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Protein

Ubiquitin carboxyl-terminal hydrolase CYLD

Gene

Cyld

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Deubiquitinase that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Has endodeubiquitinase activity. Plays an important role in the regulation of pathways leading to NF-kappa-B activation. Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation. Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules. Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis. Required for normal cell cycle progress and normal cytokinesis. Inhibits nuclear translocation of NF-kappa-B (By similarity). Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation. Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells. Negatively regulates TNFRSF11A signaling and osteoclastogenesis. Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (PubMed:25134987). Also able to remove linear ('Met-1'-linked) polyubiquitin chains to regulate innate immunity: recruited to the LUBAC complex and, together with OTULIN, restricts linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (By similarity).By similarity8 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei597NucleophilePROSITE-ProRule annotation1
Metal bindingi784Zinc 1By similarity1
Metal bindingi787Zinc 1By similarity1
Metal bindingi795Zinc 2By similarity1
Metal bindingi798Zinc 2By similarity1
Metal bindingi813Zinc 1By similarity1
Metal bindingi816Zinc 1By similarity1
Metal bindingi821Zinc 2By similarity1
Metal bindingi829Zinc 2By similarity1
Active sitei867Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment Source: MGI
  • homeostasis of number of cells Source: MGI
  • innate immune response Source: UniProtKB
  • necroptotic process Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of NF-kappaB import into nucleus Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of T cell differentiation Source: MGI
  • positive regulation of cellular protein localization Source: MGI
  • positive regulation of extrinsic apoptotic signaling pathway Source: MGI
  • positive regulation of T cell differentiation Source: MGI
  • positive regulation of T cell receptor signaling pathway Source: MGI
  • protein deubiquitination Source: MGI
  • protein K63-linked deubiquitination Source: UniProtKB
  • protein linear deubiquitination Source: UniProtKB
  • regulation of B cell differentiation Source: MGI
  • regulation of cilium assembly Source: UniProtKB
  • regulation of intrinsic apoptotic signaling pathway Source: MGI
  • regulation of microtubule cytoskeleton organization Source: MGI
  • regulation of mitotic cell cycle Source: MGI
  • regulation of protein binding Source: MGI
  • regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
  • ripoptosome assembly involved in necroptotic process Source: MGI
  • ubiquitin-dependent protein catabolic process Source: InterPro
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Immunity, Innate immunity, Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.19.12. 3474.
ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
R-MMU-5357786. TNFR1-induced proapoptotic signaling.
R-MMU-5357905. Regulation of TNFR1 signaling.
R-MMU-5357956. TNFR1-induced NFkappaB signaling pathway.
R-MMU-5689880. Ub-specific processing proteases.
R-MMU-936440. Negative regulators of RIG-I/MDA5 signaling.

Protein family/group databases

MEROPSiC67.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase CYLD (EC:3.4.19.12By similarity)
Alternative name(s):
Deubiquitinating enzyme CYLD
Ubiquitin thioesterase CYLD
Ubiquitin-specific-processing protease CYLD
Gene namesi
Name:Cyld
Synonyms:Cyld1, Kiaa0849
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1921506. Cyld.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • ciliary basal body Source: UniProtKB
  • ciliary tip Source: UniProtKB
  • cytosol Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: MGI
  • microtubule Source: UniProtKB-KW
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • spindle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Microtubule

Pathology & Biotechi

Disruption phenotypei

No obvious phenotype, but mice are highly susceptible to carcinogens and are prone to chemically induced skin tumors. The number of natural killer T-cells is much reduced. Animals are highly susceptible to bacteria-induced pneumonia, due to an over active innate immune response. Animals spontaneously develop colonic inflammation, due to constitutive expression of several proinflammatory genes in the colon. Animals exhibit abnormal osteoclast differentiation, leading to osteoporosis.5 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806991 – 952Ubiquitin carboxyl-terminal hydrolase CYLDAdd BLAST952

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei383PhosphoserineBy similarity1
Modified residuei414PhosphoserineCombined sources1
Modified residuei418PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on several serine residues by IKKA and/or IKKB in response to immune stimuli. Phosphorylation requires IKBKG. Phosphorylation abolishes TRAF2 deubiquitination, interferes with the activation of Jun kinases, and strongly reduces CD40-dependent gene activation by NF-kappa-B (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ80TQ2.
PaxDbiQ80TQ2.
PeptideAtlasiQ80TQ2.
PRIDEiQ80TQ2.

PTM databases

iPTMnetiQ80TQ2.
PhosphoSitePlusiQ80TQ2.
SwissPalmiQ80TQ2.

Expressioni

Inductioni

Up-regulated by TNFRSF11A.1 Publication

Gene expression databases

BgeeiENSMUSG00000036712.
CleanExiMM_CYLD.
ExpressionAtlasiQ80TQ2. baseline and differential.
GenevisibleiQ80TQ2. MM.

Interactioni

Subunit structurei

Interacts (via CAP-Gly domain) with IKBKG/NEMO (via proline-rich C-terminal region). Interacts with TRAF2 and TRIP. Interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE and DDX58 (By similarity). Interacts (via CAP-Gly domain) with microtubules. Interacts with HDAC6 and BCL3. Interacts with SQSTM1 and MAP3K7. Identified in a complex with TRAF6 and SQSTM1. Interacts with CEP350 (By similarity). Interacts with RNF31 (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Bcl3Q9Z2F65EBI-943859,EBI-943884
Hdac6Q9Z2V53EBI-943859,EBI-1009256
ItchQ8C8632EBI-943859,EBI-851782
Tuba1aP683695EBI-943859,EBI-400542

GO - Molecular functioni

Protein-protein interaction databases

BioGridi216612. 15 interactors.
DIPiDIP-35656N.
IntActiQ80TQ2. 4 interactors.
MINTiMINT-7561827.
STRINGi10090.ENSMUSP00000096119.

Structurei

3D structure databases

ProteinModelPortaliQ80TQ2.
SMRiQ80TQ2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini153 – 198CAP-Gly 1PROSITE-ProRule annotationAdd BLAST46
Domaini253 – 286CAP-Gly 2PROSITE-ProRule annotationAdd BLAST34
Domaini488 – 531CAP-Gly 3PROSITE-ProRule annotationAdd BLAST44
Domaini588 – 946USPAdd BLAST359

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni106 – 589Interaction with TRIPBy similarityAdd BLAST484
Regioni390 – 465Interaction with TRAF2By similarityAdd BLAST76
Regioni466 – 680Interaction with IKBKG/NEMOBy similarityAdd BLAST215

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 3 CAP-Gly domains.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3556. Eukaryota.
ENOG410XP6I. LUCA.
GeneTreeiENSGT00390000018123.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ80TQ2.
KOiK08601.
OrthoDBiEOG091G015D.
PhylomeDBiQ80TQ2.

Family and domain databases

Gene3Di2.30.30.190. 3 hits.
InterProiIPR000938. CAP-Gly_domain.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF01302. CAP_GLY. 2 hits.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM01052. CAP_GLY. 3 hits.
[Graphical view]
SUPFAMiSSF74924. SSF74924. 3 hits.
PROSITEiPS00845. CAP_GLY_1. 1 hit.
PS50245. CAP_GLY_2. 2 hits.
PS00972. USP_1. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 2 (identifier: Q80TQ2-1) [UniParc]FASTAAdd to basket

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
MSSGLWSQEK VTSPYWEERI FYLLLQECSV TDKQTQKLLK VPKGSIGQYI
60 70 80 90 100
QDRSVGHSRV PSTKGKKNQI GLKILEQPHA VLFVDEKDVV EINEKFTELL
110 120 130 140 150
LAITNCEERL SLFRNRLRLS KGLQVDVGSP VKVQLRSGEE KFPGVVRFRG
160 170 180 190 200
PLLAERTVSG IFFGVELLEE GRGQGFTDGV YQGKQLFQCD EDCGVFVALD
210 220 230 240 250
KLELIEDDDN GLESDFAGPG DTMQVEPPPL EINSRVSLKV GESTESGTVI
260 270 280 290 300
FCDVLPGKES LGYFVGVDMD NPIGNWDGRF DGVQLCSFAS VESTILLHIN
310 320 330 340 350
DIIPDSVTQE RRPPKLAFMS RGVGDKGSSS HNKPKVTGST SDPGSRNRSE
360 370 380 390 400
LFYTLNGSSV DSQQSKSKNP WYIDEVAEDP AKSLTEMSSD FGHSSPPPQP
410 420 430 440 450
PSMNSLSSEN RFHSLPFSLT KMPNTNGSMA HSPLSLSVQS VMGELNSTPV
460 470 480 490 500
QESPPLPISS GNAHGLEVGS LAEVKENPPF YGVIRWIGQP PGLSDVLAGL
510 520 530 540 550
ELEDECAGCT DGTFRGTRYF TCALKKALFV KLKSCRPDSR FASLQPVSNQ
560 570 580 590 600
IERCNSLAFG GYLSEVVEEN TPPKMEKEGL EIMIGKKKGI QGHYNSCYLD
610 620 630 640 650
STLFCLFAFS SALDTVLLRP KEKNDIEYYS ETQELLRTEI VNPLRIYGYV
660 670 680 690 700
CATKIMKLRK ILEKVEAASG FTSEEKDPEE FLNILFHDIL RVEPLLKIRS
710 720 730 740 750
AGQKVQDCNF YQIFMEKNEK VGVPTIQQLL EWSFINSNLK FAEAPSCLII
760 770 780 790 800
QMPRFGKDFK LFKKIFPSLE LNITDLLEDT PRQCRICGGL AMYECRECYD
810 820 830 840 850
DPDISAGKIK QFCKTCSTQV HLHPRRLNHS YHPVSLPKDL PDWDWRHGCI
860 870 880 890 900
PCQKMELFAV LCIETSHYVA FVKYGKDDSA WLFFDSMADR DGGQNGFNIP
910 920 930 940 950
QVTPCPEVGE YLKMSLEDLH SLDSRRIQGC ARRLLCDAYM CMYQSPTMSL

YK
Length:952
Mass (Da):106,586
Last modified:August 16, 2004 - v2
Checksum:i0AC0C7D4FF215A9C
GO
Isoform 1 (identifier: Q80TQ2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     304-304: P → PALS

Show »
Length:955
Mass (Da):106,857
Checksum:iE8D55AE26D90241F
GO
Isoform 3 (identifier: Q80TQ2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     305-318: DSVTQERRPPKLAF → GTSKNILDQQLKGK
     319-952: Missing.

Show »
Length:318
Mass (Da):35,288
Checksum:i23465D36304356BF
GO

Sequence cautioni

The sequence BAC65671 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti403M → V in BAC30222 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011278304P → PALS in isoform 1. 1 Publication1
Alternative sequenceiVSP_011279305 – 318DSVTQ…PKLAF → GTSKNILDQQLKGK in isoform 3. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_011280319 – 952Missing in isoform 3. 1 PublicationAdd BLAST634

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK122389 mRNA. Translation: BAC65671.1. Different initiation.
AK039054 mRNA. Translation: BAC30222.1.
AK042764 mRNA. Translation: BAC31357.1.
BC042438 mRNA. Translation: AAH42438.1.
BC049879 mRNA. Translation: AAH49879.1.
CCDSiCCDS22513.1. [Q80TQ2-1]
CCDS52633.1. [Q80TQ2-2]
RefSeqiNP_001121642.1. NM_001128170.2. [Q80TQ2-2]
NP_001121643.1. NM_001128171.2. [Q80TQ2-1]
NP_775545.1. NM_173369.3. [Q80TQ2-1]
XP_006531477.1. XM_006531414.1. [Q80TQ2-2]
XP_006531478.1. XM_006531415.1. [Q80TQ2-2]
XP_006531479.1. XM_006531416.3. [Q80TQ2-2]
XP_006531480.1. XM_006531417.2. [Q80TQ2-2]
XP_006531481.1. XM_006531418.2. [Q80TQ2-2]
XP_011246825.1. XM_011248523.2. [Q80TQ2-2]
XP_011246826.1. XM_011248524.1. [Q80TQ2-2]
XP_011246827.1. XM_011248525.2. [Q80TQ2-2]
XP_017168478.1. XM_017312989.1. [Q80TQ2-2]
UniGeneiMm.490395.

