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

Transcription factor SOX-9

Gene

SOX9

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

Functioni

Plays an important role in the normal skeletal development. May regulate the expression of other genes involved in chondrogenesis by acting as a transcription factor for these genes.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi105 – 17369HMG boxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_264178. deactivation of the beta-catenin transactivating complex.
SignaLinkiP48436.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor SOX-9
Gene namesi
Name:SOX9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:11204. SOX9.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  • nuclear transcription factor complex Source: Ensembl
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Campomelic dysplasia (CMD1)10 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA rare, often lethal, osteochondrodysplasia characterized by congenital bowing and angulation of long bones. Other skeletal defects include unusually small scapula, deformed pelvis and spine, and a missing pair of ribs. Craniofacial and ear defects are common. Most patients die soon after birth due to respiratory distress which has been attributed to hypoplasia of the tracheobronchial cartilage and small thoracic cage. Up to two-thirds of affected XY individuals have genital defects or may develop as phenotypic females.

See also OMIM:114290
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti76 – 761A → E in CMD1; dimerization and the resulting capacity to activate promoters via dimeric binding sites is lost; other features of the protein function remain unaltered. 1 Publication
VAR_063642
Natural varianti108 – 1081P → L in CMD1. 1 Publication
VAR_003735
Natural varianti112 – 1121F → L in CMD1; loss of DNA binding. 2 Publications
VAR_003736
Natural varianti112 – 1121F → S in CMD1. 1 Publication
VAR_003737
Natural varianti113 – 1131M → T in CMD1. 1 Publication
VAR_063643
Natural varianti113 – 1131M → V in CMD1; residual DNA binding and transactivation of regulated genes. 1 Publication
VAR_063644
Natural varianti119 – 1191A → V in CMD1; almost no loss of DNA binding. 2 Publications
VAR_003738
Natural varianti143 – 1431W → R in CMD1. 1 Publication
VAR_003739
Natural varianti152 – 1521R → P in CMD1. 1 Publication
VAR_003740
Natural varianti154 – 1541F → L in CMD1; 5% of wild-type DNA binding activity; transcriptional activation is only reduced to 26% of wild-type activity. 1 Publication
VAR_008529
Natural varianti158 – 1581A → T in CMD1; 17% of wild-type DNA binding activity; shows a 2-fold reduction in nuclear import efficiency; transcriptional activation is only reduced to 62% of wild-type activity. 1 Publication
VAR_008530
Natural varianti165 – 1651H → Q in CMD1; residual DNA binding and transactivation of regulated genes. 1 Publication
VAR_063645
Natural varianti165 – 1651H → Y in CMD1; loss of DNA binding. 2 Publications
Corresponds to variant rs28940282 [ dbSNP | Ensembl ].
VAR_008531
Natural varianti170 – 1701P → L in CMD1. 1 Publication
VAR_063646
Natural varianti170 – 1701P → R in CMD1. 2 Publications
VAR_003741
Natural varianti173 – 1731K → E in CMD1. 1 Publication
VAR_063647
Natural varianti354 – 3563Missing in CMD1.
VAR_003742
46,XX sex reversal 2 (SRXX2)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA condition in which male gonads develop in a genetic female (female to male sex reversal).

See also OMIM:278850

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi114290. phenotype.
278850. phenotype.
Orphaneti2138. 46,XX ovotesticular disorder of sex development.
393. 46,XX testicular disorder of sex development.
140. Campomelic dysplasia.
718. Isolated Pierre Robin syndrome.
PharmGKBiPA36041.

Polymorphism and mutation databases

BioMutaiSOX9.
DMDMi1351096.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 509509Transcription factor SOX-9PRO_0000048739Add
BLAST

Proteomic databases

MaxQBiP48436.
PaxDbiP48436.
PRIDEiP48436.

PTM databases

PhosphoSiteiP48436.

Expressioni

Gene expression databases

BgeeiP48436.
CleanExiHS_SOX9.
GenevisibleiP48436. HS.

Organism-specific databases

HPAiCAB022456.
CAB068240.
HPA001758.

Interactioni

Protein-protein interaction databases

BioGridi112545. 17 interactions.
DIPiDIP-61319N.
IntActiP48436. 1 interaction.
STRINGi9606.ENSP00000245479.

Structurei

Secondary structure

1
509
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi111 – 12616Combined sources
Helixi132 – 14312Combined sources
Helixi148 – 16821Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1S9Mmodel-A101-177[»]
1SX9model-A101-177[»]
4EUWX-ray2.77A98-181[»]
ProteinModelPortaliP48436.
SMRiP48436. Positions 103-174.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi339 – 37840Gln/Pro-richAdd
BLAST
Compositional biasi342 – 3465Poly-Pro

Sequence similaritiesi

Contains 1 HMG box DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG295709.
GeneTreeiENSGT00760000118988.
HOGENOMiHOG000108876.
HOVERGENiHBG002061.
InParanoidiP48436.
KOiK18435.
OMAiSTFTYMS.
OrthoDBiEOG7Q2N5K.
PhylomeDBiP48436.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
InterProiIPR009071. HMG_box_dom.
IPR029548. SOX-9.
IPR022151. Sox_N.
[Graphical view]
PANTHERiPTHR10270:SF212. PTHR10270:SF212. 1 hit.
PfamiPF00505. HMG_box. 1 hit.
PF12444. Sox_N. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P48436-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNLLDPFMKM TDEQEKGLSG APSPTMSEDS AGSPCPSGSG SDTENTRPQE
60 70 80 90 100
NTFPKGEPDL KKESEEDKFP VCIREAVSQV LKGYDWTLVP MPVRVNGSSK
110 120 130 140 150
NKPHVKRPMN AFMVWAQAAR RKLADQYPHL HNAELSKTLG KLWRLLNESE
160 170 180 190 200
KRPFVEEAER LRVQHKKDHP DYKYQPRRRK SVKNGQAEAE EATEQTHISP
210 220 230 240 250
NAIFKALQAD SPHSSSGMSE VHSPGEHSGQ SQGPPTPPTT PKTDVQPGKA
260 270 280 290 300
DLKREGRPLP EGGRQPPIDF RDVDIGELSS DVISNIETFD VNEFDQYLPP
310 320 330 340 350
NGHPGVPATH GQVTYTGSYG ISSTAATPAS AGHVWMSKQQ APPPPPQQPP
360 370 380 390 400
QAPPAPQAPP QPQAAPPQQP AAPPQQPQAH TLTTLSSEPG QSQRTHIKTE
410 420 430 440 450
QLSPSHYSEQ QQHSPQQIAY SPFNLPHYSP SYPPITRSQY DYTDHQNSSS
460 470 480 490 500
YYSHAAGQGT GLYSTFTYMN PAQRPMYTPI ADTSGVPSIP QTHSPQHWEQ

PVYTQLTRP
Length:509
Mass (Da):56,137
Last modified:February 1, 1996 - v1
Checksum:i9289CFBB8D6631A2
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti76 – 761A → E in CMD1; dimerization and the resulting capacity to activate promoters via dimeric binding sites is lost; other features of the protein function remain unaltered. 1 Publication
VAR_063642
Natural varianti108 – 1081P → L in CMD1. 1 Publication
VAR_003735
Natural varianti112 – 1121F → L in CMD1; loss of DNA binding. 2 Publications
VAR_003736
Natural varianti112 – 1121F → S in CMD1. 1 Publication
VAR_003737
Natural varianti113 – 1131M → T in CMD1. 1 Publication
VAR_063643
Natural varianti113 – 1131M → V in CMD1; residual DNA binding and transactivation of regulated genes. 1 Publication
VAR_063644
Natural varianti119 – 1191A → V in CMD1; almost no loss of DNA binding. 2 Publications
VAR_003738
Natural varianti143 – 1431W → R in CMD1. 1 Publication
VAR_003739
Natural varianti152 – 1521R → P in CMD1. 1 Publication
VAR_003740
Natural varianti154 – 1541F → L in CMD1; 5% of wild-type DNA binding activity; transcriptional activation is only reduced to 26% of wild-type activity. 1 Publication
VAR_008529
Natural varianti158 – 1581A → T in CMD1; 17% of wild-type DNA binding activity; shows a 2-fold reduction in nuclear import efficiency; transcriptional activation is only reduced to 62% of wild-type activity. 1 Publication
VAR_008530
Natural varianti165 – 1651H → Q in CMD1; residual DNA binding and transactivation of regulated genes. 1 Publication
VAR_063645
Natural varianti165 – 1651H → Y in CMD1; loss of DNA binding. 2 Publications
Corresponds to variant rs28940282 [ dbSNP | Ensembl ].
VAR_008531
Natural varianti170 – 1701P → L in CMD1. 1 Publication
VAR_063646
Natural varianti170 – 1701P → R in CMD1. 2 Publications
VAR_003741
Natural varianti173 – 1731K → E in CMD1. 1 Publication
VAR_063647
Natural varianti354 – 3563Missing in CMD1.
VAR_003742

