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Protein

26S proteasome non-ATPase regulatory subunit 10

Gene

PSMD10

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

Functioni

Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pahway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.
Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101843-MONOMER.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-HSA-1236974. ER-Phagosome pathway.
R-HSA-1236978. Cross-presentation of soluble exogenous antigens (endosomes).
R-HSA-174084. Autodegradation of Cdh1 by Cdh1:APC/C.
R-HSA-174113. SCF-beta-TrCP mediated degradation of Emi1.
R-HSA-174154. APC/C:Cdc20 mediated degradation of Securin.
R-HSA-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-HSA-174184. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
R-HSA-180534. Vpu mediated degradation of CD4.
R-HSA-180585. Vif-mediated degradation of APOBEC3G.
R-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-195253. Degradation of beta-catenin by the destruction complex.
R-HSA-202424. Downstream TCR signaling.
R-HSA-211733. Regulation of activated PAK-2p34 by proteasome mediated degradation.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-349425. Autodegradation of the E3 ubiquitin ligase COP1.
R-HSA-350562. Regulation of ornithine decarboxylase (ODC).
R-HSA-382556. ABC-family proteins mediated transport.
R-HSA-450408. AUF1 (hnRNP D0) binds and destabilizes mRNA.
R-HSA-4608870. Asymmetric localization of PCP proteins.
R-HSA-4641257. Degradation of AXIN.
R-HSA-4641258. Degradation of DVL.
R-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362768. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
R-HSA-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5610780. Degradation of GLI1 by the proteasome.
R-HSA-5610783. Degradation of GLI2 by the proteasome.
R-HSA-5610785. GLI3 is processed to GLI3R by the proteasome.
R-HSA-5632684. Hedgehog 'on' state.
R-HSA-5658442. Regulation of RAS by GAPs.
R-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5676590. NIK-->noncanonical NF-kB signaling.
R-HSA-5678895. Defective CFTR causes cystic fibrosis.
R-HSA-5687128. MAPK6/MAPK4 signaling.
R-HSA-5689603. UCH proteinases.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-68827. CDT1 association with the CDC6:ORC:origin complex.
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-69017. CDK-mediated phosphorylation and removal of Cdc6.
R-HSA-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-HSA-69481. G2/M Checkpoints.
R-HSA-69601. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
R-HSA-8852276. The role of GTSE1 in G2/M progression after G2 checkpoint.
R-HSA-8854050. FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
26S proteasome non-ATPase regulatory subunit 10
Alternative name(s):
26S proteasome regulatory subunit p28
Gankyrin
p28(GANK)
Gene namesi
Name:PSMD10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:9555. PSMD10.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • intermediate filament cytoskeleton Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • proteasome complex Source: UniProtKB
  • proteasome regulatory particle Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi182E → A: Abolishes interaction with RB1. 1 Publication1

Organism-specific databases

DisGeNETi5716.
OpenTargetsiENSG00000101843.
PharmGKBiPA33900.

Chemistry databases

ChEMBLiCHEMBL2331054.

Polymorphism and mutation databases

BioMutaiPSMD10.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670451 – 22626S proteasome non-ATPase regulatory subunit 10Add BLAST226

Proteomic databases

EPDiO75832.
MaxQBiO75832.
PaxDbiO75832.
PeptideAtlasiO75832.
PRIDEiO75832.
TopDownProteomicsiO75832-1. [O75832-1]

2D gel databases

OGPiO75832.

PTM databases

iPTMnetiO75832.
PhosphoSitePlusiO75832.

Expressioni

Tissue specificityi

Tends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000101843.
CleanExiHS_PSMD10.
ExpressionAtlasiO75832. baseline and differential.
GenevisibleiO75832. HS.

Organism-specific databases

HPAiCAB010434.
HPA002920.

Interactioni

Subunit structurei

Part of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex. Interacts with ARHGDIA and increases the interaction between ARHGDIA and RHOA, hence promotes ARHGDIA inactivation of RHOA and ROCK.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAGEA4P433585EBI-752185,EBI-743122
PSMC4P4368617EBI-752185,EBI-743997

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111688. 66 interactors.
DIPiDIP-39026N.
IntActiO75832. 24 interactors.
MINTiMINT-254757.
STRINGi9606.ENSP00000217958.

