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Protein

Kit ligand

Gene

KITLG

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

Functioni

Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

BioCyciZFISH:ENSG00000049130-MONOMER.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1433559. Regulation of KIT signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP21583.

Names & Taxonomyi

Protein namesi
Recommended name:
Kit ligand
Alternative name(s):
Mast cell growth factor
Short name:
MGF
Stem cell factor
Short name:
SCF
c-Kit ligand
Cleaved into the following chain:
Soluble KIT ligand
Short name:
sKITLG
Gene namesi
Name:KITLG
Synonyms:MGF, SCF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6343. KITLG.

Subcellular locationi

Isoform 2 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 214ExtracellularSequence analysisAdd BLAST189
Transmembranei215 – 237HelicalSequence analysisAdd BLAST23
Topological domaini238 – 273CytoplasmicSequence analysisAdd BLAST36

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • extracellular region Source: Reactome
  • extracellular space Source: Ensembl
  • filopodium Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • lamellipodium Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Hyperpigmentation with or without hypopigmentation, familial progressive (FPHH)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age. Hyperpigmentation has variable intensity, and sometimes is associated with cafe-au-lait macules and larger hypopigmented ash-leaf macules.
See also OMIM:145250
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06323736N → S in FPHH; gain-of-function mutation; sKITLG reveales that the mutant Ser-36 sKITLG increases the content of the melanin by 109% compared with the wild-type sKITLG; tyrosinase activity is significantly increased by the mutant sKITLG compared to wild-type control. 1 PublicationCorresponds to variant rs121918653dbSNPEnsembl.1
Deafness, congenital, unilateral or asymmetric (DCUA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant form of non-syndromic, sensorineural deafness characterized by inability to hear affecting one ear. Some patients suffers from asymmetric, bilateral hearing loss.
See also OMIM:616697
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07622267 – 68HC → R in DCUA; loss of cell membrane association. 1 Publication2

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi4254.
MalaCardsiKITLG.
MIMi145250. phenotype.
611664. phenotype.
616697. phenotype.
OpenTargetsiENSG00000049130.
Orphaneti280628. Familial progressive hyper- and hypopigmentation.
79146. Familial progressive hyperpigmentation.
363494. Testicular non seminomatous germ cell tumor.
PharmGKBiPA30129.

Chemistry databases

ChEMBLiCHEMBL2346489.

Polymorphism and mutation databases

BioMutaiKITLG.
DMDMi134289.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Add BLAST25
ChainiPRO_000003191326 – 273Kit ligandAdd BLAST248
ChainiPRO_000040339126 – 190Soluble KIT ligandAdd BLAST165

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 114
Disulfide bondi68 ↔ 163
Glycosylationi90N-linked (GlcNAc...); partial1 Publication1
Glycosylationi118N-linked (GlcNAc...); partial1 Publication1
Glycosylationi145N-linked (GlcNAc...)1 Publication1
Glycosylationi167O-linked (GalNAc...)1 Publication1
Glycosylationi168O-linked (GalNAc...)1 Publication1
Glycosylationi180O-linked (GalNAc...)1 Publication1
Glycosylationi195N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

A soluble form (sKITLG) is produced by proteolytic processing of isoform 1 in the extracellular domain.1 Publication
Found in two differentially glycosylated forms, LMW-SCF and HMW-SCF. LMW-SCF is fully N-glycosylated at Asn-145, partially N-glycosylated at Asn-90, O-glycosylated at Ser-167, Thr-168 and Thr-180, and not glycosylated at Asn-97 or Asn-118. HMW-SCF is N-glycosylated at Asn-118, Asn-90 and Asn-145, O-glycosylated at Ser-167, Thr-168 and Thr-180, and not glycosylated at Asn-97.1 Publication
A soluble form exists as a cleavage product of the extracellular domain.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei97Not glycosylated1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP21583.
PaxDbiP21583.
PeptideAtlasiP21583.
PRIDEiP21583.

PTM databases

iPTMnetiP21583.
PhosphoSitePlusiP21583.

Miscellaneous databases

PMAP-CutDBP21583.

