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Protein

Tuberin

Gene

Tsc2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5.By similarity

GO - Molecular functioni

GO - Biological processi

  • cell projection organization Source: MGI
  • cellular response to insulin stimulus Source: MGI
  • glucose import Source: MGI
  • heart development Source: MGI
  • insulin-like growth factor receptor signaling pathway Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of cell size Source: MGI
  • negative regulation of phosphatidylinositol 3-kinase signaling Source: MGI
  • negative regulation of protein kinase activity Source: MGI
  • negative regulation of protein kinase B signaling Source: MGI
  • negative regulation of TORC1 signaling Source: ParkinsonsUK-UCL
  • negative regulation of TOR signaling Source: MGI
  • neural tube closure Source: MGI
  • phosphatidylinositol 3-kinase signaling Source: MGI
  • positive chemotaxis Source: MGI
  • positive regulation of autophagy Source: ParkinsonsUK-UCL
  • positive regulation of macroautophagy Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein import into nucleus Source: MGI
  • protein kinase B signaling Source: MGI
  • protein localization Source: MGI
  • protein transport into plasma membrane raft Source: MGI
  • regulation of endocytosis Source: MGI
  • regulation of insulin receptor signaling pathway Source: MGI
  • regulation of small GTPase mediated signal transduction Source: InterPro
  • response to hypoxia Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Names & Taxonomyi

Protein namesi
Recommended name:
Tuberin
Alternative name(s):
Tuberous sclerosis 2 protein homolog
Gene namesi
Name:Tsc2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:102548. Tsc2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • lysosome Source: MGI
  • membrane Source: MGI
  • perinuclear region of cytoplasm Source: MGI
  • TSC1-TSC2 complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 18141814TuberinPRO_0000065655Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei540 – 5401PhosphoserineBy similarity
Modified residuei664 – 6641PhosphoserineBy similarity
Modified residuei927 – 9271PhosphothreonineBy similarity
Modified residuei939 – 9391Phosphoserine; by PKB/AKT1By similarity
Modified residuei981 – 9811PhosphoserineBy similarity
Modified residuei1132 – 11321PhosphoserineCombined sources
Modified residuei1155 – 11551PhosphoserineBy similarity
Modified residuei1339 – 13391PhosphoserineBy similarity
Modified residuei1340 – 13401PhosphoserineBy similarity
Modified residuei1348 – 13481PhosphoserineBy similarity
Modified residuei1388 – 13881PhosphoserineBy similarity
Modified residuei1412 – 14121PhosphoserineBy similarity
Modified residuei1419 – 14191PhosphoserineBy similarity
Modified residuei1421 – 14211PhosphoserineBy similarity
Modified residuei1451 – 14511Phosphoserine; by AMPKBy similarity
Modified residuei1455 – 14551PhosphoserineBy similarity
Modified residuei1465 – 14651Phosphothreonine; by PKB/AKT1By similarity
Modified residuei1772 – 17721PhosphoserineCombined sources
Modified residuei1805 – 18051Phosphoserine; by RPS6KA1By similarity

Post-translational modificationi

Phosphorylation at Ser-1388, Ser-1419 or Ser-1421 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1465 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it and leads to negatively regulates the mTORC1 complex. Phosphorylated at Ser-1805 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK1.By similarity
Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2 independently of its phosphorylation status leading to subsequent degradation; association with TSC1 protects from ubiquitination.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ61037.
MaxQBiQ61037.
PRIDEiQ61037.

PTM databases

iPTMnetiQ61037.
PhosphoSiteiQ61037.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

CleanExiMM_TSC2.

Interactioni

Subunit structurei

Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1. May also interact with the adapter molecule RABEP1. The final complex contains TSC2 and RABEP1 linked to RAB5. Interacts with HSPA1 and HSPA8. Interacts with DAPK1. Interacts with FBXW5. Interacts with NAA10 (via C-terminal domain). Interacts with RRAGA (polyubiquitinated).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Tsc1Q9EP535EBI-7924402,EBI-1202690

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ61037. 5 interactions.
MINTiMINT-5068541.

Structurei

3D structure databases

ProteinModelPortaliQ61037.
SMRiQ61037. Positions 1520-1675.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1532 – 1766235Rap-GAPPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 Rap-GAP domain.PROSITE-ProRule annotation

Phylogenomic databases

HOVERGENiHBG018005.
InParanoidiQ61037.
PhylomeDBiQ61037.

