O15553 (MEFV_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyrin

Alternative name(s):
Marenostrin

Gene names

Name:	MEFV
Synonyms:	MEF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	781 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probably controls the inflammatory response in myelomonocytic cells at the level of the cytoskeleton organization. Ref.7 Ref.9
Subunit structure	Interacts with PSTPIP1. Ref.10
Subcellular location	Isoform 1: Cytoplasm › cytoskeleton. Note: Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles. Ref.2 Ref.8 Ref.9 Isoform 2: Nucleus Ref.2 Ref.8 Ref.9.
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, 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. Ref.7
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.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.27 Ref.28 Ref.29 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.11 Ref.23 Ref.26
Sequence similarities	Contains 1 B box-type zinc finger. Contains 1 B30.2/SPRY domain. Contains 1 DAPIN domain.

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Cytoplasm Cytoskeleton Microtubule Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Amyloidosis Disease mutation
Domain	Zinc-finger
Ligand	Actin-binding Metal-binding Zinc
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inflammatory 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_component	cytosol 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_function	actin 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 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 781

781

Pyrin

PRO_0000220364

Regions

Domain

1 – 92

92

DAPIN

Domain

580 – 775

196

B30.2/SPRY

Zinc finger

370 – 412

43

B box-type

Motif

420 – 437

18

Nuclear localization signal Potential

Natural variations

Alternative sequence

93 – 303

211

Missing in isoform 2.

VSP_008223

Natural variant

33

1

V → L.
Corresponds to variant rs11466016 [ dbSNP | Ensembl ].

VAR_048398

Natural variant

42

1

R → W in arFMF.

VAR_028326

Natural variant

108

1

S → R in arFMF. Ref.28

VAR_028327

Natural variant

110

1

L → P in arFMF. Ref.21
Corresponds to variant rs11466018 [ dbSNP | Ensembl ].

VAR_016824

Natural variant

138

1

G → A Association with renal amyloidosis. Ref.24

VAR_016825

Natural variant

148

1

E → Q in arFMF and adFMF; common mutation; associated with S-369 and Q-408 in cis; associated with I-694 in some patients. Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.28
Corresponds to variant rs3743930 [ dbSNP | Ensembl ].

VAR_009051

Natural variant

148

1

E → V in arFMF. Ref.28

VAR_028328

Natural variant

163

1

E → A in arFMF. Ref.27

VAR_028329

Natural variant

167

1

E → D in arFMF. Ref.28

VAR_009052

Natural variant

177

1

T → I in arFMF. Ref.28

VAR_028330

Natural variant

202

1

R → Q. Ref.4 Ref.14
Corresponds to variant rs224222 [ dbSNP | Ensembl ].

VAR_009053

Natural variant

230

1

E → K in arFMF. Ref.6

VAR_016826

Natural variant

267

1

T → I in arFMF. Ref.28

VAR_009054

Natural variant

319

1

E → K in arFMF. Ref.27

VAR_028331

Natural variant

369

1

P → S in arFMF; reduced penetrance among Ashkenazi Jews; associated with Q-148 and Q-408 in cis. Ref.17
Corresponds to variant rs11466023 [ dbSNP | Ensembl ].

VAR_009055

Natural variant

408

1

R → Q in arFMF; associated with Q-148 and S-369 in cis. Ref.17
Corresponds to variant rs11466024 [ dbSNP | Ensembl ].

VAR_009056

Natural variant

440

1

Q → E.
Corresponds to variant rs11466026 [ dbSNP | Ensembl ].

VAR_024376

Natural variant

474

1

E → K in arFMF. Ref.28

VAR_028332

Natural variant

478

1

H → Y in adFMF; severe. Ref.26

VAR_028333

Natural variant

479

1

F → L in arFMF. Ref.17 Ref.28

VAR_009057

Natural variant

585

1

F → L.
Corresponds to variant rs11466043 [ dbSNP | Ensembl ].

VAR_028334

Natural variant

591

1

I → T in arFMF; unknown pathological significance. Ref.25
Corresponds to variant rs11466045 [ dbSNP | Ensembl ].

