MEFV_HUMAN
ID MEFV_HUMAN Reviewed; 781 AA.
AC O15553; D3DUC0; F5H0Q3; Q3MJ84; Q96PN4; Q96PN5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Pyrin {ECO:0000303|PubMed:9288758};
DE AltName: Full=Marenostrin {ECO:0000303|PubMed:11115844};
GN Name=MEFV {ECO:0000303|PubMed:11115844, ECO:0000312|HGNC:HGNC:6998};
GN Synonyms=MEF, TRIM20 {ECO:0000303|PubMed:26347139};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARFMF ILE-680; VAL-694
RP AND ALA-726.
RC TISSUE=Leukocyte;
RX PubMed=9288758; DOI=10.1016/s0092-8674(00)80539-5;
RA Aksentijevich I., Centola M., Deng Z., Sood R., Balow J.E. Jr., Wood G.,
RA Zaks N., Mansfield E., Chen X., Eisenberg S., Vedula A., Shafran N.,
RA Raben N., Pras E., Pras M., Kastner D.L., Blake T., Baxevanis A.D.,
RA Robbins C., Krizman D., Collins F.S., Liu P.P., Chen X., Shohat M.,
RA Hamon M., Kahan T., Cercek A., Rotter J.I., Fischel-Ghodsian N.,
RA Richards N., Shelton D.A., Gumucio D., Yokoyama Y., Mangelsdorf M.,
RA Orsborn A., Richards R.I., Ricke D.O., Buckingham J.M., Moyzis R.K.,
RA Deaven L.L., Doggett N.A.;
RT "Ancient missense mutations in a new member of the RoRet gene family are
RT likely to cause familial Mediterranean fever.";
RL Cell 90:797-807(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Leukocyte;
RX PubMed=11115844; DOI=10.1093/hmg/9.20.3001;
RA Papin S., Duquesnoy P., Cazeneuve C., Pantel J., Coppey-Moisan M.,
RA Dargemont C., Amselem S.;
RT "Alternative splicing at the MEFV locus involved in familial Mediterranean
RT fever regulates translocation of the marenostrin/pyrin protein to the
RT nucleus.";
RL Hum. Mol. Genet. 9:3001-3009(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-202.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 305-754, AND VARIANTS ARFMF ILE-680 AND
RP ILE-694.
RX PubMed=9288094; DOI=10.1038/ng0997-25;
RA Bernot A., Clepet C., Dasilva C., Devaud C., Petit J.-L., Caloustian C.,
RA Cruaud C., Samson D., Pulcini F., Weissenbach J., Heilig R., Notanicola C.,
RA Domingo C., Rozenbaum M., Benchetrit E., Topaloglu R., Dewalle M.,
RA Dross C., Hadjari P., Dupont M., Demaille J.G., Touitou I., Smaoui N.,
RA Nedelec B., Mery J.-P., Chaabouni H., Delpech M., Grateau G.;
RT "A candidate gene for familial Mediterranean fever.";
RL Nat. Genet. 17:25-31(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 96-303 AND 599-781, AND VARIANTS ARFMF
RP LYS-230 AND HIS-653.
RC TISSUE=Blood;
RX PubMed=11470495; DOI=10.1016/s0027-5107(01)00221-4;
RA Timmann C., Muntau B., Kuhne K., Gelhaus A., Horstmann R.D.;
RT "Two novel mutations R653H and E230K in the Mediterranean fever gene
RT associated with disease.";
RL Mutat. Res. 479:235-239(2001).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=10807793;
RA Centola M., Wood G., Frucht D.M., Galon J., Aringer M., Farrell C.,
RA Kingma D.W., Horwitz M.E., Mansfield E., Holland S.M., O'Shea J.J.,
RA Rosenberg H.F., Malech H.L., Kastner D.L.;
RT "The gene for familial Mediterranean fever, MEFV, is expressed in early
RT leukocyte development and is regulated in response to inflammatory
RT mediators.";
RL Blood 95:3223-3231(2000).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10666224;
RA Tidow N., Chen X., Muller C., Kawano S., Gombart A.F., Fischel-Ghodsian N.,
RA Koeffler H.P.;
RT "Hematopoietic-specific expression of MEFV, the gene mutated in familial
RT Mediterranean fever, and subcellular localization of its corresponding
RT protein, pyrin.";
RL Blood 95:1451-1455(2000).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11468188; DOI=10.1182/blood.v98.3.851;
RA Mansfield E., Chae J.J., Komarow H.D., Brotz T.M., Frucht D.M.,
RA Aksentijevich I., Kastner D.L.;
RT "The familial Mediterranean fever protein, pyrin, associates with
RT microtubules and colocalizes with actin filaments.";
RL Blood 98:851-859(2001).
RN [10]
RP INTERACTION WITH PYCARD, AND SUBCELLULAR LOCATION.
RX PubMed=11498534; DOI=10.1074/jbc.m104730200;
RA Richards N., Schaner P., Diaz A., Stuckey J., Shelden E., Wadhwa A.,
RA Gumucio D.L.;
RT "Interaction between pyrin and the apoptotic speck protein (ASC) modulates
RT ASC-induced apoptosis.";
RL J. Biol. Chem. 276:39320-39329(2001).
RN [11]
RP INTERACTION WITH PSTPIP1.
RX PubMed=14595024; DOI=10.1073/pnas.2135380100;
RA Shoham N.G., Centola M., Mansfield E., Hull K.M., Wood G., Wise C.A.,
RA Kastner D.L.;
RT "Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean
RT fever and PAPA syndrome as disorders in the same pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13501-13506(2003).
RN [12]
RP DISEASE.
RX PubMed=12384939; DOI=10.1002/art.10575;
RA Notarnicola C., Didelot M.-N., Kone-Paut I., Seguret F., Demaille J.,
RA Touitou I.;
RT "Reduced MEFV messenger RNA expression in patients with familial
RT Mediterranean fever.";
RL Arthritis Rheum. 46:2785-2793(2002).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF LEU-16 AND PHE-24.
RX PubMed=16037825; DOI=10.1038/sj.cdd.4401734;
RA Yu J.W., Wu J., Zhang Z., Datta P., Ibrahimi I., Taniguchi S., Sagara J.,
RA Fernandes-Alnemri T., Alnemri E.S.;
RT "Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC
RT oligomerization.";
RL Cell Death Differ. 13:236-249(2006).
RN [14]
RP INTERACTION WITH CASP1, AND CHARACTERIZATION OF VARIANTS ILE-680; VAL-694
RP AND ALA-726.
RX PubMed=16785446; DOI=10.1073/pnas.0602081103;
RA Chae J.J., Wood G., Masters S.L., Richard K., Park G., Smith B.J.,
RA Kastner D.L.;
RT "The B30.2 domain of pyrin, the familial Mediterranean fever protein,
RT interacts directly with caspase-1 to modulate IL-1beta production.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9982-9987(2006).
RN [15]
RP FUNCTION, INTERACTION WITH CASP1; CASP5; NLRP1; NLRP2; NLRP3 AND IL1B, AND
RP CHARACTERIZATION OF VARIANT VAL-694.
RX PubMed=17431422; DOI=10.1038/sj.cdd.4402142;
RA Papin S., Cuenin S., Agostini L., Martinon F., Werner S., Beer H.D.,
RA Grutter C., Grutter M., Tschopp J.;
RT "The SPRY domain of Pyrin, mutated in familial Mediterranean fever
RT patients, interacts with inflammasome components and inhibits proIL-1beta
RT processing.";
RL Cell Death Differ. 14:1457-1466(2007).
RN [16]
RP FUNCTION, SUBUNIT, INTERACTION WITH PYCARD AND PSTPIP1, INDUCTION BY
RP RETROVIRAL INFECTION, AND DOMAIN.
RX PubMed=17964261; DOI=10.1016/j.molcel.2007.08.029;
RA Yu J.W., Fernandes-Alnemri T., Datta P., Wu J., Juliana C., Solorzano L.,
RA McCormick M., Zhang Z., Alnemri E.S.;
RT "Pyrin activates the ASC pyroptosome in response to engagement by
RT autoinflammatory PSTPIP1 mutants.";
RL Mol. Cell 28:214-227(2007).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RELA AND NFKBIA, PROBABLE
RP CLEAVAGE BY CASP-1, AND MUTAGENESIS OF ASP-330.
