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Protein

Tumor susceptibility gene 101 protein

Gene

TSG101

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

Functioni

Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).6 Publications

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • DNA binding Source: ProtInc
  • ligand-dependent nuclear receptor transcription coactivator activity Source: Ensembl
  • protein homodimerization activity Source: UniProtKB
  • transcription corepressor activity Source: ProtInc
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • virion binding Source: UniProtKB

GO - Biological processi

  • autophagosome maturation Source: ParkinsonsUK-UCL
  • autophagy Source: ParkinsonsUK-UCL
  • cell cycle arrest Source: Ensembl
  • cell division Source: UniProtKB-KW
  • endosomal transport Source: Reactome
  • endosome to lysosome transport Source: Ensembl
  • intracellular transport of virus Source: Reactome
  • keratinocyte differentiation Source: Ensembl
  • multivesicular body assembly Source: ParkinsonsUK-UCL
  • negative regulation of cell proliferation Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: Ensembl
  • positive regulation of exosomal secretion Source: UniProtKB
  • positive regulation of ubiquitin-dependent endocytosis Source: Ensembl
  • positive regulation of viral budding via host ESCRT complex Source: UniProtKB
  • positive regulation of viral process Source: UniProtKB
  • positive regulation of viral release from host cell Source: UniProtKB
  • protein monoubiquitination Source: Ensembl
  • protein transport Source: UniProtKB-KW
  • regulation of cell growth Source: Ensembl
  • regulation of extracellular exosome assembly Source: UniProtKB
  • regulation of MAP kinase activity Source: UniProtKB
  • regulation of viral budding via host ESCRT complex Source: UniProtKB
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: UniProtKB
  • viral budding Source: UniProtKB
  • viral budding via host ESCRT complex Source: ParkinsonsUK-UCL
  • viral life cycle Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Growth regulation, Host-virus interaction, Protein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-162588. Budding and maturation of HIV virion.
R-HSA-174490. Membrane binding and targetting of GAG proteins.
R-HSA-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor susceptibility gene 101 protein
Alternative name(s):
ESCRT-I complex subunit TSG101
Gene namesi
Name:TSG101
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:15971. TSG101.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • early endosome Source: UniProtKB
  • endosome Source: UniProtKB
  • endosome membrane Source: Reactome
  • ESCRT I complex Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • late endosome Source: BHF-UCL
  • late endosome membrane Source: UniProtKB-SubCell
  • multivesicular body Source: HGNC
  • nucleolus Source: HPA
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi43 – 431V → A: Reduces interaction with ubiquitin; inhibits down-regulation of EGFR. 1 Publication
Mutagenesisi45 – 451N → A: Reduces interaction with ubiquitin. No effect on MGRN1-binding. 3 Publications
Mutagenesisi46 – 461D → A: Reduces interaction with ubiquitin. 1 Publication
Mutagenesisi63 – 631Y → A: Reduces interaction with HIV-1 p6; impairs HIV-1 budding. 1 Publication
Mutagenesisi88 – 881F → A: Reduces interaction with ubiquitin; no effect on in interaction with HIV-1 p6. 1 Publication
Mutagenesisi89 – 891V → A: No change in interaction with p6; no effect on HIV-1 budding. 1 Publication
Mutagenesisi95 – 951M → A: Reduces interaction with VPS37B and HIV-1 p6; abolishes interaction with PDCD6IP; impairs HIV-1 budding; inhibits down-regulation of EGFR. Abolishes MGRN1-binding. 5 Publications
Mutagenesisi141 – 1411V → A: Reduces interaction with HIV-1 p6. 1 Publication
Mutagenesisi158 – 1625Missing : Abolishes interaction with CEP55 and midbody localization; no effect on interaction with ESCRT-I proteins, PDCD6IP and viral proteins. 1 Publication
Mutagenesisi158 – 1603PPN → AAA: Abolishes interaction with CEP55. 1 Publication
Mutagenesisi368 – 3714RKQF → AAAA: Loss of interaction with VPS28. No effect on interaction with VPS37C. 1 Publication

Organism-specific databases

MalaCardsiTSG101.
PharmGKBiPA38068.

Chemistry

ChEMBLiCHEMBL6157.

Polymorphism and mutation databases

BioMutaiTSG101.
DMDMi9789790.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 390389Tumor susceptibility gene 101 proteinPRO_0000082606Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources
Modified residuei220 – 2201PhosphothreonineCombined sources

Post-translational modificationi

Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1. Ubiquitination inactivates it, possibly by regulating its shuttling between an active membrane-bound protein and an inactive soluble form. Ubiquitination by MGRN1 requires the presence of UBE2D1.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99816.
MaxQBiQ99816.
PaxDbiQ99816.
PeptideAtlasiQ99816.
PRIDEiQ99816.

PTM databases

iPTMnetiQ99816.
PhosphoSiteiQ99816.

Expressioni

Tissue specificityi

Heart, brain, placenta, lung, liver, skeletal, kidney and pancreas.

Gene expression databases

BgeeiENSG00000074319.
CleanExiHS_TSG101.
ExpressionAtlasiQ99816. baseline and differential.
GenevisibleiQ99816. HS.

Organism-specific databases

HPAiCAB004283.
HPA006161.

Interactioni

Subunit structurei

Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoechiometry. Interacts with VPS37A, VPS37B and VPS37C. Interacts with ubiquitin, stathmin, GMCL, DMAP1 and AATF (By similarity). Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoechiometry. Interacts with HGS; the interaction mediates the association with the ESCRT-0 complex. Interacts with GGA1 and GGA3. Interacts (via UEV domain) with PDCD6IP/AIP1. Interacts with VPS28, SNF8 and VPS36. Self-associates. Interacts with MVB12A; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D. Interacts with LRSAM1. Interacts with CEP55; the interaction is required for cytokinesis but not for viral budding. Interacts with PDCD6. Interacts with HIV-1 p6. Interacts with human spumavirus Gag. Interacts with HTLV-1 Gag. Interacts with Ebola virus VP40. Interacts with EIAV p9; the interaction has been shown in vitro. Interacts with MGRN1.By similarity26 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD2APQ9Y5K62EBI-346882,EBI-298152
CEP55D3DR374EBI-346882,EBI-10173536
CEP55Q53EZ417EBI-346882,EBI-747776
DAXXQ9UER74EBI-346882,EBI-77321
FAM9BQ8IZU03EBI-346882,EBI-10175124
HAUS1Q96CS23EBI-346882,EBI-2514791
HGSO149644EBI-346882,EBI-740220
HgsQ99LI83EBI-346882,EBI-2119135From a different organism.
IQGAP1P469405EBI-346882,EBI-297509
KIFC3Q9BVG83EBI-346882,EBI-2125614
KRT13A1A4E93EBI-346882,EBI-10171552
KRT31Q153233EBI-346882,EBI-948001
LITAFQ997323EBI-346882,EBI-725647
LRSAM1Q6UWE05EBI-346882,EBI-720984
MGRN1O602914EBI-346882,EBI-2129851
PDLIM7Q9NR123EBI-346882,EBI-350517
PTPN23Q9H3S72EBI-346882,EBI-724478
ROCK1Q134644EBI-346882,EBI-876651
SYCE1Q8N0S23EBI-346882,EBI-6872807
TAX1BP1Q86VP13EBI-346882,EBI-529518
USHBP1Q8N6Y03EBI-346882,EBI-739895
VPS28Q9UK416EBI-346882,EBI-727424
VPS37AQ8NEZ23EBI-346882,EBI-2850578
VPS37AQ8NEZ2-25EBI-346882,EBI-10270911
VPS37CA5D8V63EBI-346882,EBI-2559305

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113102. 155 interactions.
DIPiDIP-31809N.
IntActiQ99816. 105 interactions.
MINTiMINT-234338.
STRINGi9606.ENSP00000251968.

Chemistry

BindingDBiQ99816.