VAR_016827

Natural variant

632

1

G → S in arFMF. Ref.29

VAR_028335

Natural variant

640

1

I → M in arFMF. Ref.29

VAR_028336

Natural variant

641

1

I → F in arFMF. Ref.29

VAR_028337

Natural variant

646

1

P → L in arFMF. Ref.29

VAR_028338

Natural variant

649

1

L → P in arFMF. Ref.29

VAR_028339

Natural variant

653

1

R → H in arFMF. Ref.6 Ref.28 Ref.29

VAR_016828

Natural variant

656

1

E → A in arFMF. Ref.29

VAR_028340

Natural variant

661

1

D → N in arFMF. Ref.29

VAR_028341

Natural variant

675

1

S → N in arFMF. Ref.22 Ref.29

VAR_016829

Natural variant

678

1

G → E in arFMF. Ref.29

VAR_028342

Natural variant

680

1

M → I in arFMF and adFMF. Ref.1 Ref.5 Ref.15 Ref.17 Ref.18 Ref.19 Ref.23 Ref.28
Corresponds to variant rs28940580 [ dbSNP | Ensembl ].

VAR_028343

Natural variant

680

1

M → L in arFMF. Ref.22 Ref.29

VAR_016830

Natural variant

681

1

T → I in arFMF. Ref.15 Ref.29

VAR_009059

Natural variant

688

1

Y → C in arFMF. Ref.29

VAR_028344

Natural variant

692

1

Missing in arFMF.

VAR_009060

Natural variant

694

1

M → I in arFMF and adFMF; associated with Q-148 in some patients. Ref.5 Ref.15 Ref.18 Ref.19 Ref.23 Ref.28 Ref.29
Corresponds to variant rs28940578 [ dbSNP | Ensembl ].

VAR_009061

Natural variant

694

1

M → L in arFMF. Ref.29

VAR_028345

Natural variant

694

1

M → V in arFMF and adFMF; very common mutation particularly in North African Jews; can be associated with amyloidosis development. Ref.1 Ref.15 Ref.17 Ref.18 Ref.19 Ref.21 Ref.23 Ref.28 Ref.29

VAR_009062

Natural variant

694

1

Missing in arFMF and adFMF. Ref.15 Ref.23

VAR_009063

Natural variant

695

1

K → M in arFMF. Ref.29

VAR_028346

Natural variant

695

1

K → R in arFMF; reduced penetrance among Ashkenazi Jews. Ref.19 Ref.28 Ref.29

VAR_009064

Natural variant

702

1

S → C in one patient with familial Mediterranean fever. Ref.29

VAR_028347

Natural variant

704

1

V → I in arFMF. Ref.29

VAR_028348

Natural variant

705

1

P → S in arFMF. Ref.29

VAR_028349

Natural variant

720

1

I → M in arFMF. Ref.28 Ref.29

VAR_028350

Natural variant

726

1

V → A in arFMF; common mutation; in Iraqi and Ashkenazi Jews, Druze, Armenians. Ref.1 Ref.15 Ref.17 Ref.18 Ref.19 Ref.28 Ref.29
Corresponds to variant rs28940579 [ dbSNP | Ensembl ].

VAR_009065

Natural variant

743

1

F → L in arFMF. Ref.29

VAR_028351

Natural variant

744

1

A → S in arFMF; uncertain pathological significance. Ref.27 Ref.28 Ref.29

VAR_009066

Natural variant

758

1

P → S in arFMF. Ref.29

VAR_028352

Natural variant

761

1

R → H in arFMF. Ref.17 Ref.19 Ref.28 Ref.29

VAR_009067

Natural variant

780

1

P → T in arFMF. Ref.29

VAR_028353

Secondary structure

1

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781

Helix Strand Turn

Details...

Helix

590 – 594

5

Turn

604 – 606

3

Beta strand

611 – 613

3

Beta strand

619 – 622

4

Beta strand

637 – 639

3

Beta strand

642 – 645

4

Beta strand

650 – 658

9

Beta strand

665 – 671

7

Beta strand

676 – 678

3

Helix

684 – 686

3

Beta strand

688 – 695

8

Beta strand

698 – 701

4

Beta strand

716 – 723

8

Turn

724 – 727

4

Beta strand

728 – 733

6

Turn

734 – 737

4

Beta strand

738 – 743

6

Beta strand

752 – 757

6

Helix

762 – 764

3

Beta strand

770 – 773

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (FL) [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 3692E5E6E9FC8204	FASTA	781	86,444
	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
	Isoform 2 (D2) [UniParc]. Checksum: 34C7379A052C74EF	FASTA	570	64,494
	10 20 30 40 50 60 MAKTPSDHLL STLEELVPYD FEKFKFKLQN TSVQKEHSRI PRSQIQRARP VKMATLLVTY 70 80 90 100 110 120 YGEEYAVQLT LQVLRAINQR LLAEELHRAA IQGRPPDTAA SPRCHAQEGD PVDGTCVRDS 130 140 150 160 170 180 CSFPEAVSGH PQASGSRSPG CPRCQDSHER KSPGSLSPQP LPQCKRHLKQ VQLLFCEDHD 190 200 210 220 230 240 EPICLICSLS QEHQGHRVRP IEEVALEHKK KIQKQLEHLK KLRKSGEEQR SYGEEKAVSF 250 260 270 280 290 300 LKQTEALKQR VQRKLEQVYY FLEQQEHFFV ASLEDVGQMV GQIRKAYDTR VSQDIALLDA 310 320 330 340 350 360 LIGELEAKEC QSEWELLQDI GDILHRAKTV PVPEKWTTPQ EIKQKIQLLH QKSEFVEKST 370 380 390 400 410 420 KYFSETLRSE MEMFNVPELI GAQAHAVNVI LDAETAYPNL IFSDDLKSVR LGNKWERLPD 430 440 450 460 470 480 GPQRFDSCII VLGSPSFLSG RRYWEVEVGD KTAWILGACK TSISRKGNMT LSPENGYWVV 490 500 510 520 530 540 IMMKENEYQA SSVPPTRLLI KEPPKRVGIF VDYRVGSISF YNVTARSHIY TFASCSFSGP 550 560 570 LQPIFSPGTR DGGKNTAPLT ICPVGGQGPD

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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. , 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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
+	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.

IPI

IPI00007367.
IPI00375378.

RefSeq

NP_000234.1. NM_000243.2.
NP_001185465.1. NM_001198536.1.

UniGene

Hs.632221.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WL1	X-ray	1.35	A	586-776	[»]

ProteinModelPortal

O15553.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-206922.

STRING

9606.ENSP00000219596.

PTM databases

PhosphoSite

O15553.

Proteomic databases

PaxDb

O15553.

PRIDE

O15553.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000219596; ENSP00000219596; ENSG00000103313.
ENST00000536379; ENSP00000445079; ENSG00000103313.

GeneID

4210.

KEGG

hsa:4210.

UCSC

uc002cun.1. human.
uc021tbx.1. human.

Organism-specific databases

CTD

4210.

GeneCards

GC16M003295.

HGNC

HGNC:6998. MEFV.

MIM

134610. phenotype.
249100. phenotype.
608107. gene.

neXtProt

NX_O15553.

Orphanet

342. Familial mediterranean fever.

PharmGKB

PA30736.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG328286.

HOGENOM

HOG000113552.

HOVERGEN

HBG006343.

InParanoid

O15553.

KO

K12803.

OMA

FNVPELI.

OrthoDB

EOG4DV5M1.

PhylomeDB

O15553.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O15553.

Bgee

O15553.

CleanEx

HS_MEFV.

Genevestigator

O15553.

GermOnline

ENSG00000103313. Homo sapiens.

Family and domain databases

Gene3D

1.10.533.10. 1 hit.

InterPro

IPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR008985. ConA-like_lec_gl_sf.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR006574. PRY.
IPR018355. SPla/RYanodine_receptor_subgr.
IPR003877. SPRY_rcpt.
IPR000315. Znf_B-box.
[Graphical view]

Pfam

PF02758. PYRIN. 1 hit.
PF00622. SPRY. 1 hit.
PF00643. zf-B_box. 1 hit.
[Graphical view]

PRINTS

PR01407. BUTYPHLNCDUF.

SMART

SM00336. BBOX. 1 hit.
SM00589. PRY. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 1 hit.
SSF47986. DEATH_like. 1 hit.

PROSITE

PS50188. B302_SPRY. 1 hit.
PS50824. DAPIN. 1 hit.
PS50119. ZF_BBOX. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB01394. Colchicine.

EvolutionaryTrace

O15553.

GenomeRNAi

4210.

NextBio

16586.

SOURCE

Search...

Entry information

Entry name

MEFV_HUMAN

Accession

Primary (citable) accession number: O15553
Secondary accession number(s): D3DUC0 , Q3MJ84, Q96PN4, Q96PN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.