Homo sapiens Protein: RBM4
InnateDB Protein IDBP-604294.3
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol RBM4
Protein Name RNA binding motif protein 4
Synonyms LARK; RBM4A; ZCCHC21; ZCRB3A;
Species Homo sapiens
Ensembl Protein ENSP00000432020
InnateDB Gene IDBG-59531 (RBM4)
Protein Structure
UniProt Annotation
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 AGO2- containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro. {ECO:0000269PubMed:12628928, ECO:0000269PubMed:16260624, ECO:0000269PubMed:16777844, ECO:0000269PubMed:16934801, ECO:0000269PubMed:17284590, ECO:0000269PubMed:17932509, ECO:0000269PubMed:19801630, ECO:0000269PubMed:21343338, ECO:0000269PubMed:21518792}.
Subcellular Localization Nucleus. Nucleus, nucleolus. Nucleus speckle. Cytoplasm. Cytoplasmic granule. 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.
Disease Associations
Tissue Specificity Expressed in the cerebellum. Expressed in neurons and glial cells, including layers II neurons in the frontal cortex and CA1 pyramidal neurons in the hippocampus. Expressed in heart, liver, pancreas, skeletal muscle, placenta, primary fibroblasts and peripheral blood monocytes (at protein level). Ubiquitously expressed. Highly expressed in heart, placenta and skeletal muscle. Weakly expressed in pancreas, kidney, liver, lung and brain. {ECO:0000269PubMed:12628928, ECO:0000269PubMed:16260624, ECO:0000269PubMed:16777844, ECO:0000269PubMed:18708123}.
Number of Interactions This gene and/or its encoded proteins are associated with 100 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.
Experimentally validated
Total 100 [view]
Protein-Protein 95 [view]
Protein-DNA 5 [view]
Protein-RNA 0
Predicted by orthology
Total 1 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0003676 nucleic acid binding
GO:0003723 RNA binding
GO:0003729 mRNA binding
GO:0003730 mRNA 3'-UTR binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0035198 miRNA binding
GO:0044822 poly(A) RNA binding
GO:0097157 pre-mRNA intronic binding
GO:0097158 pre-mRNA intronic pyrimidine-rich binding
Biological Process
GO:0000381 regulation of alternative mRNA splicing, via spliceosome
GO:0002190 cap-independent translational initiation
GO:0002192 IRES-dependent translational initiation
GO:0006396 RNA processing
GO:0006397 mRNA processing
GO:0008380 RNA splicing
GO:0017148 negative regulation of translation
GO:0030154 cell differentiation
GO:0032055 negative regulation of translation in response to stress
GO:0035278 negative regulation of translation involved in gene silencing by miRNA
GO:0043153 entrainment of circadian clock by photoperiod
GO:0045947 negative regulation of translational initiation
GO:0046685 response to arsenic-containing substance
GO:0046822 regulation of nucleocytoplasmic transport
GO:0051149 positive regulation of muscle cell differentiation
GO:0051403 stress-activated MAPK cascade
GO:0097167 circadian regulation of translation
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0010494 cytoplasmic stress granule
GO:0016607 nuclear speck
Protein Structure and Domains
InterPro IPR000504 RNA recognition motif domain
PFAM PF00076
Post-translational Modifications
SwissProt Q9BWF3
PhosphoSite PhosphoSite-Q9BWF3
UniProt Splice Variant
Entrez Gene 5936
UniGene Hs.728823
OMIM 602571
HPRD 03982
EMBL AK097592 AK303984 AL832566 AP001157 BC000307 BC021120 BC032735 BC064960 U89505
GenPept AAC51293 AAH00307 AAH21120 AAH32735 AAH64960 BAG53492 BAG64902 CAH10593