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Protein

NLR family CARD domain-containing protein 4

Gene

NLRC4

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

Functioni

Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi169 – 176ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • ATP binding Source: HGNC
  • cysteine-type endopeptidase inhibitor activity Source: GO_Central
  • magnesium ion binding Source: HGNC
  • protein homodimerization activity Source: HGNC
  • ubiquitin-protein transferase activity Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000091106-MONOMER.
ReactomeiR-HSA-6803207. TP53 Regulates Transcription of Caspase Activators and Caspases.
R-HSA-844623. The IPAF inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
NLR family CARD domain-containing protein 4
Alternative name(s):
CARD, LRR, and NACHT-containing protein
Short name:
Clan protein
Caspase recruitment domain-containing protein 12
Ice protease-activating factor
Short name:
Ipaf
Gene namesi
Name:NLRC4
Synonyms:CARD12, CLAN, CLAN1, IPAF
ORF Names:UNQ6189/PRO20215
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:16412. NLRC4.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • intracellular Source: HGNC
  • IPAF inflammasome complex Source: UniProtKB
  • nucleus Source: GO_Central
  • spindle microtubule Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Autoinflammation with infantile enterocolitis (AIFEC)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by neonatal-onset enterocolitis, periodic fever, and fatal or near-fatal episodes of autoinflammation. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy, recurrent febrile episodes with splenomegaly, and sometimes hematologic disturbances, arthralgias, or myalgias.
See also OMIM:616050
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072484337T → S in AIFEC; results in a gain of function mutation with constitutive activation of caspase-1. 1 PublicationCorresponds to variant rs587777840dbSNPEnsembl.1
Natural variantiVAR_072485341V → A in AIFEC; results in a gain of function mutation with constitutive activation of caspase-1. 1 PublicationCorresponds to variant rs587781260dbSNPEnsembl.1
Familial cold autoinflammatory syndrome 4 (FCAS4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of autoinflammatory syndrome, a rare autosomal dominant systemic disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold.
See also OMIM:616115
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072645443H → P in FCAS4; the mutation increases oligomerization of the NLRC4 protein; results in hyperactivation of caspase-1 with an increase in IL1B protein secretion. 1 PublicationCorresponds to variant rs606231460dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi58484.
MalaCardsiNLRC4.
MIMi616050. phenotype.
616115. phenotype.
OpenTargetsiENSG00000091106.
PharmGKBiPA162397671.

Polymorphism and mutation databases

BioMutaiNLRC4.
DMDMi20138032.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001440871 – 1024NLR family CARD domain-containing protein 4Add BLAST1024

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei533PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Ser-533 following infection of macrophages with S.typhimurium (Salmonella). Phosphorylation is essential for NLRC4 inflammasome function to promote caspase-1 activation and pyroptosis. PRKCD phosphorylates Ser-533 in vitro (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9NPP4.
PeptideAtlasiQ9NPP4.
PRIDEiQ9NPP4.

PTM databases

iPTMnetiQ9NPP4.
PhosphoSitePlusiQ9NPP4.

Expressioni

Tissue specificityi

Isoform 2 is expressed ubiquitously, although highly expressed in lung and spleen. Isoform 1 is highly expressed in lung, followed by leukocytes especially monocytes, lymph node, colon, brain, prostate, placenta, spleen, bone marrow and fetal liver. Isoform 4 is only detected in brain.

Gene expression databases

BgeeiENSG00000091106.
CleanExiHS_NLRC4.
GenevisibleiQ9NPP4. HS.

Organism-specific databases

HPAiHPA006592.

Interactioni

Subunit structurei

Component of the NLRC4 inflammasome (By similarity). Homooligomer. Interacts with ASC, pro-caspase-1, NOD2, BCL10 and NALP1 (NAC) by CARD-CARD interaction. Interacts with EIF2AK2/PKR.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-1222527,EBI-1222527
CASP1P294664EBI-1222527,EBI-516667

GO - Molecular functioni

  • protein homodimerization activity Source: HGNC

Protein-protein interaction databases

BioGridi121814. 13 interactors.
DIPiDIP-38428N.
IntActiQ9NPP4. 4 interactors.
MINTiMINT-201147.
STRINGi9606.ENSP00000354159.

Structurei

3D structure databases

ProteinModelPortaliQ9NPP4.
SMRiQ9NPP4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 88CARDPROSITE-ProRule annotationAdd BLAST88
Domaini163 – 476NACHTPROSITE-ProRule annotationAdd BLAST314
Repeati578 – 598LRR 1Add BLAST21
Repeati656 – 679LRR 2Add BLAST24
Repeati735 – 758LRR 3Add BLAST24
Repeati762 – 785LRR 4Add BLAST24
Repeati787 – 812LRR 5Add BLAST26
Repeati824 – 847LRR 6Add BLAST24
Repeati848 – 870LRR 7Add BLAST23
Repeati878 – 902LRR 8Add BLAST25
Repeati911 – 933LRR 9Add BLAST23
Repeati936 – 963LRR 10Add BLAST28
Repeati965 – 985LRR 11Add BLAST21
Repeati999 – 1021LRR 12Add BLAST23

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni95 – 298Nucleotide-binding domain (NBD)By similarityAdd BLAST204
Regioni356 – 463Winged-helix domain (WHD)By similarityAdd BLAST108

Domaini

In an autoinhibited form the C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. An ADP-mediated interaction between the NBD and the WHD also contributes to the autoinhibition (By similarity).By similarity

Sequence similaritiesi

Contains 1 CARD domain.PROSITE-ProRule annotation
Contains 12 LRR (leucine-rich) repeats.Curated
Contains 1 NACHT domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IHIG. Eukaryota.
ENOG410YI2E. LUCA.
GeneTreeiENSGT00500000044782.
HOGENOMiHOG000059630.
HOVERGENiHBG050790.
InParanoidiQ9NPP4.
KOiK12805.
OMAiDLFVWNV.
OrthoDBiEOG091G0A33.
PhylomeDBiQ9NPP4.
TreeFamiTF336864.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NPP4-1) [UniParc]FASTAAdd to basket
Also known as: CLANA

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
MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA
60 70 80 90 100
ARGIIHMILK KGSESCNLFL KSLKEWNYPL FQDLNGQSLF HQTSEGDLDD
110 120 130 140 150
LAQDLKDLYH TPSFLNFYPL GEDIDIIFNL KSTFTEPVLW RKDQHHHRVE
160 170 180 190 200
QLTLNGLLQA LQSPCIIEGE SGKGKSTLLQ RIAMLWGSGK CKALTKFKFV
210 220 230 240 250
FFLRLSRAQG GLFETLCDQL LDIPGTIRKQ TFMAMLLKLR QRVLFLLDGY
260 270 280 290 300
NEFKPQNCPE IEALIKENHR FKNMVIVTTT TECLRHIRQF GALTAEVGDM
310 320 330 340 350
TEDSAQALIR EVLIKELAEG LLLQIQKSRC LRNLMKTPLF VVITCAIQMG
360 370 380 390 400
ESEFHSHTQT TLFHTFYDLL IQKNKHKHKG VAASDFIRSL DHCGDLALEG
410 420 430 440 450
VFSHKFDFEL QDVSSVNEDV LLTTGLLCKY TAQRFKPKYK FFHKSFQEYT
460 470 480 490 500
AGRRLSSLLT SHEPEEVTKG NGYLQKMVSI SDITSTYSSL LRYTCGSSVE
510 520 530 540 550
ATRAVMKHLA AVYQHGCLLG LSIAKRPLWR QESLQSVKNT TEQEILKAIN
560 570 580 590 600
INSFVECGIH LYQESTSKSA LSQEFEAFFQ GKSLYINSGN IPDYLFDFFE
610 620 630 640 650
HLPNCASALD FIKLDFYGGA MASWEKAAED TGGIHMEEAP ETYIPSRAVS
660 670 680 690 700
LFFNWKQEFR TLEVTLRDFS KLNKQDIRYL GKIFSSATSL RLQIKRCAGV
710 720 730 740 750
AGSLSLVLST CKNIYSLMVE ASPLTIEDER HITSVTNLKT LSIHDLQNQR
760 770 780 790 800
LPGGLTDSLG NLKNLTKLIM DNIKMNEEDA IKLAEGLKNL KKMCLFHLTH
810 820 830 840 850
LSDIGEGMDY IVKSLSSEPC DLEEIQLVSC CLSANAVKIL AQNLHNLVKL
860 870 880 890 900
SILDLSENYL EKDGNEALHE LIDRMNVLEQ LTALMLPWGC DVQGSLSSLL
910 920 930 940 950
KHLEEVPQLV KLGLKNWRLT DTEIRILGAF FGKNPLKNFQ QLNLAGNRVS
960 970 980 990 1000
SDGWLAFMGV FENLKQLVFF DFSTKEFLPD PALVRKLSQV LSKLTFLQEA
1010 1020
RLVGWQFDDD DLSVITGAFK LVTA
Length:1,024
Mass (Da):116,159
Last modified:January 31, 2002 - v2
Checksum:i49378DBB54938E0F
GO
Isoform 2 (identifier: Q9NPP4-2) [UniParc]FASTAAdd to basket
Also known as: CLANB

The sequence of this isoform differs from the canonical sequence as follows:
     89-753: Missing.