RX PubMed=18577712; DOI=10.1182/blood-2008-01-134932;
RA Chae J.J., Wood G., Richard K., Jaffe H., Colburn N.T., Masters S.L.,
RA Gumucio D.L., Shoham N.G., Kastner D.L.;
RT "The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1
RT and activates NF-kappaB through its N-terminal fragment.";
RL Blood 112:1794-1803(2008).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PSTPIP1; VASP AND
RP ACTR3.
RX PubMed=19109554; DOI=10.3181/0806-rm-184;
RA Waite A.L., Schaner P., Hu C., Richards N., Balci-Peynircioglu B., Hong A.,
RA Fox M., Gumucio D.L.;
RT "Pyrin and ASC co-localize to cellular sites that are rich in polymerizing
RT actin.";
RL Exp. Biol. Med. (Maywood) 234:40-52(2009).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19584923; DOI=10.1371/journal.pone.0006147;
RA Waite A.L., Schaner P., Richards N., Balci-Peynircioglu B., Masters S.L.,
RA Brydges S.D., Fox M., Hong A., Yilmaz E., Kastner D.L., Reinherz E.L.,
RA Gumucio D.L.;
RT "Pyrin Modulates the Intracellular Distribution of PSTPIP1.";
RL PLoS ONE 4:E6147-E6147(2009).
RN [20]
RP FUNCTION, INTERACTION WITH ATG16L1; BECN1; GABARAP; GABARAPL1; GABARAPL2;
RP MAP1LC3A; MAP1LC3C; NLRP3; TRIM21 AND ULK1, SUBCELLULAR LOCATION, INDUCTION
RP BY IFNG, DEGRADATION BY AUTOPHAGY, CHARACTERIZATION OF VARIANTS ARFMF
RP ILE-680; VAL-694 AND ALA-726, AND MUTAGENESIS OF 397-ILE--HIS-404;
RP 470-TYR--GLY-488 AND 523-SER--ASP-530.
RX PubMed=26347139; DOI=10.1083/jcb.201503023;
RA Kimura T., Jain A., Choi S.W., Mandell M.A., Schroder K., Johansen T.,
RA Deretic V.;
RT "TRIM-mediated precision autophagy targets cytoplasmic regulators of innate
RT immunity.";
RL J. Cell Biol. 210:973-989(2015).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 586-776.
RX PubMed=19729025; DOI=10.1016/j.jmb.2009.08.059;
RA Weinert C., Grutter C., Roschitzki-Voser H., Mittl P.R., Grutter M.G.;
RT "The crystal structure of human pyrin b30.2 domain: implications for
RT mutations associated with familial Mediterranean fever.";
RL J. Mol. Biol. 394:226-236(2009).
RN [22]
RP VARIANTS ARFMF, AND VARIANT GLN-202.
RX PubMed=9668175; DOI=10.1093/hmg/7.8.1317;
RA Bernot A., da Silva C., Petit J.-L., Cruaud C., Caloustian C., Castet V.,
RA Ahmed-Arab M., Dross C., Dupont M., Cattan D., Smaoui N., Dode C.,
RA Pecheux C., Nedelec B., Medaxian J., Rozenbaum M., Rosner I., Delpech M.,
RA Grateau G., Demaille J., Weissenbach J., Touitou I.;
RT "Non-founder mutations in the MEFV gene establish this gene as the cause of
RT familial Mediterranean fever (FMF).";
RL Hum. Mol. Genet. 7:1317-1325(1998).
RN [23]
RP VARIANTS ARFMF ILE-680; ILE-681; ILE-694; VAL-694; MET-694 DEL AND ALA-726.
RX PubMed=10024914; DOI=10.1093/qjmed/91.9.603;
RA Booth D.R., Gillmore J.D., Booth S.E., Pepys M.B., Hawkins P.N.;
RT "Pyrin/marenostrin mutations in familial Mediterranean fever.";
RL QJM 91:603-606(1998).
RN [24]
RP VARIANTS ARFMF.
RX PubMed=10090880; DOI=10.1086/302327;
RA Aksentijevich I., Torosyan Y., Samuels J., Centola M., Pras E., Chae J.J.,
RA Oddoux C., Wood G., Azzaro M.P., Palumbo G., Giustolisi R., Pras M.,
RA Ostrer H., Kastner D.L.;
RT "Mutation and haplotype studies of familial Mediterranean fever reveal new
RT ancestral relationships and evidence for a high carrier frequency with
RT reduced penetrance in the Ashkenazi Jewish population.";
RL Am. J. Hum. Genet. 64:949-962(1999).
RN [25]
RP VARIANTS ARFMF GLN-148; SER-369; GLN-408; LEU-479; ILE-680; VAL-694;
RP ALA-726 AND HIS-761.
RX PubMed=10364520; DOI=10.1086/302459;
RA Cazeneuve C., Sarkisian T., Pecheux C., Dervichian M., Nedelec B.,
RA Reinert P., Ayvazyan A., Kouyoumdjian J.-C., Ajrapetyan H., Delpech M.,
RA Goossens M., Dode C., Grateau G., Amselem S.;
RT "MEFV-Gene analysis in Armenian patients with familial Mediterranean fever:
RT diagnostic value and unfavorable renal prognosis of the M694V homozygous
RT genotype-genetic and therapeutic implications.";
RL Am. J. Hum. Genet. 65:88-97(1999).
RN [26]
RP VARIANTS ARFMF ILE-680; ILE-694; VAL-694 AND ALA-726.
RX PubMed=10234504; DOI=10.1038/sj.ejhg.5200303;
RA Shohat M., Magal N., Shohat T., Chen X., Dagan T., Mimouni A., Danon Y.,
RA Lotan R., Ogur G., Sirin A., Schlezinger M., Halpern G.J., Schwabe A.,
RA Kastner D., Rotter J.I., Fischel-Ghodsian N.;
RT "Phenotype-genotype correlation in familial Mediterranean fever: evidence
RT for an association between Met694Val and amyloidosis.";
RL Eur. J. Hum. Genet. 7:287-292(1999).
RN [27]
RP VARIANTS ARFMF GLN-148; ILE-680; ILE-694; VAL-694; ARG-695; ALA-726 AND
RP HIS-761.
RX PubMed=10612841;
RX DOI=10.1002/(sici)1098-1004(200001)15:1<118::aid-humu29>3.0.co;2-5;
RA Akar N., Misiroglu M., Yalcinkaya F., Akar E., Cakar N., Tumer N.,
RA Akcakus M., Tastan H., Matzner Y.;
RT "MEFV mutations in Turkish patients suffering from familial Mediterranean
RT fever.";
RL Hum. Mutat. 15:118-119(2000).
RN [28]
RP VARIANT GLN-148.
RX PubMed=10737995;
RX DOI=10.1002/(sici)1098-1004(200004)15:4<385::aid-humu22>3.0.co;2-a;
RA Ben-Chetrit E., Lerer I., Malamud E., Domingo C., Abeliovich D.;
RT "The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a
RT sequence variant?";
RL Hum. Mutat. 15:385-386(2000).
RN [29]
RP VARIANTS ARFMF PRO-110; GLN-148 AND VAL-694.
RX PubMed=10854105; DOI=10.1038/sj.ejhg.5200462;
RA Domingo C., Touitou I., Bayou A., Ozen S., Notarnicola C., Dewalle M.,
RA Demaille J., Buades R., Sayadat C., Levy M., Ben-Chetrit E.;
RT "Familial Mediterranean fever in the 'Chuetas' of Mallorca: a question of
RT Jewish origin or genetic heterogeneity.";
RL Eur. J. Hum. Genet. 8:242-246(2000).
RN [30]
RP VARIANTS ARFMF ASN-675 AND LEU-680.
RX PubMed=10842288;
RX DOI=10.1002/(sici)1096-8628(20000605)92:4<241::aid-ajmg3>3.0.co;2-g;
RA Dode C., Pecheux C., Cazeneuve C., Cattan D., Dervichian M., Goossens M.,
RA Delpech M., Amselem S., Grateau G.;
RT "Mutations in the MEFV gene in a large series of patients with a clinical
RT diagnosis of familial Mediterranean fever.";
RL Am. J. Med. Genet. 92:241-246(2000).