Family and domain databases

Gene3Di1.25.10.10. 3 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000331. Rap_GAP_dom.
IPR003913. Tuberin.
IPR018515. Tuberin-type_domain.
IPR024584. Tuberin_N.
[Graphical view]
PANTHERiPTHR10063:SF1. PTHR10063:SF1. 4 hits.
PfamiPF11864. DUF3384. 1 hit.
PF02145. Rap_GAP. 1 hit.
PF03542. Tuberin. 1 hit.
[Graphical view]
PRINTSiPR01431. TUBERIN.
SUPFAMiSSF111347. SSF111347. 1 hit.
SSF48371. SSF48371. 1 hit.
PROSITEiPS50085. RAPGAP. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform G (identifier: Q61037-1) [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
MAKPTSKDSG LKEKFKILLG LGTSRPNPRC AEGKQTEFII TSEILRELSG
60 70 80 90 100
ECGLNNRIRM IGQICDVAKT KKLEEHAVEA LWKAVSDLLQ PERPPEARHA
110 120 130 140 150
VLTLLKAIVQ GQGDRLGVLR ALFFKVIKDY PSNEDLHERL EVFKALTDNG
160 170 180 190 200
RHITYLEEEL AEFVLQWMDV GLSSEFLLVL VNLVKFNSCY LDEYIASMVH
210 220 230 240 250
MICLLCIRTV SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI ITLCRTINVK
260 270 280 290 300
ELCEPCWKLM RNLLGTHLGH SAIYNMCRIM EDRSYMEDAP LLRGAVFFVG
310 320 330 340 350
MALWGAHRLY SLKNSPTSVL PSFYEAMTCP NEVVSYEIVL SITRLIKKYR
360 370 380 390 400
KELQAVTWDI LLDIIERLLQ QLQNLDSPEL KTIVHDLLTT VEELCDQNEF
410 420 430 440 450
HGSQERYYEL VESYADQRPE SSLLNLISYR AQSIHPAKDG WIQNLQLLME
460 470 480 490 500
RFFRNECRSA VAIKVLDVLS FVLLIIRQFY EEELINSVVI SQLSHIPEDK
510 520 530 540 550
DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS PPPELEERDL
560 570 580 590 600
AVHSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYESL ISHIQLHYKH
610 620 630 640 650
GYSLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCLCDCME
660 670 680 690 700
LDRASEKKAS GPLSPPTGPP SPVPMGPAVR LGYLPYSLLF RVLLQCLKQE
710 720 730 740 750
SDWKVLKLVL SRLPESLRYK VLIFTSPCSV DQLSSALCSM LSAPKTLERL
760 770 780 790 800
RGTPEGFSRT DLHLAVVPVL TALISYHNYL DKTRQREMVY CLEQGLIYRC
810 820 830 840 850
ASQCVVALAI CSVEMPDIII KALPVLVVKL THISATASMA IPLLEFLSTL
860 870 880 890 900
ARLPHLYRNF VPEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC
910 920 930 940 950
RLPFRKDFVP YITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSLRIA
960 970 980 990 1000
RAPKQGLNNS PPVKEFKESC AAEAFRCRSI SVSEHVVRSR IQTSLTSASL
1010 1020 1030 1040 1050
GSADENSMAQ ADDNLKNLHL ELTETCLDMM ARYVFSNFTA VPKRSPVGEF
1060 1070 1080 1090 1100
LLAGGRTKTW LVGNKLVTVT TSVGTGTRSL LGLDSGDLQG GSDSSSDPST
1110 1120 1130 1140 1150
HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG VLDTSAPYSP
1160 1170 1180 1190 1200
GGSASLGPQT AVAAKPEKPP AGAQLPTAEK TNLAAYVPLL TQGWAEILVR
1210 1220 1230 1240 1250
RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHGHAPVQ
1260 1270 1280 1290 1300
VIVSATGCTA KPPTLPRSNT VASFSSLYQP SCQGQLHRSV SWADSAMVLE
1310 1320 1330 1340 1350
EGSPGETQVP VEPPELEDFE AALGTDRHCQ RPDTYSRSSS ASSQEEKSHL
1360 1370 1380 1390 1400
EELAAGGIPI ERAISSEGAR PAVDLSFQPS QPLSKSSSSP ELQTLQDILG
1410 1420 1430 1440 1450
DLGDKIDIGR LSPEAKVRSQ SGILDGEAAT WSATGEESRI TVPPEGPLPS
1460 1470 1480 1490 1500
SSPRSPSGLR PRGYTISDSA PSRRGKRVER DNFKSRAAAS SAEKVPGINP
1510 1520 1530 1540 1550
SFVFLQLYHS PFFGDESNKP ILLPNESFER SVQLLDQIPS YDTHKIAVLY
1560 1570 1580 1590 1600
VGEGQSSSEL AILSNEHGSY RYTEFLTGLG RLIELKDCQP DKVYLGGLDV
1610 1620 1630 1640 1650
CGEDGQFTYC WHDDIMQAVF HIATLMPTKD VDKHRCDKKR HLGNDFVSII
1660 1670 1680 1690 1700
YNDSGEDFKL GTIKQGQFNF VHVIITPLDY KCNLLTLQCR KDGPACKCEW
1710 1720 1730 1740 1750
WRQPGEIVVW ALPVVMELTV TILLCHLQMA SQVHHSRSNP TDIYPSKWIA
1760 1770 1780 1790 1800
RLRHIKRLRQ RIREEVHYSN PSLPLMHPPA HTKAPAQAPE ATPTYETGQR
1810
KRLISSVDDF TEFV
Length:1,814
Mass (Da):202,071
Last modified:November 1, 1996 - v1
Checksum:i913AB87194AADA5B
GO
Isoform A (identifier: Q61037-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     79-115: Missing.

Show »
Length:1,777
Mass (Da):197,982
Checksum:iEC1013448D7CECCE
GO
Isoform B (identifier: Q61037-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     534-572: Missing.

Show »
Length:1,775
Mass (Da):197,891
Checksum:i9D54C4EF90B89C4E
GO
Isoform C (identifier: Q61037-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     947-990: Missing.

Show »
Length:1,770
Mass (Da):197,163
Checksum:i6BA34A440D4378C6
GO
Isoform D (identifier: Q61037-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1271-1293: Missing.

Show »
Length:1,791
Mass (Da):199,550
Checksum:iE616D6579FAF310F
GO
Isoform E (identifier: Q61037-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1245-1258: GHAPVQVIVSATGC → RDTALYKSLSVPAAG
     1271-1293: Missing.
     1693-1728: GPACKCEWWRQPGEIVVWALPVVMELTVTILLCHLQ → MEGLVDTSVAKIVSDRNLSFVARQMALHAN

Show »
Length:1,786
Mass (Da):198,914
Checksum:iEDC8768C66FBFE76
GO
Isoform F (identifier: Q61037-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     947-989: Missing.
     1245-1258: GHAPVQVIVSATGC → RDTALYKSLSVPAAG
     1271-1293: Missing.
     1693-1728: GPACKCEWWRQPGEIVVWALPVVMELTVTILLCHLQ → MEGLVDTSVAKIVSDRNLSFVARQMALHAN
     1776-1814: Missing.

Show »
Length:1,704
Mass (Da):189,855
Checksum:iF6A528C77739AE59
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti161 – 1611Missing in AAA86902 (PubMed:8833243).Curated
Sequence conflicti161 – 1611Missing in AAA86901 (PubMed:8833243).Curated
Sequence conflicti269 – 2691G → S in AAA86902 (PubMed:8833243).Curated
Sequence conflicti269 – 2691G → S in AAA86901 (PubMed:8833243).Curated
Sequence conflicti462 – 4621A → R in AAA86902 (PubMed:8833243).Curated
Sequence conflicti462 – 4621A → R in AAA86901 (PubMed:8833243).Curated
Sequence conflicti476 – 4761I → N in AAA86902 (PubMed:8833243).Curated
Sequence conflicti476 – 4761I → N in AAA86901 (PubMed:8833243).Curated
Sequence conflicti549 – 5491D → N in AAA86902 (PubMed:8833243).Curated
Sequence conflicti549 – 5491D → N in AAA86901 (PubMed:8833243).Curated
Sequence conflicti707 – 7071K → N in AAD27867 (PubMed:10584558).Curated
Sequence conflicti861 – 8622VP → AA in AAA86902 (PubMed:8833243).Curated
Sequence conflicti861 – 8622VP → AA in AAA86901 (PubMed:8833243).Curated
Sequence conflicti1127 – 11271R → P in AAA86902 (PubMed:8833243).Curated
Sequence conflicti1127 – 11271R → P in AAA86901 (PubMed:8833243).Curated
Sequence conflicti1665 – 16651Missing in AAA86902 (PubMed:8833243).Curated
Sequence conflicti1665 – 16651Missing in AAA86901 (PubMed:8833243).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei79 – 11537Missing in isoform A. CuratedVSP_004473Add
BLAST
Alternative sequencei534 – 57239Missing in isoform B. CuratedVSP_004474Add
BLAST
Alternative sequencei947 – 99044Missing in isoform C. CuratedVSP_004476Add
BLAST
Alternative sequencei947 – 98943Missing in isoform F. CuratedVSP_004475Add
BLAST
Alternative sequencei1245 – 125814GHAPV…SATGC → RDTALYKSLSVPAAG in isoform E and isoform F. CuratedVSP_004477Add
BLAST
Alternative sequencei1271 – 129323Missing in isoform D, isoform E and isoform F. CuratedVSP_004478Add
BLAST
Alternative sequencei1693 – 172836GPACK…LCHLQ → MEGLVDTSVAKIVSDRNLSF VARQMALHAN in isoform E and isoform F. CuratedVSP_004479Add
BLAST
Alternative sequencei1776 – 181439Missing in isoform F. CuratedVSP_004480Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37775 mRNA. Translation: AAA86902.1.
U37775 mRNA. Translation: AAA86901.1.
U39818 mRNA. Translation: AAB18754.1.
AB009371 Genomic DNA. Translation: BAA28845.1.
AF132986 mRNA. Translation: AAD27867.1.
UniGeneiMm.30435.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37775 mRNA. Translation: AAA86902.1.
U37775 mRNA. Translation: AAA86901.1.
U39818 mRNA. Translation: AAB18754.1.
AB009371 Genomic DNA. Translation: BAA28845.1.
AF132986 mRNA. Translation: AAD27867.1.
UniGeneiMm.30435.

