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O15553 (MEFV_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pyrin
Alternative name(s):
Marenostrin
Gene names
Name:MEFV
Synonyms:MEF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length781 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 (Ref.13). Has also been shown to inhibit IL1B production (Ref.14, Ref.15). 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. Ref.7 Ref.9 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19

Subunit structure

Homotrimer. Interacts (via the B box-type zinc finger) with PSTPIP1. Interacts (via the B30.2/SPRY domain) with CASP1 p20 and p10 subunits, CASP5, NLRP1, NLRP2 AND NLRP3. Interacts with NFKBIA, PYCARD, RELA and IL1B but not processed IL1B. Interacts weakly with VASP and ACTR3. Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Subcellular location

Isoform 1: Cytoplasmcytoskeleton. Cell projectionruffle. Cell projectionlamellipodium. Nucleus Ref.2 Ref.8 Ref.9 Ref.10 Ref.17 Ref.18 Ref.19. 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. Ref.2 Ref.8 Ref.9 Ref.10 Ref.17 Ref.18 Ref.19

Isoform 2: Nucleus Ref.2 Ref.8 Ref.9 Ref.10 Ref.17 Ref.18 Ref.19.

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. Ref.2 Ref.7 Ref.8

Developmental stage

First detected in bone marrow promyelocytes. Expression increases throughout myelocyte differentiation and peaks in the mature myelomonocytic cells. Ref.7

Induction

In monocytes, by treatment with colchicine and IFN-alpha, by the proinflammatory cytokines IFNG/IFN-gamma and TNF, by bacterial lipopolysaccharides (LPS) and by retroviral infection. 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. Ref.7 Ref.16

Domain

The B box-type zinc finger interacts, possibly intramolecularly, with the DAPIN domain; this may be an autoinhibitory mechanism released by PSTPIP1 binding.

Post-translational modification

Cleaved by CASP1 Probable. The N-terminal cleavage product localizes to the nucleus as a filamentous network and to the cytoplasm, interacts more strongly with RELA and NFKBIA than the full-length protein, enhances the nuclear localization of RELA and induces NFKBIA proteolysis. The C-terminal cleavage product localizes to the cytoplasm.

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5 Ref.6 Ref.12 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.30 Ref.34 Ref.39

Sequence similarities

Contains 1 B box-type zinc finger.

Contains 1 B30.2/SPRY domain.

Contains 1 DAPIN domain.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCell projection
Cytoplasm
Cytoskeleton
Microtubule
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAmyloidosis
Disease mutation
   DomainCoiled coil
Zinc-finger
   LigandActin-binding
Metal-binding
Zinc
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processinflammatory response

Inferred from direct assay Ref.9. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

negative regulation of inflammatory response

Inferred from mutant phenotype PubMed 16403826. Source: BHF-UCL

negative regulation of interleukin-1 beta production

Inferred from mutant phenotype PubMed 20041150. Source: BHF-UCL

negative regulation of interleukin-12 production

Inferred from mutant phenotype PubMed 20041150. Source: BHF-UCL

negative regulation of macrophage inflammatory protein 1 alpha production

Inferred from mutant phenotype PubMed 20041150. Source: BHF-UCL

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of cysteine-type endopeptidase activity

Inferred from direct assay PubMed 19158676. Source: UniProtKB

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

microtubule associated complex

Inferred from direct assay Ref.9. Source: UniProtKB

nucleus

Inferred from direct assay Ref.2. Source: UniProtKB

   Molecular_functionactin binding

Inferred from direct assay Ref.9. Source: UniProtKB

zinc ion binding

Non-traceable author statement Ref.2. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15553-2)

Also known as: FL;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O15553-1)

Also known as: D2;

The sequence of this isoform differs from the canonical sequence as follows:
     93-303: Missing.
Isoform 3 (identifier: O15553-3)

The sequence of this isoform differs from the canonical sequence as follows:
     93-303: Missing.
     587-781: VPELIGAQAH...ICPVGGQGPD → DHSPQHGLGS...GADWRSGTCC