RN [31]
RP VARIANTS ADFMF GLN-148; ILE-680; ILE-694; MET-694 DEL AND VAL-694.
RX PubMed=10787449; DOI=10.1093/qjmed/93.4.217;
RA Booth D.R., Gillmore J.D., Lachmann H.J., Booth S.E., Bybee A.,
RA Soytuerk M., Akar S., Pepys M.B., Tunca M., Hawkins P.N.;
RT "The genetic basis of autosomal dominant familial Mediterranean fever.";
RL QJM 93:217-221(2000).
RN [32]
RP REVIEW ON ARFMF VARIANTS.
RX PubMed=11464238; DOI=10.1038/sj.ejhg.5200658;
RA Touitou I.;
RT "The spectrum of familial mediterranean fever (FMF) mutations.";
RL Eur. J. Hum. Genet. 9:473-483(2001).
RN [33]
RP VARIANT FMF THR-591.
RX PubMed=12124996; DOI=10.1002/humu.10103;
RA Aldea A., Casademont J., Arostegui J.I., Rius J., Maso M., Vives J.,
RA Yague J.;
RT "I591T MEFV mutation in a Spanish kindred: is it a mild mutation, a benign
RT polymorphism, or a variant influenced by another modifier?";
RL Hum. Mutat. 20:148-150(2002).
RN [34]
RP VARIANT ADFMF TYR-478.
RX PubMed=14679589; DOI=10.1002/ajmg.a.20296;
RA Aldea A., Campistol J.M., Arostegui J.I., Rius J., Maso M., Vives J.,
RA Yaguee J.;
RT "A severe autosomal-dominant periodic inflammatory disorder with renal AA
RT amyloidosis and colchicine resistance associated to the MEFV H478Y variant
RT in a Spanish kindred: an unusual familial Mediterranean fever phenotype or
RT another MEFV-associated periodic inflammatory disorder?";
RL Am. J. Med. Genet. A 124:67-73(2004).
RN [35]
RP VARIANTS ARFMF ALA-163 AND LYS-319, AND VARIANT SER-744.
RX PubMed=15024744; DOI=10.1002/humu.9229;
RA Aldea A., Calafell F., Arostegui J.I., Lao O., Rius J., Plaza S., Maso M.,
RA Vives J., Buades J., Yaguee J.;
RT "The west side story: MEFV haplotype in Spanish FMF patients and controls,
RT and evidence of high LD and a recombination 'hot-spot' at the MEFV locus.";
RL Hum. Mutat. 23:399-399(2004).
RN [36]
RP VARIANTS ARFMF ARG-108; GLN-148; VAL-148; ASP-167; ILE-177; ILE-267;
RP LYS-474; LEU-479; HIS-653; ILE-680; ILE-694; VAL-694; ARG-695; MET-720;
RP ALA-726; SER-744 AND HIS-761.
RX PubMed=16378925; DOI=10.1016/j.ejmg.2005.05.010;
RA Medlej-Hashim M., Serre J.-L., Corbani S., Saab O., Jalkh N., Delague V.,
RA Chouery E., Salem N., Loiselet J., Lefranc G., Megarbane A.;
RT "Familial Mediterranean fever (FMF) in Lebanon and Jordan: a population
RT genetics study and report of three novel mutations.";
RL Eur. J. Med. Genet. 48:412-420(2005).
RN [37]
RP VARIANTS ARFMF SER-632; MET-640; PHE-641; LEU-646; PRO-649; HIS-653;
RP ALA-656; ASN-661; ASN-675; GLU-678; LEU-680; ILE-681; CYS-688; ILE-694;
RP LEU-694; VAL-694; MET-695; ARG-695; ILE-704; SER-705; MET-720; ALA-726;
RP LEU-743; SER-744; SER-758; HIS-761 AND THR-780, AND VARIANT CYS-702.
RX PubMed=16730661; DOI=10.1016/j.bbrc.2006.04.185;
RA Goulielmos G.N., Fragouli E., Aksentijevich I., Sidiropoulos P.,
RA Boumpas D.T., Eliopoulos E.;
RT "Mutational analysis of the PRYSPRY domain of pyrin and implications for
RT familial mediterranean fever (FMF).";
RL Biochem. Biophys. Res. Commun. 345:1326-1332(2006).
RN [38]
RP VARIANT ARFMF LYS-694.
RX PubMed=23031807; DOI=10.1016/j.gene.2012.09.073;
RA Yesilada E., Taskapan H., Gulbay G.;
RT "Prevalence of known mutations and a novel missense mutation (M694K) in the
RT MEFV gene in a population from the Eastern Anatolia Region of Turkey.";
RL Gene 511:371-374(2012).
RN [39]
RP VARIANTS ILE-267; SER-369; GLN-408; ALA-577; ASN-577 AND SER-577, AND
RP INVOLVEMENT IN AUTOSOMAL DOMINANT INFLAMMATORY DISEASE.
RX PubMed=23505238; DOI=10.1136/annrheumdis-2012-202580;
RA Stoffels M., Szperl A., Simon A., Netea M.G., Plantinga T.S.,
RA van Deuren M., Kamphuis S., Lachmann H.J., Cuppen E., Kloosterman W.P.,
RA Frenkel J., van Diemen C.C., Wijmenga C., van Gijn M., van der Meer J.W.;
RT "MEFV mutations affecting pyrin amino acid 577 cause autosomal dominant
RT autoinflammatory disease.";
RL Ann. Rheum. Dis. 73:455-461(2014).
RN [40]
RP VARIANTS ARFMF PRO-110; GLN-148; TRP-196; LYS-230; VAL-247; LEU-283;
RP ARG-304; ALA-632; ILE-680; ILE-694; VAL-694; ARG-695; ALA-726; SER-744 AND
RP HIS-761, AND VARIANT GLN-202.
RX PubMed=24929125; DOI=10.1016/j.gene.2014.06.019;
RA Gunesacar R., Celik M.M., Arica V., Elmacioglu S., Ozturk O.H.;
RT "Frequency of MEFV gene mutations in Hatay province, Mediterranean region
RT of Turkey and report of a novel missense mutation (I247V).";
RL Gene 546:195-199(2014).
RN [41]
RP VARIANT PAAND ARG-242, INVOLVEMENT IN PAAND, FUNCTION, PHOSPHORYLATION AT
RP SER-242, INTERACTION WITH YWHAB; YWHAE; YWHAG; YWHAH; YWHAQ AND YWHAZ,
RP CHARACTERIZATION OF VARIANT PAAND ARG-242, CHARACTERIZATION OF VARIANT
RP GLN-202, AND CHARACTERIZATION OF VARIANTS ARFMF ARG-304; ILE-680; ILE-694
RP AND ALA-726.
RX PubMed=27030597; DOI=10.1126/scitranslmed.aaf1471;
RA Masters S.L., Lagou V., Jeru I., Baker P.J., Van Eyck L., Parry D.A.,
RA Lawless D., De Nardo D., Garcia-Perez J.E., Dagley L.F., Holley C.L.,
RA Dooley J., Moghaddas F., Pasciuto E., Jeandel P.Y., Sciot R., Lyras D.,
RA Webb A.I., Nicholson S.E., De Somer L., van Nieuwenhove E., Ruuth-Praz J.,
RA Copin B., Cochet E., Medlej-Hashim M., Megarbane A., Schroder K., Savic S.,
RA Goris A., Amselem S., Wouters C., Liston A.;
RT "Familial autoinflammation with neutrophilic dermatosis reveals a
RT regulatory mechanism of pyrin activation.";
RL Sci. Transl. Med. 8:332ra45-332ra45(2016).
RN [42]
RP VARIANT PAAND LYS-244, CHARACTERIZATION OF VARIANT PAAND LYS-244, FUNCTION,
RP INTERACTION WITH YWHAE AND YWHAQ, INTERACTION WITH PSTPIP1, AND MUTAGENESIS
RP OF SER-208 AND GLU-244.
RX PubMed=28835462; DOI=10.1136/annrheumdis-2017-211473;
RA Moghaddas F., Llamas R., De Nardo D., Martinez-Banaclocha H.,
RA Martinez-Garcia J.J., Mesa-Del-Castillo P., Baker P.J., Gargallo V.,
RA Mensa-Vilaro A., Canna S., Wicks I.P., Pelegrin P., Arostegui J.I.,
RA Masters S.L.;
RT "A novel pyrin-associated autoinflammation with neutrophilic dermatosis
RT mutation further defines 14-3-3 binding of pyrin and distinction to
RT Familial Mediterranean Fever.";
RL Ann. Rheum. Dis. 76:2085-2094(2017).
CC -!- FUNCTION: Involved in the regulation of innate immunity and the
CC inflammatory response in response to IFNG/IFN-gamma (PubMed:10807793,
CC PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554,
CC PubMed:19584923, PubMed:16037825, PubMed:27030597, PubMed:28835462,
CC PubMed:16785446, PubMed:17431422, PubMed:26347139). Organizes
CC autophagic machinery by serving as a platform for the assembly of ULK1,
CC Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes
CC specific autophagy targets, thus coordinating target recognition with
CC assembly of the autophagic apparatus and initiation of autophagy
CC (PubMed:16785446, PubMed:17431422, PubMed:26347139). Acts as an
CC autophagy receptor for the degradation of several inflammasome
CC components, including CASP1, NLRP1 and NLRP3, hence preventing
CC excessive IL1B- and IL18-mediated inflammation (PubMed:16785446,
CC PubMed:17431422, PubMed:26347139). However, it can also have a positive
CC effect in the inflammatory pathway, acting as an innate immune sensor
CC that triggers PYCARD/ASC specks formation, caspase-1 activation, and
CC IL1B and IL18 production (PubMed:16037825, PubMed:27030597,
CC PubMed:28835462). Together with AIM2, also acts as a mediator of
CC pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of
CC host defense against pathogens, in response to bacterial infection (By
CC similarity). It is required for PSTPIP1-induced PYCARD/ASC
CC oligomerization and inflammasome formation (PubMed:10807793,
CC PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554,
CC PubMed:19584923). Recruits PSTPIP1 to inflammasomes, and is required
CC for PSTPIP1 oligomerization (PubMed:10807793, PubMed:11468188,
CC PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923).
CC {ECO:0000250|UniProtKB:Q9JJ26, ECO:0000269|PubMed:10807793,
CC ECO:0000269|PubMed:11468188, ECO:0000269|PubMed:16037825,
CC ECO:0000269|PubMed:16785446, ECO:0000269|PubMed:17431422,
CC ECO:0000269|PubMed:17964261, ECO:0000269|PubMed:18577712,
CC ECO:0000269|PubMed:19109554, ECO:0000269|PubMed:19584923,
CC ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:27030597,
CC ECO:0000269|PubMed:28835462}.
CC -!- SUBUNIT: Homotrimer. Interacts (via the B box-type zinc finger) with
CC PSTPIP1 (PubMed:14595024, PubMed:17964261, PubMed:19109554,
CC PubMed:28835462). Interacts (via the B30.2/SPRY domain) with several
CC components of the inflammasome complex, including CASP1 p20 and p10
CC subunits, CASP5, PYCARD, NLRP1, NLRP2 AND NLRP3, as well as with
CC unprocessed IL1B; this interaction may lead to autophagic degradation
CC of these proteins (PubMed:11498534, PubMed:16785446, PubMed:17431422,
CC PubMed:17964261, PubMed:26347139). Component of the AIM2 PANoptosome
CC complex, a multiprotein complex that drives inflammatory cell death
CC (PANoptosis) (By similarity). Interacts with NFKBIA and RELA
CC (PubMed:18577712). Interacts weakly with VASP and ACTR3
CC (PubMed:19109554). Interacts with active ULK1 (phosphorylated on 'Ser-
CC 317') and BECN1 simultaneously. Also interacts with ATG16L1 (via WD
CC repeats), and with ATG8 family members, including GABARAP, GABARAPL1
CC and, to a lesser extent, GABARAPL2, MAP1LC3A/LC3A and MAP1LC3C/LC3C.
CC Interacts with TRIM21 (PubMed:26347139, PubMed:28835462). Interacts
CC with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ AND YWHAZ; the interaction is
CC required for the down-regulation of pyrin pro-inflammatory activity
CC (PubMed:27030597, PubMed:28835462). {ECO:0000250|UniProtKB:Q9JJ26,
CC ECO:0000269|PubMed:11498534, ECO:0000269|PubMed:14595024,
CC ECO:0000269|PubMed:16785446, ECO:0000269|PubMed:17431422,
CC ECO:0000269|PubMed:17964261, ECO:0000269|PubMed:18577712,
CC ECO:0000269|PubMed:19109554, ECO:0000269|PubMed:26347139,
CC ECO:0000269|PubMed:27030597, ECO:0000269|PubMed:28835462}.
CC -!- INTERACTION:
CC O15553; P29466: CASP1; NbExp=2; IntAct=EBI-7644532, EBI-516667;
CC O15553; O15553: MEFV; NbExp=8; IntAct=EBI-7644532, EBI-7644532;
CC O15553; O43586: PSTPIP1; NbExp=4; IntAct=EBI-7644532, EBI-1050964;
CC O15553; Q9ULZ3: PYCARD; NbExp=8; IntAct=EBI-7644532, EBI-751215;
CC O15553-2; P29466: CASP1; NbExp=3; IntAct=EBI-15588296, EBI-516667;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:11468188, ECO:0000269|PubMed:19109554}. Cell
CC projection, ruffle {ECO:0000269|PubMed:11468188}. Cell projection,
CC lamellipodium {ECO:0000269|PubMed:11468188}. Nucleus
CC {ECO:0000269|PubMed:11115844}. Cytoplasm {ECO:0000269|PubMed:10666224,
CC ECO:0000269|PubMed:11498534, ECO:0000269|PubMed:18577712,
CC ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:26347139}. Cytoplasmic
CC vesicle, autophagosome {ECO:0000269|PubMed:26347139}. Note=Associated
CC with microtubules and with the filamentous actin of perinuclear
CC filaments and peripheral lamellar ruffles (PubMed:11468188). In pre-
CC apoptotic cells, colocalizes with PYCARD/ASC in large specks
CC (inflammasomes) (PubMed:11468188). In migrating monocytes, strongly
CC polarized at the leading edge of the cell where it colocalizes with
CC polymerizing actin and PYCARD/ASC (PubMed:11468188).
CC {ECO:0000269|PubMed:11468188}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:11115844}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=FL;
CC IsoId=O15553-2; Sequence=Displayed;
CC Name=2; Synonyms=D2;
CC IsoId=O15553-1; Sequence=VSP_008223;
CC Name=3;
CC IsoId=O15553-3; Sequence=VSP_008223, VSP_047663;
CC -!- TISSUE SPECIFICITY: Expressed in peripheral blood leukocytes,
CC particularly in mature granulocytes and to a lesser extent in monocytes
CC but not in lymphocytes. Detected in spleen, lung and muscle, probably
CC as a result of leukocyte infiltration in these tissues. Not expressed
CC in thymus, prostate, testis, ovary, small intestine, colon, heart,
CC brain, placenta, liver, kidney, pancreas. Expression detected in
CC several myeloid leukemic, colon cancer, and prostate cancer cell lines.
CC {ECO:0000269|PubMed:10666224, ECO:0000269|PubMed:10807793,
CC ECO:0000269|PubMed:11115844}.
CC -!- DEVELOPMENTAL STAGE: First detected in bone marrow promyelocytes.
CC Expression increases throughout myelocyte differentiation and peaks in
CC the mature myelomonocytic cells. {ECO:0000269|PubMed:10807793}.
CC -!- INDUCTION: In monocytes, up-regulated by treatment with colchicine and
CC IFN-alpha, by the pro-inflammatory cytokines IFNG/IFN-gamma and TNF, by
CC bacterial lipopolysaccharides (LPS) and by retroviral infection.
CC Repressed in monocytes by the anti-inflammatory cytokines
CC IL10/interleukin-10, TGFB1 and IL4/interleukin-4. In neutrophils and
CC macrophages, up-regulated by IFNG/IFN-gamma with a peak after 8 hours
CC of treatment. {ECO:0000269|PubMed:10807793,
CC ECO:0000269|PubMed:17964261, ECO:0000269|PubMed:26347139}.
CC -!- DOMAIN: The B box-type zinc finger interacts, possibly
CC intramolecularly, with the pyrin domain; this may be an autoinhibitory
CC mechanism released by PSTPIP1 binding. {ECO:0000269|PubMed:17964261}.