3D structure databases

ProteinModelPortaliQ61037.
SMRiQ61037. Positions 1520-1675.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ61037. 5 interactions.
MINTiMINT-5068541.

PTM databases

iPTMnetiQ61037.
PhosphoSiteiQ61037.

Proteomic databases

EPDiQ61037.
MaxQBiQ61037.
PRIDEiQ61037.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:102548. Tsc2.

Phylogenomic databases

HOVERGENiHBG018005.
InParanoidiQ61037.
PhylomeDBiQ61037.

Miscellaneous databases

ChiTaRSiTsc2. mouse.
PROiQ61037.
SOURCEiSearch...

Gene expression databases

CleanExiMM_TSC2.

Family and domain databases

Gene3Di1.25.10.10. 3 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000331. Rap_GAP_dom.
IPR003913. Tuberin.
IPR018515. Tuberin-type_domain.
IPR024584. Tuberin_N.
[Graphical view]
PANTHERiPTHR10063:SF1. PTHR10063:SF1. 4 hits.
PfamiPF11864. DUF3384. 1 hit.
PF02145. Rap_GAP. 1 hit.
PF03542. Tuberin. 1 hit.
[Graphical view]
PRINTSiPR01431. TUBERIN.
SUPFAMiSSF111347. SSF111347. 1 hit.
SSF48371. SSF48371. 1 hit.
PROSITEiPS50085. RAPGAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, developmental expression, and evidence for alternative splicing of the murine tuberous sclerosis (TSC2) gene product."
    Kim K.K., Pajak L., Wang H., Field L.J.
    Cell. Mol. Biol. Res. 41:515-526(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS A; B; C; D; E; F AND G).
    Tissue: Heart.
  2. "Expression and differential splicing of the mouse TSC2 homolog."
    Olsson P.G., Schofield J.N., Edwards Y.H., Frischauf A.M.
    Mamm. Genome 7:212-215(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
  3. "Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III."
    Sarker A.H., Ikeda S., Nakano H., Terato H., Ide H., Imai K., Akiyama K., Tsutsui K., Bo Z., Kubo K., Yamamoto K., Yasui A., Yoshida M.C., Seki S.
    J. Mol. Biol. 282:761-774(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 1-199.
    Strain: BALB/cJ.
    Tissue: Leukocyte.
  4. "Genetic variants of the tuberous sclerosis 2 tumour suppressor gene in mouse t haplotypes."
    Kleymenova E.V., Declue J.E., Walker C.L.
    Genet. Res. 74:139-144(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 119-1805.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1132 AND SER-1772, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.

Entry informationi

Entry nameiTSC2_MOUSE
AccessioniPrimary (citable) accession number: Q61037
Secondary accession number(s): P97723
, P97724, P97725, P97727, Q61007, Q61008, Q9WUF6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: May 11, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.