UniProtKB - O15553 (MEFV_HUMAN)
Pyrin
MEFV
Functioni
Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923, PubMed:16037825, PubMed:27030597, PubMed:28835462, PubMed:16785446, PubMed:17431422, PubMed:26347139).
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 (PubMed:16785446, PubMed:17431422, PubMed:26347139).
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 can also have a positive effect in the inflammatory pathway, acting as an innate immune sensor that triggers PYCARD/ASC specks formation, caspase-1 activation, and IL1B and IL18 production (PubMed:16037825, PubMed:27030597, PubMed:28835462).
Together with AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (By similarity).
It is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923).
Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923).
By similarity12 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 370 – 412 | B box-typePROSITE-ProRule annotationAdd BLAST | 43 |
GO - Molecular functioni
- actin binding Source: UniProtKB
- identical protein binding Source: IntAct
- ubiquitin protein ligase activity Source: GO_Central
- zinc ion binding Source: UniProtKB
GO - Biological processi
- inflammatory response Source: UniProtKB
- innate immune response Source: GO_Central
- 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
- pattern recognition receptor signaling pathway Source: ComplexPortal
- positive regulation of autophagy Source: UniProtKB
- positive regulation of cysteine-type endopeptidase activity Source: UniProtKB
- positive regulation of interleukin-1 beta production Source: ComplexPortal
- protein ubiquitination Source: GO_Central
- pyroptosis Source: ComplexPortal
- pyroptosome complex assembly Source: UniProtKB
- regulation of gene expression Source: GO_Central
- regulation of interleukin-1 beta production Source: UniProtKB
- response to interferon-gamma Source: UniProtKB
Keywordsi
Molecular function | Actin-binding |
Biological process | Immunity, Inflammatory response, Innate immunity |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | O15553 |
Reactomei | R-HSA-844456, The NLRP3 inflammasome R-HSA-9660826, Purinergic signaling in leishmaniasis infection |
SignaLinki | O15553 |
SIGNORi | O15553 |
Names & Taxonomyi
Protein namesi | Recommended name: Pyrin1 PublicationAlternative name(s): Marenostrin1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6998, MEFV |
MIMi | 608107, gene |
neXtProti | NX_O15553 |
VEuPathDBi | HostDB:ENSG00000103313 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 5 Publications
Cytoskeleton
- cytoskeleton 2 Publications
Nucleus
- Nucleus 1 Publication
Other locations
- ruffle 1 Publication
- lamellipodium 1 Publication
- autophagosome 1 Publication
Note: Associated with microtubules and with the filamentous actin of perinuclear filaments and peripheral lamellar ruffles (PubMed:11468188). In pre-apoptotic cells, colocalizes with PYCARD/ASC in large specks (inflammasomes) (PubMed:11468188). In migrating monocytes, strongly polarized at the leading edge of the cell where it colocalizes with polymerizing actin and PYCARD/ASC (PubMed:11468188).1 Publication
Nucleus
- Nucleus 1 Publication
Cytoskeleton
- microtubule Source: ComplexPortal
- microtubule associated complex Source: UniProtKB
Cytosol
- cytosol Source: HPA
- inflammasome complex Source: ComplexPortal
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- autophagosome Source: UniProtKB-SubCell
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle Source: UniProtKB-KW
- lamellipodium Source: UniProtKB-SubCell
- ruffle Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Microtubule, NucleusPathology & Biotechi
Involvement in diseasei
Familial Mediterranean fever, autosomal recessive (ARFMF)18 Publications