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46629 mRNA. Translation: CAA86598.1.
S74506, S74504, S74505 Genomic DNA. Translation: AAB32870.1.
BT006875 mRNA. Translation: AAP35521.1.
CH471099 Genomic DNA. Translation: EAW89102.1.
BC007951 mRNA. Translation: AAH07951.1.
BC056420 mRNA. Translation: AAH56420.1.
CCDSiCCDS11689.1.
PIRiA55204.
RefSeqiNP_000337.1. NM_000346.3.
UniGeneiHs.647409.

Genome annotation databases

EnsembliENST00000245479; ENSP00000245479; ENSG00000125398.
GeneIDi6662.
KEGGihsa:6662.
UCSCiuc002jiw.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46629 mRNA. Translation: CAA86598.1.
S74506, S74504, S74505 Genomic DNA. Translation: AAB32870.1.
BT006875 mRNA. Translation: AAP35521.1.
CH471099 Genomic DNA. Translation: EAW89102.1.
BC007951 mRNA. Translation: AAH07951.1.
BC056420 mRNA. Translation: AAH56420.1.
CCDSiCCDS11689.1.
PIRiA55204.
RefSeqiNP_000337.1. NM_000346.3.
UniGeneiHs.647409.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1S9Mmodel-A101-177[»]
1SX9model-A101-177[»]
4EUWX-ray2.77A98-181[»]
ProteinModelPortaliP48436.
SMRiP48436. Positions 103-174.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112545. 17 interactions.
DIPiDIP-61319N.
IntActiP48436. 1 interaction.
STRINGi9606.ENSP00000245479.

PTM databases

PhosphoSiteiP48436.

Polymorphism and mutation databases

BioMutaiSOX9.
DMDMi1351096.

Proteomic databases

MaxQBiP48436.
PaxDbiP48436.
PRIDEiP48436.

Protocols and materials databases

DNASUi6662.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245479; ENSP00000245479; ENSG00000125398.
GeneIDi6662.
KEGGihsa:6662.
UCSCiuc002jiw.3. human.

Organism-specific databases

CTDi6662.
GeneCardsiGC17P070117.
GeneReviewsiSOX9.
HGNCiHGNC:11204. SOX9.
HPAiCAB022456.
CAB068240.
HPA001758.
MIMi114290. phenotype.
278850. phenotype.
608160. gene.
neXtProtiNX_P48436.
Orphaneti2138. 46,XX ovotesticular disorder of sex development.
393. 46,XX testicular disorder of sex development.
140. Campomelic dysplasia.
718. Isolated Pierre Robin syndrome.
PharmGKBiPA36041.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG295709.
GeneTreeiENSGT00760000118988.
HOGENOMiHOG000108876.
HOVERGENiHBG002061.
InParanoidiP48436.
KOiK18435.
OMAiSTFTYMS.
OrthoDBiEOG7Q2N5K.
PhylomeDBiP48436.

Enzyme and pathway databases

ReactomeiREACT_264178. deactivation of the beta-catenin transactivating complex.
SignaLinkiP48436.

Miscellaneous databases

ChiTaRSiSOX9. human.
GeneWikiiSOX9.
GenomeRNAii6662.
NextBioi25973.
PROiP48436.
SOURCEiSearch...

