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Protein

Pyrin

Gene

MEFV

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:16785446, PubMed:17431422, PubMed:26347139). However, it may also have a positive effect in the inflammatory pathway. In different experimental systems, it has been shown to activate IL1B production (PubMed:16037825). It has also been shown to be required for PSTPIP1-induced PYCARD oligomerization and for formation of inflammasomes. Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923).10 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri370 – 412B box-typePROSITE-ProRule annotationAdd BLAST43

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • inflammatory response Source: UniProtKB
  • negative regulation of cytokine production involved in inflammatory response Source: UniProtKB
  • negative regulation of inflammatory response Source: BHF-UCL
  • negative regulation of interleukin-12 production Source: BHF-UCL
  • negative regulation of interleukin-1 beta production Source: BHF-UCL
  • negative regulation of macrophage inflammatory protein 1 alpha production Source: BHF-UCL
  • negative regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity Source: UniProtKB
  • response to interferon-gamma Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

Actin-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000103313-MONOMER.
ReactomeiR-HSA-844456. The NLRP3 inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
Pyrin
Alternative name(s):
Marenostrin
Gene namesi
Name:MEFV
Synonyms:MEF, TRIM201 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:6998. MEFV.

Subcellular locationi

Isoform 1 :
  • Cytoplasmcytoskeleton
  • Cell projectionruffle
  • Cell projectionlamellipodium
  • Nucleus
  • Cytoplasm 1 Publication
  • Cytoplasmic vesicleautophagosome 1 Publication

  • Note: Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles. In pre-apoptotic cells, colocalizes with PYCARD/ASC in large specks (inflammasomes). In migrating monocytes, strongly polarized at the leading edge of the cell where it colocalizes with polymerizing actin and PYCARD/ASC.

GO - Cellular componenti

  • autophagosome Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB-KW
  • cytosol Source: Reactome
  • lamellipodium Source: UniProtKB-SubCell
  • microtubule Source: UniProtKB-KW
  • microtubule associated complex Source: UniProtKB
  • nucleus Source: UniProtKB
  • ruffle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Microtubule, Nucleus

Pathology & Biotechi

Involvement in diseasei

Familial Mediterranean fever, autosomal recessive (ARFMF)17 Publications
The disease is caused by mutations affecting the gene represented in this entry. The disease-associated mutations in the B30.2/SPRY domain perturb ULK1 recruitment and autophagic degradation of inflammasome components, including NLRP3, and hence may contribute to the inflammatory phenotype associated with ARFMF.1 Publication
Disease descriptionA hereditary periodic fever syndrome characterized by recurrent episodic fever, serosal inflammation and pain in the abdomen, chest or joints. It is frequently complicated by reactive amyloidosis, which leads to renal failure and can be prophylactically treated with colchicine.
See also OMIM:249100
Familial Mediterranean fever, autosomal dominant (ADFMF)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary periodic fever syndrome characterized by periodic fever, serosal inflammation and pain in the abdomen, chest or joints as seen also in the autosomal recessive form of the disease. It is associated with reactive renal amyloidosis and characterized by colchicine unresponsiveness.
See also OMIM:134610

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi16L → P: Does not form MEFV- and PSTPIP1-containing perinuclear specks. 1 Publication1
Mutagenesisi24F → S: Does not form MEFV- and PSTPIP1-containing perinuclear specks. 1 Publication1
Mutagenesisi330D → A: Loss of cleavage by CASP1. 1 Publication1
Mutagenesisi397 – 404Missing : No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 470-Y--G-488 and 523-S--D-530. 8
Mutagenesisi470 – 488Missing : No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 397-I--H-404 and 523-S--D-530. Add BLAST19
Mutagenesisi523 – 530Missing : No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 397-I--H-404 and 470-Y--G-488. 8

Keywords - Diseasei

Amyloidosis, Disease mutation

Organism-specific databases

DisGeNETi4210.
MalaCardsiMEFV.
MIMi134610. phenotype.
249100. phenotype.
OpenTargetsiENSG00000103313.
Orphaneti117. Behcet disease.
342. Familial Mediterranean fever.
329967. Intermittent hydrarthrosis.
PharmGKBiPA30736.

Polymorphism and mutation databases

BioMutaiMEFV.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002203641 – 781PyrinAdd BLAST781

Post-translational modificationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei330 – 331Cleavage; by CASP1Curated2

Proteomic databases

EPDiO15553.
PaxDbiO15553.
PeptideAtlasiO15553.
PRIDEiO15553.

PTM databases

iPTMnetiO15553.
PhosphoSitePlusiO15553.

Expressioni

Tissue specificityi

Expressed in peripheral blood leukocytes, particularly in mature granulocytes and to a lesser extent in monocytes but not in lymphocytes. Detected in spleen, lung and muscle, probably as a result of leukocyte infiltration in these tissues. Not expressed in thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, liver, kidney, pancreas. Expression detected in several myeloid leukemic, colon cancer, and prostate cancer cell lines.3 Publications

Developmental stagei

First detected in bone marrow promyelocytes. Expression increases throughout myelocyte differentiation and peaks in the mature myelomonocytic cells.1 Publication

Inductioni

In monocytes, up-regulated by treatment with colchicine and IFN-alpha, by the proinflammatory cytokines IFNG/IFN-gamma and TNF, by bacterial lipopolysaccharides (LPS) and by retroviral infection. Repressed in monocytes by the antiinflammatory cytokines IL10/interleukin-10, TGFB1 and IL4/interleukin-4. In neutrophils and macrophages, up-regulated by IFNG/IFN-gamma with a peak after 8 hours of treatment.3 Publications

Gene expression databases

BgeeiENSG00000103313.
CleanExiHS_MEFV.
ExpressionAtlasiO15553. baseline and differential.

Interactioni

Subunit structurei

Homotrimer. Interacts (via the B box-type zinc finger) with PSTPIP1 (PubMed:14595024, PubMed:17964261, PubMed:19109554). Interacts (via the B30.2/SPRY domain) with several components of the inflammasome complex, including CASP1 p20 and p10 subunits, CASP5, PYCARD, NLRP1, NLRP2 AND NLRP3, as well as with unprocessed IL1B; this interaction may lead to autophagic degradation of these proteins (PubMed:11498534, PubMed:16785446, PubMed:17431422, PubMed:17964261, PubMed:26347139). Interacts with NFKBIA and RELA (PubMed:18577712). Interacts weakly with VASP and ACTR3 (PubMed:19109554). Interacts with active ULK1 (phosphorylated on 'Ser-317') and BECN1 simultaneously. Also interacts with ATG16L1 (via WD repeats), and with ATG8 family members, including GABARAP, GABARAPL1 and, to a lesser extent, GABARAPL2, MAP1LC3A/LC3A and MAP1LC3C/LC3C. Interacts with TRIM21 (PubMed:26347139).8 Publications

GO - Molecular functioni

  • actin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110374. 12 interactors.
DIPiDIP-41878N.
IntActiO15553. 2 interactors.
MINTiMINT-206922.
STRINGi9606.ENSP00000219596.

Structurei

Secondary structure

1781
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 15Combined sources11
Helixi18 – 28Combined sources11
Helixi42 – 47Combined sources6
Turni50 – 52Combined sources3
Helixi53 – 60Combined sources8
Helixi63 – 76Combined sources14
Helixi80 – 92Combined sources13
Helixi414 – 519Combined sources106
Helixi524 – 528Combined sources5
Helixi531 – 539Combined sources9
Helixi551 – 583Combined sources33
Helixi584 – 586Combined sources3
Helixi590 – 594Combined sources5
Turni604 – 606Combined sources3
Beta strandi611 – 613Combined sources3
Beta strandi619 – 622Combined sources4
Beta strandi637 – 639Combined sources3
Beta strandi642 – 645Combined sources4
Beta strandi650 – 658Combined sources9
Beta strandi665 – 671Combined sources7
Beta strandi676 – 678Combined sources3
Helixi684 – 686Combined sources3
Beta strandi688 – 695Combined sources8
Beta strandi698 – 701Combined sources4
Beta strandi707 – 709Combined sources3
Beta strandi716 – 723Combined sources8
Turni724 – 727Combined sources4
Beta strandi728 – 733Combined sources6
Turni734 – 737Combined sources4
Beta strandi738 – 743Combined sources6
Beta strandi752 – 757Combined sources6
Helixi762 – 764Combined sources3
Beta strandi770 – 773Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MPCNMR-A1-92[»]
2WL1X-ray1.35A586-776[»]
4CG4X-ray2.40A/B/C/D/E/F414-781[»]
ProteinModelPortaliO15553.
SMRiO15553.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15553.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 92PyrinPROSITE-ProRule annotationAdd BLAST92
Domaini580 – 775B30.2/SPRYPROSITE-ProRule annotationAdd BLAST196

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni266 – 280Interaction with RELA1 PublicationAdd BLAST15
Regioni420 – 582Required for homotrimerization and induction of pyroptosomesAdd BLAST163

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili413 – 442Sequence analysisAdd BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi420 – 437Nuclear localization signalSequence analysisAdd BLAST18

Domaini

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

Sequence similaritiesi

Contains 1 B box-type zinc finger.PROSITE-ProRule annotation
Contains 1 B30.2/SPRY domain.PROSITE-ProRule annotation
Contains 1 pyrin domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri370 – 412B box-typePROSITE-ProRule annotationAdd BLAST43

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG2177. Eukaryota.
ENOG4111G04. LUCA.
GeneTreeiENSGT00760000118993.
HOGENOMiHOG000113552.
HOVERGENiHBG006343.
InParanoidiO15553.
KOiK12803.
OMAiPQCERHM.
OrthoDBiEOG091G05W2.
PhylomeDBiO15553.
TreeFamiTF351091.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR013320. ConA-like_dom.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR006574. PRY.
IPR003877. SPRY_dom.
IPR000315. Znf_B-box.
[Graphical view]
PfamiPF13765. PRY. 1 hit.
PF02758. PYRIN. 1 hit.
PF00622. SPRY. 1 hit.
PF00643. zf-B_box. 1 hit.
[Graphical view]
PRINTSiPR01407. BUTYPHLNCDUF.
SMARTiSM00336. BBOX. 1 hit.
SM00589. PRY. 1 hit.
SM01289. PYRIN. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEiPS50188. B302_SPRY. 1 hit.
PS50824. DAPIN. 1 hit.
PS50119. ZF_BBOX. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15553-2) [UniParc]FASTAAdd to basket
Also known as: FL

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAKTPSDHLL STLEELVPYD FEKFKFKLQN TSVQKEHSRI PRSQIQRARP
60 70 80 90 100
VKMATLLVTY YGEEYAVQLT LQVLRAINQR LLAEELHRAA IQEYSTQENG
110 120 130 140 150
TDDSAASSSL GENKPRSLKT PDHPEGNEGN GPRPYGGGAA SLRCSQPEAG
160 170 180 190 200
RGLSRKPLSK RREKASEGLD AQGKPRTRSP ALPGGRSPGP CRALEGGQAE
210 220 230 240 250
VRLRRNASSA GRLQGLAGGA PGQKECRPFE VYLPSGKMRP RSLEVTISTG
260 270 280 290 300
EKAPANPEIL LTLEEKTAAN LDSATEPRAR PTPDGGASAD LKEGPGNPEH
310 320 330 340 350
SVTGRPPDTA ASPRCHAQEG DPVDGTCVRD SCSFPEAVSG HPQASGSRSP
360 370 380 390 400
GCPRCQDSHE RKSPGSLSPQ PLPQCKRHLK QVQLLFCEDH DEPICLICSL
410 420 430 440 450
SQEHQGHRVR PIEEVALEHK KKIQKQLEHL KKLRKSGEEQ RSYGEEKAVS
460 470 480 490 500
FLKQTEALKQ RVQRKLEQVY YFLEQQEHFF VASLEDVGQM VGQIRKAYDT
510 520 530 540 550
RVSQDIALLD ALIGELEAKE CQSEWELLQD IGDILHRAKT VPVPEKWTTP
560 570 580 590 600
QEIKQKIQLL HQKSEFVEKS TKYFSETLRS EMEMFNVPEL IGAQAHAVNV
610 620 630 640 650
ILDAETAYPN LIFSDDLKSV RLGNKWERLP DGPQRFDSCI IVLGSPSFLS
660 670 680 690 700
GRRYWEVEVG DKTAWILGAC KTSISRKGNM TLSPENGYWV VIMMKENEYQ
710 720 730 740 750
ASSVPPTRLL IKEPPKRVGI FVDYRVGSIS FYNVTARSHI YTFASCSFSG
760 770 780
PLQPIFSPGT RDGGKNTAPL TICPVGGQGP D
Length:781
Mass (Da):86,444
Last modified:January 1, 1998 - v1
Checksum:i3692E5E6E9FC8204
GO
Isoform 2 (identifier: O15553-1) [UniParc]FASTAAdd to basket
Also known as: D2

The sequence of this isoform differs from the canonical sequence as follows:
     93-303: Missing.

Show »
Length:570
Mass (Da):64,494
Checksum:i34C7379A052C74EF
GO
Isoform 3 (identifier: O15553-3) [UniParc]FASTAAdd to basket

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

Show »
Length:445
Mass (Da):50,837
Checksum:iE157099AC115F36C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04839833V → L.Corresponds to variant rs11466016dbSNPEnsembl.1
Natural variantiVAR_02832642R → W in arFMF. Corresponds to variant rs61754767dbSNPEnsembl.1
Natural variantiVAR_028327108S → R in arFMF. 1 PublicationCorresponds to variant rs104895103dbSNPEnsembl.1
Natural variantiVAR_016824110L → P in arFMF. 2 PublicationsCorresponds to variant rs11466018dbSNPEnsembl.1
Natural variantiVAR_016825138G → A Association with renal amyloidosis. 1 Publication1
Natural variantiVAR_009051148E → Q in arFMF and adFMF; common mutation; associated with S-369 and Q-408 in cis; associated with I-694 in some patients. 7 PublicationsCorresponds to variant rs3743930dbSNPEnsembl.1
Natural variantiVAR_028328148E → V in arFMF. 1 PublicationCorresponds to variant rs104895076dbSNPEnsembl.1
Natural variantiVAR_028329163E → A in arFMF. 1 PublicationCorresponds to variant rs104895106dbSNPEnsembl.1
Natural variantiVAR_009052167E → D in arFMF. 1 PublicationCorresponds to variant rs104895079dbSNPEnsembl.1
Natural variantiVAR_028330177T → I in arFMF. 1 PublicationCorresponds to variant rs104895143dbSNPEnsembl.1
Natural variantiVAR_072382196G → W in a Turkish patient with arFMF; unknown pathological significance. 1 PublicationCorresponds to variant rs104895179dbSNPEnsembl.1
Natural variantiVAR_009053202R → Q.3 PublicationsCorresponds to variant rs224222dbSNPEnsembl.1
Natural variantiVAR_016826230E → K in arFMF. 2 PublicationsCorresponds to variant rs104895080dbSNPEnsembl.1
Natural variantiVAR_072383247I → V in a Turkish patient with arFMF; unknown pathological significance. 1 Publication1
Natural variantiVAR_009054267T → I in arFMF. 2 PublicationsCorresponds to variant rs104895081dbSNPEnsembl.1
Natural variantiVAR_072384283P → L in Turkish patients with arFMF; unknown pathological significance. 1 PublicationCorresponds to variant rs104895119dbSNPEnsembl.1
Natural variantiVAR_072385304G → R in a Turkish patient with arFMF; unknown pathological significance. 1 PublicationCorresponds to variant rs75977701dbSNPEnsembl.1
Natural variantiVAR_028331319E → K in arFMF. 1 PublicationCorresponds to variant rs104895110dbSNPEnsembl.1
Natural variantiVAR_009055369P → S in arFMF; reduced penetrance among Ashkenazi Jews; associated with Q-148 and Q-408 in cis. 2 PublicationsCorresponds to variant rs11466023dbSNPEnsembl.1
Natural variantiVAR_009056408R → Q in arFMF; associated with Q-148 and S-369 in cis. 2 PublicationsCorresponds to variant rs11466024dbSNPEnsembl.1
Natural variantiVAR_024376440Q → E.Corresponds to variant rs11466026dbSNPEnsembl.1
Natural variantiVAR_028332474E → K in arFMF. 1 PublicationCorresponds to variant rs104895104dbSNPEnsembl.1
Natural variantiVAR_028333478H → Y in adFMF; severe. 1 PublicationCorresponds to variant rs104895105dbSNPEnsembl.1
Natural variantiVAR_009057479F → L in arFMF. 2 PublicationsCorresponds to variant rs104895083dbSNPEnsembl.1
Natural variantiVAR_070795577T → A Probable disease-associated mutation found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. 1 Publication1
Natural variantiVAR_070796577T → N Probable disease-associated mutation found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. 1 Publication1
Natural variantiVAR_070797577T → S Probable disease-associated mutation found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. 1 PublicationCorresponds to variant rs104895193dbSNPEnsembl.1
Natural variantiVAR_028334585F → L.Corresponds to variant rs11466043dbSNPEnsembl.1
Natural variantiVAR_016827591I → T in arFMF; unknown pathological significance. 1 PublicationCorresponds to variant rs11466045dbSNPEnsembl.1
Natural variantiVAR_072386632G → A in a Turkish patient with arFMF; unknown pathological significance. 1 Publication1
Natural variantiVAR_028335632G → S in arFMF. 1 PublicationCorresponds to variant rs104895128dbSNPEnsembl.1
Natural variantiVAR_028336640I → M in arFMF. 1 PublicationCorresponds to variant rs104895115dbSNPEnsembl.1
Natural variantiVAR_028337641I → F in arFMF. 1 PublicationCorresponds to variant rs104895147dbSNPEnsembl.1
Natural variantiVAR_028338646P → L in arFMF. 1 PublicationCorresponds to variant rs104895107dbSNPEnsembl.1
Natural variantiVAR_028339649L → P in arFMF. 1 PublicationCorresponds to variant rs104895108dbSNPEnsembl.1
Natural variantiVAR_016828653R → H in arFMF. 3 PublicationsCorresponds to variant rs104895085dbSNPEnsembl.1
Natural variantiVAR_028340656E → A in arFMF. 1 PublicationCorresponds to variant rs104895086dbSNPEnsembl.1
Natural variantiVAR_028341661D → N in arFMF. 1 PublicationCorresponds to variant rs104895120dbSNPEnsembl.1
Natural variantiVAR_016829675S → N in arFMF. 2 PublicationsCorresponds to variant rs104895087dbSNPEnsembl.1
Natural variantiVAR_028342678G → E in arFMF. 1 PublicationCorresponds to variant rs104895088dbSNPEnsembl.1
Natural variantiVAR_028343680M → I in arFMF and adFMF; reduced CASP1 interaction; decreased interaction with ULK1 and diminished NLRP3 degradation after induction of autophagy by starvation; when associated with V-694 (PubMed:26347139). 11 PublicationsCorresponds to variant rs28940580dbSNPEnsembl.1
Natural variantiVAR_016830680M → L in arFMF. 2 PublicationsCorresponds to variant rs104895089dbSNPEnsembl.1
Natural variantiVAR_009059681T → I in arFMF. 2 PublicationsCorresponds to variant rs104895090dbSNPEnsembl.1
Natural variantiVAR_028344688Y → C in arFMF. 1 PublicationCorresponds to variant rs104895122dbSNPEnsembl.1
Natural variantiVAR_009060692Missing in arFMF. 1
Natural variantiVAR_009061694M → I in arFMF and adFMF; associated with Q-148 in some patients. 8 PublicationsCorresponds to variant rs28940578dbSNPEnsembl.1
Natural variantiVAR_070798694M → K in arFMF. 1 Publication1
Natural variantiVAR_028345694M → L in arFMF. 1 PublicationCorresponds to variant rs61752717dbSNPEnsembl.1
Natural variantiVAR_009062694M → V in arFMF and adFMF; very common mutation particularly in North African Jews; can be associated with amyloidosis development; reduced interaction with CASP1 and with ULK1 and diminished NLRP3 degradation after induction of autophagy by starvation (PubMed:16785446) (PubMed:26347139); effect on autophagic NLRP3 degradation is increased; when associated with I-680; no effect on interaction with CASP1, CASP5, NLRP1, NLRP2 or NLRP3 (PubMed:17431422). 13 PublicationsCorresponds to variant rs61752717dbSNPEnsembl.1
Natural variantiVAR_009063694Missing in arFMF and adFMF. 2 Publications1
Natural variantiVAR_028346695K → M in arFMF. 1 PublicationCorresponds to variant rs104895094dbSNPEnsembl.1
Natural variantiVAR_009064695K → R in arFMF; reduced penetrance among Ashkenazi Jews. 4 PublicationsCorresponds to variant rs104895094dbSNPEnsembl.1
Natural variantiVAR_028347702S → C in one patient with familial Mediterranean fever. 1 PublicationCorresponds to variant rs104895166dbSNPEnsembl.1
Natural variantiVAR_028348704V → I in arFMF. 1 PublicationCorresponds to variant rs104895096dbSNPEnsembl.1
Natural variantiVAR_028349705P → S in arFMF. 1 PublicationCorresponds to variant rs104895145dbSNPEnsembl.1
Natural variantiVAR_028350720I → M in arFMF. 2 PublicationsCorresponds to variant rs104895102dbSNPEnsembl.1
Natural variantiVAR_009065726V → A in arFMF; common mutation; in Iraqi and Ashkenazi Jews, Druze, Armenians; reduced interaction with CASP1 and ULK1 and diminished NLRP3 degradation after induction of autophagy by starvation; when associated with I-680 and V-694; no effect on CASP1 activation. 9 PublicationsCorresponds to variant rs28940579dbSNPEnsembl.1
Natural variantiVAR_028351743F → L in arFMF. 1 PublicationCorresponds to variant rs104895152dbSNPEnsembl.1
Natural variantiVAR_009066744A → S in arFMF; uncertain pathological significance. 4 PublicationsCorresponds to variant rs61732874dbSNPEnsembl.1
Natural variantiVAR_028352758P → S in arFMF. 1 PublicationCorresponds to variant rs104895114dbSNPEnsembl.1
Natural variantiVAR_009067761R → H in arFMF. 5 PublicationsCorresponds to variant rs104895097dbSNPEnsembl.1
Natural variantiVAR_028353780P → T in arFMF. 1 PublicationCorresponds to variant rs104895154dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00822393 – 303Missing in isoform 2 and isoform 3. CuratedAdd BLAST211
Alternative sequenceiVSP_047663587 – 781VPELI…GQGPD → DHSPQHGLGSWEERDYTQHS MQGPKQGVPCLSLLSGQCNL APLNANAQDFFPYLIFLRSS GADWRSGTCC in isoform 3. CuratedAdd BLAST195