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 781781Pyrin
PRO_0000220364

Regions

Domain1 – 9292DAPIN
Domain580 – 775196B30.2/SPRY
Zinc finger370 – 41243B box-type
Region266 – 28015Interaction with RELA
Region420 – 582163Required for homotrimerization and induction of pyroptosomes
Coiled coil413 – 44230 Potential
Motif420 – 43718Nuclear localization signal Potential

Sites

Site330 – 3312Cleavage; by CASP1 Probable

Natural variations

Alternative sequence93 – 303211Missing in isoform 2 and isoform 3.
VSP_008223
Alternative sequence587 – 781195VPELI…GQGPD → DHSPQHGLGSWEERDYTQHS MQGPKQGVPCLSLLSGQCNL APLNANAQDFFPYLIFLRSS GADWRSGTCC in isoform 3.
VSP_047663
Natural variant331V → L.
Corresponds to variant rs11466016 [ dbSNP | Ensembl ].
VAR_048398
Natural variant421R → W in arFMF.
Corresponds to variant rs61754767 [ dbSNP | Ensembl ].
VAR_028326
Natural variant1081S → R in arFMF. Ref.36
VAR_028327
Natural variant1101L → P in arFMF. Ref.28
Corresponds to variant rs11466018 [ dbSNP | Ensembl ].
VAR_016824
Natural variant1381G → A Association with renal amyloidosis. Ref.32
VAR_016825
Natural variant1481E → Q in arFMF and adFMF; common mutation; associated with S-369 and Q-408 in cis; associated with I-694 in some patients. Ref.24 Ref.26 Ref.27 Ref.28 Ref.30 Ref.36
Corresponds to variant rs3743930 [ dbSNP | Ensembl ].
VAR_009051
Natural variant1481E → V in arFMF. Ref.36
VAR_028328
Natural variant1631E → A in arFMF. Ref.35
VAR_028329
Natural variant1671E → D in arFMF. Ref.36
VAR_009052
Natural variant1771T → I in arFMF. Ref.36
VAR_028330
Natural variant2021R → Q. Ref.4 Ref.21
Corresponds to variant rs224222 [ dbSNP | Ensembl ].
VAR_009053
Natural variant2301E → K in arFMF. Ref.6
Corresponds to variant rs104895080 [ dbSNP | Ensembl ].
VAR_016826
Natural variant2671T → I in arFMF. Ref.36 Ref.39
Corresponds to variant rs104895081 [ dbSNP | Ensembl ].
VAR_009054
Natural variant3191E → K in arFMF. Ref.35
VAR_028331
Natural variant3691P → S in arFMF; reduced penetrance among Ashkenazi Jews; associated with Q-148 and Q-408 in cis. Ref.24 Ref.39
Corresponds to variant rs11466023 [ dbSNP | Ensembl ].
VAR_009055
Natural variant4081R → Q in arFMF; associated with Q-148 and S-369 in cis. Ref.24 Ref.39
Corresponds to variant rs11466024 [ dbSNP | Ensembl ].
VAR_009056
Natural variant4401Q → E.
Corresponds to variant rs11466026 [ dbSNP | Ensembl ].
VAR_024376
Natural variant4741E → K in arFMF. Ref.36
VAR_028332
Natural variant4781H → Y in adFMF; severe. Ref.34
VAR_028333
Natural variant4791F → L in arFMF. Ref.24 Ref.36
VAR_009057
Natural variant5771T → A Probable disease-associated mutation found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. Ref.39
VAR_070795
Natural variant5771T → N Probable disease-associated mutation found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. Ref.39
VAR_070796
Natural variant5771T → S Probable disease-associated mutation found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. Ref.39
Corresponds to variant rs104895193 [ dbSNP | Ensembl ].
VAR_070797
Natural variant5851F → L.
Corresponds to variant rs11466043 [ dbSNP | Ensembl ].
VAR_028334
Natural variant5911I → T in arFMF; unknown pathological significance. Ref.33
Corresponds to variant rs11466045 [ dbSNP | Ensembl ].
