Description: Homo sapiens Mediterranean fever (MEFV), transcript variant 1, mRNA. RefSeq Summary (NM_000243): This gene encodes a protein, also known as pyrin or marenostrin, that is an important modulator of innate immunity. Mutations in this gene are associated with Mediterranean fever, a hereditary periodic fever syndrome. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr16:3,292,028-3,306,627 Size: 14,600 Total Exon Count: 10 Strand: - Coding Region Position: hg19 chr16:3,293,141-3,306,587 Size: 13,447 Coding Exon Count: 10
ID:MEFV_HUMAN DESCRIPTION: RecName: Full=Pyrin; AltName: Full=Marenostrin; FUNCTION: Probably controls the inflammatory response in myelomonocytic cells at the level of the cytoskeleton organization. SUBUNIT: Interacts with PSTPIP1. SUBCELLULAR LOCATION: Isoform 1: Cytoplasm, cytoskeleton. Note=Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles. SUBCELLULAR LOCATION: Isoform 2: Nucleus. 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. DEVELOPMENTAL STAGE: First detected in bone marrow promyelocytes. Expression increases throughout myelocyte differentiation and peaks in the mature myelomonocytic cells. INDUCTION: In monocytes, by treatment with colchicine and IFN- alpha, and by the proinflammatory cytokines IFNG/IFN-gamma, TNF and bacterial lipopolysaccharides (LPS). Repressed in monocytes by the antiinflammatory cytokines IL10/interleukin-10, TGFB1 and IL4/interleukin-4. In neutrophils, colchicine, TNF, bacterial lipopolysaccharides (LPS), IL10/interleukin-10, INF-alpha and IL4/interleukin-4 have no effect on expression. IFNG/IFN-gamma increases expression in neutrophils. DISEASE: Defects in MEFV are the cause of familial Mediterranean fever autosomal recessive (ARFMF) [MIM:249100]. ARFMF is an inherited disorder characterized by recurrent episodic fever, serosal inflammation and pain in the abdomen, chest or joints. ARFMF is frequently complicated by amyloidosis, which leads to renal failure and can be prophylactically treated with colchicine. ARFMF primarily affects ancestral ethnic groups living around the Mediterranean basin: North African Jews, Armenians, Arabs and Turks. The disease is also distributed in other populations including Greeks, Cypriots, Italians and Spanish, although at a lower prevalence. DISEASE: Defects in MEFV are the cause of familial Mediterranean fever autosomal dominant (ADFMF) [MIM:134610]. ADFMF is 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 renal amyloidosis and characterized by colchicine unresponsiveness. SIMILARITY: Contains 1 B box-type zinc finger. SIMILARITY: Contains 1 B30.2/SPRY domain. SIMILARITY: Contains 1 DAPIN domain. WEB RESOURCE: Name=INFEVERS; Note=Repertory of FMF and hereditary autoinflammatory disorders mutations; URL="http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=1"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MEFV";
amyloidosis Dode, C. et al. 2002, Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks., Nephrology, dialysis, transplantation. 2002 Jul;17(7):1212-7.
[PubMed 12105243]
In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.
amyloidosis Aganna, E. et al. 2004, Allelic variants in genes associated with hereditary periodic fever syndromes as susceptibility factors for reactive systemic AA amyloidosis, Genes and immunity. 2004 Jun;5(4):289-93.
[PubMed 15071491]
Although allelic variants in HPFs genes are not major susceptibility factors for AA amyloidosis in chronic inflammatory disease, low-penetrance variants of MEFV and TNFRSF1A may have clinically significant proinflammatory effects.
amyloidosis Mansour I et al. 2001, Familial Mediterranean fever in Lebanon: mutation spectrum evidence for cases in Maronites Greek orthodoxes Greek catholics Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations., European journal of human genetics. 2001 Jan;9(1):51-5.
[PubMed 11175300]
The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I).
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15553
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002376 immune system process GO:0006954 inflammatory response GO:0010508 positive regulation of autophagy GO:0032691 negative regulation of interleukin-1 beta production GO:0032695 negative regulation of interleukin-12 production GO:0034341 response to interferon-gamma GO:0045087 innate immune response GO:0050728 negative regulation of inflammatory response GO:0071641 negative regulation of macrophage inflammatory protein 1 alpha production GO:1900016 negative regulation of cytokine production involved in inflammatory response GO:1900226 negative regulation of NLRP3 inflammasome complex assembly GO:2001056 positive regulation of cysteine-type endopeptidase activity