InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MEFV

Summary

InnateDB Protein

IDBP-594984.3

Last Modified

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

Gene Symbol

MEFV

Protein Name

Mediterranean fever

Synonyms

FMF; MEF; TRIM20;

Species

Homo sapiens

Ensembl Protein

ENSP00000445079

InnateDB Gene

IDBG-11729 (MEFV)

Protein Structure

UniProt Annotation

Function

Involved in innate immunity and the inflammatory response. Interacts with several components of the inflammasome complex, a large oligomeric structure which recruits and activates CASP1 and ultimately induces maturation of cytokines such as IL1B. However, the exact role of MEFV in the inflammatory pathway is uncertain as contradictory effects on IL1B processing have been reported in different experimental systems. Has been shown to activate IL1B production (PubMed:16037825). Has also been shown to inhibit IL1B production (PubMed:16785446, PubMed:17431422). Also required for PSTPIP1-induced PYCARD oligomerization and for formation of pyroptosomes, large supramolecular structures composed of oligomerized PYCARD dimers which form prior to inflammatory apoptosis. Can reduce PYCARD-induced apoptosis. Recruits PSTPIP1 to pyroptosomes, and required for PSTPIP1 oligomerization. {ECO:0000269PubMed:10807793, ECO:0000269PubMed:11468188, ECO:0000269PubMed:16037825, ECO:0000269PubMed:16785446, ECO:0000269PubMed:17431422, ECO:0000269PubMed:17964261, ECO:0000269PubMed:18577712, ECO:0000269PubMed:19109554, ECO:0000269PubMed:19584923}.

Subcellular Localization

Isoform 1: Cytoplasm, cytoskeleton. Cell projection, ruffle. Cell projection, lamellipodium. Nucleus. Note=Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles. In pre- apoptotic cells, colocalizes with PYCARD/ASC in large specks (pyroptosomes). In migrating monocytes, strongly polarized at the leading edge of the cell where it colocalizes with polymerizing actin and PYCARD/ASC.Isoform 2: Nucleus.

Disease Associations

Familial Mediterranean fever, autosomal recessive (ARFMF) [MIM:249100]: A hereditary periodic fever syndrome characterized by recurrent episodic fever, serosal inflammation and pain in the abdomen, chest or joints. It is frequently complicated by reactive amyloidosis, which leads to renal failure and can be prophylactically treated with colchicine. {ECO:0000269PubMed:10024914, ECO:0000269PubMed:10090880, ECO:0000269PubMed:10234504, ECO:0000269PubMed:10364520, ECO:0000269PubMed:10612841, ECO:0000269PubMed:10842288, ECO:0000269PubMed:10854105, ECO:0000269PubMed:11470495, ECO:0000269PubMed:15024744, ECO:0000269PubMed:16378925, ECO:0000269PubMed:16730661, ECO:0000269PubMed:23031807, ECO:0000269PubMed:9288094, ECO:0000269PubMed:9288758, ECO:0000269PubMed:9668175}. Note=The disease is caused by mutations affecting the gene represented in this entry.Familial Mediterranean fever, autosomal dominant (ADFMF) [MIM:134610]: A hereditary periodic fever syndrome characterized by periodic fever, serosal inflammation and pain in the abdomen, chest or joints as seen also in the autosomal recessive form of the disease. It is associated with reactive renal amyloidosis and characterized by colchicine unresponsiveness. {ECO:0000269PubMed:10787449, ECO:0000269PubMed:14679589}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in peripheral blood leukocytes, particularly in mature granulocytes and to a lesser extent in monocytes but not in lymphocytes. Detected in spleen, lung and muscle, probably as a result of leukocyte infiltration in these tissues. Not expressed in thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, liver, kidney, pancreas. Expression detected in several myeloid leukemic, colon cancer, and prostate cancer cell lines. {ECO:0000269PubMed:10666224, ECO:0000269PubMed:10807793, ECO:0000269PubMed:11115844}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.

Experimentally validated
Total	20 [view]
Protein-Protein	18 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0005515	protein binding
GO:0008270	zinc ion binding

Biological Process

GO:0006954	inflammatory response
GO:0032691	negative regulation of interleukin-1 beta production
GO:0032695	negative regulation of interleukin-12 production
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0050728	negative regulation of inflammatory response
GO:0071641	negative regulation of macrophage inflammatory protein 1 alpha production
GO:2001056	positive regulation of cysteine-type endopeptidase activity

Cellular Component

GO:0001726	ruffle
GO:0005622	intracellular
GO:0005634	nucleus
GO:0005829	cytosol
GO:0005874	microtubule
GO:0005875	microtubule associated complex
GO:0030027	lamellipodium

Protein Structure and Domains

PDB ID

InterPro

IPR000315 Zinc finger, B-box
IPR001870 B30.2/SPRY domain
IPR003877 SPRY domain
IPR003879 Butyrophylin-like
IPR004020 DAPIN domain
IPR006574 SPRY-associated
IPR008985 Concanavalin A-like lectin/glucanases superfamily
IPR011029 Death-like domain

PFAM

PF00643
PF00622
PF02758
PF13765

PRINTS

PR01407

PIRSF

SMART

SM00336
SM00449
SM00589

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt