Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cyclin-dependent kinase 6

Gene

CDK6

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

Functioni

Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663).10 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei43ATPPROSITE-ProRule annotation1
Active sitei145Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi19 – 27ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: BHF-UCL
  • cyclin binding Source: BHF-UCL
  • cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • FBXO family protein binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • astrocyte development Source: UniProtKB
  • cell cycle arrest Source: UniProtKB
  • cell dedifferentiation Source: BHF-UCL
  • cell division Source: UniProtKB-KW
  • cellular response to phorbol 13-acetate 12-myristate Source: UniProtKB
  • dentate gyrus development Source: UniProtKB
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • generation of neurons Source: UniProtKB
  • gliogenesis Source: BHF-UCL
  • hematopoietic stem cell differentiation Source: Ensembl
  • lateral ventricle development Source: UniProtKB
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of cell differentiation Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cellular senescence Source: UniProtKB
  • negative regulation of epithelial cell proliferation Source: BHF-UCL
  • negative regulation of monocyte differentiation Source: UniProtKB
  • negative regulation of myeloid cell differentiation Source: UniProtKB
  • negative regulation of osteoblast differentiation Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • Notch signaling pathway Source: Ensembl
  • positive regulation of cell-matrix adhesion Source: BHF-UCL
  • positive regulation of fibroblast proliferation Source: BHF-UCL
  • positive regulation of gene expression Source: Ensembl
  • protein phosphorylation Source: BHF-UCL
  • regulation of cell motility Source: UniProtKB
  • regulation of erythrocyte differentiation Source: BHF-UCL
  • regulation of G2/M transition of mitotic cell cycle Source: GO_Central
  • regulation of gene expression Source: BHF-UCL
  • regulation of hematopoietic stem cell differentiation Source: Ensembl
  • response to virus Source: UniProtKB
  • signal transduction Source: GO_Central
  • T cell differentiation in thymus Source: Ensembl
  • type B pancreatic cell development Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Differentiation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.22. 2681.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-69231. Cyclin D associated events in G1.
SignaLinkiQ00534.
SIGNORiQ00534.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 6 (EC:2.7.11.22)
Alternative name(s):
Cell division protein kinase 6
Serine/threonine-protein kinase PLSTIRE
Gene namesi
Name:CDK6
Synonyms:CDKN6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:1777. CDK6.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cyclin D2-CDK6 complex Source: Ensembl
  • cyclin-dependent protein kinase holoenzyme complex Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
  • nucleus Source: BHF-UCL
  • ruffle Source: BHF-UCL

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Microcephaly 12, primary, autosomal recessive (MCPH12)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small.
See also OMIM:616080
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072638197A → T in MCPH12. 1 PublicationCorresponds to variant dbSNP:rs606231255Ensembl.1

Keywords - Diseasei

Disease mutation, Primary microcephaly

Organism-specific databases

DisGeNETi1021.
MalaCardsiCDK6.
MIMi612223. phenotype.
616080. phenotype.
OpenTargetsiENSG00000105810.
Orphaneti2512. Autosomal recessive primary microcephaly.
PharmGKBiPA103.

Chemistry databases

ChEMBLiCHEMBL2508.
DrugBankiDB09073. Palbociclib.
GuidetoPHARMACOLOGYi1978.

Polymorphism and mutation databases

BioMutaiCDK6.
DMDMi266423.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000857891 – 326Cyclin-dependent kinase 6Add BLAST326

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei13PhosphotyrosineCombined sources1
Modified residuei24PhosphotyrosineCombined sources1
Modified residuei49PhosphothreonineCombined sources1
Modified residuei70PhosphothreonineCombined sources1
Modified residuei177Phosphothreonine1 Publication1
Modified residuei264N6-acetyllysineCombined sources1
Modified residuei325PhosphothreonineCombined sources1

Post-translational modificationi

Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ00534.
MaxQBiQ00534.
PaxDbiQ00534.
PeptideAtlasiQ00534.
PRIDEiQ00534.

PTM databases

iPTMnetiQ00534.
PhosphoSitePlusiQ00534.

Expressioni

Tissue specificityi

Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells.2 Publications

Inductioni

Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry.2 Publications

Gene expression databases

BgeeiENSG00000105810.
CleanExiHS_CDK6.
GenevisibleiQ00534. HS.

Organism-specific databases

HPAiCAB004363.
HPA002637.

Interactioni

Subunit structurei

Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177 (By similarity). Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding. Interacts with Kaposi's sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V-cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and thus lead to viral reactivation by reducing viral LANA levels.By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cyclin binding Source: BHF-UCL
  • FBXO family protein binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi107456. 119 interactors.
DIPiDIP-687N.
IntActiQ00534. 95 interactors.
MINTiMINT-232049.
STRINGi9606.ENSP00000265734.

