InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DICER1

Summary

InnateDB Protein

IDBP-589944.3

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

ENSP00000437256

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:0035198	miRNA binding
GO:0046872	metal ion binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001525	angiogenesis
GO:0001942	hair follicle development
GO:0006396	RNA processing
GO:0008283	cell proliferation
GO:0009791	post-embryonic development
GO:0010070	zygote asymmetric cell division
GO:0010467	gene expression
GO:0010468	regulation of gene expression
GO:0010626	negative regulation of Schwann cell proliferation
GO:0010628	positive regulation of gene expression
GO:0014040	positive regulation of Schwann cell differentiation
GO:0019827	stem cell maintenance
GO:0021522	spinal cord motor neuron differentiation
GO:0021675	nerve development
GO:0021889	olfactory bulb interneuron differentiation
GO:0021987	cerebral cortex development
GO:0030324	lung development
GO:0030326	embryonic limb morphogenesis
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:0031069	hair follicle morphogenesis
GO:0031641	regulation of myelination
GO:0031643	positive regulation of myelination
GO:0032290	peripheral nervous system myelin formation
GO:0035116	embryonic hindlimb morphogenesis
GO:0035196	production of miRNAs involved in gene silencing by miRNA
GO:0035264	multicellular organism growth
GO:0042487	regulation of odontogenesis of dentin-containing tooth
GO:0045069	regulation of viral genome replication
GO:0045087	innate immune response (InnateDB)
GO:0045595	regulation of cell differentiation
GO:0045664	regulation of neuron differentiation
GO:0048255	mRNA stabilization
GO:0048536	spleen development
GO:0048565	digestive tract development
GO:0048608	reproductive structure development
GO:0048713	regulation of oligodendrocyte differentiation
GO:0048730	epidermis morphogenesis
GO:0048754	branching morphogenesis of an epithelial tube
GO:0048812	neuron projection morphogenesis
GO:0048856	anatomical structure development
GO:0050767	regulation of neurogenesis
GO:0051225	spindle assembly
GO:0051252	regulation of RNA metabolic process
GO:0051607	defense response to virus
GO:0051726	regulation of cell cycle
GO:0055013	cardiac muscle cell development
GO:0060119	inner ear receptor cell development
GO:0060576	intestinal epithelial cell development
GO:0070173	regulation of enamel mineralization
GO:0071335	hair follicle cell proliferation
GO:0090501	RNA phosphodiester bond hydrolysis
GO:0090502	RNA phosphodiester bond hydrolysis, endonucleolytic
GO:2000628	regulation of miRNA metabolic process
GO:2000630	positive regulation of miRNA metabolic process

Cellular Component

GO:0005737	cytoplasm
GO:0005793	endoplasmic reticulum-Golgi intermediate compartment
GO:0005829	cytosol
GO:0016442	RISC complex
GO:0030424	axon
GO:0030425	dendrite
GO:0030426	growth cone

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