VAR_016827
Natural variant6321G → S in arFMF. Ref.37
VAR_028335
Natural variant6401I → M in arFMF. Ref.37
VAR_028336
Natural variant6411I → F in arFMF. Ref.37
VAR_028337
Natural variant6461P → L in arFMF. Ref.37
VAR_028338
Natural variant6491L → P in arFMF. Ref.37
VAR_028339
Natural variant6531R → H in arFMF. Ref.6 Ref.36 Ref.37
VAR_016828
Natural variant6561E → A in arFMF. Ref.37
VAR_028340
Natural variant6611D → N in arFMF. Ref.37
VAR_028341
Natural variant6751S → N in arFMF. Ref.29 Ref.37
VAR_016829
Natural variant6781G → E in arFMF. Ref.37
VAR_028342
Natural variant6801M → I in arFMF and adFMF; reduced CASP1 interaction. Ref.1 Ref.5 Ref.14 Ref.22 Ref.24 Ref.25 Ref.26 Ref.30 Ref.36
Corresponds to variant rs28940580 [ dbSNP | Ensembl ].
VAR_028343
Natural variant6801M → L in arFMF. Ref.29 Ref.37
VAR_016830
Natural variant6811T → I in arFMF. Ref.22 Ref.37
VAR_009059
Natural variant6881Y → C in arFMF. Ref.37
VAR_028344
Natural variant6921Missing in arFMF.
VAR_009060
Natural variant6941M → I in arFMF and adFMF; associated with Q-148 in some patients. Ref.5 Ref.22 Ref.25 Ref.26 Ref.30 Ref.36 Ref.37
Corresponds to variant rs28940578 [ dbSNP | Ensembl ].
VAR_009061
Natural variant6941M → K in arFMF. Ref.38
VAR_070798
Natural variant6941M → L in arFMF; no effect on CASP1 activation. Ref.37
VAR_028345
Natural variant6941M → V in arFMF and adFMF; very common mutation particularly in North African Jews; can be associated with amyloidosis development; reduced interaction with CASP1 (PubMed:16785446); no effect on interaction with CASP1, CASP5, NLRP1, NLRP2 or NLRP3 (PubMed:17431422). Ref.1 Ref.14 Ref.15 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28 Ref.30 Ref.36 Ref.37
VAR_009062
Natural variant6941Missing in arFMF and adFMF. Ref.22 Ref.30
VAR_009063
Natural variant6951K → M in arFMF. Ref.37
Corresponds to variant rs104895094 [ dbSNP | Ensembl ].
VAR_028346
Natural variant6951K → R in arFMF; reduced penetrance among Ashkenazi Jews. Ref.26 Ref.36 Ref.37
Corresponds to variant rs104895094 [ dbSNP | Ensembl ].
VAR_009064
Natural variant7021S → C in one patient with familial Mediterranean fever. Ref.37
VAR_028347
Natural variant7041V → I in arFMF. Ref.37
VAR_028348
Natural variant7051P → S in arFMF. Ref.37
VAR_028349
Natural variant7201I → M in arFMF. Ref.36 Ref.37
VAR_028350
Natural variant7261V → A in arFMF; common mutation; in Iraqi and Ashkenazi Jews, Druze, Armenians; reduced CASP1 interaction; no effect on CASP1 activation. Ref.1 Ref.14 Ref.22 Ref.24 Ref.25 Ref.26 Ref.36 Ref.37
Corresponds to variant rs28940579 [ dbSNP | Ensembl ].
VAR_009065
Natural variant7431F → L in arFMF. Ref.37
VAR_028351
Natural variant7441A → S in arFMF; uncertain pathological significance. Ref.35 Ref.36 Ref.37
Corresponds to variant rs61732874 [ dbSNP | Ensembl ].
VAR_009066
Natural variant7581P → S in arFMF. Ref.37
VAR_028352
Natural variant7611R → H in arFMF. Ref.24 Ref.26 Ref.36 Ref.37
VAR_009067
Natural variant7801P → T in arFMF. Ref.37
VAR_028353

Experimental info

Mutagenesis161L → P: Does not form MEFV- and PSTPIP1-expressing perinuclear specks. Ref.13
Mutagenesis241F → S: Does not form MEFV- and PSTPIP1-expressing perinuclear specks. Ref.13
Mutagenesis3301D → A: Not cleaved by CASP1. Ref.17