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF018080 mRNA. Translation: AAB70557.1.
CH471112 Genomic DNA. Translation: EAW85382.1.
CH471112 Genomic DNA. Translation: EAW85383.1.
BC101511 mRNA. Translation: AAI01512.1.
BC101537 mRNA. Translation: AAI01538.1.
Y14441 mRNA. Translation: CAA74793.1.
AJ003147 Genomic DNA. Translation: CAA05906.1.
AF111163 Genomic DNA. Translation: AAD26152.1.
AF301150 Genomic DNA. Translation: AAK97223.1.
AF301151 Genomic DNA. Translation: AAK97224.1.
CCDSiCCDS10498.1. [O15553-2]
CCDS55981.1. [O15553-3]
RefSeqiNP_000234.1. NM_000243.2. [O15553-2]
NP_001185465.1. NM_001198536.1.
UniGeneiHs.632221.

Genome annotation databases

EnsembliENST00000219596; ENSP00000219596; ENSG00000103313. [O15553-2]
ENST00000536379; ENSP00000445079; ENSG00000103313. [O15553-1]
ENST00000541159; ENSP00000438711; ENSG00000103313. [O15553-3]
GeneIDi4210.
KEGGihsa:4210.
UCSCiuc002cun.1. human. [O15553-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF018080 mRNA. Translation: AAB70557.1.
CH471112 Genomic DNA. Translation: EAW85382.1.
CH471112 Genomic DNA. Translation: EAW85383.1.
BC101511 mRNA. Translation: AAI01512.1.
BC101537 mRNA. Translation: AAI01538.1.
Y14441 mRNA. Translation: CAA74793.1.
AJ003147 Genomic DNA. Translation: CAA05906.1.
AF111163 Genomic DNA. Translation: AAD26152.1.
AF301150 Genomic DNA. Translation: AAK97223.1.
AF301151 Genomic DNA. Translation: AAK97224.1.
CCDSiCCDS10498.1. [O15553-2]
CCDS55981.1. [O15553-3]
RefSeqiNP_000234.1. NM_000243.2. [O15553-2]
NP_001185465.1. NM_001198536.1.
UniGeneiHs.632221.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MPCNMR-A1-92[»]
2WL1X-ray1.35A586-776[»]
4CG4X-ray2.40A/B/C/D/E/F414-781[»]
ProteinModelPortaliO15553.
SMRiO15553.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110374. 12 interactors.
DIPiDIP-41878N.
IntActiO15553. 2 interactors.
MINTiMINT-206922.
STRINGi9606.ENSP00000219596.

PTM databases

iPTMnetiO15553.
PhosphoSitePlusiO15553.

Polymorphism and mutation databases

BioMutaiMEFV.

Proteomic databases

EPDiO15553.
PaxDbiO15553.
PeptideAtlasiO15553.
PRIDEiO15553.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219596; ENSP00000219596; ENSG00000103313. [O15553-2]
ENST00000536379; ENSP00000445079; ENSG00000103313. [O15553-1]
ENST00000541159; ENSP00000438711; ENSG00000103313. [O15553-3]
GeneIDi4210.
KEGGihsa:4210.
UCSCiuc002cun.1. human. [O15553-2]

Organism-specific databases

CTDi4210.
DisGeNETi4210.
GeneCardsiMEFV.
GeneReviewsiMEFV.
HGNCiHGNC:6998. MEFV.
MalaCardsiMEFV.
MIMi134610. phenotype.
249100. phenotype.
608107. gene.
neXtProtiNX_O15553.
OpenTargetsiENSG00000103313.
Orphaneti117. Behcet disease.
342. Familial Mediterranean fever.
329967. Intermittent hydrarthrosis.
PharmGKBiPA30736.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2177. Eukaryota.
ENOG4111G04. LUCA.
GeneTreeiENSGT00760000118993.
HOGENOMiHOG000113552.
HOVERGENiHBG006343.
InParanoidiO15553.
KOiK12803.
OMAiPQCERHM.
OrthoDBiEOG091G05W2.
PhylomeDBiO15553.
TreeFamiTF351091.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000103313-MONOMER.
ReactomeiR-HSA-844456. The NLRP3 inflammasome.

Miscellaneous databases

EvolutionaryTraceiO15553.
GeneWikiiMEFV.
GenomeRNAii4210.
PROiO15553.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103313.
CleanExiHS_MEFV.
ExpressionAtlasiO15553. baseline and differential.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR013320. ConA-like_dom.
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR006574. PRY.
IPR003877. SPRY_dom.
IPR000315. Znf_B-box.
[Graphical view]
PfamiPF13765. PRY. 1 hit.
PF02758. PYRIN. 1 hit.
PF00622. SPRY. 1 hit.
PF00643. zf-B_box. 1 hit.
[Graphical view]
PRINTSiPR01407. BUTYPHLNCDUF.
SMARTiSM00336. BBOX. 1 hit.
SM00589. PRY. 1 hit.
SM01289. PYRIN. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEiPS50188. B302_SPRY. 1 hit.
PS50824. DAPIN. 1 hit.
PS50119. ZF_BBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMEFV_HUMAN
AccessioniPrimary (citable) accession number: O15553
Secondary accession number(s): D3DUC0
, F5H0Q3, Q3MJ84, Q96PN4, Q96PN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 171 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Degraded along with the delivery of its substrates to autolysosomal compartments (at protein level).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.