CC -!- PTM: Cleaved by CASP1 (Probable). The N-terminal cleavage product
CC localizes to the nucleus as a filamentous network and to the cytoplasm,
CC interacts more strongly with RELA and NFKBIA than the full-length
CC protein, enhances the nuclear localization of RELA and induces NFKBIA
CC proteolysis. The C-terminal cleavage product localizes to the cytoplasm
CC (Probable). {ECO:0000305|PubMed:18577712}.
CC -!- PTM: Phosphorylation at Ser-242 is required for the interaction with
CC 14-3-3 proteins and down-regulation of pyrin pro-inflammatory activity.
CC {ECO:0000269|PubMed:27030597}.
CC -!- PTM: Degraded along with the delivery of its substrates to
CC autolysosomal compartments (at protein level).
CC {ECO:0000269|PubMed:26347139}.
CC -!- DISEASE: Familial Mediterranean fever, autosomal recessive (ARFMF)
CC [MIM:249100]: A hereditary periodic fever syndrome characterized by
CC recurrent episodic fever, serosal inflammation and pain in the abdomen,
CC chest or joints. It is frequently complicated by reactive amyloidosis,
CC which leads to renal failure and can be prophylactically treated with
CC colchicine. {ECO:0000269|PubMed:10024914, ECO:0000269|PubMed:10090880,
CC ECO:0000269|PubMed:10234504, ECO:0000269|PubMed:10364520,
CC ECO:0000269|PubMed:10612841, ECO:0000269|PubMed:10842288,
CC ECO:0000269|PubMed:10854105, ECO:0000269|PubMed:11470495,
CC ECO:0000269|PubMed:15024744, ECO:0000269|PubMed:16378925,
CC ECO:0000269|PubMed:16730661, ECO:0000269|PubMed:23031807,
CC ECO:0000269|PubMed:24929125, ECO:0000269|PubMed:26347139,
CC ECO:0000269|PubMed:27030597, ECO:0000269|PubMed:9288094,
CC ECO:0000269|PubMed:9288758, ECO:0000269|PubMed:9668175}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. The disease-associated mutations in the B30.2/SPRY domain
CC perturb ULK1 recruitment and autophagic degradation of inflammasome
CC components, including NLRP3, and hence may contribute to the
CC inflammatory phenotype associated with ARFMF.
CC {ECO:0000269|PubMed:26347139}.
CC -!- DISEASE: Familial Mediterranean fever, autosomal dominant (ADFMF)
CC [MIM:134610]: A hereditary periodic fever syndrome characterized by
CC periodic fever, serosal inflammation and pain in the abdomen, chest or
CC joints as seen also in the autosomal recessive form of the disease. It
CC is associated with reactive renal amyloidosis and characterized by
CC colchicine unresponsiveness. {ECO:0000269|PubMed:10787449,
CC ECO:0000269|PubMed:14679589}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pyrin-associated autoinflammatory disease (PAAND)
CC [MIM:608068]: An autosomal dominant autoinflammatory disorder
CC characterized by childhood onset of recurrent episodes of fever,
CC neutrophilic dermatosis, myalgia and arthralgia. The neutrophilic
CC dermatosis comprises a spectrum of clinical manifestations, including
CC severe acne, sterile skin abscesses, pyoderma gangrenosum, and
CC neutrophilic small-vessel vasculitis. Pathological examination of
CC affected skin shows a dense, predominantly neutrophilic, vascular,
CC perivascular, and interstitial infiltrate. PAAND has incomplete
CC penetrance and variable expressivity. {ECO:0000269|PubMed:27030597,
CC ECO:0000269|PubMed:28835462}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=INFEVERS; Note=Repertory of FMF and hereditary
CC autoinflammatory disorders mutations;
CC URL="https://infevers.umai-montpellier.fr/web/search.php?n=1";
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DR EMBL; AF018080; AAB70557.1; -; mRNA.
DR EMBL; CH471112; EAW85382.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85383.1; -; Genomic_DNA.
DR EMBL; BC101511; AAI01512.1; -; mRNA.
DR EMBL; BC101537; AAI01538.1; -; mRNA.
DR EMBL; Y14441; CAA74793.1; -; mRNA.
DR EMBL; AJ003147; CAA05906.1; -; Genomic_DNA.
DR EMBL; AF111163; AAD26152.1; -; Genomic_DNA.
DR EMBL; AF301150; AAK97223.1; -; Genomic_DNA.
DR EMBL; AF301151; AAK97224.1; -; Genomic_DNA.
DR CCDS; CCDS10498.1; -. [O15553-2]
DR CCDS; CCDS55981.1; -. [O15553-3]
DR RefSeq; NP_000234.1; NM_000243.2. [O15553-2]
DR RefSeq; NP_001185465.1; NM_001198536.1. [O15553-3]
DR PDB; 2MPC; NMR; -; A=1-92.
DR PDB; 2WL1; X-ray; 1.35 A; A=586-776.
DR PDB; 4CG4; X-ray; 2.40 A; A/B/C/D/E/F=414-781.
DR PDBsum; 2MPC; -.
DR PDBsum; 2WL1; -.
DR PDBsum; 4CG4; -.
DR AlphaFoldDB; O15553; -.
DR SMR; O15553; -.
DR BioGRID; 110374; 18.
DR ComplexPortal; CPX-4143; Pyrin inflammasome.
DR DIP; DIP-41878N; -.
DR IntAct; O15553; 6.
DR MINT; O15553; -.
DR STRING; 9606.ENSP00000219596; -.
DR GlyGen; O15553; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15553; -.
DR PhosphoSitePlus; O15553; -.
DR BioMuta; MEFV; -.
DR EPD; O15553; -.
DR MassIVE; O15553; -.
DR PaxDb; O15553; -.
DR PeptideAtlas; O15553; -.
DR PRIDE; O15553; -.
DR ProteomicsDB; 25411; -.
DR ProteomicsDB; 48755; -. [O15553-2]
DR ProteomicsDB; 48756; -. [O15553-1]
DR Antibodypedia; 10781; 223 antibodies from 32 providers.
DR DNASU; 4210; -.
DR Ensembl; ENST00000219596.6; ENSP00000219596.1; ENSG00000103313.13. [O15553-2]
DR Ensembl; ENST00000536379.5; ENSP00000445079.1; ENSG00000103313.13. [O15553-1]
DR Ensembl; ENST00000541159.5; ENSP00000438711.1; ENSG00000103313.13. [O15553-3]
DR GeneID; 4210; -.
DR KEGG; hsa:4210; -.
DR MANE-Select; ENST00000219596.6; ENSP00000219596.1; NM_000243.3; NP_000234.1.
DR UCSC; uc002cun.1; human. [O15553-2]
DR CTD; 4210; -.
DR DisGeNET; 4210; -.
DR GeneCards; MEFV; -.
DR GeneReviews; MEFV; -.
DR HGNC; HGNC:6998; MEFV.
DR HPA; ENSG00000103313; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; MEFV; -.
DR MIM; 134610; phenotype.
DR MIM; 249100; phenotype.
DR MIM; 608068; phenotype.
DR MIM; 608107; gene.
DR neXtProt; NX_O15553; -.
DR OpenTargets; ENSG00000103313; -.
DR Orphanet; 117; Behcet disease.
DR Orphanet; 342; Familial Mediterranean fever.
DR Orphanet; 329967; Intermittent hydrarthrosis.
DR Orphanet; 3243; Sweet syndrome.
DR PharmGKB; PA30736; -.
DR VEuPathDB; HostDB:ENSG00000103313; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000161955; -.
DR HOGENOM; CLU_685051_0_0_1; -.
DR InParanoid; O15553; -.
DR OMA; CQRHMKQ; -.
DR OrthoDB; 651627at2759; -.
DR PhylomeDB; O15553; -.
DR TreeFam; TF351091; -.
DR PathwayCommons; O15553; -.
DR Reactome; R-HSA-844456; The NLRP3 inflammasome.
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SignaLink; O15553; -.
DR SIGNOR; O15553; -.
DR BioGRID-ORCS; 4210; 14 hits in 1069 CRISPR screens.
DR ChiTaRS; MEFV; human.
DR EvolutionaryTrace; O15553; -.
DR GeneWiki; MEFV; -.
DR GenomeRNAi; 4210; -.
DR Pharos; O15553; Tbio.
DR PRO; PR:O15553; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O15553; protein.
DR Bgee; ENSG00000103313; Expressed in buccal mucosa cell and 105 other tissues.
DR ExpressionAtlas; O15553; baseline and differential.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0061702; C:inflammasome complex; IPI:ComplexPortal.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IC:ComplexPortal.
DR GO; GO:0005875; C:microtubule associated complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:BHF-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:BHF-UCL.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IMP:BHF-UCL.
DR GO; GO:0071641; P:negative regulation of macrophage inflammatory protein 1 alpha production; IMP:BHF-UCL.
DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IMP:UniProtKB.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:ComplexPortal.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0070269; P:pyroptosis; IC:ComplexPortal.
DR GO; GO:1904270; P:pyroptosome complex assembly; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0032651; P:regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:0034341; P:response to interferon-gamma; IDA:UniProtKB.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 2.60.120.920; -; 1.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR003879; Butyrophylin_SPRY.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR006574; PRY.
DR InterPro; IPR028841; Pyrin.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR000315; Znf_B-box.
DR PANTHER; PTHR24103:SF606; PTHR24103:SF606; 2.
DR Pfam; PF13765; PRY; 1.
DR Pfam; PF02758; PYRIN; 1.
DR Pfam; PF00622; SPRY; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR PRINTS; PR01407; BUTYPHLNCDUF.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00589; PRY; 1.
DR SMART; SM01289; PYRIN; 1.
DR SMART; SM00449; SPRY; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Amyloidosis;
KW Cell projection; Coiled coil; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW Disease variant; Immunity; Inflammatory response; Innate immunity;
KW Metal-binding; Microtubule; Nucleus; Phosphoprotein; Reference proteome;
KW Zinc; Zinc-finger.
FT CHAIN 1..781
FT /note="Pyrin"
FT /id="PRO_0000220364"
FT DOMAIN 1..92
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 580..775
FT /note="B30.2/SPRY"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT ZN_FING 370..412
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 93..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..280
FT /note="Interaction with RELA"
FT /evidence="ECO:0000269|PubMed:18577712"
FT REGION 270..322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 420..582
FT /note="Required for homotrimerization and induction of
FT pyroptosomes"
FT /evidence="ECO:0000269|PubMed:17964261"
FT COILED 413..442
FT /evidence="ECO:0000255"
FT MOTIF 420..437
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 93..115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..171
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 330..331
FT /note="Cleavage; by CASP1"
FT /evidence="ECO:0000305"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27030597"
FT VAR_SEQ 93..303
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_008223"
FT VAR_SEQ 587..781
FT /note="VPELIGAQAHAVNVILDAETAYPNLIFSDDLKSVRLGNKWERLPDGPQRFDS
FT CIIVLGSPSFLSGRRYWEVEVGDKTAWILGACKTSISRKGNMTLSPENGYWVVIMMKEN
FT EYQASSVPPTRLLIKEPPKRVGIFVDYRVGSISFYNVTARSHIYTFASCSFSGPLQPIF
FT SPGTRDGGKNTAPLTICPVGGQGPD -> DHSPQHGLGSWEERDYTQHSMQGPKQGVPC
FT LSLLSGQCNLAPLNANAQDFFPYLIFLRSSGADWRSGTCC (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_047663"
FT VARIANT 33
FT /note="V -> L (in dbSNP:rs11466016)"
FT /id="VAR_048398"
FT VARIANT 42
FT /note="R -> W (in arFMF; dbSNP:rs61754767)"
FT /id="VAR_028326"
FT VARIANT 108
FT /note="S -> R (in arFMF; dbSNP:rs104895103)"
FT /evidence="ECO:0000269|PubMed:16378925"
FT /id="VAR_028327"
FT VARIANT 110
FT /note="L -> P (in arFMF; dbSNP:rs11466018)"
FT /evidence="ECO:0000269|PubMed:10854105,
FT ECO:0000269|PubMed:24929125"
FT /id="VAR_016824"
FT VARIANT 148
FT /note="E -> Q (in arFMF and adFMF; likely benign variant;
FT associated with S-369 and Q-408 in cis; associated with I-
FT 694 in some patients; dbSNP:rs3743930)"
FT /evidence="ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:10612841, ECO:0000269|PubMed:10737995,
FT ECO:0000269|PubMed:10787449, ECO:0000269|PubMed:10854105,
FT ECO:0000269|PubMed:16378925, ECO:0000269|PubMed:24929125"
FT /id="VAR_009051"
FT VARIANT 148
FT /note="E -> V (in arFMF; dbSNP:rs104895076)"
FT /evidence="ECO:0000269|PubMed:16378925"
FT /id="VAR_028328"
FT VARIANT 163
FT /note="E -> A (in arFMF; dbSNP:rs104895106)"
FT /evidence="ECO:0000269|PubMed:15024744"
FT /id="VAR_028329"
FT VARIANT 167
FT /note="E -> D (in arFMF; dbSNP:rs104895079)"
FT /evidence="ECO:0000269|PubMed:16378925"
FT /id="VAR_009052"
FT VARIANT 177
FT /note="T -> I (in arFMF; dbSNP:rs104895143)"
FT /evidence="ECO:0000269|PubMed:16378925"
FT /id="VAR_028330"
FT VARIANT 196
FT /note="G -> W (in arFMF; unknown pathological significance;
FT dbSNP:rs104895179)"
FT /evidence="ECO:0000269|PubMed:24929125"
FT /id="VAR_072382"
FT VARIANT 202
FT /note="R -> Q (benign variant; no effect on PYCARD/ASC
FT inflammasome formation; dbSNP:rs224222)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:24929125, ECO:0000269|PubMed:27030597,
FT ECO:0000269|PubMed:9668175"
FT /id="VAR_009053"
FT VARIANT 230
FT /note="E -> K (in arFMF; dbSNP:rs104895080)"
FT /evidence="ECO:0000269|PubMed:11470495,
FT ECO:0000269|PubMed:24929125"
FT /id="VAR_016826"
FT VARIANT 242
FT /note="S -> R (in PAAND; results in constitutive
FT inflammasome activation; increased PYCARD/ASC specks
FT formation; increased caspase-1 activation and IL1B
FT production; loss of S-242 phosphorylation; loss of
FT interaction with 14-3-3 proteins; dbSNP:rs104895127)"
FT /evidence="ECO:0000269|PubMed:27030597"
FT /id="VAR_084466"
FT VARIANT 244
FT /note="E -> K (in PAAND; results in constitutive
FT inflammasome activation; increased PYCARD/ASC specks
FT formation; increased caspase-1 activation and IL1B and IL18
FT production; decreased interaction with 14-3-3 proteins; no
FT effect on interaction with PSTPIP1)"
FT /evidence="ECO:0000269|PubMed:28835462"
FT /id="VAR_084467"
FT VARIANT 247
FT /note="I -> V (in arFMF; unknown pathological significance;
FT dbSNP:rs1472692347)"
FT /evidence="ECO:0000269|PubMed:24929125"
FT /id="VAR_072383"
FT VARIANT 267
FT /note="T -> I (in arFMF; dbSNP:rs104895081)"
FT /evidence="ECO:0000269|PubMed:16378925,
FT ECO:0000269|PubMed:23505238"
FT /id="VAR_009054"
FT VARIANT 283
FT /note="P -> L (in arFMF; unknown pathological significance;
FT dbSNP:rs104895119)"
FT /evidence="ECO:0000269|PubMed:24929125"
FT /id="VAR_072384"
FT VARIANT 304
FT /note="G -> R (in arFMF; unknown pathological significance;
FT no effect on PYCARD/ASC inflammasome formation;
FT dbSNP:rs75977701)"
FT /evidence="ECO:0000269|PubMed:24929125,
FT ECO:0000269|PubMed:27030597"
FT /id="VAR_072385"
FT VARIANT 319
FT /note="E -> K (in arFMF; dbSNP:rs104895110)"
FT /evidence="ECO:0000269|PubMed:15024744"
FT /id="VAR_028331"
FT VARIANT 369
FT /note="P -> S (in arFMF; unknown pathological significance;
FT associated with Q-148 and Q-408 in cis; dbSNP:rs11466023)"
FT /evidence="ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:23505238"
FT /id="VAR_009055"
FT VARIANT 408
FT /note="R -> Q (in arFMF; associated with Q-148 and S-369 in
FT cis; dbSNP:rs11466024)"
FT /evidence="ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:23505238"
FT /id="VAR_009056"
FT VARIANT 440
FT /note="Q -> E (in dbSNP:rs11466026)"
FT /id="VAR_024376"
FT VARIANT 474
FT /note="E -> K (in arFMF; dbSNP:rs104895104)"
FT /evidence="ECO:0000269|PubMed:16378925"
FT /id="VAR_028332"
FT VARIANT 478
FT /note="H -> Y (in adFMF; severe; dbSNP:rs104895105)"
FT /evidence="ECO:0000269|PubMed:14679589"
FT /id="VAR_028333"
FT VARIANT 479
FT /note="F -> L (in arFMF; dbSNP:rs104895083)"
FT /evidence="ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:16378925"
FT /id="VAR_009057"
FT VARIANT 577
FT /note="T -> A (probable disease-associated variant found in
FT an autosomal dominant autoinflammatory disease with some
FT similarities to familial Mediterranean fever)"
FT /evidence="ECO:0000269|PubMed:23505238"
FT /id="VAR_070795"
FT VARIANT 577
FT /note="T -> N (probable disease-associated variant found in
FT an autosomal dominant autoinflammatory disease with some
FT similarities to familial Mediterranean fever;
FT dbSNP:rs1057516210)"
FT /evidence="ECO:0000269|PubMed:23505238"
FT /id="VAR_070796"
FT VARIANT 577
FT /note="T -> S (probable disease-associated variant found in
FT an autosomal dominant autoinflammatory disease with some
FT similarities to familial Mediterranean fever;
FT dbSNP:rs104895193)"
FT /evidence="ECO:0000269|PubMed:23505238"
FT /id="VAR_070797"
FT VARIANT 585
FT /note="F -> L (in dbSNP:rs11466043)"
FT /id="VAR_028334"
FT VARIANT 591
FT /note="I -> T (in arFMF; unknown pathological significance;
FT dbSNP:rs11466045)"
FT /evidence="ECO:0000269|PubMed:12124996"
FT /id="VAR_016827"
FT VARIANT 632
FT /note="G -> A (in arFMF; unknown pathological significance;
FT dbSNP:rs967990798)"
FT /evidence="ECO:0000269|PubMed:24929125"
FT /id="VAR_072386"
FT VARIANT 632
FT /note="G -> S (in arFMF; dbSNP:rs104895128)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028335"
FT VARIANT 640
FT /note="I -> M (in arFMF; dbSNP:rs104895115)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028336"
FT VARIANT 641
FT /note="I -> F (in arFMF; dbSNP:rs104895147)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028337"
FT VARIANT 646
FT /note="P -> L (in arFMF; dbSNP:rs104895107)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028338"
FT VARIANT 649
FT /note="L -> P (in arFMF; dbSNP:rs104895108)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028339"
FT VARIANT 653
FT /note="R -> H (in arFMF; dbSNP:rs104895085)"
FT /evidence="ECO:0000269|PubMed:11470495,
FT ECO:0000269|PubMed:16378925, ECO:0000269|PubMed:16730661"
FT /id="VAR_016828"
FT VARIANT 656
FT /note="E -> A (in arFMF; dbSNP:rs104895086)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028340"
FT VARIANT 661
FT /note="D -> N (in arFMF; dbSNP:rs104895120)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028341"
FT VARIANT 675
FT /note="S -> N (in arFMF; dbSNP:rs104895087)"
FT /evidence="ECO:0000269|PubMed:10842288,
FT ECO:0000269|PubMed:16730661"
FT /id="VAR_016829"
FT VARIANT 678
FT /note="G -> E (in arFMF; dbSNP:rs104895088)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028342"
FT VARIANT 680
FT /note="M -> I (in arFMF and adFMF; reduced CASP1
FT interaction; decreased interaction with ULK1 and diminished
FT NLRP3 degradation after induction of autophagy by
FT starvation; when associated with V-694 (PubMed:26347139);
FT no effect on PYCARD/ASC inflammasome formation; no effect
FT on interaction with 14-3-3 proteins; dbSNP:rs28940580)"
FT /evidence="ECO:0000269|PubMed:10024914,
FT ECO:0000269|PubMed:10234504, ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:10612841, ECO:0000269|PubMed:10787449,
FT ECO:0000269|PubMed:16378925, ECO:0000269|PubMed:16785446,
FT ECO:0000269|PubMed:24929125, ECO:0000269|PubMed:26347139,
FT ECO:0000269|PubMed:27030597, ECO:0000269|PubMed:9288094,
FT ECO:0000269|PubMed:9288758"
FT /id="VAR_028343"
FT VARIANT 680
FT /note="M -> L (in arFMF; dbSNP:rs104895089)"
FT /evidence="ECO:0000269|PubMed:10842288,
FT ECO:0000269|PubMed:16730661"
FT /id="VAR_016830"
FT VARIANT 681
FT /note="T -> I (in arFMF; dbSNP:rs104895090)"
FT /evidence="ECO:0000269|PubMed:10024914,
FT ECO:0000269|PubMed:16730661"
FT /id="VAR_009059"
FT VARIANT 688
FT /note="Y -> C (in arFMF; dbSNP:rs104895122)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028344"
FT VARIANT 692
FT /note="Missing (in arFMF; dbSNP:rs104895093)"
FT /id="VAR_009060"
FT VARIANT 694
FT /note="M -> I (in arFMF and adFMF; associated with Q-148 in
FT some patients; no effect on PYCARD/ASC inflammasome
FT formation; no effect on interaction with 14-3-3 proteins;
FT dbSNP:rs28940578)"
FT /evidence="ECO:0000269|PubMed:10024914,
FT ECO:0000269|PubMed:10234504, ECO:0000269|PubMed:10612841,
FT ECO:0000269|PubMed:10787449, ECO:0000269|PubMed:16378925,
FT ECO:0000269|PubMed:16730661, ECO:0000269|PubMed:24929125,
FT ECO:0000269|PubMed:27030597, ECO:0000269|PubMed:9288094"
FT /id="VAR_009061"
FT VARIANT 694
FT /note="M -> K (in arFMF; dbSNP:rs1596350022)"
FT /evidence="ECO:0000269|PubMed:23031807"
FT /id="VAR_070798"
FT VARIANT 694
FT /note="M -> L (in arFMF; dbSNP:rs61752717)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028345"
FT VARIANT 694
FT /note="M -> V (in arFMF and adFMF; very common mutation
FT particularly in North African Jews; can be associated with
FT amyloidosis development; reduced interaction with CASP1 and
FT with ULK1 and diminished NLRP3 degradation after induction
FT of autophagy by starvation (PubMed:16785446)
FT (PubMed:26347139); effect on autophagic NLRP3 degradation
FT is increased; when associated with I-680; no effect on
FT interaction with CASP1, CASP5, NLRP1, NLRP2 or NLRP3
FT (PubMed:17431422); dbSNP:rs61752717)"
FT /evidence="ECO:0000269|PubMed:10024914,
FT ECO:0000269|PubMed:10234504, ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:10612841, ECO:0000269|PubMed:10787449,
FT ECO:0000269|PubMed:10854105, ECO:0000269|PubMed:16378925,
FT ECO:0000269|PubMed:16730661, ECO:0000269|PubMed:16785446,
FT ECO:0000269|PubMed:17431422, ECO:0000269|PubMed:24929125,
FT ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:9288758"
FT /id="VAR_009062"
FT VARIANT 694
FT /note="Missing (in arFMF and adFMF)"
FT /evidence="ECO:0000269|PubMed:10024914,