Structurei

Secondary structure

1226
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 8Combined sources3
Helixi9 – 15Combined sources7
Helixi19 – 28Combined sources10
Helixi30 – 34Combined sources5
Turni38 – 40Combined sources3
Helixi43 – 50Combined sources8
Helixi53 – 62Combined sources10
Beta strandi71 – 73Combined sources3
Helixi76 – 83Combined sources8
Helixi86 – 94Combined sources9
Helixi109 – 115Combined sources7
Helixi119 – 127Combined sources9
Helixi142 – 148Combined sources7
Helixi152 – 160Combined sources9
Helixi175 – 181Combined sources7
Helixi185 – 193Combined sources9
Helixi208 – 211Combined sources4
Helixi216 – 224Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QYMX-ray2.80A2-226[»]
1TR4NMR-A1-226[»]
1UOHX-ray2.00A1-226[»]
4NIKX-ray2.50A1-226[»]
ProteinModelPortaliO75832.
SMRiO75832.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75832.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati3 – 36ANK 1Add BLAST34
Repeati37 – 69ANK 2Add BLAST33
Repeati70 – 102ANK 3Add BLAST33
Repeati103 – 135ANK 4Add BLAST33
Repeati136 – 168ANK 5Add BLAST33
Repeati169 – 201ANK 6Add BLAST33
Repeati202 – 226ANK 7Add BLAST25

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 71Interaction with RB11 PublicationAdd BLAST71
Regioni1 – 37Required for nuclear localizationAdd BLAST37
Regioni39 – 226Interaction with RELAAdd BLAST188
Regioni171 – 226Interaction with RB11 PublicationAdd BLAST56

Sequence similaritiesi

Contains 7 ANK repeats.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG4412. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00860000133720.
HOGENOMiHOG000158359.
HOVERGENiHBG053737.
InParanoidiO75832.
KOiK06694.
OMAiCSAGHTN.
OrthoDBiEOG091G0KEZ.
PhylomeDBiO75832.
TreeFamiTF106234.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75832-1) [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
MEGCVSNLMV CNLAYSGKLE ELKESILADK SLATRTDQDS RTALHWACSA
60 70 80 90 100
GHTEIVEFLL QLGVPVNDKD DAGWSPLHIA ASAGRDEIVK ALLGKGAQVN
110 120 130 140 150
AVNQNGCTPL HYAASKNRHE IAVMLLEGGA NPDAKDHYEA TAMHRAAAKG
160 170 180 190 200
NLKMIHILLY YKASTNIQDT EGNTPLHLAC DEERVEEAKL LVSQGASIYI
210 220
ENKEEKTPLQ VAKGGLGLIL KRMVEG
Length:226
Mass (Da):24,428
Last modified:November 1, 1998 - v1
Checksum:i57158E33146EC7C8
GO
Isoform 2 (identifier: O75832-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-226: GNLKMIHILL...GLILKRMVEG → DT

Show »
Length:151
Mass (Da):16,137
Checksum:iBEA968FE1439F3CC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti196A → T in AAV38495 (Ref. 5) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043043150 – 226GNLKM…RMVEG → DT in isoform 2. 2 PublicationsAdd BLAST77

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009619 mRNA. Translation: BAA33215.1.
D83197 mRNA. Translation: BAA34594.1.
AY057056 mRNA. Translation: AAL25260.1.
AK295996 mRNA. Translation: BAG58771.1.
BT019689 mRNA. Translation: AAV38495.1.
AL031177 Genomic DNA. Translation: CAA20117.1.
AL031177 Genomic DNA. Translation: CAI43131.1.
BC011960 mRNA. Translation: AAH11960.1.
CCDSiCCDS14536.1. [O75832-1]
CCDS14537.1. [O75832-2]
RefSeqiNP_002805.1. NM_002814.3. [O75832-1]
NP_736606.1. NM_170750.2. [O75832-2]
UniGeneiHs.522752.

Genome annotation databases

EnsembliENST00000217958; ENSP00000217958; ENSG00000101843. [O75832-1]
ENST00000361815; ENSP00000354906; ENSG00000101843. [O75832-2]
GeneIDi5716.
KEGGihsa:5716.
UCSCiuc004enp.3. human. [O75832-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009619 mRNA. Translation: BAA33215.1.
D83197 mRNA. Translation: BAA34594.1.
AY057056 mRNA. Translation: AAL25260.1.
AK295996 mRNA. Translation: BAG58771.1.
BT019689 mRNA. Translation: AAV38495.1.
AL031177 Genomic DNA. Translation: CAA20117.1.
AL031177 Genomic DNA. Translation: CAI43131.1.
BC011960 mRNA. Translation: AAH11960.1.
CCDSiCCDS14536.1. [O75832-1]
CCDS14537.1. [O75832-2]
RefSeqiNP_002805.1. NM_002814.3. [O75832-1]
NP_736606.1. NM_170750.2. [O75832-2]
UniGeneiHs.522752.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QYMX-ray2.80A2-226[»]
1TR4NMR-A1-226[»]
1UOHX-ray2.00A1-226[»]
4NIKX-ray2.50A1-226[»]
ProteinModelPortaliO75832.
SMRiO75832.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111688. 66 interactors.
DIPiDIP-39026N.
IntActiO75832. 24 interactors.
MINTiMINT-254757.
STRINGi9606.ENSP00000217958.