Expressioni

Developmental stagei

Acts in the early stages of hematopoiesis.

Gene expression databases

BgeeiENSG00000049130.
CleanExiHS_KITLG.
ExpressionAtlasiP21583. baseline and differential.
GenevisibleiP21583. HS.

Organism-specific databases

HPAiCAB004569.

Interactioni

Subunit structurei

Homodimer, non-covalently linked (Probable). Heterotetramer with KIT, binding two KIT molecules; thereby mediates KIT dimerization and subsequent activation by autophosphorylation.Curated1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
KITP107212EBI-1379527,EBI-1379503

GO - Molecular functioni

  • stem cell factor receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi110410. 7 interactors.
IntActiP21583. 2 interactors.
STRINGi9606.ENSP00000228280.

Chemistry databases

BindingDBiP21583.

Structurei

Secondary structure

1273
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi30 – 32Combined sources3
Helixi37 – 46Combined sources10
Beta strandi53 – 56Combined sources4
Turni59 – 63Combined sources5
Helixi66 – 68Combined sources3
Helixi70 – 85Combined sources16
Beta strandi92 – 94Combined sources3
Helixi97 – 114Combined sources18
Beta strandi120 – 122Combined sources3
Beta strandi132 – 135Combined sources4
Helixi137 – 149Combined sources13
Turni150 – 152Combined sources3
Beta strandi157 – 160Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EXZX-ray2.30A/B/C/D26-166[»]
1SCFX-ray2.20A/B/C/D1-273[»]
2E9WX-ray3.50C/D26-166[»]
ProteinModelPortaliP21583.
SMRiP21583.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21583.

Family & Domainsi

Sequence similaritiesi

Belongs to the SCF family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF3Y. Eukaryota.
ENOG410XYQR. LUCA.
GeneTreeiENSGT00390000018272.
HOVERGENiHBG036146.
InParanoidiP21583.
KOiK05461.
OMAiVKTKGIC.
OrthoDBiEOG091G0I23.
PhylomeDBiP21583.
TreeFamiTF330811.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003452. SCF.
[Graphical view]
PANTHERiPTHR11574. PTHR11574. 1 hit.
PfamiPF02404. SCF. 1 hit.
[Graphical view]
PIRSFiPIRSF015599. SCF. 1 hit.
SUPFAMiSSF47266. SSF47266. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: P21583-1) [UniParc]FASTAAdd to basket
Also known as: SCF248

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
MKKTQTWILT CIYLQLLLFN PLVKTEGICR NRVTNNVKDV TKLVANLPKD
60 70 80 90 100
YMITLKYVPG MDVLPSHCWI SEMVVQLSDS LTDLLDKFSN ISEGLSNYSI
110 120 130 140 150
IDKLVNIVDD LVECVKENSS KDLKKSFKSP EPRLFTPEEF FRIFNRSIDA
160 170 180 190 200
FKDFVVASET SDCVVSSTLS PEKDSRVSVT KPFMLPPVAA SSLRNDSSSS
210 220 230 240 250
NRKAKNPPGD SSLHWAAMAL PALFSLIIGF AFGALYWKKR QPSLTRAVEN
260 270
IQINEEDNEI SMLQEKEREF QEV
Length:273
Mass (Da):30,899
Last modified:May 1, 1991 - v1
Checksum:i19FD362CB59C6607
GO
Isoform 2 (identifier: P21583-2) [UniParc]FASTAAdd to basket
Also known as: SCF220

The sequence of this isoform differs from the canonical sequence as follows:
     174-202: DSRVSVTKPFMLPPVAASSLRNDSSSSNR → G

Show »
Length:245
Mass (Da):27,867
Checksum:i937AEA64456DF4FA
GO
Isoform 3 (identifier: P21583-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-35: Missing.
     36-43: NVKDVTKL → MPSCLAAQ

