 31:1812-1821(2011).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-79 AND LYS-92, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [27]
RP STRUCTURE BY NMR OF 1-77.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RNA binding domain 1 in RNA-binding protein 30.";
RL Submitted (OCT-2006) to the PDB data bank.
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:12628928, ECO:0000269|PubMed:16260624,
CC ECO:0000269|PubMed:16777844, ECO:0000269|PubMed:16934801,
CC ECO:0000269|PubMed:17284590, ECO:0000269|PubMed:17932509,
CC ECO:0000269|PubMed:19801630, ECO:0000269|PubMed:21343338,
CC ECO:0000269|PubMed:21518792}.
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.
CC {ECO:0000269|PubMed:12628928, ECO:0000269|PubMed:16934801,
CC ECO:0000269|PubMed:17284590, ECO:0000269|PubMed:17932509,
CC ECO:0000269|PubMed:19801630, ECO:0000269|PubMed:21343338}.
CC -!- INTERACTION:
CC Q9BWF3; Q86V38: ATN1; NbExp=3; IntAct=EBI-2856454, EBI-11954292;
CC Q9BWF3; P02489: CRYAA; NbExp=3; IntAct=EBI-2856454, EBI-6875961;
CC Q9BWF3; P22607: FGFR3; NbExp=3; IntAct=EBI-2856454, EBI-348399;
CC Q9BWF3; Q92876: KLK6; NbExp=3; IntAct=EBI-2856454, EBI-2432309;
CC Q9BWF3-1; P60842: EIF4A1; NbExp=3; IntAct=EBI-15621561, EBI-73449;
CC Q9BWF3-1; Q04637: EIF4G1; NbExp=4; IntAct=EBI-15621561, EBI-73711;
CC Q9BWF3-1; Q99814: EPAS1; NbExp=6; IntAct=EBI-15621561, EBI-447470;
CC Q9BWF3-2; P01100: FOS; NbExp=3; IntAct=EBI-25856809, EBI-852851;
CC Q9BWF3-2; P62993: GRB2; NbExp=3; IntAct=EBI-25856809, EBI-401755;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Nucleus speckle.
CC Cytoplasm. Cytoplasmic granule. 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.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9BWF3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BWF3-2; Sequence=VSP_013414, VSP_013416;
CC Name=3;
CC IsoId=Q9BWF3-3; Sequence=VSP_013413, VSP_013415;
CC Name=4;
CC IsoId=Q9BWF3-4; Sequence=VSP_044493;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebellum. Expressed in neurons
CC and glial cells, including layers II neurons in the frontal cortex and
CC CA1 pyramidal neurons in the hippocampus. Expressed in heart, liver,
CC pancreas, skeletal muscle, placenta, primary fibroblasts and peripheral
CC blood monocytes (at protein level). Ubiquitously expressed. Highly
CC expressed in heart, placenta and skeletal muscle. Weakly expressed in
CC pancreas, kidney, liver, lung and brain. {ECO:0000269|PubMed:12628928,
CC ECO:0000269|PubMed:16260624, ECO:0000269|PubMed:16777844,
CC ECO:0000269|PubMed:18708123}.
CC -!- DEVELOPMENTAL STAGE: Found to be expressed in fetal brain. Down-
CC regulated in fetal Down syndrome (DS) brain.
CC {ECO:0000269|PubMed:12469345}.
CC -!- PTM: Phosphorylation on Ser-309 is induced upon cell muscle
CC differentiation (By similarity). Phosphorylated. Phosphorylated in
CC vitro on Ser-309 by SRPK1. Phosphorylation on Ser-309 is induced upon
CC cell stress signaling, which alters its subcellular localization and
CC may modulate its activity on IRES-mediated mRNA translation.
CC {ECO:0000250, ECO:0000269|PubMed:17284590}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to an intron retention.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be due to exon skipping. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC51293.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U89505; AAC51293.1; ALT_FRAME; mRNA.
DR EMBL; AK097592; BAG53492.1; -; mRNA.
DR EMBL; AK303984; BAG64902.1; -; mRNA.
DR EMBL; AL832566; CAH10593.1; -; mRNA.
DR EMBL; AP001157; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000307; AAH00307.1; -; mRNA.
DR EMBL; BC021120; AAH21120.1; -; mRNA.
DR EMBL; BC032735; AAH32735.1; -; mRNA.
DR EMBL; BC064960; AAH64960.1; -; mRNA.
DR CCDS; CCDS41676.1; -. [Q9BWF3-1]
DR CCDS; CCDS55776.1; -. [Q9BWF3-3]
DR CCDS; CCDS55777.1; -. [Q9BWF3-4]
DR RefSeq; NP_001185772.1; NM_001198843.1. [Q9BWF3-3]
DR RefSeq; NP_001185773.1; NM_001198844.1. [Q9BWF3-4]
DR RefSeq; NP_002887.2; NM_002896.3. [Q9BWF3-1]
DR PDB; 2DNQ; NMR; -; A=1-77.
DR PDBsum; 2DNQ; -.
DR AlphaFoldDB; Q9BWF3; -.
DR SMR; Q9BWF3; -.
DR BioGRID; 111871; 309.
DR DIP; DIP-44199N; -.
DR IntAct; Q9BWF3; 169.
DR MINT; Q9BWF3; -.
DR STRING; 9606.ENSP00000386894; -.
DR MoonDB; Q9BWF3; Predicted.
DR GlyGen; Q9BWF3; 7 sites, 2 O-linked glycans (7 sites).
DR iPTMnet; Q9BWF3; -.
DR PhosphoSitePlus; Q9BWF3; -.
DR SwissPalm; Q9BWF3; -.
DR BioMuta; RBM4; -.
DR DMDM; 62511089; -.
DR EPD; Q9BWF3; -.
DR jPOST; Q9BWF3; -.
DR MassIVE; Q9BWF3; -.
DR MaxQB; Q9BWF3; -.
DR PaxDb; Q9BWF3; -.
DR PeptideAtlas; Q9BWF3; -.
DR PRIDE; Q9BWF3; -.
DR ProteomicsDB; 17633; -.
DR ProteomicsDB; 79272; -. [Q9BWF3-1]
DR ProteomicsDB; 79273; -. [Q9BWF3-2]
DR ProteomicsDB; 79274; -. [Q9BWF3-3]
DR Antibodypedia; 7534; 238 antibodies from 27 providers.
DR DNASU; 5936; -.
DR Ensembl; ENST00000310092.12; ENSP00000309166.8; ENSG00000173933.21. [Q9BWF3-1]
DR Ensembl; ENST00000396053.9; ENSP00000413497.3; ENSG00000173933.21. [Q9BWF3-4]
DR Ensembl; ENST00000398692.8; ENSP00000381680.4; ENSG00000173933.21. [Q9BWF3-3]
DR Ensembl; ENST00000408993.6; ENSP00000386561.2; ENSG00000173933.21. [Q9BWF3-1]
DR Ensembl; ENST00000409406.1; ENSP00000386894.1; ENSG00000173933.21. [Q9BWF3-1]
DR Ensembl; ENST00000483858.5; ENSP00000435821.1; ENSG00000173933.21. [Q9BWF3-2]
DR Ensembl; ENST00000530235.1; ENSP00000432150.1; ENSG00000173933.21. [Q9BWF3-3]
DR Ensembl; ENST00000532968.1; ENSP00000432020.1; ENSG00000173933.21. [Q9BWF3-2]
DR GeneID; 5936; -.
DR KEGG; hsa:5936; -.
DR MANE-Select; ENST00000310092.12; ENSP00000309166.8; NM_002896.4; NP_002887.2.
DR UCSC; uc001oiv.4; human. [Q9BWF3-1]
DR CTD; 5936; -.
DR DisGeNET; 5936; -.
DR GeneCards; RBM4; -.
DR HGNC; HGNC:9901; RBM4.
DR HPA; ENSG00000173933; Low tissue specificity.
DR MIM; 602571; gene.
DR neXtProt; NX_Q9BWF3; -.
DR OpenTargets; ENSG00000173933; -.
DR PharmGKB; PA34266; -.
DR VEuPathDB; HostDB:ENSG00000173933; -.
DR eggNOG; KOG0109; Eukaryota.
DR GeneTree; ENSGT00940000154421; -.
DR HOGENOM; CLU_045263_0_0_1; -.
DR InParanoid; Q9BWF3; -.
DR OMA; ACNTTPE; -.
DR OrthoDB; 1563362at2759; -.
DR PhylomeDB; Q9BWF3; -.
DR TreeFam; TF320661; -.
DR PathwayCommons; Q9BWF3; -.
DR Reactome; R-HSA-400253; Circadian Clock.
DR SignaLink; Q9BWF3; -.
DR SIGNOR; Q9BWF3; -.
DR BioGRID-ORCS; 5936; 156 hits in 1078 CRISPR screens.
DR ChiTaRS; RBM4; human.
DR EvolutionaryTrace; Q9BWF3; -.
DR GeneWiki; RBM4; -.
DR GenomeRNAi; 5936; -.
DR Pharos; Q9BWF3; Tbio.
DR PRO; PR:Q9BWF3; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BWF3; protein.
DR Bgee; ENSG00000173933; Expressed in cortical plate and 188 other tissues.
DR ExpressionAtlas; Q9BWF3; baseline and differential.
DR Genevisible; Q9BWF3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0030332; F:cyclin binding; IPI:UniProtKB.
DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0097157; F:pre-mRNA intronic binding; IDA:UniProtKB.
DR GO; GO:0097158; F:pre-mRNA intronic pyrimidine-rich binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002190; P:cap-independent translational initiation; IDA:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IEA:Ensembl.
DR GO; GO:0097167; P:circadian regulation of translation; ISS:UniProtKB.
