MEFV_RAT
ID MEFV_RAT Reviewed; 747 AA.
AC Q9JJ25; A0A0G2JYG3;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Pyrin {ECO:0000303|PubMed:10818206};
GN Name=Mefv {ECO:0000303|PubMed:10818206, ECO:0000312|RGD:61889};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=10818206; DOI=10.1007/s003350010082;
RA Chae J.J., Centola M., Aksentijevich I., Dutra A., Tran M., Wood G.,
RA Nagaraju K., Kingma D.W., Liu P.P., Kastner D.L.;
RT "Isolation, genomic organization, and expression analysis of the mouse and
RT rat homologs of MEFV, the gene for familial Mediterranean fever.";
RL Mamm. Genome 11:428-435(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
CC -!- FUNCTION: Involved in the regulation of innate immunity and the
CC inflammatory response in response to IFNG/IFN-gamma. 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. Acts
CC as an autophagy receptor for the degradation of several inflammasome
CC components, including CASP1, NLRP1 and NLRP3, hence preventing
CC excessive IL1B- and IL18-mediated inflammation. However, it can also
CC have a positive effect in the inflammatory pathway, acting as an innate
CC immune sensor that triggers PYCARD/ASC specks formation, caspase-1
CC activation, and IL1B and IL18 production (By similarity). Together with
CC AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis
CC (PANoptosis), an integral part of host defense against pathogens, in
CC response to bacterial infection (By similarity). It is required for
CC PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation.
CC Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1
CC oligomerization (By similarity). {ECO:0000250|UniProtKB:O15553,
CC ECO:0000250|UniProtKB:Q9JJ26}.
CC -!- SUBUNIT: Homotrimer. Interacts (via the B box-type zinc finger) with
CC PSTPIP1. Interacts (via the B30.2/SPRY domain) with several components
CC of the inflammasome complex, including CASP1 p20 and p10 subunits,
CC CASP5, PYCARD, NLRP1, NLRP2 AND NLRP3, as well as with unprocessed
CC IL1B; this interaction may lead to autophagic degradation of these
CC proteins (By similarity). Component of the AIM2 PANoptosome complex, a
CC multiprotein complex that drives inflammatory cell death (PANoptosis)
CC (By similarity). Interacts with NFKBIA and RELA. Interacts weakly with
CC VASP and ACTR3. 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. Interacts with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ
CC AND YWHAZ; the interaction is required for the down-regulation of pyrin
CC pro-inflammatory activity (By similarity).
CC {ECO:0000250|UniProtKB:O15553, ECO:0000250|UniProtKB:Q9JJ26}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:O15553}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:O15553}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:O15553}. Cytoplasm
CC {ECO:0000250|UniProtKB:O15553}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:O15553}. Nucleus {ECO:0000250|UniProtKB:O15553}.
CC Note=Associated with microtubules and with the filamentous actin of
CC perinuclear filaments and peripheral lamellar ruffles. In pre-apoptotic
CC cells, colocalizes with PYCARD/ASC in large specks (pyroptosomes). In
CC migrating monocytes, strongly polarized at the leading edge of the cell
CC where it colocalizes with polymerizing actin and PYCARD/ASC (By
CC similarity). {ECO:0000250|UniProtKB:O15553}.
CC -!- TISSUE SPECIFICITY: Expressed in spleen and, to a lesser degree in the
CC lung. Not expressed in thymus, testis, ovary, heart, brain, liver,
CC kidney and muscle. {ECO:0000269|PubMed:10818206}.
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:0000250|UniProtKB:O15553}.
CC -!- PTM: Degraded along with the delivery of its substrates to
CC autolysosomal compartments (at protein level).
CC {ECO:0000250|UniProtKB:O15553}.
CC -!- CAUTION: Lacks the B30.2/SPRY domain found in the human ortholog, thus
CC may have divergent function(s). {ECO:0000305}.
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DR EMBL; AF143410; AAF03767.1; -; mRNA.
DR EMBL; AABR07072080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_113822.1; NM_031634.1.
DR AlphaFoldDB; Q9JJ25; -.
DR SMR; Q9JJ25; -.
DR STRING; 10116.ENSRNOP00000011073; -.
DR iPTMnet; Q9JJ25; -.
DR PhosphoSitePlus; Q9JJ25; -.