Note: No experimental confirmation available.
Show »
Length:238
Mass (Da):26,667
Checksum:i7D6B1E487BE3709B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55L → S in AAD22048 (PubMed:10049787).Curated1
Sequence conflicti55L → S in AAK92486 (Ref. 4) Curated1
Sequence conflicti128K → R in AAD22048 (PubMed:10049787).Curated1
Sequence conflicti128K → R in AAK92486 (Ref. 4) Curated1
Sequence conflicti134L → F in AAD22048 (PubMed:10049787).Curated1
Sequence conflicti134L → F in AAK92486 (Ref. 4) Curated1

Polymorphismi

Genetic variants in KITLG define the skin/hair/eye pigmentation variation locus 7 (SHEP7) [MIMi:611664]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.
A non-coding SNP (dbSNP:rs12821256) has been shown to be associated with classic blond hair color in Europeans. This SNP is located 350 kb upstream from KITLG, in an enhancer specifically active in the hair follicle environment. It alters a LEF1 binding site, reducing LEF1 responsiveness in cultured keratinocytes. This SNP is not associated with eye pigmentation. It is most prevalent in Northern Europe (PubMed:24880339).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06323736N → S in FPHH; gain-of-function mutation; sKITLG reveales that the mutant Ser-36 sKITLG increases the content of the melanin by 109% compared with the wild-type sKITLG; tyrosinase activity is significantly increased by the mutant sKITLG compared to wild-type control. 1 PublicationCorresponds to variant rs121918653dbSNPEnsembl.1
Natural variantiVAR_04265254T → A.Corresponds to variant rs3741457dbSNPEnsembl.1
Natural variantiVAR_07622267 – 68HC → R in DCUA; loss of cell membrane association. 1 Publication2
Natural variantiVAR_076223104L → V Found in a patient with Waardenburg syndrome type 2 (WS2) and hearing loss; unknown pathological significance; reduces secretion. 1 Publication1
Natural variantiVAR_063238210D → Y.Corresponds to variant rs41283112dbSNPEnsembl.1
Natural variantiVAR_042653232F → Y.Corresponds to variant rs12721563dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0327621 – 35Missing in isoform 3. 1 PublicationAdd BLAST35
Alternative sequenceiVSP_03276336 – 43NVKDVTKL → MPSCLAAQ in isoform 3. 1 Publication8
Alternative sequenceiVSP_006022174 – 202DSRVS…SSSNR → G in isoform 2. 6 PublicationsAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59964 mRNA. Translation: AAA85450.1.
AF119835 mRNA. Translation: AAD22048.1.
AF400436 mRNA. Translation: AAK92485.1.
AF400437 mRNA. Translation: AAK92486.1.
AK290319 mRNA. Translation: BAF83008.1.
AK293002 mRNA. Translation: BAF85691.1.
CR749222 mRNA. Translation: CAH18078.1.
CH471054 Genomic DNA. Translation: EAW97417.1.
BC069733 mRNA. Translation: AAH69733.1.
BC069783 mRNA. Translation: AAH69783.1.
BC069797 mRNA. Translation: AAH69797.1.
BC074725 mRNA. Translation: AAH74725.1.
BC126166 mRNA. Translation: AAI26167.1.
BC143899 mRNA. Translation: AAI43900.1.
S42571 mRNA. Translation: AAB22846.2.
CCDSiCCDS31867.1. [P21583-2]
CCDS31868.1. [P21583-1]
PIRiA35974.
B61190.
S29052.
RefSeqiNP_000890.1. NM_000899.4. [P21583-1]
NP_003985.2. NM_003994.5. [P21583-2]
UniGeneiHs.1048.
Hs.661108.

