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UniProtKB - O15553 (MEFV_HUMAN)

Protein

Pyrin

Gene

MEFV

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

Regions

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

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • zinc ion binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionActin-binding
Biological processImmunity, Inflammatory response, Innate immunity
LigandMetal-binding, Zinc

Enzyme and pathway databases

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103313.11
HGNCiHGNC:6998 MEFV
MIMi608107 gene
neXtProtiNX_O15553

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
GeneReviewsiMEFV
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
ProteomicsDBi48755
48756 [O15553-1]

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 Expressed in 81 organ(s), highest expression level in blood
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

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi110374, 15 interactors
DIPiDIP-41878N
IntActiO15553, 4 interactors
MINTiO15553
STRINGi9606.ENSP00000219596

Structurei

Secondary structure

1781
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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.

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
GeneTreeiENSGT00760000118838
HOGENOMiHOG000113552
HOVERGENiHBG006343
InParanoidiO15553
KOiK12803
OMAiGTHDGGK
OrthoDBiEOG091G05W2
PhylomeDBiO15553
TreeFamiTF351091

Family and domain databases

CDDicd00021 BBOX, 1 hit
InterProiView protein in InterPro
IPR001870 B30.2/SPRY
IPR003879 Butyrophylin_SPRY
IPR013320 ConA-like_dom_sf
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR006574 PRY
IPR028841 Pyrin
IPR003877 SPRY_dom
IPR000315 Znf_B-box
PANTHERiPTHR45323 PTHR45323, 2 hits
PfamiView protein in Pfam
PF13765 PRY, 1 hit
PF02758 PYRIN, 1 hit
PF00622 SPRY, 1 hit
PF00643 zf-B_box, 1 hit
PRINTSiPR01407 BUTYPHLNCDUF
SMARTiView protein in SMART
SM00336 BBOX, 1 hit
SM00589 PRY, 1 hit
SM01289 PYRIN, 1 hit
SM00449 SPRY, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50188 B302_SPRY, 1 hit
PS50824 DAPIN, 1 hit
PS50119 ZF_BBOX, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W6Z2F8W6Z2_HUMAN
Pyrin
MEFV
601Annotation score:
F5H2E5F5H2E5_HUMAN
Pyrin
MEFV
613Annotation score:
F5H6N9F5H6N9_HUMAN
Pyrin
MEFV
490Annotation score:
F5GZV9F5GZV9_HUMAN
Pyrin
MEFV
402Annotation score:
F5H595F5H595_HUMAN
Pyrin
MEFV
644Annotation score:
E3P8H6E3P8H6_HUMAN
Pyrin/marenostrin variant del2345
MEFV
101Annotation score:
D2DTW1D2DTW1_HUMAN
Pyrin/marenostrin variant del234
MEFV
95Annotation score:
I3L0S7I3L0S7_HUMAN
Pyrin
MEFV
306Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04839833V → L. Corresponds to variant dbSNP:rs11466016EnsemblClinVar.1
Natural variantiVAR_02832642R → W in arFMF. Corresponds to variant dbSNP:rs61754767EnsemblClinVar.1
Natural variantiVAR_028327108S → R in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895103EnsemblClinVar.1
Natural variantiVAR_016824110L → P in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs11466018EnsemblClinVar.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 dbSNP:rs3743930EnsemblClinVar.1
Natural variantiVAR_028328148E → V in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895076EnsemblClinVar.1
Natural variantiVAR_028329163E → A in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895106EnsemblClinVar.1
Natural variantiVAR_009052167E → D in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895079EnsemblClinVar.1
Natural variantiVAR_028330177T → I in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895143EnsemblClinVar.1
Natural variantiVAR_072382196G → W in a Turkish patient with arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895179EnsemblClinVar.1
Natural variantiVAR_009053202R → Q3 PublicationsCorresponds to variant dbSNP:rs224222EnsemblClinVar.1
Natural variantiVAR_016826230E → K in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895080EnsemblClinVar.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 dbSNP:rs104895081EnsemblClinVar.1
Natural variantiVAR_072384283P → L in Turkish patients with arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895119EnsemblClinVar.1
Natural variantiVAR_072385304G → R in a Turkish patient with arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs75977701EnsemblClinVar.1
Natural variantiVAR_028331319E → K in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895110EnsemblClinVar.1
Natural variantiVAR_009055369P → S in arFMF; unknown pathological significance; associated with Q-148 and Q-408 in cis. 2 PublicationsCorresponds to variant dbSNP:rs11466023EnsemblClinVar.1
Natural variantiVAR_009056408R → Q in arFMF; associated with Q-148 and S-369 in cis. 2 PublicationsCorresponds to variant dbSNP:rs11466024EnsemblClinVar.1
Natural variantiVAR_024376440Q → E. Corresponds to variant dbSNP:rs11466026EnsemblClinVar.1
Natural variantiVAR_028332474E → K in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895104EnsemblClinVar.1
Natural variantiVAR_028333478H → Y in adFMF; severe. 1 PublicationCorresponds to variant dbSNP:rs104895105EnsemblClinVar.1
Natural variantiVAR_009057479F → L in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895083EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs1057516210Ensembl.1
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 dbSNP:rs104895193EnsemblClinVar.1
Natural variantiVAR_028334585F → L. Corresponds to variant dbSNP:rs11466043Ensembl.1
Natural variantiVAR_016827591I → T in arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs11466045EnsemblClinVar.1
Natural variantiVAR_072386632G → A in a Turkish patient with arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs967990798Ensembl.1
Natural variantiVAR_028335632G → S in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895128EnsemblClinVar.1
Natural variantiVAR_028336640I → M in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895115EnsemblClinVar.1
Natural variantiVAR_028337641I → F in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895147EnsemblClinVar.1
Natural variantiVAR_028338646P → L in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895107EnsemblClinVar.1
Natural variantiVAR_028339649L → P in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895108EnsemblClinVar.1
Natural variantiVAR_016828653R → H in arFMF. 3 PublicationsCorresponds to variant dbSNP:rs104895085EnsemblClinVar.1
Natural variantiVAR_028340656E → A in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895086EnsemblClinVar.1
Natural variantiVAR_028341661D → N in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895120EnsemblClinVar.1
Natural variantiVAR_016829675S → N in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895087EnsemblClinVar.1
Natural variantiVAR_028342678G → E in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895088EnsemblClinVar.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 dbSNP:rs28940580EnsemblClinVar.1
Natural variantiVAR_016830680M → L in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895089EnsemblClinVar.1
Natural variantiVAR_009059681T → I in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895090EnsemblClinVar.1
Natural variantiVAR_028344688Y → C in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895122EnsemblClinVar.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 dbSNP:rs28940578EnsemblClinVar.1
Natural variantiVAR_070798694M → K in arFMF. 1 Publication1
Natural variantiVAR_028345694M → L in arFMF. 1 PublicationCorresponds to variant dbSNP:rs61752717EnsemblClinVar.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 dbSNP:rs61752717EnsemblClinVar.1
Natural variantiVAR_009063694Missing in arFMF and adFMF. 2 Publications1
Natural variantiVAR_028346695K → M in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895094EnsemblClinVar.1
Natural variantiVAR_009064695K → R in arFMF; reduced penetrance among Ashkenazi Jews. 4 PublicationsCorresponds to variant dbSNP:rs104895094EnsemblClinVar.1
Natural variantiVAR_028347702S → C in one patient with familial Mediterranean fever. 1 PublicationCorresponds to variant dbSNP:rs104895166EnsemblClinVar.1
Natural variantiVAR_028348704V → I in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895096EnsemblClinVar.1
Natural variantiVAR_028349705P → S in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895145EnsemblClinVar.1
Natural variantiVAR_028350720I → M in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895102EnsemblClinVar.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 dbSNP:rs28940579EnsemblClinVar.1
Natural variantiVAR_028351743F → L in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895152EnsemblClinVar.1
Natural variantiVAR_009066744A → S in arFMF; uncertain pathological significance. 4 PublicationsCorresponds to variant dbSNP:rs61732874EnsemblClinVar.1
Natural variantiVAR_028352758P → S in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895114EnsemblClinVar.1
Natural variantiVAR_009067761R → H in arFMF. 5 PublicationsCorresponds to variant dbSNP:rs104895097EnsemblClinVar.1
Natural variantiVAR_028353780P → T in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895154EnsemblClinVar.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

Similar proteinsi

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, 15 interactors
DIPiDIP-41878N
IntActiO15553, 4 interactors
MINTiO15553
STRINGi9606.ENSP00000219596

PTM databases

iPTMnetiO15553
PhosphoSitePlusiO15553

Polymorphism and mutation databases

BioMutaiMEFV

Proteomic databases

EPDiO15553
PaxDbiO15553
PeptideAtlasiO15553
PRIDEiO15553
ProteomicsDBi48755
48756 [O15553-1]

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
EuPathDBiHostDB:ENSG00000103313.11
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
GeneTreeiENSGT00760000118838
HOGENOMiHOG000113552
HOVERGENiHBG006343
InParanoidiO15553
KOiK12803
OMAiGTHDGGK
OrthoDBiEOG091G05W2
PhylomeDBiO15553
TreeFamiTF351091

Enzyme and pathway databases

ReactomeiR-HSA-844456 The NLRP3 inflammasome

Miscellaneous databases

EvolutionaryTraceiO15553
GeneWikiiMEFV
GenomeRNAii4210
PROiPR:O15553
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103313 Expressed in 81 organ(s), highest expression level in blood
CleanExiHS_MEFV
ExpressionAtlasiO15553 baseline and differential

Family and domain databases

CDDicd00021 BBOX, 1 hit
InterProiView protein in InterPro
IPR001870 B30.2/SPRY
IPR003879 Butyrophylin_SPRY
IPR013320 ConA-like_dom_sf
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR006574 PRY
IPR028841 Pyrin
IPR003877 SPRY_dom
IPR000315 Znf_B-box
PANTHERiPTHR45323 PTHR45323, 2 hits
PfamiView protein in Pfam
PF13765 PRY, 1 hit
PF02758 PYRIN, 1 hit
PF00622 SPRY, 1 hit
PF00643 zf-B_box, 1 hit
PRINTSiPR01407 BUTYPHLNCDUF
SMARTiView protein in SMART
SM00336 BBOX, 1 hit
SM00589 PRY, 1 hit
SM01289 PYRIN, 1 hit
SM00449 SPRY, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50188 B302_SPRY, 1 hit
PS50824 DAPIN, 1 hit
PS50119 ZF_BBOX, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMEFV_HUMAN
AccessioniPrimary (citable) accession number: O15553
Secondary accession number(s): D3DUC0
, F5H0Q3, Q3MJ84, Q96PN4, Q96PN5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 189 of the entry and version 1 of the sequence. See 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

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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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