Secondary structure

..................................... 781
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (FL) [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 3692E5E6E9FC8204

FASTA78186,444
        10         20         30         40         50         60 
MAKTPSDHLL STLEELVPYD FEKFKFKLQN TSVQKEHSRI PRSQIQRARP VKMATLLVTY 

        70         80         90        100        110        120 
YGEEYAVQLT LQVLRAINQR LLAEELHRAA IQEYSTQENG TDDSAASSSL GENKPRSLKT 

       130        140        150        160        170        180 
PDHPEGNEGN GPRPYGGGAA SLRCSQPEAG RGLSRKPLSK RREKASEGLD AQGKPRTRSP 

       190        200        210        220        230        240 
ALPGGRSPGP CRALEGGQAE VRLRRNASSA GRLQGLAGGA PGQKECRPFE VYLPSGKMRP 

       250        260        270        280        290        300 
RSLEVTISTG EKAPANPEIL LTLEEKTAAN LDSATEPRAR PTPDGGASAD LKEGPGNPEH 

       310        320        330        340        350        360 
SVTGRPPDTA ASPRCHAQEG DPVDGTCVRD SCSFPEAVSG HPQASGSRSP GCPRCQDSHE 

       370        380        390        400        410        420 
RKSPGSLSPQ PLPQCKRHLK QVQLLFCEDH DEPICLICSL SQEHQGHRVR PIEEVALEHK 

       430        440        450        460        470        480 
KKIQKQLEHL KKLRKSGEEQ RSYGEEKAVS FLKQTEALKQ RVQRKLEQVY YFLEQQEHFF 

       490        500        510        520        530        540 
VASLEDVGQM VGQIRKAYDT RVSQDIALLD ALIGELEAKE CQSEWELLQD IGDILHRAKT 

       550        560        570        580        590        600 
VPVPEKWTTP QEIKQKIQLL HQKSEFVEKS TKYFSETLRS EMEMFNVPEL IGAQAHAVNV 

       610        620        630        640        650        660 
ILDAETAYPN LIFSDDLKSV RLGNKWERLP DGPQRFDSCI IVLGSPSFLS GRRYWEVEVG 

       670        680        690        700        710        720 
DKTAWILGAC KTSISRKGNM TLSPENGYWV VIMMKENEYQ ASSVPPTRLL IKEPPKRVGI 

       730        740        750        760        770        780 
FVDYRVGSIS FYNVTARSHI YTFASCSFSG PLQPIFSPGT RDGGKNTAPL TICPVGGQGP 


D 

« Hide

Isoform 2 (D2) [UniParc].

Checksum: 34C7379A052C74EF
Show »

FASTA57064,494
Isoform 3 [UniParc].

Checksum: E157099AC115F36C
Show »

FASTA44550,837

References

« Hide 'large scale' references
[1]"Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever."
Aksentijevich I., Centola M., Deng Z., Sood R., Balow J.E. Jr., Wood G., Zaks N., Mansfield E., Chen X., Eisenberg S., Vedula A., Shafran N., Raben N., Pras E., Pras M., Kastner D.L., Blake T., Baxevanis A.D. expand/collapse author list , Robbins C., Krizman D., Collins F.S., Liu P.P., Chen X., Shohat M., Hamon M., Kahan T., Cercek A., Rotter J.I., Fischel-Ghodsian N., Richards N., Shelton D.A., Gumucio D., Yokoyama Y., Mangelsdorf M., Orsborn A., Richards R.I., Ricke D.O., Buckingham J.M., Moyzis R.K., Deaven L.L., Doggett N.A.
Cell 90:797-807(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARFMF ILE-680; VAL-694 AND ALA-726.
Tissue: Leukocyte.
[2]"Alternative splicing at the MEFV locus involved in familial Mediterranean fever regulates translocation of the marenostrin/pyrin protein to the nucleus."
Papin S., Duquesnoy P., Cazeneuve C., Pantel J., Coppey-Moisan M., Dargemont C., Amselem S.
Hum. Mol. Genet. 9:3001-3009(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
Tissue: Leukocyte.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-202.
Tissue: Placenta.
[5]"A candidate gene for familial Mediterranean fever."
Bernot A., Clepet C., Dasilva C., Devaud C., Petit J.-L., Caloustian C., Cruaud C., Samson D., Pulcini F., Weissenbach J., Heilig R., Notanicola C., Domingo C., Rozenbaum M., Benchetrit E., Topaloglu R., Dewalle M., Dross C. expand/collapse author list , Hadjari P., Dupont M., Demaille J.G., Touitou I., Smaoui N., Nedelec B., Mery J.-P., Chaabouni H., Delpech M., Grateau G.
Nat. Genet. 17:25-31(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 305-754, VARIANTS ARFMF ILE-680 AND ILE-694.
[6]"Two novel mutations R653H and E230K in the Mediterranean fever gene associated with disease."
Timmann C., Muntau B., Kuhne K., Gelhaus A., Horstmann R.D.
Mutat. Res. 479:235-239(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 96-303 AND 599-781, VARIANTS ARFMF LYS-230 AND HIS-653.
Tissue: Blood.
[7]"The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators."
Centola M., Wood G., Frucht D.M., Galon J., Aringer M., Farrell C., Kingma D.W., Horwitz M.E., Mansfield E., Holland S.M., O'Shea J.J., Rosenberg H.F., Malech H.L., Kastner D.L.
Blood 95:3223-3231(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
[8]"Hematopoietic-specific expression of MEFV, the gene mutated in familial Mediterranean fever, and subcellular localization of its corresponding protein, pyrin."
Tidow N., Chen X., Muller C., Kawano S., Gombart A.F., Fischel-Ghodsian N., Koeffler H.P.
Blood 95:1451-1455(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]"The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments."
Mansfield E., Chae J.J., Komarow H.D., Brotz T.M., Frucht D.M., Aksentijevich I., Kastner D.L.
Blood 98:851-859(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]"Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis."
Richards N., Schaner P., Diaz A., Stuckey J., Shelden E., Wadhwa A., Gumucio D.L.
J. Biol. Chem. 276:39320-39329(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PYCARD, SUBCELLULAR LOCATION.
[11]"Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway."
Shoham N.G., Centola M., Mansfield E., Hull K.M., Wood G., Wise C.A., Kastner D.L.
Proc. Natl. Acad. Sci. U.S.A. 100:13501-13506(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PSTPIP1.
[12]"Reduced MEFV messenger RNA expression in patients with familial Mediterranean fever."
Notarnicola C., Didelot M.-N., Kone-Paut I., Seguret F., Demaille J., Touitou I.
Arthritis Rheum. 46:2785-2793(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[13]"Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization."
Yu J.W., Wu J., Zhang Z., Datta P., Ibrahimi I., Taniguchi S., Sagara J., Fernandes-Alnemri T., Alnemri E.S.
Cell Death Differ. 13:236-249(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LEU-16 AND PHE-24.
[14]"The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production."
Chae J.J., Wood G., Masters S.L., Richard K., Park G., Smith B.J., Kastner D.L.
Proc. Natl. Acad. Sci. U.S.A. 103:9982-9987(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CASP1, CHARACTERIZATION OF VARIANTS ILE-680; VAL-694 AND ALA-726.