Chemistry databases

ChEMBLiCHEMBL2331054.

PTM databases

iPTMnetiO75832.
PhosphoSitePlusiO75832.

Polymorphism and mutation databases

BioMutaiPSMD10.

2D gel databases

OGPiO75832.

Proteomic databases

EPDiO75832.
MaxQBiO75832.
PaxDbiO75832.
PeptideAtlasiO75832.
PRIDEiO75832.
TopDownProteomicsiO75832-1. [O75832-1]

Protocols and materials databases

DNASUi5716.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000217958; ENSP00000217958; ENSG00000101843. [O75832-1]
ENST00000361815; ENSP00000354906; ENSG00000101843. [O75832-2]
GeneIDi5716.
KEGGihsa:5716.
UCSCiuc004enp.3. human. [O75832-1]

Organism-specific databases

CTDi5716.
DisGeNETi5716.
GeneCardsiPSMD10.
HGNCiHGNC:9555. PSMD10.
HPAiCAB010434.
HPA002920.
MIMi300880. gene.
neXtProtiNX_O75832.
OpenTargetsiENSG00000101843.
PharmGKBiPA33900.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4412. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00860000133720.
HOGENOMiHOG000158359.
HOVERGENiHBG053737.
InParanoidiO75832.
KOiK06694.
OMAiCSAGHTN.
OrthoDBiEOG091G0KEZ.
PhylomeDBiO75832.
TreeFamiTF106234.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101843-MONOMER.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-HSA-1236974. ER-Phagosome pathway.
R-HSA-1236978. Cross-presentation of soluble exogenous antigens (endosomes).
R-HSA-174084. Autodegradation of Cdh1 by Cdh1:APC/C.
R-HSA-174113. SCF-beta-TrCP mediated degradation of Emi1.
R-HSA-174154. APC/C:Cdc20 mediated degradation of Securin.
R-HSA-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-HSA-174184. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
R-HSA-180534. Vpu mediated degradation of CD4.
R-HSA-180585. Vif-mediated degradation of APOBEC3G.
R-HSA-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-HSA-195253. Degradation of beta-catenin by the destruction complex.
R-HSA-202424. Downstream TCR signaling.
R-HSA-211733. Regulation of activated PAK-2p34 by proteasome mediated degradation.
R-HSA-2467813. Separation of Sister Chromatids.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-349425. Autodegradation of the E3 ubiquitin ligase COP1.
R-HSA-350562. Regulation of ornithine decarboxylase (ODC).
R-HSA-382556. ABC-family proteins mediated transport.
R-HSA-450408. AUF1 (hnRNP D0) binds and destabilizes mRNA.
R-HSA-4608870. Asymmetric localization of PCP proteins.
R-HSA-4641257. Degradation of AXIN.
R-HSA-4641258. Degradation of DVL.
R-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362768. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
R-HSA-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5610780. Degradation of GLI1 by the proteasome.
R-HSA-5610783. Degradation of GLI2 by the proteasome.
R-HSA-5610785. GLI3 is processed to GLI3R by the proteasome.
R-HSA-5632684. Hedgehog 'on' state.
R-HSA-5658442. Regulation of RAS by GAPs.
R-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5676590. NIK-->noncanonical NF-kB signaling.
R-HSA-5678895. Defective CFTR causes cystic fibrosis.
R-HSA-5687128. MAPK6/MAPK4 signaling.
R-HSA-5689603. UCH proteinases.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-68827. CDT1 association with the CDC6:ORC:origin complex.
R-HSA-68949. Orc1 removal from chromatin.
R-HSA-69017. CDK-mediated phosphorylation and removal of Cdc6.
R-HSA-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-HSA-69481. G2/M Checkpoints.
R-HSA-69601. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
R-HSA-8852276. The role of GTSE1 in G2/M progression after G2 checkpoint.
R-HSA-8854050. FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiPSMD10. human.
EvolutionaryTraceiO75832.
GeneWikiiPSMD10.
GenomeRNAii5716.
PROiO75832.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101843.
CleanExiHS_PSMD10.
ExpressionAtlasiO75832. baseline and differential.
GenevisibleiO75832. HS.

Family and domain databases

Gene3Di1.25.40.20. 2 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 5 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPSD10_HUMAN
AccessioniPrimary (citable) accession number: O75832
Secondary accession number(s): Q5U0B2, Q8IZK9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2002
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 170 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was initially identified as a genuine component of the 26S proteasome.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.