Structurei

Secondary structure

1
390
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi5 – 117Combined sources
Turni12 – 143Combined sources
Helixi18 – 3114Combined sources
Beta strandi35 – 4410Combined sources
Turni47 – 493Combined sources
Beta strandi51 – 6212Combined sources
Beta strandi67 – 759Combined sources
Turni78 – 825Combined sources
Beta strandi86 – 894Combined sources
Beta strandi95 – 973Combined sources
Beta strandi100 – 1034Combined sources
Beta strandi107 – 1093Combined sources
Helixi112 – 1154Combined sources
Turni119 – 1213Combined sources
Helixi124 – 13714Combined sources
Beta strandi140 – 1434Combined sources
Helixi230 – 29970Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KPPNMR-A1-145[»]
1KPQNMR-A1-145[»]
1M4PNMR-A1-145[»]
1M4QNMR-A1-145[»]
1S1QX-ray2.00A/C1-145[»]
2F0RX-ray2.26A/B1-145[»]
3IV1X-ray2.50A/B/C/D/E/F/G/H229-304[»]
3OBQX-ray1.40A2-145[»]
3OBSX-ray1.50A2-145[»]
3OBUX-ray1.60A2-145[»]
3OBXX-ray1.60A2-145[»]
3P9GX-ray1.80A2-145[»]
3P9HX-ray1.80A2-145[»]
4EJEX-ray2.20A/B1-145[»]
4YC1X-ray2.00A/B/C1-145[»]
ProteinModelPortaliQ99816.
SMRiQ99816. Positions 3-143, 228-379.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99816.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 145144UEVPROSITE-ProRule annotationAdd
BLAST
Domaini322 – 39069SBPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni158 – 1625Interaction with CEP55

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili235 – 31682Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi320 – 3234PTAP motif

Domaini

The UEV domain is required for the interaction of the complex with ubiquitin. It also mediates the interaction with PTAP/PSAP motifs of HIV-1 P6 protein and human spumaretrovirus Gag protein.
The coiled coil domain may interact with stathmin.
The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif independently.

Sequence similaritiesi

Contains 1 SB (steadiness box) domain.PROSITE-ProRule annotation
Contains 1 UEV (ubiquitin E2 variant) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2391. Eukaryota.
ENOG410XT2Q. LUCA.
GeneTreeiENSGT00530000064004.
HOGENOMiHOG000247008.
HOVERGENiHBG057450.
InParanoidiQ99816.
KOiK12183.
OMAiPVMDSYV.
OrthoDBiEOG091G0HRA.
PhylomeDBiQ99816.
TreeFamiTF312917.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR017916. SB_dom.
IPR016135. UBQ-conjugating_enzyme/RWD.
IPR008883. UEV_N.
[Graphical view]
PfamiPF05743. UEV. 1 hit.
PF09454. Vps23_core. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS51312. SB. 1 hit.
PS51322. UEV. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Note: Additional isoforms seem to exist. Several shorter isoforms are detected in primary breast cancers and other tumors.
Isoform 1 (identifier: Q99816-1) [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
MAVSESQLKK MVSKYKYRDL TVRETVNVIT LYKDLKPVLD SYVFNDGSSR
60 70 80 90 100
ELMNLTGTIP VPYRGNTYNI PICLWLLDTY PYNPPICFVK PTSSMTIKTG
110 120 130 140 150
KHVDANGKIY LPYLHEWKHP QSDLLGLIQV MIVVFGDEPP VFSRPISASY
160 170 180 190 200
PPYQATGPPN TSYMPGMPGG ISPYPSGYPP NPSGYPGCPY PPGGPYPATT
210 220 230 240 250
SSQYPSQPPV TTVGPSRDGT ISEDTIRASL ISAVSDKLRW RMKEEMDRAQ
260 270 280 290 300
AELNALKRTE EDLKKGHQKL EEMVTRLDQE VAEVDKNIEL LKKKDEELSS
310 320 330 340 350
ALEKMENQSE NNDIDEVIIP TAPLYKQILN LYAEENAIED TIFYLGEALR
360 370 380 390
RGVIDLDVFL KHVRLLSRKQ FQLRALMQKA RKTAGLSDLY
Length:390
Mass (Da):43,944
Last modified:August 1, 1998 - v2
Checksum:iADD6912FC22DF162
GO
Isoform 2 (identifier: Q99816-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     15-119: Missing.

Note: Detected in normal as well as cancer tissues.
Show »
Length:285
Mass (Da):31,732
Checksum:i035C70BEC887273D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti343 – 3431F → L in AAH02487 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti167 – 1671M → I.
Corresponds to variant rs34385327 [ dbSNP | Ensembl ].
VAR_034572

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei15 – 119105Missing in isoform 2. CuratedVSP_004440Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82130 mRNA. Translation: AAC52083.1.
BC002487 mRNA. Translation: AAH02487.1.
CCDSiCCDS7842.1. [Q99816-1]
RefSeqiNP_006283.1. NM_006292.3. [Q99816-1]
UniGeneiHs.523512.