[15]"The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing."
Papin S., Cuenin S., Agostini L., Martinon F., Werner S., Beer H.D., Grutter C., Grutter M., Tschopp J.
Cell Death Differ. 14:1457-1466(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CASP1; CASP5; NLRP1; NLRP2; NLRP3 AND IL1B, CHARACTERIZATION OF VARIANT VAL-694.
[16]"Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants."
Yu J.W., Fernandes-Alnemri T., Datta P., Wu J., Juliana C., Solorzano L., McCormick M., Zhang Z., Alnemri E.S.
Mol. Cell 28:214-227(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH PYCARD AND PSTPIP1, INDUCTION BY RETROVIRAL INFECTION.
[17]"The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment."
Chae J.J., Wood G., Richard K., Jaffe H., Colburn N.T., Masters S.L., Gumucio D.L., Shoham N.G., Kastner D.L.
Blood 112:1794-1803(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RELA AND NFKBIA, PROBABLE CLEAVAGE BY CASP-1, MUTAGENESIS OF ASP-330.
[18]"Pyrin and ASC co-localize to cellular sites that are rich in polymerizing actin."
Waite A.L., Schaner P., Hu C., Richards N., Balci-Peynircioglu B., Hong A., Fox M., Gumucio D.L.
Exp. Biol. Med. (Maywood) 234:40-52(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PSTPIP1; VASP AND ACTR3.
[19]"Pyrin Modulates the Intracellular Distribution of PSTPIP1."
Waite A.L., Schaner P., Richards N., Balci-Peynircioglu B., Masters S.L., Brydges S.D., Fox M., Hong A., Yilmaz E., Kastner D.L., Reinherz E.L., Gumucio D.L.
PLoS ONE 4:E6147-E6147(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[20]"The crystal structure of human pyrin b30.2 domain: implications for mutations associated with familial Mediterranean fever."
Weinert C., Grutter C., Roschitzki-Voser H., Mittl P.R., Grutter M.G.
J. Mol. Biol. 394:226-236(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 586-776.
[21]"Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF)."
Bernot A., da Silva C., Petit J.-L., Cruaud C., Caloustian C., Castet V., Ahmed-Arab M., Dross C., Dupont M., Cattan D., Smaoui N., Dode C., Pecheux C., Nedelec B., Medaxian J., Rozenbaum M., Rosner I., Delpech M. expand/collapse author list , Grateau G., Demaille J., Weissenbach J., Touitou I.
Hum. Mol. Genet. 7:1317-1325(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF, VARIANT GLN-202.
[22]"Pyrin/marenostrin mutations in familial Mediterranean fever."
Booth D.R., Gillmore J.D., Booth S.E., Pepys M.B., Hawkins P.N.
QJM 91:603-606(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF ILE-680; ILE-681; ILE-694; VAL-694; MET-694 DEL AND ALA-726.
[23]"Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population."
Aksentijevich I., Torosyan Y., Samuels J., Centola M., Pras E., Chae J.J., Oddoux C., Wood G., Azzaro M.P., Palumbo G., Giustolisi R., Pras M., Ostrer H., Kastner D.L.
Am. J. Hum. Genet. 64:949-962(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF.
[24]"MEFV-Gene analysis in Armenian patients with familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications."
Cazeneuve C., Sarkisian T., Pecheux C., Dervichian M., Nedelec B., Reinert P., Ayvazyan A., Kouyoumdjian J.-C., Ajrapetyan H., Delpech M., Goossens M., Dode C., Grateau G., Amselem S.
Am. J. Hum. Genet. 65:88-97(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF GLN-148; SER-369; GLN-408; LEU-479; ILE-680; VAL-694; ALA-726 AND HIS-761.
[25]"Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis."
Shohat M., Magal N., Shohat T., Chen X., Dagan T., Mimouni A., Danon Y., Lotan R., Ogur G., Sirin A., Schlezinger M., Halpern G.J., Schwabe A., Kastner D., Rotter J.I., Fischel-Ghodsian N.
Eur. J. Hum. Genet. 7:287-292(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF ILE-680; ILE-694; VAL-694 AND ALA-726.
[26]"MEFV mutations in Turkish patients suffering from familial Mediterranean fever."
Akar N., Misiroglu M., Yalcinkaya F., Akar E., Cakar N., Tumer N., Akcakus M., Tastan H., Matzner Y.
Hum. Mutat. 15:118-119(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF GLN-148; ILE-680; ILE-694; VAL-694; ARG-695; ALA-726 AND HIS-761.
[27]"The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant?"
Ben-Chetrit E., Lerer I., Malamud E., Domingo C., Abeliovich D.