Familial Mediterranean fever, autosomal dominant (ADFMF)2 Publications
Pyrin-associated autoinflammatory disease (PAAND)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_084466 | 242 | S → R in PAAND; results in constitutive inflammasome activation; increased PYCARD/ASC specks formation; increased caspase-1 activation and IL1B production; loss of S-242 phosphorylation; loss of interaction with 14-3-3 proteins. 1 PublicationCorresponds to variant dbSNP:rs104895127EnsemblClinVar. | 1 | |
Natural variantiVAR_084467 | 244 | E → K in PAAND; results in constitutive inflammasome activation; increased PYCARD/ASC specks formation; increased caspase-1 activation and IL1B and IL18 production; decreased interaction with 14-3-3 proteins; no effect on interaction with PSTPIP1. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 16 | L → P: Does not form MEFV- and PSTPIP1-containing perinuclear specks. 1 Publication | 1 | |
Mutagenesisi | 24 | F → S: Does not form MEFV- and PSTPIP1-containing perinuclear specks. 1 Publication | 1 | |
Mutagenesisi | 208 | S → A: Loss of interaction with 14-3-3 proteins. 1 Publication | 1 | |
Mutagenesisi | 244 | E → D: No effect on PYCARD/ASC specks formation. No effect on interaction with 14-3-3 proteins. 1 Publication | 1 | |
Mutagenesisi | 244 | E → P: No effect on PYCARD/ASC specks formation. Increased interaction with 14-3-3 proteins. 1 Publication | 1 | |
Mutagenesisi | 244 | E → R: Increased PYCARD/ASC specks formation. Decreased interaction with 14-3-3 proteins. 1 Publication | 1 | |
Mutagenesisi | 330 | D → A: Loss of cleavage by CASP1. 1 Publication | 1 | |
Mutagenesisi | 397 – 404 | Missing : No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 470-Y--G-488 and 523-S--D-530. | 8 | |
Mutagenesisi | 470 – 488 | Missing : No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 397-I--H-404 and 523-S--D-530. Add BLAST | 19 | |
Mutagenesisi | 523 – 530 | Missing : 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 variantOrganism-specific databases
DisGeNETi | 4210 |
GeneReviewsi | MEFV |
MalaCardsi | MEFV |
MIMi | 134610, phenotype 249100, phenotype 608068, phenotype |
OpenTargetsi | ENSG00000103313 |
Orphaneti | 117, Behcet disease 342, Familial Mediterranean fever 329967, Intermittent hydrarthrosis 3243, Sweet syndrome |
PharmGKBi | PA30736 |
Miscellaneous databases
Pharosi | O15553, Tbio |
Genetic variation databases
BioMutai | MEFV |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220364 | 1 – 781 | PyrinAdd BLAST | 781 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 242 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 330 – 331 | Cleavage; by CASP1Curated | 2 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O15553 |
MassIVEi | O15553 |
PaxDbi | O15553 |
PeptideAtlasi | O15553 |
PRIDEi | O15553 |
ProteomicsDBi | 25411 48755 [O15553-2] 48756 [O15553-1] |
PTM databases
GlyGeni | O15553, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O15553 |
PhosphoSitePlusi | O15553 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSG00000103313, Expressed in blood and 110 other tissues |
ExpressionAtlasi | O15553, baseline and differential |
Organism-specific databases
HPAi | ENSG00000103313, Tissue enhanced (bone marrow, lymphoid tissue) |
Interactioni
Subunit structurei
Homotrimer.
Interacts (via the B box-type zinc finger) with PSTPIP1 (PubMed:14595024, PubMed:17964261, PubMed:19109554, PubMed:28835462).
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).
Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity).
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, PubMed:28835462).
Interacts with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ AND YWHAZ; the interaction is required for the down-regulation of pyrin pro-inflammatory activity (PubMed:27030597, PubMed:28835462).