Genome annotation databases

EnsembliENST00000251968; ENSP00000251968; ENSG00000074319. [Q99816-1]
GeneIDi7251.
KEGGihsa:7251.
UCSCiuc001mor.4. human. [Q99816-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U82130 mRNA. Translation: AAC52083.1.
BC002487 mRNA. Translation: AAH02487.1.
CCDSiCCDS7842.1. [Q99816-1]
RefSeqiNP_006283.1. NM_006292.3. [Q99816-1]
UniGeneiHs.523512.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KPPNMR-A1-145[»]
1KPQNMR-A1-145[»]
1M4PNMR-A1-145[»]
1M4QNMR-A1-145[»]
1S1QX-ray2.00A/C1-145[»]
2F0RX-ray2.26A/B1-145[»]
3IV1X-ray2.50A/B/C/D/E/F/G/H229-304[»]
3OBQX-ray1.40A2-145[»]
3OBSX-ray1.50A2-145[»]
3OBUX-ray1.60A2-145[»]
3OBXX-ray1.60A2-145[»]
3P9GX-ray1.80A2-145[»]
3P9HX-ray1.80A2-145[»]
4EJEX-ray2.20A/B1-145[»]
4YC1X-ray2.00A/B/C1-145[»]
ProteinModelPortaliQ99816.
SMRiQ99816. Positions 3-143, 228-379.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113102. 155 interactions.
DIPiDIP-31809N.
IntActiQ99816. 105 interactions.
MINTiMINT-234338.
STRINGi9606.ENSP00000251968.

Chemistry

BindingDBiQ99816.
ChEMBLiCHEMBL6157.

PTM databases

iPTMnetiQ99816.
PhosphoSiteiQ99816.

Polymorphism and mutation databases

BioMutaiTSG101.
DMDMi9789790.

Proteomic databases

EPDiQ99816.
MaxQBiQ99816.
PaxDbiQ99816.
PeptideAtlasiQ99816.
PRIDEiQ99816.

Protocols and materials databases

DNASUi7251.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000251968; ENSP00000251968; ENSG00000074319. [Q99816-1]
GeneIDi7251.
KEGGihsa:7251.
UCSCiuc001mor.4. human. [Q99816-1]

Organism-specific databases

CTDi7251.
GeneCardsiTSG101.
HGNCiHGNC:15971. TSG101.
HPAiCAB004283.
HPA006161.
MalaCardsiTSG101.
MIMi601387. gene.
neXtProtiNX_Q99816.
PharmGKBiPA38068.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2391. Eukaryota.
ENOG410XT2Q. LUCA.
GeneTreeiENSGT00530000064004.
HOGENOMiHOG000247008.
HOVERGENiHBG057450.
InParanoidiQ99816.
KOiK12183.
OMAiPVMDSYV.
OrthoDBiEOG091G0HRA.
PhylomeDBiQ99816.
TreeFamiTF312917.

Enzyme and pathway databases

ReactomeiR-HSA-162588. Budding and maturation of HIV virion.
R-HSA-174490. Membrane binding and targetting of GAG proteins.
R-HSA-917729. Endosomal Sorting Complex Required For Transport (ESCRT).

Miscellaneous databases

ChiTaRSiTSG101. human.
EvolutionaryTraceiQ99816.
GeneWikiiTSG101.
GenomeRNAii7251.
PROiQ99816.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000074319.
CleanExiHS_TSG101.
ExpressionAtlasiQ99816. baseline and differential.
GenevisibleiQ99816. HS.

Family and domain databases

Gene3Di3.10.110.10. 1 hit.
InterProiIPR017916. SB_dom.
IPR016135. UBQ-conjugating_enzyme/RWD.
IPR008883. UEV_N.
[Graphical view]
PfamiPF05743. UEV. 1 hit.
PF09454. Vps23_core. 1 hit.
[Graphical view]
SUPFAMiSSF54495. SSF54495. 1 hit.
PROSITEiPS51312. SB. 1 hit.
PS51322. UEV. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTS101_HUMAN
AccessioniPrimary (citable) accession number: Q99816
Secondary accession number(s): Q9BUM5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: August 1, 1998
Last modified: September 7, 2016
This is version 185 of the entry and version 2 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 11
    Human chromosome 11: 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

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.