DR PaxDb; Q9JJ25; -.
DR PRIDE; Q9JJ25; -.
DR GeneID; 58923; -.
DR KEGG; rno:58923; -.
DR UCSC; RGD:61889; rat.
DR CTD; 4210; -.
DR RGD; 61889; Mefv.
DR eggNOG; KOG2177; Eukaryota.
DR InParanoid; Q9JJ25; -.
DR OrthoDB; 423686at2759; -.
DR PhylomeDB; Q9JJ25; -.
DR Reactome; R-RNO-844456; The NLRP3 inflammasome.
DR PRO; PR:Q9JJ25; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000008134; Expressed in spleen and 12 other tissues.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0061702; C:inflammasome complex; ISO:RGD.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005875; C:microtubule associated complex; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
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; ISS: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; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0071641; P:negative regulation of macrophage inflammatory protein 1 alpha production; ISO:RGD.
DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:1904270; P:pyroptosome complex assembly; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0032651; P:regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0034341; P:response to interferon-gamma; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0034021; P:response to silicon dioxide; IEP:RGD.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR028841; Pyrin.
DR InterPro; IPR000315; Znf_B-box.
DR PANTHER; PTHR24103:SF606; PTHR24103:SF606; 2.
DR Pfam; PF02758; PYRIN; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
PE 2: Evidence at transcript level;
KW Actin-binding; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Immunity; Inflammatory response;
KW Innate immunity; Metal-binding; Microtubule; Nucleus; Reference proteome;
KW Zinc; Zinc-finger.
FT CHAIN 1..747
FT /note="Pyrin"
FT /id="PRO_0000220366"
FT DOMAIN 1..92
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT ZN_FING 442..479
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 89..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 487..645
FT /note="Required for homotrimerization and induction of
FT pyroptosomes"
FT /evidence="ECO:0000250|UniProtKB:O15553"
FT REGION 698..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 479..508
FT /evidence="ECO:0000255"
FT COMPBIAS 149..164
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 442
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 445
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 465
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 471
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT CONFLICT 122
FT /note="P -> L (in Ref. 1; AAF03767)"
FT /evidence="ECO:0000305"
FT CONFLICT 200..203
FT /note="PQEC -> TPQNA (in Ref. 1; AAF03767)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="R -> RN (in Ref. 1; AAF03767)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="E -> ET (in Ref. 1; AAF03767)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="H -> C (in Ref. 1; AAF03767)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 747 AA; 83743 MW; 72690E5EA0C122E8 CRC64;
MANTRVDHLL NTLEELLPYE LEKFKFKLHT TSLEKGHSRI PLSLVKMARP IKLTRLLLTY
YGEEYAVRLT LQILRATNQR QLAEELHKAT GPEHLTEENG VGGSVQSSAE NKDKGVKGSD
VPGEDEAQQN DDESDILPPI QAEVGKGPQK KSLAKRKDQR GPESLDSQTK PGARSAAPLY
RRTLVTQSPG DKENRAGAQP QECQLCREAA RSTAMSQGGE RSRRLKCICL QERSDPGVLK
LPLTQKKENP QIQKLFRLKR KQEMAVSFVR EATLNGRTTG TLEKGVGIPE HSMMLDEETS
RNMSSKISLT REKRCTASWT ENGNGGPETP ETLGETVSSI LCDSCSPKVL LSLGEKLAQT
PEDPASLGQA ASKGRSRDKV ACPLCHTQGE LPAKACVQSS CSCSVAPGDP KASGRHSICF
QCQSSRAGKS CEAQSPQFLP QCPRHMKQVQ LLFCEDHREP ICLICRLSQE HQGHRVRPIE
EAALQYKEQI RKQLERLREM RGYVEEHKLP ADKKAEDFLK QTETQKQRIS CPLEKLFQFL
EQQEQLFVTW LQELVQTIGK VRETYYTQVS LLDKLIGELE AKQDQPEWEL MQDIGATLHR
AETMTASELL GIPPGVKEKL HLLYQKSKSA EKNMQRFSEM LGSEMAFSAS DVATREGCRP
STTKAQALIP TVHLKCDGAH TQDFDVILCA ELEAGGSEPQ DYLHPSSAQD TPELHEIHSQ
NNKRKFKSFL KWKPSFSRTD RCLRTCW
