InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RBM4

Summary

InnateDB Protein

IDBP-604290.3

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

ENSP00000435821

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}.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	0
DNA-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