DR GO; GO:0035883; P:enteroendocrine cell differentiation; IEA:Ensembl.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0002192; P:IRES-dependent translational initiation of linear mRNA; IDA:UniProtKB.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IDA:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0032055; P:negative regulation of translation in response to stress; IDA:UniProtKB.
DR GO; GO:0045947; P:negative regulation of translational initiation; IDA:UniProtKB.
DR GO; GO:0031016; P:pancreas development; IEA:Ensembl.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; IDA:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0046822; P:regulation of nucleocytoplasmic transport; IDA:UniProtKB.
DR GO; GO:0046685; P:response to arsenic-containing substance; IDA:UniProtKB.
DR GO; GO:0006396; P:RNA processing; TAS:ProtInc.
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 3D-structure; 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..364
FT /note="RNA-binding protein 4"
FT /id="PRO_0000081754"
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..364
FT /note="Interaction with TNPO3"
FT /evidence="ECO:0000269|PubMed:12628928"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17284590"
FT CROSSLNK 79
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 92
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 139..177
FT /note="KRMHVQLSTSRLRTAPGMGDQSGCYRCGKEGHWSKECPI -> EPPSLGRGL
FT NTRLCAENGWISKRRGLVKITAVGWLVMKK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_013414"
FT VAR_SEQ 139..143
FT /note="KRMHV -> GMCVG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013413"
FT VAR_SEQ 140..364
FT /note="RMHVQLSTSRLRTAPGMGDQSGCYRCGKEGHWSKECPIDRSGRVADLTEQYN
FT EQYGAVRTPYTMSYGDSLYYNNAYGALDAYYKRCRAARSYEAVAAAAASVYNYAEQTLS
FT QLPQVQNTAMASHLTSTSLDPYDRHLLPTSGAAATAAAAAAAAAAVTAASTSYYGRDRS
FT PLRRATAPVPTVGEGYGYGHESELSQASAAARNSLYDMARYEREQYADRARYSAF ->
FT ITPVTEGYCCCNKGHTYIFKNCNLILESRKSRRC (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044493"
FT VAR_SEQ 144..364
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013415"
FT VAR_SEQ 178..364
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_013416"
FT MUTAGEN 37
FT /note="Y->A: Abrogates regulation of alternative splice
FT site selection; when associated with A-39; A-113 and A-
FT 115."
FT /evidence="ECO:0000269|PubMed:12628928"
FT MUTAGEN 39
FT /note="F->A: Abrogates regulation of alternative splice
FT site selection; when associated with A-37; A-113 and A-
FT 115."
FT /evidence="ECO:0000269|PubMed:12628928"
FT MUTAGEN 113
FT /note="Y->A: Abrogates regulation of alternative splice
FT site selection; when associated with A-37; A-39 and A-115."
FT /evidence="ECO:0000269|PubMed:12628928"
FT MUTAGEN 115
FT /note="F->A: Abrogates regulation of alternative splice
FT site selection; when associated with A-37; A-39 and A-113."
FT /evidence="ECO:0000269|PubMed:12628928"
FT MUTAGEN 309
FT /note="S->A: Inhibits IRES-mediated mRNA translation. Does
FT not inhibit interaction with EIF4A1. Inhibits localization
FT in cytoplasm and cytoplasmic granules upon cell muscle
FT differentiation. Inhibits negative regulation of
FT translation involved in gene silencing by miRNA."
FT /evidence="ECO:0000269|PubMed:17284590,
FT ECO:0000269|PubMed:19801630, ECO:0000269|PubMed:21518792"
FT CONFLICT 52
FT /note="I -> M (in Ref. 2; BAG64902)"
FT /evidence="ECO:0000305"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:2DNQ"
FT HELIX 15..23
FT /evidence="ECO:0007829|PDB:2DNQ"
FT STRAND 28..34
FT /evidence="ECO:0007829|PDB:2DNQ"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:2DNQ"
FT HELIX 45..55
FT /evidence="ECO:0007829|PDB:2DNQ"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:2DNQ"
SQ SEQUENCE 364 AA; 40314 MW; 3EA1C80D4C9122A2 CRC64;
MVKLFIGNLP REATEQEIRS LFEQYGKVLE CDIIKNYGFV HIEDKTAAED AIRNLHHYKL
HGVNINVEAS KNKSKTSTKL HVGNISPTCT NKELRAKFEE YGPVIECDIV KDYAFVHMER
AEDAVEAIRG LDNTEFQGKR MHVQLSTSRL RTAPGMGDQS GCYRCGKEGH WSKECPIDRS
GRVADLTEQY NEQYGAVRTP YTMSYGDSLY YNNAYGALDA YYKRCRAARS YEAVAAAAAS
VYNYAEQTLS QLPQVQNTAM ASHLTSTSLD PYDRHLLPTS GAAATAAAAA AAAAAVTAAS
TSYYGRDRSP LRRATAPVPT VGEGYGYGHE SELSQASAAA RNSLYDMARY EREQYADRAR
YSAF