By similarity10 PublicationsBinary interactionsi
O15553
With | #Exp. | IntAct |
---|---|---|
CASP1 [P29466] | 2 | EBI-7644532,EBI-516667 |
itself | 8 | EBI-7644532,EBI-7644532 |
PSTPIP1 [O43586] | 4 | EBI-7644532,EBI-1050964 |
PYCARD [Q9ULZ3] | 8 | EBI-7644532,EBI-751215 |
Isoform 1 [O15553-2]
With | #Exp. | IntAct |
---|---|---|
CASP1 [P29466] | 3 | EBI-15588296,EBI-516667 |
GO - Molecular functioni
- actin binding Source: UniProtKB
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 110374, 18 interactors |
ComplexPortali | CPX-4143, Pyrin inflammasome |
DIPi | DIP-41878N |
IntActi | O15553, 6 interactors |
MINTi | O15553 |
STRINGi | 9606.ENSP00000219596 |
Miscellaneous databases
RNActi | O15553, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O15553 |
SMRi | O15553 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O15553 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1 – 92 | PyrinPROSITE-ProRule annotationAdd BLAST | 92 | |
Domaini | 580 – 775 | B30.2/SPRYPROSITE-ProRule annotationAdd BLAST | 196 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 93 – 226 | DisorderedSequence analysisAdd BLAST | 134 | |
Regioni | 266 – 280 | Interaction with RELA1 PublicationAdd BLAST | 15 | |
Regioni | 270 – 322 | DisorderedSequence analysisAdd BLAST | 53 | |
Regioni | 336 – 373 | DisorderedSequence analysisAdd BLAST | 38 | |
Regioni | 420 – 582 | Required for homotrimerization and induction of pyroptosomes1 PublicationAdd BLAST | 163 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 413 – 442 | Sequence analysisAdd BLAST | 30 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 420 – 437 | Nuclear localization signalSequence analysisAdd BLAST | 18 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 93 – 115 | Polar residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 154 – 171 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 338 – 352 | Polar residuesSequence analysisAdd BLAST | 15 |
Domaini
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 370 – 412 | B box-typePROSITE-ProRule annotationAdd BLAST | 43 |
Keywords - Domaini
Coiled coil, Zinc-fingerPhylogenomic databases
eggNOGi | KOG2177, Eukaryota |
GeneTreei | ENSGT00940000161955 |
HOGENOMi | CLU_685051_0_0_1 |
InParanoidi | O15553 |
OMAi | CQRHMKQ |
OrthoDBi | 651627at2759 |
PhylomeDBi | O15553 |
TreeFami | TF351091 |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 2.60.120.920, 1 hit |
InterProi | View protein in InterPro IPR001870, B30.2/SPRY IPR043136, B30.2/SPRY_sf 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 |
PANTHERi | PTHR24103:SF606, PTHR24103:SF606, 2 hits |
Pfami | View protein in Pfam PF13765, PRY, 1 hit PF02758, PYRIN, 1 hit PF00622, SPRY, 1 hit PF00643, zf-B_box, 1 hit |
PRINTSi | PR01407, BUTYPHLNCDUF |
SMARTi | View protein in SMART SM00336, BBOX, 1 hit SM00589, PRY, 1 hit SM01289, PYRIN, 1 hit SM00449, SPRY, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF49899, SSF49899, 1 hit |
PROSITEi | View protein in PROSITE PS50188, B302_SPRY, 1 hit PS50824, DAPIN, 1 hit PS50119, ZF_BBOX, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8W6Z2 | F8W6Z2_HUMAN | Pyrin | MEFV | 601 | Annotation score: | ||
F5H2E5 | F5H2E5_HUMAN | Pyrin | MEFV | 613 | Annotation score: | ||
F5H6N9 | F5H6N9_HUMAN | Pyrin | MEFV | 490 | Annotation score: | ||
F5GZV9 | F5GZV9_HUMAN | Pyrin | MEFV | 402 | Annotation score: | ||
F5H595 | F5H595_HUMAN | Pyrin | MEFV | 644 | Annotation score: | ||
I3L0S7 | I3L0S7_HUMAN | Pyrin | MEFV | 306 | Annotation score: | ||
E3P8H6 | E3P8H6_HUMAN | Pyrin | MEFV | 101 | Annotation score: | ||
D2DTW1 | D2DTW1_HUMAN | Pyrin | MEFV | 95 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048398 | 33 | V → L. Corresponds to variant dbSNP:rs11466016EnsemblClinVar. | 1 | |
Natural variantiVAR_028326 | 42 | R → W in arFMF. Corresponds to variant dbSNP:rs61754767EnsemblClinVar. | 1 | |
Natural variantiVAR_028327 | 108 | S → R in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895103EnsemblClinVar. | 1 | |
Natural variantiVAR_016824 | 110 | L → P in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs11466018EnsemblClinVar. | 1 | |
Natural variantiVAR_009051 | 148 | E → Q in arFMF and adFMF; likely benign variant; 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_028328 | 148 | E → V in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895076EnsemblClinVar. | 1 | |
Natural variantiVAR_028329 | 163 | E → A in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895106EnsemblClinVar. | 1 | |
Natural variantiVAR_009052 | 167 | E → D in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895079EnsemblClinVar. | 1 | |
Natural variantiVAR_028330 | 177 | T → I in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895143EnsemblClinVar. | 1 | |
Natural variantiVAR_072382 | 196 | G → W in arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895179EnsemblClinVar. | 1 | |
Natural variantiVAR_009053 | 202 | R → Q Benign variant; no effect on PYCARD/ASC inflammasome formation. 4 PublicationsCorresponds to variant dbSNP:rs224222EnsemblClinVar. | 1 | |
Natural variantiVAR_016826 | 230 | E → K in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895080EnsemblClinVar. | 1 | |
Natural variantiVAR_084466 | 242 | S → R in PAAND; results in constitutive inflammasome activation; increased PYCARD/ASC specks formation; increased caspase-1 activation and IL1B production; loss of S-242 phosphorylation; loss of interaction with 14-3-3 proteins. 1 PublicationCorresponds to variant dbSNP:rs104895127EnsemblClinVar. | 1 | |
Natural variantiVAR_084467 | 244 | E → K in PAAND; results in constitutive inflammasome activation; increased PYCARD/ASC specks formation; increased caspase-1 activation and IL1B and IL18 production; decreased interaction with 14-3-3 proteins; no effect on interaction with PSTPIP1. 1 Publication | 1 | |
Natural variantiVAR_072383 | 247 | I → V in arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1472692347EnsemblClinVar. | 1 | |
Natural variantiVAR_009054 | 267 | T → I in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895081EnsemblClinVar. | 1 | |
Natural variantiVAR_072384 | 283 | P → L in arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs104895119EnsemblClinVar. | 1 | |
Natural variantiVAR_072385 | 304 | G → R in arFMF; unknown pathological significance; no effect on PYCARD/ASC inflammasome formation. 2 PublicationsCorresponds to variant dbSNP:rs75977701EnsemblClinVar. | 1 | |
Natural variantiVAR_028331 | 319 | E → K in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895110EnsemblClinVar. | 1 | |
Natural variantiVAR_009055 | 369 | P → S in arFMF; unknown pathological significance; associated with Q-148 and Q-408 in cis. 2 PublicationsCorresponds to variant dbSNP:rs11466023EnsemblClinVar. | 1 | |
Natural variantiVAR_009056 | 408 | R → Q in arFMF; associated with Q-148 and S-369 in cis. 2 PublicationsCorresponds to variant dbSNP:rs11466024EnsemblClinVar. | 1 | |
Natural variantiVAR_024376 | 440 | Q → E. Corresponds to variant dbSNP:rs11466026EnsemblClinVar. | 1 | |
Natural variantiVAR_028332 | 474 | E → K in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895104EnsemblClinVar. | 1 | |
Natural variantiVAR_028333 | 478 | H → Y in adFMF; severe. 1 PublicationCorresponds to variant dbSNP:rs104895105EnsemblClinVar. | 1 | |
Natural variantiVAR_009057 | 479 | F → L in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895083EnsemblClinVar. | 1 | |
Natural variantiVAR_070795 | 577 | T → A Probable disease-associated variant found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. 1 Publication | 1 | |
Natural variantiVAR_070796 | 577 | T → N Probable disease-associated variant found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. 1 PublicationCorresponds to variant dbSNP:rs1057516210EnsemblClinVar. | 1 | |
Natural variantiVAR_070797 | 577 | T → S Probable disease-associated variant found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever. 1 PublicationCorresponds to variant dbSNP:rs104895193EnsemblClinVar. | 1 | |
Natural variantiVAR_028334 | 585 | F → L. Corresponds to variant dbSNP:rs11466043Ensembl. | 1 | |
Natural variantiVAR_016827 | 591 | I → T in arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs11466045EnsemblClinVar. | 1 | |
Natural variantiVAR_072386 | 632 | G → A in arFMF; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs967990798EnsemblClinVar. | 1 | |
Natural variantiVAR_028335 | 632 | G → S in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895128EnsemblClinVar. | 1 | |
Natural variantiVAR_028336 | 640 | I → M in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895115EnsemblClinVar. | 1 | |
Natural variantiVAR_028337 | 641 | I → F in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895147EnsemblClinVar. | 1 | |
Natural variantiVAR_028338 | 646 | P → L in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895107EnsemblClinVar. | 1 | |
Natural variantiVAR_028339 | 649 | L → P in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895108EnsemblClinVar. | 1 | |
Natural variantiVAR_016828 | 653 | R → H in arFMF. 3 PublicationsCorresponds to variant dbSNP:rs104895085EnsemblClinVar. | 1 | |
Natural variantiVAR_028340 | 656 | E → A in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895086EnsemblClinVar. | 1 | |
Natural variantiVAR_028341 | 661 | D → N in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895120EnsemblClinVar. | 1 | |
Natural variantiVAR_016829 | 675 | S → N in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895087EnsemblClinVar. | 1 | |
Natural variantiVAR_028342 | 678 | G → E in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895088EnsemblClinVar. | 1 | |
Natural variantiVAR_028343 | 680 | M → 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); no effect on PYCARD/ASC inflammasome formation; no effect on interaction with 14-3-3 proteins. 12 PublicationsCorresponds to variant dbSNP:rs28940580EnsemblClinVar. | 1 | |
Natural variantiVAR_016830 | 680 | M → L in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895089EnsemblClinVar. | 1 | |
Natural variantiVAR_009059 | 681 | T → I in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895090EnsemblClinVar. | 1 | |
Natural variantiVAR_028344 | 688 | Y → C in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895122EnsemblClinVar. | 1 | |
Natural variantiVAR_009060 | 692 | Missing in arFMF. Corresponds to variant dbSNP:rs104895093Ensembl. | 1 | |
Natural variantiVAR_009061 | 694 | M → I in arFMF and adFMF; associated with Q-148 in some patients; no effect on PYCARD/ASC inflammasome formation; no effect on interaction with 14-3-3 proteins. 9 PublicationsCorresponds to variant dbSNP:rs28940578EnsemblClinVar. | 1 | |
Natural variantiVAR_070798 | 694 | M → K in arFMF. 1 PublicationCorresponds to variant dbSNP:rs1596350022EnsemblClinVar. | 1 | |
Natural variantiVAR_028345 | 694 | M → L in arFMF. 1 PublicationCorresponds to variant dbSNP:rs61752717EnsemblClinVar. | 1 | |
Natural variantiVAR_009062 | 694 | M → 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_009063 | 694 | Missing in arFMF and adFMF. 2 Publications | 1 | |
Natural variantiVAR_028346 | 695 | K → M in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895094EnsemblClinVar. | 1 | |
Natural variantiVAR_009064 | 695 | K → R in arFMF; reduced penetrance among Ashkenazi Jews. 4 PublicationsCorresponds to variant dbSNP:rs104895094EnsemblClinVar. | 1 | |
Natural variantiVAR_028347 | 702 | S → C in one patient with familial Mediterranean fever. 1 PublicationCorresponds to variant dbSNP:rs104895166EnsemblClinVar. | 1 | |
Natural variantiVAR_028348 | 704 | V → I in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895096EnsemblClinVar. | 1 | |
Natural variantiVAR_028349 | 705 | P → S in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895145EnsemblClinVar. | 1 | |
Natural variantiVAR_028350 | 720 | I → M in arFMF. 2 PublicationsCorresponds to variant dbSNP:rs104895102EnsemblClinVar. | 1 | |
Natural variantiVAR_009065 | 726 | V → 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; no effect on interaction with 14-3-3 proteins. 10 PublicationsCorresponds to variant dbSNP:rs28940579EnsemblClinVar. | 1 | |
Natural variantiVAR_028351 | 743 | F → L in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895152EnsemblClinVar. | 1 | |
Natural variantiVAR_009066 | 744 | A → S in arFMF; uncertain pathological significance. 4 PublicationsCorresponds to variant dbSNP:rs61732874EnsemblClinVar. | 1 | |
Natural variantiVAR_028352 | 758 | P → S in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895114EnsemblClinVar. | 1 | |
Natural variantiVAR_009067 | 761 | R → H in arFMF. 5 PublicationsCorresponds to variant dbSNP:rs104895097EnsemblClinVar. | 1 | |
Natural variantiVAR_028353 | 780 | P → T in arFMF. 1 PublicationCorresponds to variant dbSNP:rs104895154EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_008223 | 93 – 303 | Missing in isoform 2 and isoform 3. CuratedAdd BLAST | 211 | |
Alternative sequenceiVSP_047663 | 587 – 781 | VPELI…GQGPD → DHSPQHGLGSWEERDYTQHS MQGPKQGVPCLSLLSGQCNL APLNANAQDFFPYLIFLRSS GADWRSGTCC in isoform 3. CuratedAdd BLAST | 195 |
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 |
CCDSi | CCDS10498.1 [O15553-2] CCDS55981.1 [O15553-3] |
RefSeqi | NP_000234.1, NM_000243.2 [O15553-2] NP_001185465.1, NM_001198536.1 [O15553-3] |
Genome annotation databases
Ensembli | ENST00000219596.6; ENSP00000219596.1; ENSG00000103313.13 ENST00000536379.5; ENSP00000445079.1; ENSG00000103313.13 [O15553-1] ENST00000541159.5; ENSP00000438711.1; ENSG00000103313.13 [O15553-3] |
GeneIDi | 4210 |
KEGGi | hsa:4210 |
MANE-Selecti | ENST00000219596.6; ENSP00000219596.1; NM_000243.3; NP_000234.1 |
UCSCi | uc002cun.1, human [O15553-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS10498.1 [O15553-2] CCDS55981.1 [O15553-3] |
RefSeqi | NP_000234.1, NM_000243.2 [O15553-2] NP_001185465.1, NM_001198536.1 [O15553-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2MPC | NMR | - | A | 1-92 | [»] | |
2WL1 | X-ray | 1.35 | A | 586-776 | [»] | |
4CG4 | X-ray | 2.40 | A/B/C/D/E/F | 414-781 | [»] | |
AlphaFoldDBi | O15553 | |||||
SMRi | O15553 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110374, 18 interactors |
ComplexPortali | CPX-4143, Pyrin inflammasome |
DIPi | DIP-41878N |
IntActi | O15553, 6 interactors |
MINTi | O15553 |
STRINGi | 9606.ENSP00000219596 |
PTM databases
GlyGeni | O15553, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O15553 |
PhosphoSitePlusi | O15553 |
Genetic variation databases
BioMutai | MEFV |
Proteomic databases
EPDi | O15553 |
MassIVEi | O15553 |
PaxDbi | O15553 |
PeptideAtlasi | O15553 |
PRIDEi | O15553 |
ProteomicsDBi | 25411 48755 [O15553-2] 48756 [O15553-1] |
Protocols and materials databases
Antibodypediai | 10781, 223 antibodies from 32 providers |
DNASUi | 4210 |
Genome annotation databases
Ensembli | ENST00000219596.6; ENSP00000219596.1; ENSG00000103313.13 ENST00000536379.5; ENSP00000445079.1; ENSG00000103313.13 [O15553-1] ENST00000541159.5; ENSP00000438711.1; ENSG00000103313.13 [O15553-3] |
GeneIDi | 4210 |
KEGGi | hsa:4210 |
MANE-Selecti | ENST00000219596.6; ENSP00000219596.1; NM_000243.3; NP_000234.1 |
UCSCi | uc002cun.1, human [O15553-2] |
Organism-specific databases
CTDi | 4210 |
DisGeNETi | 4210 |
GeneCardsi | MEFV |
GeneReviewsi | MEFV |
HGNCi | HGNC:6998, MEFV |
HPAi | ENSG00000103313, Tissue enhanced (bone marrow, lymphoid tissue) |
MalaCardsi | MEFV |
MIMi | 134610, phenotype 249100, phenotype 608068, phenotype 608107, gene |
neXtProti | NX_O15553 |
OpenTargetsi | ENSG00000103313 |
Orphaneti | 117, Behcet disease 342, Familial Mediterranean fever 329967, Intermittent hydrarthrosis 3243, Sweet syndrome |
PharmGKBi | PA30736 |
VEuPathDBi | HostDB:ENSG00000103313 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2177, Eukaryota |
GeneTreei | ENSGT00940000161955 |
HOGENOMi | CLU_685051_0_0_1 |
InParanoidi | O15553 |
OMAi | CQRHMKQ |
OrthoDBi | 651627at2759 |
PhylomeDBi | O15553 |
TreeFami | TF351091 |
Enzyme and pathway databases
PathwayCommonsi | O15553 |
Reactomei | R-HSA-844456, The NLRP3 inflammasome R-HSA-9660826, Purinergic signaling in leishmaniasis infection |
SignaLinki | O15553 |
SIGNORi | O15553 |
Miscellaneous databases
BioGRID-ORCSi | 4210, 14 hits in 1069 CRISPR screens |
ChiTaRSi | MEFV, human |
EvolutionaryTracei | O15553 |
GeneWikii | MEFV |
GenomeRNAii | 4210 |
Pharosi | O15553, Tbio |
PROi | PR:O15553 |
RNActi | O15553, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000103313, Expressed in blood and 110 other tissues |
ExpressionAtlasi | O15553, baseline and differential |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 2.60.120.920, 1 hit |
InterProi | View protein in InterPro IPR001870, B30.2/SPRY IPR043136, B30.2/SPRY_sf 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 |
PANTHERi | PTHR24103:SF606, PTHR24103:SF606, 2 hits |
Pfami | View protein in Pfam PF13765, PRY, 1 hit PF02758, PYRIN, 1 hit PF00622, SPRY, 1 hit PF00643, zf-B_box, 1 hit |
PRINTSi | PR01407, BUTYPHLNCDUF |
SMARTi | View protein in SMART SM00336, BBOX, 1 hit SM00589, PRY, 1 hit SM01289, PYRIN, 1 hit SM00449, SPRY, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF49899, SSF49899, 1 hit |
PROSITEi | View protein in PROSITE PS50188, B302_SPRY, 1 hit PS50824, DAPIN, 1 hit PS50119, ZF_BBOX, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MEFV_HUMAN | |
Accessioni | O15553Primary (citable) accession number: O15553 Secondary accession number(s): D3DUC0 Q96PN5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | January 1, 1998 | |
Last modified: | May 25, 2022 | |
This is version 210 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references