InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DICER1

Summary

InnateDB Protein

IDBP-591598.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DICER1

Protein Name

dicer 1, ribonuclease type III

Synonyms

DCR1; Dicer; Dicer1e; HERNA; MNG1; RMSE2;

Species

Homo sapiens

Ensembl Protein

ENSP00000435681

InnateDB Gene

IDBG-18522 (DICER1)

Protein Structure

UniProt Annotation

Function

Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA- induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes. {ECO:0000269PubMed:15242644, ECO:0000269PubMed:15973356, ECO:0000269PubMed:16142218, ECO:0000269PubMed:16271387, ECO:0000269PubMed:16289642, ECO:0000269PubMed:16357216, ECO:0000269PubMed:16424907, ECO:0000269PubMed:17452327, ECO:0000269PubMed:18178619, ECO:0000269PubMed:19219043}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:16424907}.

Disease Associations

Pleuropulmonary blastoma (PPB) [MIM:601200]: A rare pediatric intrathoracic neoplasm. The tumor arises from the lung, pleura, or both, and appears to be purely mesenchymal in phenotype. It lacks malignant epithelial elements, a feature that distinguishes it from the classic adult-type pulmonary blastoma. It arises during fetal lung development and is often part of an inherited cancer syndrome. The tumor contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis. Some patients have multilocular cystic nephroma, a benign kidney tumor. {ECO:0000269PubMed:19556464}. Note=The disease is caused by mutations affecting the gene represented in this entry.Goiter multinodular 1, with or without Sertoli-Leydig cell tumors (MNG1) [MIM:138800]: A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary. {ECO:0000269PubMed:21205968}. Note=The disease is caused by mutations affecting the gene represented in this entry.Rhabdomyosarcoma, embryonal, 2 (RMSE2) [MIM:180295]: A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp (PubMed:21882293). Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. These mutations do not abolish DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic (PubMed:22187960). {ECO:0000269PubMed:21882293, ECO:0000269PubMed:22187960}.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 76 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	76 [view]
Protein-Protein	74 [view]
Protein-DNA	0
Protein-RNA	2 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003677	DNA binding
GO:0003723	RNA binding
GO:0003725	double-stranded RNA binding
GO:0004386	helicase activity
GO:0004525	ribonuclease III activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016787	hydrolase activity
GO:0016891	endoribonuclease activity, producing 5'-phosphomonoesters
GO:0046872	metal ion binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006396	RNA processing
GO:0010467	gene expression
GO:0010626	negative regulation of Schwann cell proliferation
GO:0014040	positive regulation of Schwann cell differentiation
GO:0021675	nerve development
GO:0030422	production of siRNA involved in RNA interference
GO:0030423	targeting of mRNA for destruction involved in RNA interference
GO:0031054	pre-miRNA processing
GO:0031643	positive regulation of myelination
GO:0032290	peripheral nervous system myelin formation
GO:0035196	production of miRNAs involved in gene silencing by miRNA
GO:0045087	innate immune response (InnateDB)
GO:0048812	neuron projection morphogenesis
GO:0090501	RNA phosphodiester bond hydrolysis
GO:0090502	RNA phosphodiester bond hydrolysis, endonucleolytic

Cellular Component

GO:0005829	cytosol
GO:0016442	RISC complex

Protein Structure and Domains

PDB ID

InterPro

IPR000999 Ribonuclease III domain
IPR001650 Helicase, C-terminal
IPR003100 PAZ domain
IPR005034 Dicer dimerisation domain
IPR006935 Helicase/UvrB domain
IPR011545 DEAD/DEAH box helicase domain
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR014720 Double-stranded RNA-binding domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM