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Protein

Serine/threonine-protein phosphatase PGAM5, mitochondrial

Gene

PGAM5

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

Functioni

Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.3 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • phosphatase activity Source: UniProtKB
  • protein complex binding Source: UniProtKB
  • receptor signaling protein serine/threonine phosphatase activity Source: CACAO

GO - Biological processi

  • dephosphorylation Source: GOC
  • intracellular signal transduction Source: GOC
  • necroptotic process Source: UniProtKB
  • positive regulation of GTPase activity Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Necrosis

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase PGAM5, mitochondrial (EC:3.1.3.16)
Alternative name(s):
Bcl-XL-binding protein v68
Phosphoglycerate mutase family member 5
Gene namesi
Name:PGAM5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:28763. PGAM5.

Subcellular locationi

  • Mitochondrion outer membrane 1 Publication; Single-pass membrane protein 1 Publication

  • Note: Isoform 2 overexpression results in the formation of disconnected punctuate mitochondria distributed throughout the cytoplasm. Isoform 1 overexpression results in the clustering of mitochondria around the nucleus.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei7 – 2923HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi79 – 791E → A: Loss of interaction with KEAP1; when associated with A-80. 1 Publication
Mutagenesisi80 – 801S → A: Loss of interaction with KEAP1; when associated with A-79. 1 Publication
Mutagenesisi105 – 1051H → A: Loss of phosphatase activity. 1 Publication

Organism-specific databases

PharmGKBiPA143485574.

Polymorphism and mutation databases

BioMutaiPGAM5.
DMDMi150417955.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 289289Serine/threonine-protein phosphatase PGAM5, mitochondrialPRO_0000288782Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei80 – 801Phosphoserine1 Publication
Modified residuei116 – 1161N6-acetyllysine1 Publication
Modified residuei144 – 1441N6-acetyllysine1 Publication
Modified residuei191 – 1911N6-acetyllysine1 Publication

Post-translational modificationi

Both isoform 1 and isoform 2 are phosphorylated by the RIPK1/RIPK3 complex under necrotic conditions. This phosphorylation increases PGAM5 phosphatase activity.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ96HS1.
PaxDbiQ96HS1.
PRIDEiQ96HS1.

PTM databases

DEPODiQ96HS1.
PhosphoSiteiQ96HS1.

Expressioni

Gene expression databases

BgeeiQ96HS1.
CleanExiHS_PGAM5.
ExpressionAtlasiQ96HS1. baseline and differential.
GenevisibleiQ96HS1. HS.

Organism-specific databases

HPAiCAB068215.
HPA036978.
HPA036979.

Interactioni

Subunit structurei

Dimer. Forms a ternary complex with NFE2L2 and KEAP1. Interacts with BCL2L1 and MAP3K5. Upon TNF-induced necrosis, forms in complex with RIPK1, RIPK3 and MLKL; the formation of this complex leads to PGAM5 phosphorylation. Isoform 2, but not isoform 1, interacts with DNM1L; this interaction leads to DNM1L dephosphorylation and activation and eventually to mitochondria fragmentation.4 Publications

Protein-protein interaction databases

BioGridi128154. 45 interactions.
DIPiDIP-50735N.
IntActiQ96HS1. 28 interactions.
MINTiMINT-1385191.
STRINGi9606.ENSP00000438465.

Structurei

Secondary structure

1
289
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi98 – 1047Combined sources
Helixi115 – 1173Combined sources
Helixi122 – 13615Combined sources
Beta strandi143 – 1508Combined sources
Helixi151 – 16212Combined sources
Beta strandi169 – 1724Combined sources
Helixi173 – 1753Combined sources
Helixi197 – 21115Combined sources
Beta strandi223 – 2297Combined sources
Helixi231 – 24111Combined sources
Helixi246 – 2516Combined sources
Beta strandi259 – 2646Combined sources
Beta strandi270 – 2778Combined sources
Helixi283 – 2853Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3MXOX-ray1.70A/B90-289[»]
3O0TX-ray1.90A/B90-289[»]
ProteinModelPortaliQ96HS1.
SMRiQ96HS1. Positions 89-289.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96HS1.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni77 – 826Interaction with KEAP1

Domaini

The N-terminal 35 amino acids, including the potential transmembrane alpha-helix, function as a non-cleaved mitochondrial targeting sequence that targets the protein to the cytosolic side of the outer mitochondrial membrane.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG71348.
GeneTreeiENSGT00390000004796.
HOGENOMiHOG000261217.
HOVERGENiHBG105576.
InParanoidiQ96HS1.
KOiK15637.
OMAiEIIVCHA.
OrthoDBiEOG7966H1.
PhylomeDBiQ96HS1.
TreeFamiTF314977.

Family and domain databases

Gene3Di3.40.50.1240. 1 hit.
InterProiIPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
[Graphical view]
PfamiPF00300. His_Phos_1. 1 hit.
[Graphical view]
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q96HS1-1) [UniParc]FASTAAdd to basket

Also known as: PGAM5-L

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
MAFRQALQLA ACGLAGGSAA VLFSAVAVGK PRAGGDAEPR PAEPPAWAGG
60 70 80 90 100
ARPGPGVWDP NWDRREPLSL INVRKRNVES GEEELASKLD HYKAKATRHI
110 120 130 140 150
FLIRHSQYHV DGSLEKDRTL TPLGREQAEL TGLRLASLGL KFNKIVHSSM
160 170 180 190 200
TRAIETTDII SRHLPGVCKV STDLLREGAP IEPDPPVSHW KPEAVQYYED
210 220 230 240 250
GARIEAAFRN YIHRADARQE EDSYEIFICH ANVIRYIVCR ALQFPPEGWL
260 270 280
RLSLNNGSIT HLVIRPNGRV ALRTLGDTGF MPPDKITRS
Length:289
Mass (Da):32,004
Last modified:May 29, 2007 - v2
Checksum:iEE20D2F0A99FCD83
GO
Isoform 2 (identifier: Q96HS1-2) [UniParc]FASTAAdd to basket

Also known as: PGAM5-S

The sequence of this isoform differs from the canonical sequence as follows:
     240-289: RALQFPPEGWLRLSLNNGSITHLVIRPNGRVALRTLGDTGFMPPDKITRS → SIPPLLSAGDFVLLGS

Show »
Length:255
Mass (Da):28,020
Checksum:i07B881D6D8BE033C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti124 – 1241G → C in AAK60627 (PubMed:15489334).Curated
Isoform 2 (identifier: Q96HS1-2)
Sequence conflicti252 – 2521L → V in AAH08196 (PubMed:16541075).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei240 – 28950RALQF…KITRS → SIPPLLSAGDFVLLGS in isoform 2. 1 PublicationVSP_025761Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU249757 mRNA. Translation: ABX39494.1.
AC135586 Genomic DNA. No translation available.
BC008196 mRNA. Translation: AAH08196.1.
AF357523 mRNA. Translation: AAK60627.1.
CCDSiCCDS53845.1. [Q96HS1-1]
CCDS9280.1. [Q96HS1-2]
RefSeqiNP_001164014.1. NM_001170543.1. [Q96HS1-1]
NP_612642.2. NM_138575.3. [Q96HS1-2]
UniGeneiHs.102558.

Genome annotation databases

EnsembliENST00000317555; ENSP00000321503; ENSG00000247077. [Q96HS1-2]
ENST00000498926; ENSP00000438465; ENSG00000247077. [Q96HS1-1]
GeneIDi192111.
KEGGihsa:192111.
UCSCiuc001uku.3. human. [Q96HS1-2]
uc009zyv.3. human. [Q96HS1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EU249757 mRNA. Translation: ABX39494.1.
AC135586 Genomic DNA. No translation available.
BC008196 mRNA. Translation: AAH08196.1.
AF357523 mRNA. Translation: AAK60627.1.
CCDSiCCDS53845.1. [Q96HS1-1]
CCDS9280.1. [Q96HS1-2]
RefSeqiNP_001164014.1. NM_001170543.1. [Q96HS1-1]
NP_612642.2. NM_138575.3. [Q96HS1-2]
UniGeneiHs.102558.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3MXOX-ray1.70A/B90-289[»]
3O0TX-ray1.90A/B90-289[»]
ProteinModelPortaliQ96HS1.
SMRiQ96HS1. Positions 89-289.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128154. 45 interactions.
DIPiDIP-50735N.
IntActiQ96HS1. 28 interactions.
MINTiMINT-1385191.
STRINGi9606.ENSP00000438465.

PTM databases

DEPODiQ96HS1.
PhosphoSiteiQ96HS1.

Polymorphism and mutation databases

BioMutaiPGAM5.
DMDMi150417955.

Proteomic databases

MaxQBiQ96HS1.
PaxDbiQ96HS1.
PRIDEiQ96HS1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000317555; ENSP00000321503; ENSG00000247077. [Q96HS1-2]
ENST00000498926; ENSP00000438465; ENSG00000247077. [Q96HS1-1]
GeneIDi192111.
KEGGihsa:192111.
UCSCiuc001uku.3. human. [Q96HS1-2]
uc009zyv.3. human. [Q96HS1-1]

Organism-specific databases

CTDi192111.
GeneCardsiGC12P133287.
H-InvDBHIX0017319.
HGNCiHGNC:28763. PGAM5.
HPAiCAB068215.
HPA036978.
HPA036979.
MIMi614939. gene.
neXtProtiNX_Q96HS1.
PharmGKBiPA143485574.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG71348.
GeneTreeiENSGT00390000004796.
HOGENOMiHOG000261217.
HOVERGENiHBG105576.
InParanoidiQ96HS1.
KOiK15637.
OMAiEIIVCHA.
OrthoDBiEOG7966H1.
PhylomeDBiQ96HS1.
TreeFamiTF314977.

Miscellaneous databases

ChiTaRSiPGAM5. human.
EvolutionaryTraceiQ96HS1.
GenomeRNAii192111.
NextBioi89319.
PROiQ96HS1.
SOURCEiSearch...

Gene expression databases

BgeeiQ96HS1.
CleanExiHS_PGAM5.
ExpressionAtlasiQ96HS1. baseline and differential.
GenevisibleiQ96HS1. HS.

Family and domain databases

Gene3Di3.40.50.1240. 1 hit.
InterProiIPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
[Graphical view]
PfamiPF00300. His_Phos_1. 1 hit.
[Graphical view]
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex."
    Lo S.-C., Hannink M.
    J. Biol. Chem. 281:37893-37903(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, ALTERNATIVE SPLICING, SUBUNIT, INTERACTION WITH BCL2L1 AND KEAP1, MUTAGENESIS OF GLU-79 AND SER-80.
  2. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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] (ISOFORM 2).
    Tissue: Cervix.
  4. "In vitro selection and characterization of Bcl-X(L)-binding proteins from a mix of tissue-specific mRNA display libraries."
    Hammond P.W., Alpin J., Rise C.E., Wright M., Kreider B.L.
    J. Biol. Chem. 276:20898-20906(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 124-157.
    Tissue: Kidney.
  5. "PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria."
    Lo S.-C., Hannink M.
    Exp. Cell Res. 314:1789-1803(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, INTERACTION WITH NFE2L2 AND KEAP1, FUNCTION, SUBCELLULAR LOCATION.
  6. "Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1."
    Takeda K., Komuro Y., Hayakawa T., Oguchi H., Ishida Y., Murakami S., Noguchi T., Kinoshita H., Sekine Y., Iemura S., Natsume T., Ichijo H.
    Proc. Natl. Acad. Sci. U.S.A. 106:12301-12305(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MAP3K5, MUTAGENESIS OF HIS-105.
  7. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-116; LYS-144 AND LYS-191, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways."
    Wang Z., Jiang H., Chen S., Du F., Wang X.
    Cell 148:228-243(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTIFICATION IN COMPLEX WITH RIPK1; RIPK3 AND MLKL, INTERACTION WITH DNM1L.
  11. "Crystal structure of human phosphoglycerate mutase family member 5 (PGAM5)."
    Structural genomics consortium (SGC)
    Submitted (SEP-2010) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 90-289.

Entry informationi

Entry nameiPGAM5_HUMAN
AccessioniPrimary (citable) accession number: Q96HS1
Secondary accession number(s): A9LN06, C9IZY7, Q96JB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: June 24, 2015
This is version 105 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 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.