FT ECO:0000269|PubMed:10787449"
FT /id="VAR_009063"
FT VARIANT 695
FT /note="K -> M (in arFMF; dbSNP:rs104895094)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028346"
FT VARIANT 695
FT /note="K -> R (in arFMF; reduced penetrance among Ashkenazi
FT Jews; dbSNP:rs104895094)"
FT /evidence="ECO:0000269|PubMed:10612841,
FT ECO:0000269|PubMed:16378925, ECO:0000269|PubMed:16730661,
FT ECO:0000269|PubMed:24929125"
FT /id="VAR_009064"
FT VARIANT 702
FT /note="S -> C (in one patient with familial Mediterranean
FT fever; dbSNP:rs104895166)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028347"
FT VARIANT 704
FT /note="V -> I (in arFMF; dbSNP:rs104895096)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028348"
FT VARIANT 705
FT /note="P -> S (in arFMF; dbSNP:rs104895145)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028349"
FT VARIANT 720
FT /note="I -> M (in arFMF; dbSNP:rs104895102)"
FT /evidence="ECO:0000269|PubMed:16378925,
FT ECO:0000269|PubMed:16730661"
FT /id="VAR_028350"
FT VARIANT 726
FT /note="V -> A (in arFMF; common mutation; in Iraqi and
FT Ashkenazi Jews, Druze, Armenians; reduced interaction with
FT CASP1 and ULK1 and diminished NLRP3 degradation after
FT induction of autophagy by starvation; when associated with
FT I-680 and V-694; no effect on CASP1 activation; no effect
FT on interaction with 14-3-3 proteins; dbSNP:rs28940579)"
FT /evidence="ECO:0000269|PubMed:10024914,
FT ECO:0000269|PubMed:10234504, ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:10612841, ECO:0000269|PubMed:16378925,
FT ECO:0000269|PubMed:16730661, ECO:0000269|PubMed:16785446,
FT ECO:0000269|PubMed:24929125, ECO:0000269|PubMed:27030597,
FT ECO:0000269|PubMed:9288758"
FT /id="VAR_009065"
FT VARIANT 743
FT /note="F -> L (in arFMF; dbSNP:rs104895152)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028351"
FT VARIANT 744
FT /note="A -> S (in arFMF; uncertain pathological
FT significance; dbSNP:rs61732874)"
FT /evidence="ECO:0000269|PubMed:15024744,
FT ECO:0000269|PubMed:16378925, ECO:0000269|PubMed:16730661,
FT ECO:0000269|PubMed:24929125"
FT /id="VAR_009066"
FT VARIANT 758
FT /note="P -> S (in arFMF; dbSNP:rs104895114)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028352"
FT VARIANT 761
FT /note="R -> H (in arFMF; dbSNP:rs104895097)"
FT /evidence="ECO:0000269|PubMed:10364520,
FT ECO:0000269|PubMed:10612841, ECO:0000269|PubMed:16378925,
FT ECO:0000269|PubMed:16730661, ECO:0000269|PubMed:24929125"
FT /id="VAR_009067"
FT VARIANT 780
FT /note="P -> T (in arFMF; dbSNP:rs104895154)"
FT /evidence="ECO:0000269|PubMed:16730661"
FT /id="VAR_028353"
FT MUTAGEN 16
FT /note="L->P: Does not form MEFV- and PSTPIP1-containing
FT perinuclear specks."
FT /evidence="ECO:0000269|PubMed:16037825"
FT MUTAGEN 24
FT /note="F->S: Does not form MEFV- and PSTPIP1-containing
FT perinuclear specks."
FT /evidence="ECO:0000269|PubMed:16037825"
FT MUTAGEN 208
FT /note="S->A: Loss of interaction with 14-3-3 proteins."
FT /evidence="ECO:0000269|PubMed:28835462"
FT MUTAGEN 244
FT /note="E->D: No effect on PYCARD/ASC specks formation. No
FT effect on interaction with 14-3-3 proteins."
FT /evidence="ECO:0000269|PubMed:28835462"
FT MUTAGEN 244
FT /note="E->P: No effect on PYCARD/ASC specks formation.
FT Increased interaction with 14-3-3 proteins."
FT /evidence="ECO:0000269|PubMed:28835462"
FT MUTAGEN 244
FT /note="E->R: Increased PYCARD/ASC specks formation.
FT Decreased interaction with 14-3-3 proteins."
FT /evidence="ECO:0000269|PubMed:28835462"
FT MUTAGEN 330
FT /note="D->A: Loss of cleavage by CASP1."
FT /evidence="ECO:0000269|PubMed:18577712"
FT MUTAGEN 397..404
FT /note="Missing: No effect on GABARAP-binding. Loss of
FT GABARAP-binding; when associated with 470-Y--G-488 and 523-
FT S--D-530."
FT MUTAGEN 470..488
FT /note="Missing: No effect on GABARAP-binding. Loss of
FT GABARAP-binding; when associated with 397-I--H-404 and 523-
FT S--D-530."
FT MUTAGEN 523..530
FT /note="Missing: No effect on GABARAP-binding. Loss of
FT GABARAP-binding; when associated with 397-I--H-404 and 470-
FT Y--G-488."
FT HELIX 5..15
FT /evidence="ECO:0007829|PDB:2MPC"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:2MPC"
FT HELIX 42..47
FT /evidence="ECO:0007829|PDB:2MPC"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:2MPC"
FT HELIX 53..60
FT /evidence="ECO:0007829|PDB:2MPC"
FT HELIX 63..76
FT /evidence="ECO:0007829|PDB:2MPC"
FT HELIX 80..92
FT /evidence="ECO:0007829|PDB:2MPC"
FT HELIX 414..519
FT /evidence="ECO:0007829|PDB:4CG4"
FT HELIX 524..528
FT /evidence="ECO:0007829|PDB:4CG4"
FT HELIX 531..539
FT /evidence="ECO:0007829|PDB:4CG4"
FT HELIX 551..583
FT /evidence="ECO:0007829|PDB:4CG4"
FT HELIX 584..586
FT /evidence="ECO:0007829|PDB:4CG4"
FT HELIX 590..594
FT /evidence="ECO:0007829|PDB:2WL1"
FT TURN 604..606
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 611..613
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 619..622
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 637..639
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 642..645
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 650..658
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 665..671
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 676..678
FT /evidence="ECO:0007829|PDB:2WL1"
FT HELIX 684..686
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 688..695
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 698..701
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 707..709
FT /evidence="ECO:0007829|PDB:4CG4"
FT STRAND 716..723
FT /evidence="ECO:0007829|PDB:2WL1"
FT TURN 724..727
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 728..733
FT /evidence="ECO:0007829|PDB:2WL1"
FT TURN 734..737
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 738..743
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 752..757
FT /evidence="ECO:0007829|PDB:2WL1"
FT HELIX 762..764
FT /evidence="ECO:0007829|PDB:2WL1"
FT STRAND 770..773
FT /evidence="ECO:0007829|PDB:2WL1"
SQ SEQUENCE 781 AA; 86444 MW; 3692E5E6E9FC8204 CRC64;
MAKTPSDHLL STLEELVPYD FEKFKFKLQN TSVQKEHSRI PRSQIQRARP VKMATLLVTY
YGEEYAVQLT LQVLRAINQR LLAEELHRAA IQEYSTQENG TDDSAASSSL GENKPRSLKT
PDHPEGNEGN GPRPYGGGAA SLRCSQPEAG RGLSRKPLSK RREKASEGLD AQGKPRTRSP
ALPGGRSPGP CRALEGGQAE VRLRRNASSA GRLQGLAGGA PGQKECRPFE VYLPSGKMRP
RSLEVTISTG EKAPANPEIL LTLEEKTAAN LDSATEPRAR PTPDGGASAD LKEGPGNPEH
SVTGRPPDTA ASPRCHAQEG DPVDGTCVRD SCSFPEAVSG HPQASGSRSP GCPRCQDSHE
RKSPGSLSPQ PLPQCKRHLK QVQLLFCEDH DEPICLICSL SQEHQGHRVR PIEEVALEHK
KKIQKQLEHL KKLRKSGEEQ RSYGEEKAVS FLKQTEALKQ RVQRKLEQVY YFLEQQEHFF
VASLEDVGQM VGQIRKAYDT RVSQDIALLD ALIGELEAKE CQSEWELLQD IGDILHRAKT
VPVPEKWTTP QEIKQKIQLL HQKSEFVEKS TKYFSETLRS EMEMFNVPEL IGAQAHAVNV
ILDAETAYPN LIFSDDLKSV RLGNKWERLP DGPQRFDSCI IVLGSPSFLS GRRYWEVEVG
DKTAWILGAC KTSISRKGNM TLSPENGYWV VIMMKENEYQ ASSVPPTRLL IKEPPKRVGI
FVDYRVGSIS FYNVTARSHI YTFASCSFSG PLQPIFSPGT RDGGKNTAPL TICPVGGQGP
D