Genome annotation databases

EnsembliENST00000228280; ENSP00000228280; ENSG00000049130. [P21583-1]
ENST00000347404; ENSP00000054216; ENSG00000049130. [P21583-2]
GeneIDi4254.
KEGGihsa:4254.
UCSCiuc001tav.4. human. [P21583-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Protein Spotlight

two's company - Issue 163 of August 2014

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M59964 mRNA. Translation: AAA85450.1.
AF119835 mRNA. Translation: AAD22048.1.
AF400436 mRNA. Translation: AAK92485.1.
AF400437 mRNA. Translation: AAK92486.1.
AK290319 mRNA. Translation: BAF83008.1.
AK293002 mRNA. Translation: BAF85691.1.
CR749222 mRNA. Translation: CAH18078.1.
CH471054 Genomic DNA. Translation: EAW97417.1.
BC069733 mRNA. Translation: AAH69733.1.
BC069783 mRNA. Translation: AAH69783.1.
BC069797 mRNA. Translation: AAH69797.1.
BC074725 mRNA. Translation: AAH74725.1.
BC126166 mRNA. Translation: AAI26167.1.
BC143899 mRNA. Translation: AAI43900.1.
S42571 mRNA. Translation: AAB22846.2.
CCDSiCCDS31867.1. [P21583-2]
CCDS31868.1. [P21583-1]
PIRiA35974.
B61190.
S29052.
RefSeqiNP_000890.1. NM_000899.4. [P21583-1]
NP_003985.2. NM_003994.5. [P21583-2]
UniGeneiHs.1048.
Hs.661108.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EXZX-ray2.30A/B/C/D26-166[»]
1SCFX-ray2.20A/B/C/D1-273[»]
2E9WX-ray3.50C/D26-166[»]
ProteinModelPortaliP21583.
SMRiP21583.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110410. 7 interactors.
IntActiP21583. 2 interactors.
STRINGi9606.ENSP00000228280.

Chemistry databases

BindingDBiP21583.
ChEMBLiCHEMBL2346489.

PTM databases

iPTMnetiP21583.
PhosphoSitePlusiP21583.

Polymorphism and mutation databases

BioMutaiKITLG.
DMDMi134289.

Proteomic databases

MaxQBiP21583.
PaxDbiP21583.
PeptideAtlasiP21583.
PRIDEiP21583.

Protocols and materials databases

DNASUi4254.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000228280; ENSP00000228280; ENSG00000049130. [P21583-1]
ENST00000347404; ENSP00000054216; ENSG00000049130. [P21583-2]
GeneIDi4254.
KEGGihsa:4254.
UCSCiuc001tav.4. human. [P21583-1]

Organism-specific databases

CTDi4254.
DisGeNETi4254.
GeneCardsiKITLG.
HGNCiHGNC:6343. KITLG.
HPAiCAB004569.
MalaCardsiKITLG.
MIMi145250. phenotype.
184745. gene.
611664. phenotype.
616697. phenotype.
neXtProtiNX_P21583.
OpenTargetsiENSG00000049130.
Orphaneti280628. Familial progressive hyper- and hypopigmentation.
79146. Familial progressive hyperpigmentation.
363494. Testicular non seminomatous germ cell tumor.
PharmGKBiPA30129.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF3Y. Eukaryota.
ENOG410XYQR. LUCA.
GeneTreeiENSGT00390000018272.
HOVERGENiHBG036146.
InParanoidiP21583.
KOiK05461.
OMAiVKTKGIC.
OrthoDBiEOG091G0I23.
PhylomeDBiP21583.
TreeFamiTF330811.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000049130-MONOMER.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1433559. Regulation of KIT signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
SIGNORiP21583.

Miscellaneous databases

ChiTaRSiKITLG. human.
EvolutionaryTraceiP21583.
GeneWikiiStem_cell_factor.
GenomeRNAii4254.
PMAP-CutDBP21583.
PROiP21583.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000049130.
CleanExiHS_KITLG.
ExpressionAtlasiP21583. baseline and differential.
GenevisibleiP21583. HS.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003452. SCF.
[Graphical view]
PANTHERiPTHR11574. PTHR11574. 1 hit.
PfamiPF02404. SCF. 1 hit.
[Graphical view]
PIRSFiPIRSF015599. SCF. 1 hit.
SUPFAMiSSF47266. SSF47266. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiSCF_HUMAN
AccessioniPrimary (citable) accession number: P21583
Secondary accession number(s): A0AV09
, A8K2Q4, B7ZLM4, Q16487, Q68DZ2, Q7M4N8, Q9UQK7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: November 30, 2016
This is version 163 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  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.