Genome annotation databases

EnsembliENSMUST00000098519; ENSMUSP00000096119; ENSMUSG00000036712. [Q80TQ2-2]
ENSMUST00000109626; ENSMUSP00000105254; ENSMUSG00000036712. [Q80TQ2-1]
ENSMUST00000209532; ENSMUSP00000147654; ENSMUSG00000036712. [Q80TQ2-2]
ENSMUST00000209559; ENSMUSP00000147426; ENSMUSG00000036712. [Q80TQ2-1]
ENSMUST00000211554; ENSMUSP00000148037; ENSMUSG00000036712. [Q80TQ2-1]
GeneIDi74256.
KEGGimmu:74256.
UCSCiuc009mrt.3. mouse. [Q80TQ2-1]
uc033jgq.1. mouse. [Q80TQ2-3]
uc033jgr.1. mouse. [Q80TQ2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK122389 mRNA. Translation: BAC65671.1. Different initiation.
AK039054 mRNA. Translation: BAC30222.1.
AK042764 mRNA. Translation: BAC31357.1.
BC042438 mRNA. Translation: AAH42438.1.
BC049879 mRNA. Translation: AAH49879.1.
CCDSiCCDS22513.1. [Q80TQ2-1]
CCDS52633.1. [Q80TQ2-2]
RefSeqiNP_001121642.1. NM_001128170.2. [Q80TQ2-2]
NP_001121643.1. NM_001128171.2. [Q80TQ2-1]
NP_775545.1. NM_173369.3. [Q80TQ2-1]
XP_006531477.1. XM_006531414.1. [Q80TQ2-2]
XP_006531478.1. XM_006531415.1. [Q80TQ2-2]
XP_006531479.1. XM_006531416.3. [Q80TQ2-2]
XP_006531480.1. XM_006531417.2. [Q80TQ2-2]
XP_006531481.1. XM_006531418.2. [Q80TQ2-2]
XP_011246825.1. XM_011248523.2. [Q80TQ2-2]
XP_011246826.1. XM_011248524.1. [Q80TQ2-2]
XP_011246827.1. XM_011248525.2. [Q80TQ2-2]
XP_017168478.1. XM_017312989.1. [Q80TQ2-2]
UniGeneiMm.490395.

3D structure databases

ProteinModelPortaliQ80TQ2.
SMRiQ80TQ2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi216612. 15 interactors.
DIPiDIP-35656N.
IntActiQ80TQ2. 4 interactors.
MINTiMINT-7561827.
STRINGi10090.ENSMUSP00000096119.

Protein family/group databases

MEROPSiC67.001.

PTM databases

iPTMnetiQ80TQ2.
PhosphoSitePlusiQ80TQ2.
SwissPalmiQ80TQ2.

Proteomic databases

EPDiQ80TQ2.
PaxDbiQ80TQ2.
PeptideAtlasiQ80TQ2.
PRIDEiQ80TQ2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000098519; ENSMUSP00000096119; ENSMUSG00000036712. [Q80TQ2-2]
ENSMUST00000109626; ENSMUSP00000105254; ENSMUSG00000036712. [Q80TQ2-1]
ENSMUST00000209532; ENSMUSP00000147654; ENSMUSG00000036712. [Q80TQ2-2]
ENSMUST00000209559; ENSMUSP00000147426; ENSMUSG00000036712. [Q80TQ2-1]
ENSMUST00000211554; ENSMUSP00000148037; ENSMUSG00000036712. [Q80TQ2-1]
GeneIDi74256.
KEGGimmu:74256.
UCSCiuc009mrt.3. mouse. [Q80TQ2-1]
uc033jgq.1. mouse. [Q80TQ2-3]
uc033jgr.1. mouse. [Q80TQ2-2]

Organism-specific databases

CTDi1540.
MGIiMGI:1921506. Cyld.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG3556. Eukaryota.
ENOG410XP6I. LUCA.
GeneTreeiENSGT00390000018123.
HOGENOMiHOG000006796.
HOVERGENiHBG051281.
InParanoidiQ80TQ2.
KOiK08601.
OrthoDBiEOG091G015D.
PhylomeDBiQ80TQ2.

Enzyme and pathway databases

BRENDAi3.4.19.12. 3474.
ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
R-MMU-5357786. TNFR1-induced proapoptotic signaling.
R-MMU-5357905. Regulation of TNFR1 signaling.
R-MMU-5357956. TNFR1-induced NFkappaB signaling pathway.
R-MMU-5689880. Ub-specific processing proteases.
R-MMU-936440. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

PROiQ80TQ2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036712.
CleanExiMM_CYLD.
ExpressionAtlasiQ80TQ2. baseline and differential.
GenevisibleiQ80TQ2. MM.

Family and domain databases

Gene3Di2.30.30.190. 3 hits.
InterProiIPR000938. CAP-Gly_domain.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF01302. CAP_GLY. 2 hits.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM01052. CAP_GLY. 3 hits.
[Graphical view]
SUPFAMiSSF74924. SSF74924. 3 hits.
PROSITEiPS00845. CAP_GLY_1. 1 hit.
PS50245. CAP_GLY_2. 2 hits.
PS00972. USP_1. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCYLD_MOUSE
AccessioniPrimary (citable) accession number: Q80TQ2
Secondary accession number(s): Q80VB3
, Q8BXZ3, Q8BYL9, Q8CGB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: August 16, 2004
Last modified: November 30, 2016
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.