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 24-JAN-2024, entry version 219. 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; LEU-680 AND ILE-692 DEL. RX PubMed=10842288; RX DOI=10.1002/(sici)1096-8628(20000605)92:4<241::aid-ajmg3>3.3.co;2-7; 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, AND VARIANT ARFMF TRP-42. 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 ARFMF 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:11464238, CC ECO:0000269|PubMed:11470495, ECO:0000269|PubMed:12124996, 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 19. DR ComplexPortal; CPX-4143; Pyrin inflammasome. DR DIP; DIP-41878N; -. DR IntAct; O15553; 6. DR MINT; O15553; -. DR STRING; 9606.ENSP00000219596; -. DR GlyCosmos; O15553; 1 site, 1 glycan. 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; 9606-ENSP00000219596; -. DR PeptideAtlas; O15553; -. DR ProteomicsDB; 25411; -. DR ProteomicsDB; 48755; -. [O15553-2] DR ProteomicsDB; 48756; -. [O15553-1] DR Antibodypedia; 10781; 245 antibodies from 32 providers. DR DNASU; 4210; -. DR Ensembl; ENST00000219596.6; ENSP00000219596.1; ENSG00000103313.14. [O15553-2] DR Ensembl; ENST00000536379.5; ENSP00000445079.1; ENSG00000103313.14. [O15553-1] DR Ensembl; ENST00000541159.5; ENSP00000438711.1; ENSG00000103313.14. [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 AGR; HGNC:6998; -. DR CTD; 4210; -. DR DisGeNET; 4210; -. DR GeneCards; MEFV; -. DR GeneReviews; MEFV; -. DR HGNC; HGNC:6998; MEFV. DR HPA; ENSG00000103313; Tissue enhanced (bone marrow, lung, 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; 4634371at2759; -. 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; 21 hits in 1147 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 cell types or tissues. DR ExpressionAtlas; O15553; baseline and differential. DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell. DR GO; GO:0061702; C:canonical inflammasome complex; IPI:ComplexPortal. 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:0030027; C:lamellipodium; IEA:UniProtKB-SubCell. DR GO; GO:0005874; C:microtubule; NAS: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; NAS: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:0050729; P:positive regulation of inflammatory response; ISO:ComplexPortal. 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; NAS: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 type II interferon; IDA:UniProtKB. DR CDD; cd19771; Bbox2_TRIM20; 1. DR CDD; cd08321; Pyrin_ASC-like; 1. DR CDD; cd15813; SPRY_PRY_TRIM20; 1. DR Gene3D; 2.60.120.920; -; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 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; IPR003877; SPRY_dom. DR InterPro; IPR000315; Znf_B-box. DR PANTHER; PTHR24103; E3 UBIQUITIN-PROTEIN LIGASE TRIM; 1. DR PANTHER; PTHR24103:SF606; PYRIN; 1. 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; SSF57845; B-box zinc-binding domain; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF47986; DEATH domain; 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 /evidence="ECO:0000269|PubMed:11464238" 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; FT 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; uncertain significance; FT dbSNP:rs104895179)" FT /evidence="ECO:0000269|PubMed:24929125" FT /id="VAR_072382" FT VARIANT 202 FT /note="R -> Q (benign; no effect on PYCARD/ASC inflammasome FT 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; uncertain 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; uncertain significance; FT dbSNP:rs104895119)" FT /evidence="ECO:0000269|PubMed:24929125" FT /id="VAR_072384" FT VARIANT 304 FT /note="G -> R (in ARFMF; uncertain significance; no effect FT on PYCARD/ASC inflammasome formation; 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; uncertain significance; FT 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; uncertain significance; FT 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 (found in an autosomal dominant FT autoinflammatory disease with some similarities to familial FT Mediterranean fever; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:23505238" FT /id="VAR_070795" FT VARIANT 577 FT /note="T -> N (found in an autosomal dominant FT autoinflammatory disease with some similarities to familial FT Mediterranean fever; likely pathogenic; FT dbSNP:rs1057516210)" FT /evidence="ECO:0000269|PubMed:23505238" FT /id="VAR_070796" FT VARIANT 577 FT /note="T -> S (found in an autosomal dominant FT autoinflammatory disease with some similarities to familial FT Mediterranean fever; likely pathogenic; 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; likely benign; dbSNP:rs11466045)" FT /evidence="ECO:0000269|PubMed:12124996" FT /id="VAR_016827" FT VARIANT 632 FT /note="G -> A (in ARFMF; uncertain 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; results in decreased interaction with ULK1 and FT diminished NLRP3 degradation after induction of autophagy FT by starvation when associated in cis with V-694 FT (PubMed:26347139); no effect on PYCARD/ASC inflammasome FT formation; no effect on interaction with 14-3-3 proteins; FT 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 /evidence="ECO:0000269|PubMed:10842288" FT /id="VAR_009060" FT VARIANT 694 FT /note="M -> I (in ARFMF and ADFMF; no effect on PYCARD/ASC FT inflammasome formation; no effect on interaction with FT 14-3-3 proteins; 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; probable risk factor FT for amyloidosis development; reduced interaction with CASP1 FT and with ULK1 and diminished NLRP3 degradation after FT induction of autophagy by starvation (PubMed:16785446) FT (PubMed:26347139); effect on autophagic NLRP3 degradation FT is increased when associated in cis with I-680; no effect FT on 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 in cis FT with I-680 and V-694; no effect on CASP1 activation; no FT effect on interaction with 14-3-3 proteins; FT 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 significance; FT 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 FT 523-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 FT 523-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 FT 470-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 //