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Protein

Potassium voltage-gated channel subfamily C member 3

Gene

KCNC3

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

Functioni

Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics (PubMed:10712820, PubMed:26997484, PubMed:22289912, PubMed:23734863, PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:25756792). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells. Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca2+ channels and cellular Ca2+ homeostasis (By similarity). Required for normal motor function (PubMed:23734863, PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:25756792). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484).By similarity8 Publications

GO - Molecular functioni

  • delayed rectifier potassium channel activity Source: GO_Central
  • voltage-gated potassium channel activity Source: UniProtKB

GO - Biological processi

  • potassium ion transmembrane transport Source: UniProtKB
  • protein homooligomerization Source: InterPro
  • protein tetramerization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000131398-MONOMER.
ReactomeiR-HSA-1296072. Voltage gated Potassium channels.

Protein family/group databases

TCDBi1.A.1.2.13. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily C member 3
Alternative name(s):
KSHIIID
Voltage-gated potassium channel subunit Kv3.3
Gene namesi
Name:KCNC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6235. KCNC3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 290CytoplasmicCuratedAdd BLAST290
Transmembranei291 – 309Helical; Name=Segment S1Sequence analysisAdd BLAST19
Transmembranei351 – 370Helical; Name=Segment S2Sequence analysisAdd BLAST20
Topological domaini371 – 379CytoplasmicSequence analysis9
Transmembranei380 – 398Helical; Name=Segment S3Sequence analysisAdd BLAST19
Transmembranei412 – 434Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST23
Topological domaini435 – 447CytoplasmicSequence analysisAdd BLAST13
Transmembranei448 – 469Helical; Name=Segment S5Sequence analysisAdd BLAST22
Transmembranei518 – 539Helical; Name=Segment S6Sequence analysisAdd BLAST22
Topological domaini540 – 757CytoplasmicCuratedAdd BLAST218

GO - Cellular componenti

  • axon Source: UniProtKB-SubCell
  • cell cortex Source: UniProtKB-SubCell
  • cell junction Source: UniProtKB-KW
  • cytoskeleton Source: UniProtKB-SubCell
  • dendrite Source: UniProtKB-SubCell
  • dendritic spine membrane Source: UniProtKB-SubCell
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
  • presynaptic membrane Source: UniProtKB-SubCell
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia 13 (SCA13)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSpinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA13 is an autosomal dominant cerebellar ataxia (ADCA) characterized by slow progression and variable age at onset, ranging from childhood to late adulthood. Mental retardation can be present in some patients.
See also OMIM:605259
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074194129D → N in SCA13; unknown pathological significance; changes channel activity; shifts the voltage dependence of activation. 1 Publication1
Natural variantiVAR_074196366R → H in SCA13; unknown pathological significance; dominant negative that decreases channel activity; decreases protein abundance; decreases protein stability; decreases localization to the plasma membrane; no effect on tetramerization. 2 PublicationsCorresponds to variant rs769502387dbSNPEnsembl.1
Natural variantiVAR_029530420R → H in SCA13; dominant negative that induces loss of channel activity; decreases protein abundance; decreases protein stability; decreases localization to the plasma membrane and alters the localization of the wild-type protein; impairs N-glycosylation; no effect on tetramerization. 6 PublicationsCorresponds to variant rs104894699dbSNPEnsembl.1
Natural variantiVAR_074197423R → H in SCA13; dominant negative that reduces channel activity; alters gating; decreases protein abundance; decreases localization to the plasma membrane; no effect on tetramerization. 5 Publications1
Natural variantiVAR_029531448F → L in SCA13; alters gating; slows channel closing; decreases protein abundance; no effect on localization to the plasma membrane; no effect on N-glycosylation; no effect on tetramerization. 4 PublicationsCorresponds to variant rs104894700dbSNPEnsembl.1
Natural variantiVAR_074198477D → N in SCA13; unknown pathological significance; no effect on channel activity. 1 PublicationCorresponds to variant rs148033381dbSNPEnsembl.1
Natural variantiVAR_074199535V → M in SCA13; changes channel activity; shifts the voltage dependence of activation. 1 Publication1
Natural variantiVAR_074200591S → G in SCA13; unknown pathological significance; reduces channel activity; shifts the voltage dependence of activation. 1 PublicationCorresponds to variant rs549394447dbSNPEnsembl.1
Natural variantiVAR_074201643G → S in SCA13; unknown pathological significance; no effect on channel activity. 1 PublicationCorresponds to variant rs778523009dbSNPEnsembl.1
Natural variantiVAR_074202645P → R in SCA13; unknown pathological significance; no effect on channel activity. 1 Publication1
Natural variantiVAR_074203746D → N in SCA13; unknown pathological significance; no effect on channel activity. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 78Missing : Loss of N-type inactivation. 1 PublicationAdd BLAST78
Mutagenesisi366R → K or A: Decreases protein abundance. 1 Publication1
Mutagenesisi420R → K or A: Decreases protein abundance. 1 Publication1
Mutagenesisi423R → K or A: Decreases protein abundance. 1 Publication1
Mutagenesisi592G → R: Loss of interaction with ACTR3. No effect on voltage-dependent channel opening or current amplitude, but decreased rate of inactivation during prolonged depolarization. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

DisGeNETi3748.
MalaCardsiKCNC3.
MIMi605259. phenotype.
OpenTargetsiENSG00000131398.
Orphaneti98768. Spinocerebellar ataxia type 13.
PharmGKBiPA30027.

Chemistry databases

ChEMBLiCHEMBL2362996.
DrugBankiDB06637. Dalfampridine.

Polymorphism and mutation databases

BioMutaiKCNC3.
DMDMi212276500.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000540551 – 757Potassium voltage-gated channel subfamily C member 3Add BLAST757

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi320N-linked (GlcNAc...)Sequence analysis1
Glycosylationi336N-linked (GlcNAc...)Sequence analysis1
Glycosylationi483N-linked (GlcNAc...)Sequence analysis1
Modified residuei625Omega-N-methylarginineBy similarity1
Modified residuei686PhosphoserineBy similarity1
Modified residuei691PhosphoserineBy similarity1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ14003.
PaxDbiQ14003.
PeptideAtlasiQ14003.
PRIDEiQ14003.

PTM databases

iPTMnetiQ14003.
PhosphoSitePlusiQ14003.

Expressioni

Gene expression databases

BgeeiENSG00000131398.
CleanExiHS_KCNC3.
ExpressionAtlasiQ14003. baseline and differential.
GenevisibleiQ14003. HS.

Organism-specific databases

HPAiHPA018041.

Interactioni

Subunit structurei

Homotetramer. Heterotetramer with KCNC1 (PubMed:23734863). Interacts (via C-terminus) with HAX1 (PubMed:26997484). Identified in a complex with ACTR3, a subunit of the Arp2/3 complex; this interaction is indirect and depends on the presence of HAX1 (PubMed:26997484). Interaction with HAX1 modulates channel gating (PubMed:26997484).2 Publications

Protein-protein interaction databases

BioGridi109950. 1 interactor.
STRINGi9606.ENSP00000434241.

Structurei

3D structure databases

ProteinModelPortaliQ14003.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 78Important for normal N-type inactivation1 PublicationAdd BLAST78

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi503 – 508Selectivity filterBy similarity6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi31 – 38Poly-Pro8
Compositional biasi39 – 42Poly-Gln4
Compositional biasi81 – 85Poly-Gly5
Compositional biasi229 – 234Poly-Gly6
Compositional biasi577 – 587Poly-ProAdd BLAST11
Compositional biasi596 – 599Poly-Pro4
Compositional biasi668 – 673Poly-Ala6

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.Curated
The cytoplasmic N-terminus mediates N-type inactivation.1 Publication
The C-terminal cytoplasmic tail contributes to the regulation of channel inactivation and to the interaction with HAX1 and the Arp2/3 complex.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3713. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231012.
HOVERGENiHBG105862.
InParanoidiQ14003.
KOiK04889.
OMAiGTWWRRW.
OrthoDBiEOG091G0EJL.
PhylomeDBiQ14003.
TreeFamiTF352511.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003974. K_chnl_volt-dep_Kv3.
IPR005404. K_chnl_volt-dep_Kv3.3.
IPR021105. K_chnl_volt-dep_Kv3_ID.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11404. Potassium_chann. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01582. KV33CHANNEL.
PR01491. KVCHANNEL.
PR01498. SHAWCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequencei

Sequence statusi: Complete.

Q14003-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSSVCVSSF RGRQGASKQQ PAPPPQPPES PPPPPLPPQQ QQPAQPGPAA
60 70 80 90 100
SPAGPPAPRG PGDRRAEPCP GLPAAAMGRH GGGGGDSGKI VINVGGVRHE
110 120 130 140 150
TYRSTLRTLP GTRLAGLTEP EAAARFDYDP GADEFFFDRH PGVFAYVLNY
160 170 180 190 200
YRTGKLHCPA DVCGPLFEEE LGFWGIDETD VEACCWMTYR QHRDAEEALD
210 220 230 240 250
SFEAPDPAGA ANAANAAGAH DGGLDDEAGA GGGGLDGAGG ELKRLCFQDA
260 270 280 290 300
GGGAGGPPGG AGGAGGTWWR RWQPRVWALF EDPYSSRAAR YVAFASLFFI
310 320 330 340 350
LISITTFCLE THEGFIHISN KTVTQASPIP GAPPENITNV EVETEPFLTY
360 370 380 390 400
VEGVCVVWFT FEFLMRITFC PDKVEFLKSS LNIIDCVAIL PFYLEVGLSG
410 420 430 440 450
LSSKAAKDVL GFLRVVRFVR ILRIFKLTRH FVGLRVLGHT LRASTNEFLL
460 470 480 490 500
LIIFLALGVL IFATMIYYAE RIGADPDDIL GSNHTYFKNI PIGFWWAVVT
510 520 530 540 550
MTTLGYGDMY PKTWSGMLVG ALCALAGVLT IAMPVPVIVN NFGMYYSLAM
560 570 580 590 600
AKQKLPKKKN KHIPRPPQPG SPNYCKPDPP PPPPPHPHHG SGGISPPPPI
610 620 630 640 650
TPPSMGVTVA GAYPAGPHTH PGLLRGGAGG LGIMGLPPLP APGEPCPLAQ
660 670 680 690 700
EEVIEINRAD PRPNGDPAAA ALAHEDCPAI DQPAMSPEDK SPITPGSRGR
710 720 730 740 750
YSRDRACFLL TDYAPSPDGS IRKATGAPPL PPQDWRKPGP PSFLPDLNAN

AAAWISP
Length:757
Mass (Da):80,578
Last modified:November 4, 2008 - v3
Checksum:iB44306B850DFD797
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07419241Q → H Rare polymorphism. 1 PublicationCorresponds to variant rs185017345dbSNPEnsembl.1
Natural variantiVAR_07419363D → G Rare polymorphism. 2 PublicationsCorresponds to variant rs375912738dbSNPEnsembl.1
Natural variantiVAR_074194129D → N in SCA13; unknown pathological significance; changes channel activity; shifts the voltage dependence of activation. 1 Publication1
Natural variantiVAR_074195263G → D Rare polymorphism; changes channel activity; activates more quickly and deactivates more slowly. 1 Publication1
Natural variantiVAR_074196366R → H in SCA13; unknown pathological significance; dominant negative that decreases channel activity; decreases protein abundance; decreases protein stability; decreases localization to the plasma membrane; no effect on tetramerization. 2 PublicationsCorresponds to variant rs769502387dbSNPEnsembl.1
Natural variantiVAR_029530420R → H in SCA13; dominant negative that induces loss of channel activity; decreases protein abundance; decreases protein stability; decreases localization to the plasma membrane and alters the localization of the wild-type protein; impairs N-glycosylation; no effect on tetramerization. 6 PublicationsCorresponds to variant rs104894699dbSNPEnsembl.1
Natural variantiVAR_074197423R → H in SCA13; dominant negative that reduces channel activity; alters gating; decreases protein abundance; decreases localization to the plasma membrane; no effect on tetramerization. 5 Publications1
Natural variantiVAR_029531448F → L in SCA13; alters gating; slows channel closing; decreases protein abundance; no effect on localization to the plasma membrane; no effect on N-glycosylation; no effect on tetramerization. 4 PublicationsCorresponds to variant rs104894700dbSNPEnsembl.1
Natural variantiVAR_074198477D → N in SCA13; unknown pathological significance; no effect on channel activity. 1 PublicationCorresponds to variant rs148033381dbSNPEnsembl.1
Natural variantiVAR_074199535V → M in SCA13; changes channel activity; shifts the voltage dependence of activation. 1 Publication1
Natural variantiVAR_074200591S → G in SCA13; unknown pathological significance; reduces channel activity; shifts the voltage dependence of activation. 1 PublicationCorresponds to variant rs549394447dbSNPEnsembl.1
Natural variantiVAR_074201643G → S in SCA13; unknown pathological significance; no effect on channel activity. 1 PublicationCorresponds to variant rs778523009dbSNPEnsembl.1
Natural variantiVAR_074202645P → R in SCA13; unknown pathological significance; no effect on channel activity. 1 Publication1
Natural variantiVAR_074203746D → N in SCA13; unknown pathological significance; no effect on channel activity. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF055989 mRNA. Translation: AAC24118.1.
AC008655 Genomic DNA. No translation available.
Z11585 Genomic DNA. Translation: CAA77671.1.
CCDSiCCDS12793.1.
PIRiS19552.
RefSeqiNP_004968.2. NM_004977.2.
XP_006723266.1. XM_006723203.2.
XP_011525228.1. XM_011526926.1.
UniGeneiHs.467146.