Chemistry databases

BindingDBiQ00534.

Structurei

Secondary structure

1326
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 11Combined sources3
Beta strandi13 – 22Combined sources10
Beta strandi25 – 32Combined sources8
Turni33 – 37Combined sources5
Beta strandi39 – 49Combined sources11
Helixi58 – 70Combined sources13
Beta strandi79 – 87Combined sources9
Beta strandi89 – 99Combined sources11
Beta strandi102 – 104Combined sources3
Helixi105 – 111Combined sources7
Turni113 – 115Combined sources3
Helixi119 – 138Combined sources20
Helixi148 – 150Combined sources3
Beta strandi151 – 153Combined sources3
Beta strandi159 – 161Combined sources3
Helixi172 – 176Combined sources5
Beta strandi180 – 182Combined sources3
Helixi183 – 185Combined sources3
Helixi188 – 191Combined sources4
Helixi199 – 214Combined sources16
Helixi224 – 235Combined sources12
Helixi240 – 242Combined sources3
Beta strandi245 – 249Combined sources5
Helixi251 – 253Combined sources3
Helixi262 – 264Combined sources3
Beta strandi266 – 268Combined sources3
Helixi271 – 280Combined sources10
Turni285 – 287Combined sources3
Helixi291 – 295Combined sources5
Helixi298 – 300Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BI7X-ray3.40A1-326[»]
1BI8X-ray2.80A/C1-326[»]
1BLXX-ray1.90A1-326[»]
1G3NX-ray2.90A/E1-326[»]
1JOWX-ray3.10B1-308[»]
1XO2X-ray2.90B1-308[»]
2EUFX-ray3.00B1-308[»]
2F2CX-ray2.80B1-308[»]
3NUPX-ray2.60A1-301[»]
3NUXX-ray2.70A1-301[»]
4AUAX-ray2.31A1-301[»]
4EZ5X-ray2.70A1-301[»]
4TTHX-ray2.90B1-326[»]
5L2IX-ray2.75A1-301[»]
5L2SX-ray2.27A1-301[»]
5L2TX-ray2.37A1-301[»]
ProteinModelPortaliQ00534.
SMRiQ00534.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00534.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 300Protein kinasePROSITE-ProRule annotationAdd BLAST288

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ00534.
KOiK02091.
OMAiEDWPQEV.
OrthoDBiEOG090B094T.
PhylomeDBiQ00534.
TreeFamiTF101022.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequencei

Sequence statusi: Complete.

Q00534-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKDGLCRAD QQYECVAEIG EGAYGKVFKA RDLKNGGRFV ALKRVRVQTG
60 70 80 90 100
EEGMPLSTIR EVAVLRHLET FEHPNVVRLF DVCTVSRTDR ETKLTLVFEH
110 120 130 140 150
VDQDLTTYLD KVPEPGVPTE TIKDMMFQLL RGLDFLHSHR VVHRDLKPQN
160 170 180 190 200
ILVTSSGQIK LADFGLARIY SFQMALTSVV VTLWYRAPEV LLQSSYATPV
210 220 230 240 250
DLWSVGCIFA EMFRRKPLFR GSSDVDQLGK ILDVIGLPGE EDWPRDVALP
260 270 280 290 300
RQAFHSKSAQ PIEKFVTDID ELGKDLLLKC LTFNPAKRIS AYSALSHPYF
310 320
QDLERCKENL DSHLPPSQNT SELNTA
Length:326
Mass (Da):36,938
Last modified:April 1, 1993 - v1
Checksum:i571733EE6BE7FD4A
GO

Polymorphismi

Genetic variations in CDK6 may influence stature as a quantitative trait, contributing to the stature quantitative trait locus 11 (STQTL11) [MIMi:612223]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041978110D → N1 PublicationCorresponds to variant dbSNP:rs35654944Ensembl.1
Natural variantiVAR_072638197A → T in MCPH12. 1 PublicationCorresponds to variant dbSNP:rs606231255Ensembl.1
Natural variantiVAR_041979199P → L in a metastatic melanoma sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66365 mRNA. Translation: CAA47008.1.
AY128534 Genomic DNA. Translation: AAM76970.1.
AK313491 mRNA. Translation: BAG36273.1.
AC000065 Genomic DNA. No translation available.
AC004128 Genomic DNA. No translation available.
AC004011 Genomic DNA. No translation available.
CH236949 Genomic DNA. Translation: EAL24146.1.
CH471091 Genomic DNA. Translation: EAW76827.1.
BC052264 mRNA. Translation: AAH52264.1.
CCDSiCCDS5628.1.
PIRiS23387.
RefSeqiNP_001138778.1. NM_001145306.1.
NP_001250.1. NM_001259.6.
XP_006715898.1. XM_006715835.2.
UniGeneiHs.119882.

Genome annotation databases

EnsembliENST00000265734; ENSP00000265734; ENSG00000105810.
ENST00000424848; ENSP00000397087; ENSG00000105810.
GeneIDi1021.
KEGGihsa:1021.
UCSCiuc010lez.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66365 mRNA. Translation: CAA47008.1.
AY128534 Genomic DNA. Translation: AAM76970.1.
AK313491 mRNA. Translation: BAG36273.1.
AC000065 Genomic DNA. No translation available.
AC004128 Genomic DNA. No translation available.
AC004011 Genomic DNA. No translation available.
CH236949 Genomic DNA. Translation: EAL24146.1.
CH471091 Genomic DNA. Translation: EAW76827.1.
BC052264 mRNA. Translation: AAH52264.1.
CCDSiCCDS5628.1.
PIRiS23387.
RefSeqiNP_001138778.1. NM_001145306.1.
NP_001250.1. NM_001259.6.
XP_006715898.1. XM_006715835.2.
UniGeneiHs.119882.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BI7X-ray3.40A1-326[»]
1BI8X-ray2.80A/C1-326[»]
1BLXX-ray1.90A1-326[»]
1G3NX-ray2.90A/E1-326[»]
1JOWX-ray3.10B1-308[»]
1XO2X-ray2.90B1-308[»]
2EUFX-ray3.00B1-308[»]
2F2CX-ray2.80B1-308[»]
3NUPX-ray2.60A1-301[»]
3NUXX-ray2.70A1-301[»]
4AUAX-ray2.31A1-301[»]
4EZ5X-ray2.70A1-301[»]
4TTHX-ray2.90B1-326[»]
5L2IX-ray2.75A1-301[»]
5L2SX-ray2.27A1-301[»]
5L2TX-ray2.37A1-301[»]
ProteinModelPortaliQ00534.
SMRiQ00534.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107456. 119 interactors.
DIPiDIP-687N.
IntActiQ00534. 95 interactors.
MINTiMINT-232049.
STRINGi9606.ENSP00000265734.

Chemistry databases

BindingDBiQ00534.
ChEMBLiCHEMBL2508.
DrugBankiDB09073. Palbociclib.
GuidetoPHARMACOLOGYi1978.

PTM databases

iPTMnetiQ00534.
PhosphoSitePlusiQ00534.

Polymorphism and mutation databases

BioMutaiCDK6.
DMDMi266423.

Proteomic databases

EPDiQ00534.
MaxQBiQ00534.
PaxDbiQ00534.
PeptideAtlasiQ00534.
PRIDEiQ00534.

Protocols and materials databases

DNASUi1021.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265734; ENSP00000265734; ENSG00000105810.
ENST00000424848; ENSP00000397087; ENSG00000105810.
GeneIDi1021.
KEGGihsa:1021.
UCSCiuc010lez.4. human.

Organism-specific databases

CTDi1021.
DisGeNETi1021.
GeneCardsiCDK6.
GeneReviewsiCDK6.
HGNCiHGNC:1777. CDK6.
HPAiCAB004363.
HPA002637.
MalaCardsiCDK6.
MIMi603368. gene.
612223. phenotype.
616080. phenotype.
neXtProtiNX_Q00534.
OpenTargetsiENSG00000105810.
Orphaneti2512. Autosomal recessive primary microcephaly.
PharmGKBiPA103.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ00534.
KOiK02091.
OMAiEDWPQEV.
OrthoDBiEOG090B094T.
PhylomeDBiQ00534.
TreeFamiTF101022.

Enzyme and pathway databases

BRENDAi2.7.11.22. 2681.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-69231. Cyclin D associated events in G1.
SignaLinkiQ00534.
SIGNORiQ00534.

Miscellaneous databases

ChiTaRSiCDK6. human.
EvolutionaryTraceiQ00534.
GeneWikiiCyclin-dependent_kinase_6.
GenomeRNAii1021.
PROiQ00534.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105810.
CleanExiHS_CDK6.
GenevisibleiQ00534. HS.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCDK6_HUMAN
AccessioniPrimary (citable) accession number: Q00534
Secondary accession number(s): A4D1G0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: February 15, 2017
This is version 189 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Over-expressed in some leukemias and malignancies (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a consequence of nearby translocations.
Enhances beta-cells engraftment in pancreatic islets of Langerhans of diabetic patients.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.