Gene expression databases

BgeeiP48436.
CleanExiHS_SOX9.
GenevisibleiP48436. HS.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
InterProiIPR009071. HMG_box_dom.
IPR029548. SOX-9.
IPR022151. Sox_N.
[Graphical view]
PANTHERiPTHR10270:SF212. PTHR10270:SF212. 1 hit.
PfamiPF00505. HMG_box. 1 hit.
PF12444. Sox_N. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene."
    Foster J.W., Dominguez-Steglich M.A., Guioli S., Kowk G., Weller P.A., Stevanovic M., Weissenbach J., Mansour S., Young I.D., Goodfellow P.N., Schafer A.J.
    Nature 372:525-530(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Testis.
  2. "Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9."
    Wagner T., Wirth J., Meyer J., Zabel B., Held M., Zimmer J., Pasantes J., Bricarelli F.D., Keutel J., Hustert E., Wolf U., Tommerup N., Schempp W., Scherer G.
    Cell 79:1111-1120(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Eye and PNS.
  6. "A SOX9 duplication and familial 46,XX developmental testicular disorder."
    Cox J.J., Willatt L., Homfray T., Woods C.G.
    N. Engl. J. Med. 364:91-93(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SRXX2.
  7. "Mutations in SRY and SOX9: testis-determining genes."
    Cameron F.J., Sinclair A.H.
    Hum. Mutat. 9:388-395(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON VARIANTS.
  8. "Mutations in SOX9, the gene responsible for Campomelic dysplasia and autosomal sex reversal."
    Kwok C., Weller P.A., Guioli S., Foster J.W., Mansour S., Zuffardi O., Punnett H.H., Dominguez-Steglich M.A., Brook J.D., Young I.D., Goodfellow P.N., Schafer A.J.
    Am. J. Hum. Genet. 57:1028-1036(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CMD1 LEU-112 AND VAL-119.
  9. "Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations."
    Meyer J., Suedbeck P., Held M., Wagner T., Schmitz M.L., Bricarelli F.D., Eggermont E., Friedrich U., Haas O.A., Kobelt A., Leroy J.G., van Maldergem L., Michel E., Mitulla B., Pfeiffer R.A., Schinzel A., Schmidt H., Scherer G.
    Hum. Mol. Genet. 6:91-98(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CMD1 LEU-108; ARG-143; PRO-152 AND ARG-170.
  10. "Novel missense mutation in the HMG box of SOX9 gene in a Japanese XY male resulted in campomelic dysplasia and severe defect in masculinization."
    Goji K., Nishijima E., Tsugawa C., Nishio H., Pokharel R.K., Matsuo M.
    Hum. Mutat. Suppl. 1:S114-S116(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CMD1 SER-112.
  11. "Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia."
    McDowall S., Argentaro A., Ranganathan S., Weller P., Mertin S., Mansour S., Tolmie J., Harley V.
    J. Biol. Chem. 274:24023-24030(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CMD1 LEU-112; VAL-119; TYR-165 AND ARG-170, 3D-STRUCTURE MODELING.
  12. Cited for: VARIANT CMD1 GLU-173.
  13. Cited for: VARIANT CMD1 TYR-165.
  14. "Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation."
    Preiss S., Argentaro A., Clayton A., John A., Jans D.A., Ogata T., Nagai T., Barroso I., Schafer A.J., Harley V.R.
    J. Biol. Chem. 276:27864-27872(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CMD1 LEU-154 AND THR-158, CHARACTERIZATION OF VARIANTS CMD1 LEU-154 AND THR-158.
  15. "Loss of DNA-dependent dimerization of the transcription factor SOX9 as a cause for campomelic dysplasia."
    Sock E., Pagon R.A., Keymolen K., Lissens W., Wegner M., Scherer G.
    Hum. Mol. Genet. 12:1439-1447(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CMD1 GLU-76.
  16. "Mutation analysis of SOX9 and single copy number variant analysis of the upstream region in eight patients with campomelic dysplasia and acampomelic campomelic dysplasia."
    Wada Y., Nishimura G., Nagai T., Sawai H., Yoshikata M., Miyagawa S., Hanita T., Sato S., Hasegawa T., Ishikawa S., Ogata T.
    Am. J. Med. Genet. A 149:2882-2885(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CMD1 THR-113 AND LEU-170.
  17. "Heterozygous SOX9 mutations allowing for residual DNA-binding and transcriptional activation lead to the acampomelic variant of campomelic dysplasia."
    Staffler A., Hammel M., Wahlbuhl M., Bidlingmaier C., Flemmer A.W., Pagel P., Nicolai T., Wegner M., Holzinger A.
    Hum. Mutat. 31:E1436-E1444(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CMD1 VAL-113 AND GLN-165, CHARACTERIZATION OF VARIANTS CMD1 VAL-113 AND GLN-165.

Entry informationi

Entry nameiSOX9_HUMAN
AccessioniPrimary (citable) accession number: P48436
Secondary accession number(s): Q53Y80
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: June 24, 2015
This is version 158 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, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.