Hum. Mutat. 15:385-386(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-148.
[28]"Familial Mediterranean fever in the 'Chuetas' of Mallorca: a question of Jewish origin or genetic heterogeneity."
Domingo C., Touitou I., Bayou A., Ozen S., Notarnicola C., Dewalle M., Demaille J., Buades R., Sayadat C., Levy M., Ben-Chetrit E.
Eur. J. Hum. Genet. 8:242-246(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF PRO-110; GLN-148 AND VAL-694.
[29]"Mutations in the MEFV gene in a large series of patients with a clinical diagnosis of familial Mediterranean fever."
Dode C., Pecheux C., Cazeneuve C., Cattan D., Dervichian M., Goossens M., Delpech M., Amselem S., Grateau G.
Am. J. Med. Genet. 92:241-246(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF ASN-675 AND LEU-680.
[30]"The genetic basis of autosomal dominant familial Mediterranean fever."
Booth D.R., Gillmore J.D., Lachmann H.J., Booth S.E., Bybee A., Soytuerk M., Akar S., Pepys M.B., Tunca M., Hawkins P.N.
QJM 93:217-221(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ADFMF GLN-148; ILE-680; ILE-694; MET-694 DEL AND VAL-694.
[31]"The spectrum of familial mediterranean fever (FMF) mutations."
Touitou I.
Eur. J. Hum. Genet. 9:473-483(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ARFMF VARIANTS.
[32]"Is the Ala138Gly alteration of MEFV gene important for amyloidosis?"
Akar E., Yalcinkaya F., Akar N.
Hum. Mutat. 17:71-71(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMF ALA-138.
[33]"I591T MEFV mutation in a Spanish kindred: is it a mild mutation, a benign polymorphism, or a variant influenced by another modifier?"
Aldea A., Casademont J., Arostegui J.I., Rius J., Maso M., Vives J., Yague J.
Hum. Mutat. 20:148-150(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FMF THR-591.
[34]"A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?"
Aldea A., Campistol J.M., Arostegui J.I., Rius J., Maso M., Vives J., Yaguee J.
Am. J. Med. Genet. A 124:67-73(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ADFMF TYR-478.
[35]"The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination 'hot-spot' at the MEFV locus."
Aldea A., Calafell F., Arostegui J.I., Lao O., Rius J., Plaza S., Maso M., Vives J., Buades J., Yaguee J.
Hum. Mutat. 23:399-399(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF ALA-163 AND LYS-319, VARIANT SER-744.
[36]"Familial Mediterranean fever (FMF) in Lebanon and Jordan: a population genetics study and report of three novel mutations."
Medlej-Hashim M., Serre J.-L., Corbani S., Saab O., Jalkh N., Delague V., Chouery E., Salem N., Loiselet J., Lefranc G., Megarbane A.
Eur. J. Med. Genet. 48:412-420(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF ARG-108; GLN-148; VAL-148; ASP-167; ILE-177; ILE-267; LYS-474; LEU-479; HIS-653; ILE-680; ILE-694; VAL-694; ARG-695; MET-720; ALA-726; SER-744 AND HIS-761.
[37]"Mutational analysis of the PRYSPRY domain of pyrin and implications for familial mediterranean fever (FMF)."
Goulielmos G.N., Fragouli E., Aksentijevich I., Sidiropoulos P., Boumpas D.T., Eliopoulos E.
Biochem. Biophys. Res. Commun. 345:1326-1332(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARFMF SER-632; MET-640; PHE-641; LEU-646; PRO-649; HIS-653; ALA-656; ASN-661; ASN-675; GLU-678; LEU-680; ILE-681; CYS-688; ILE-694; LEU-694; VAL-694; MET-695; ARG-695; ILE-704; SER-705; MET-720; ALA-726; LEU-743; SER-744; SER-758; HIS-761 AND THR-780, VARIANT CYS-702.
[38]"Prevalence of known mutations and a novel missense mutation (M694K) in the MEFV gene in a population from the Eastern Anatolia Region of Turkey."
Yesilada E., Taskapan H., Gulbay G.
Gene 511:371-374(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARFMF LYS-694.
[39]"MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant autoinflammatory disease."
Stoffels M., Szperl A., Simon A., Netea M.G., Plantinga T.S., van Deuren M., Kamphuis S., Lachmann H.J., Cuppen E., Kloosterman W.P., Frenkel J., van Diemen C.C., Wijmenga C., van Gijn M., van der Meer J.W.
Ann. Rheum. Dis. 73:455-461(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-267; SER-369; GLN-408; ALA-577; ASN-577 AND SER-577, INVOLVEMENT IN AUTOSOMAL DOMINANT INFLAMMATORY DISEASE.
+Additional computationally mapped references.