Genome annotation databases

EnsembliENST00000477616; ENSP00000434241; ENSG00000131398.
GeneIDi3748.
KEGGihsa:3748.
UCSCiuc002pru.1. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF055989 mRNA. Translation: AAC24118.1.
AC008655 Genomic DNA. No translation available.
Z11585 Genomic DNA. Translation: CAA77671.1.
CCDSiCCDS12793.1.
PIRiS19552.
RefSeqiNP_004968.2. NM_004977.2.
XP_006723266.1. XM_006723203.2.
XP_011525228.1. XM_011526926.1.
UniGeneiHs.467146.

3D structure databases

ProteinModelPortaliQ14003.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109950. 1 interactor.
STRINGi9606.ENSP00000434241.

Chemistry databases

ChEMBLiCHEMBL2362996.
DrugBankiDB06637. Dalfampridine.

Protein family/group databases

TCDBi1.A.1.2.13. the voltage-gated ion channel (vic) superfamily.

PTM databases

iPTMnetiQ14003.
PhosphoSitePlusiQ14003.

Polymorphism and mutation databases

BioMutaiKCNC3.
DMDMi212276500.

Proteomic databases

MaxQBiQ14003.
PaxDbiQ14003.
PeptideAtlasiQ14003.
PRIDEiQ14003.

Protocols and materials databases

DNASUi3748.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000477616; ENSP00000434241; ENSG00000131398.
GeneIDi3748.
KEGGihsa:3748.
UCSCiuc002pru.1. human.

Organism-specific databases

CTDi3748.
DisGeNETi3748.
GeneCardsiKCNC3.
GeneReviewsiKCNC3.
H-InvDBHIX0202872.
HGNCiHGNC:6235. KCNC3.
HPAiHPA018041.
MalaCardsiKCNC3.
MIMi176264. gene.
605259. phenotype.
neXtProtiNX_Q14003.
OpenTargetsiENSG00000131398.
Orphaneti98768. Spinocerebellar ataxia type 13.
PharmGKBiPA30027.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3713. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231012.
HOVERGENiHBG105862.
InParanoidiQ14003.
KOiK04889.
OMAiGTWWRRW.
OrthoDBiEOG091G0EJL.
PhylomeDBiQ14003.
TreeFamiTF352511.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000131398-MONOMER.
ReactomeiR-HSA-1296072. Voltage gated Potassium channels.

Miscellaneous databases

ChiTaRSiKCNC3. human.
GeneWikiiKCNC3.
GenomeRNAii3748.
PROiQ14003.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131398.
CleanExiHS_KCNC3.
ExpressionAtlasiQ14003. baseline and differential.
GenevisibleiQ14003. HS.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003974. K_chnl_volt-dep_Kv3.
IPR005404. K_chnl_volt-dep_Kv3.3.
IPR021105. K_chnl_volt-dep_Kv3_ID.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF11404. Potassium_chann. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01582. KV33CHANNEL.
PR01491. KVCHANNEL.
PR01498. SHAWCHANNEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNC3_HUMAN
AccessioniPrimary (citable) accession number: Q14003
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 4, 2008
Last modified: November 30, 2016
This is version 154 of the entry and version 3 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 19
    Human chromosome 19: 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.