Show »
Length:359
Mass (Da):40,623
Checksum:i764417DD658B1DFD
GO
Isoform 3 (identifier: Q9NPP4-3) [UniParc]FASTAAdd to basket
Also known as: CLANC

The sequence of this isoform differs from the canonical sequence as follows:
     155-156: NG → VL
     157-1024: Missing.

Show »
Length:156
Mass (Da):18,295
Checksum:i933CB2315528D67A
GO
Isoform 4 (identifier: Q9NPP4-4) [UniParc]FASTAAdd to basket
Also known as: CLAND

The sequence of this isoform differs from the canonical sequence as follows:
     90-92: FHQ → LTA
     93-1024: Missing.

Show »
Length:92
Mass (Da):10,646
Checksum:iBD090CD064330D1D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39N → D in BAF85362 (PubMed:14702039).Curated1
Sequence conflicti138V → I in AAK14776 (PubMed:11472070).Curated1
Sequence conflicti393C → R in AAK14776 (PubMed:11472070).Curated1
Sequence conflicti420V → A in AAK53443 (Ref. 4) Curated1
Sequence conflicti678R → T in AAK38730 (PubMed:11374873).Curated1
Sequence conflicti791K → E in BAG53062 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072484337T → S in AIFEC; results in a gain of function mutation with constitutive activation of caspase-1. 1 PublicationCorresponds to variant rs587777840dbSNPEnsembl.1
Natural variantiVAR_072485341V → A in AIFEC; results in a gain of function mutation with constitutive activation of caspase-1. 1 PublicationCorresponds to variant rs587781260dbSNPEnsembl.1
Natural variantiVAR_072645443H → P in FCAS4; the mutation increases oligomerization of the NLRC4 protein; results in hyperactivation of caspase-1 with an increase in IL1B protein secretion. 1 PublicationCorresponds to variant rs606231460dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00078489 – 753Missing in isoform 2. 1 PublicationAdd BLAST665
Alternative sequenceiVSP_00078790 – 92FHQ → LTA in isoform 4. 1 Publication3
Alternative sequenceiVSP_00078893 – 1024Missing in isoform 4. 1 PublicationAdd BLAST932
Alternative sequenceiVSP_000785155 – 156NG → VL in isoform 3. 1 Publication2
Alternative sequenceiVSP_000786157 – 1024Missing in isoform 3. 1 PublicationAdd BLAST868

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY032589 mRNA. Translation: AAK38730.1.
AY027787 mRNA. Translation: AAK14776.1.
AY027788 mRNA. Translation: AAK14777.1.
AY027789 mRNA. Translation: AAK14778.1.
AY027790 mRNA. Translation: AAK14779.1.
AY035391 mRNA. Translation: AAK59843.1.
AF376061 mRNA. Translation: AAK53443.1.
AY358152 mRNA. Translation: AAQ88519.1.
AK095467 mRNA. Translation: BAG53062.1.
AK292673 mRNA. Translation: BAF85362.1.
AK314762 mRNA. Translation: BAG37300.1.
AL121653 Genomic DNA. No translation available.
CH471053 Genomic DNA. Translation: EAX00452.1.
CH471053 Genomic DNA. Translation: EAX00453.1.
CH471053 Genomic DNA. Translation: EAX00454.1.
CH471053 Genomic DNA. Translation: EAX00455.1.
BC031555 mRNA. Translation: AAH31555.1.
AL389934 mRNA. Translation: CAB97523.1.
CCDSiCCDS33174.1. [Q9NPP4-1]
CCDS77400.1. [Q9NPP4-2]
RefSeqiNP_001186067.1. NM_001199138.1. [Q9NPP4-1]
NP_001186068.1. NM_001199139.1. [Q9NPP4-1]
NP_001289433.1. NM_001302504.1. [Q9NPP4-2]
NP_067032.3. NM_021209.4. [Q9NPP4-1]
UniGeneiHs.574741.

Genome annotation databases

EnsembliENST00000342905; ENSP00000339666; ENSG00000091106. [Q9NPP4-2]
ENST00000360906; ENSP00000354159; ENSG00000091106. [Q9NPP4-1]
ENST00000402280; ENSP00000385428; ENSG00000091106. [Q9NPP4-1]
ENST00000404025; ENSP00000385090; ENSG00000091106. [Q9NPP4-1]
GeneIDi58484.
KEGGihsa:58484.
UCSCiuc002roi.4. human. [Q9NPP4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY032589 mRNA. Translation: AAK38730.1.
AY027787 mRNA. Translation: AAK14776.1.
AY027788 mRNA. Translation: AAK14777.1.
AY027789 mRNA. Translation: AAK14778.1.
AY027790 mRNA. Translation: AAK14779.1.
AY035391 mRNA. Translation: AAK59843.1.
AF376061 mRNA. Translation: AAK53443.1.
AY358152 mRNA. Translation: AAQ88519.1.
AK095467 mRNA. Translation: BAG53062.1.
AK292673 mRNA. Translation: BAF85362.1.
AK314762 mRNA. Translation: BAG37300.1.
AL121653 Genomic DNA. No translation available.
CH471053 Genomic DNA. Translation: EAX00452.1.
CH471053 Genomic DNA. Translation: EAX00453.1.
CH471053 Genomic DNA. Translation: EAX00454.1.
CH471053 Genomic DNA. Translation: EAX00455.1.
BC031555 mRNA. Translation: AAH31555.1.
AL389934 mRNA. Translation: CAB97523.1.
CCDSiCCDS33174.1. [Q9NPP4-1]
CCDS77400.1. [Q9NPP4-2]
RefSeqiNP_001186067.1. NM_001199138.1. [Q9NPP4-1]
NP_001186068.1. NM_001199139.1. [Q9NPP4-1]
NP_001289433.1. NM_001302504.1. [Q9NPP4-2]
NP_067032.3. NM_021209.4. [Q9NPP4-1]
UniGeneiHs.574741.

3D structure databases

ProteinModelPortaliQ9NPP4.
SMRiQ9NPP4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121814. 13 interactors.
DIPiDIP-38428N.
IntActiQ9NPP4. 4 interactors.
MINTiMINT-201147.
STRINGi9606.ENSP00000354159.

PTM databases

iPTMnetiQ9NPP4.
PhosphoSitePlusiQ9NPP4.

Polymorphism and mutation databases

BioMutaiNLRC4.
DMDMi20138032.

Proteomic databases

PaxDbiQ9NPP4.
PeptideAtlasiQ9NPP4.
PRIDEiQ9NPP4.

Protocols and materials databases

DNASUi58484.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342905; ENSP00000339666; ENSG00000091106. [Q9NPP4-2]
ENST00000360906; ENSP00000354159; ENSG00000091106. [Q9NPP4-1]
ENST00000402280; ENSP00000385428; ENSG00000091106. [Q9NPP4-1]
ENST00000404025; ENSP00000385090; ENSG00000091106. [Q9NPP4-1]
GeneIDi58484.
KEGGihsa:58484.
UCSCiuc002roi.4. human. [Q9NPP4-1]

Organism-specific databases

CTDi58484.
DisGeNETi58484.
GeneCardsiNLRC4.
HGNCiHGNC:16412. NLRC4.
HPAiHPA006592.
MalaCardsiNLRC4.
MIMi606831. gene.
616050. phenotype.
616115. phenotype.
neXtProtiNX_Q9NPP4.
OpenTargetsiENSG00000091106.
PharmGKBiPA162397671.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHIG. Eukaryota.
ENOG410YI2E. LUCA.
GeneTreeiENSGT00500000044782.
HOGENOMiHOG000059630.
HOVERGENiHBG050790.
InParanoidiQ9NPP4.
KOiK12805.
OMAiDLFVWNV.
OrthoDBiEOG091G0A33.
PhylomeDBiQ9NPP4.
TreeFamiTF336864.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000091106-MONOMER.
ReactomeiR-HSA-6803207. TP53 Regulates Transcription of Caspase Activators and Caspases.
R-HSA-844623. The IPAF inflammasome.

Miscellaneous databases

GeneWikiiNLRC4.
GenomeRNAii58484.
PROiQ9NPP4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000091106.
CleanExiHS_NLRC4.
GenevisibleiQ9NPP4. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNLRC4_HUMAN
AccessioniPrimary (citable) accession number: Q9NPP4
Secondary accession number(s): A8K9F8
, B2RBQ3, B3KTF0, D6W580, Q96J81, Q96J82, Q96J83
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 31, 2002
Last modified: November 30, 2016
This is version 151 of the entry and version 2 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. 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.