Web resources

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF018080 mRNA. Translation: AAB70557.1.
CH471112 Genomic DNA. Translation: EAW85382.1.
CH471112 Genomic DNA. Translation: EAW85383.1.
BC101511 mRNA. Translation: AAI01512.1.
BC101537 mRNA. Translation: AAI01538.1.
Y14441 mRNA. Translation: CAA74793.1.
AJ003147 Genomic DNA. Translation: CAA05906.1.
AF111163 Genomic DNA. Translation: AAD26152.1.
AF301150 Genomic DNA. Translation: AAK97223.1.
AF301151 Genomic DNA. Translation: AAK97224.1.
RefSeqNP_000234.1. NM_000243.2.
NP_001185465.1. NM_001198536.1.
UniGeneHs.632221.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WL1X-ray1.35A586-776[»]
ProteinModelPortalO15553.
SMRO15553. Positions 13-88, 305-362, 373-412, 586-776.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110374. 2 interactions.
IntActO15553. 2 interactions.
MINTMINT-206922.
STRING9606.ENSP00000219596.

Chemistry

DrugBankDB01394. Colchicine.

PTM databases

PhosphoSiteO15553.

Proteomic databases

PaxDbO15553.
PRIDEO15553.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219596; ENSP00000219596; ENSG00000103313. [O15553-2]
ENST00000536379; ENSP00000445079; ENSG00000103313. [O15553-1]
ENST00000541159; ENSP00000438711; ENSG00000103313. [O15553-3]
GeneID4210.
KEGGhsa:4210.
UCSCuc002cun.1. human. [O15553-2]
uc021tbx.1. human. [O15553-1]

Organism-specific databases

CTD4210.
GeneCardsGC16M003295.
HGNCHGNC:6998. MEFV.
MIM134610. phenotype.
249100. phenotype.
608107. gene.
neXtProtNX_O15553.
Orphanet117. Behcet disease.
342. Familial Mediterranean fever.
329967. Intermittent hydrarthrosis.
PharmGKBPA30736.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG328286.
HOGENOMHOG000113552.
HOVERGENHBG006343.
InParanoidO15553.
KOK12803.
OMAPNLIFSD.
OrthoDBEOG7CCBQH.
PhylomeDBO15553.
TreeFamTF351091.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressO15553.
BgeeO15553.
CleanExHS_MEFV.
GenevestigatorO15553.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
4.10.45.10. 1 hit.
InterProIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR008985. ConA-like_lec_gl_sf.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR006574. PRY.
IPR028841. Pyrin.
IPR018355. SPla/RYanodine_receptor_subgr.
IPR003877. SPRY_rcpt.
IPR000315. Znf_B-box.
[Graphical view]
PANTHERPTHR24103:SF85. PTHR24103:SF85. 1 hit.
PfamPF13765. PRY. 1 hit.
PF02758. PYRIN. 1 hit.
PF00622. SPRY. 1 hit.
PF00643. zf-B_box. 1 hit.
[Graphical view]
PRINTSPR01407. BUTYPHLNCDUF.
SMARTSM00336. BBOX. 1 hit.
SM00589. PRY. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEPS50188. B302_SPRY. 1 hit.
PS50824. DAPIN. 1 hit.
PS50119. ZF_BBOX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO15553.
GeneWikiMEFV.
GenomeRNAi4210.
NextBio16586.
PROO15553.
SOURCESearch...

Entry information

Entry nameMEFV_HUMAN
AccessionPrimary (citable) accession number: O15553
Secondary accession number(s): D3DUC0 expand/collapse secondary AC list , F5H0Q3, Q3MJ84, Q96PN4, Q96PN5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM