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Protein

Serine protease HTRA2, mitochondrial

Gene

HTRA2

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

Functioni

Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.2 Publications

Catalytic activityi

Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei198Charge relay system1 Publication1
Active sitei228Charge relay system1 Publication1
Active sitei306Charge relay system1 Publication1

GO - Molecular functioni

  • peptidase activity Source: UniProtKB
  • serine-type endopeptidase activity Source: UniProtKB
  • serine-type peptidase activity Source: UniProtKB
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • adult walking behavior Source: Ensembl
  • aging Source: Ensembl
  • cellular protein catabolic process Source: ParkinsonsUK-UCL
  • cellular response to growth factor stimulus Source: UniProtKB
  • cellular response to heat Source: UniProtKB
  • cellular response to interferon-beta Source: ParkinsonsUK-UCL
  • cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • cellular response to retinoic acid Source: ParkinsonsUK-UCL
  • ceramide metabolic process Source: Ensembl
  • execution phase of apoptosis Source: UniProtKB
  • forebrain development Source: Ensembl
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: ParkinsonsUK-UCL
  • mitochondrion organization Source: Ensembl
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of neuron death Source: ParkinsonsUK-UCL
  • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • neuron development Source: Ensembl
  • pentacyclic triterpenoid metabolic process Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cell death Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • protein autoprocessing Source: ParkinsonsUK-UCL
  • proteolysis Source: UniProtKB
  • regulation of mitophagy Source: ParkinsonsUK-UCL
  • regulation of multicellular organism growth Source: Ensembl
  • response to herbicide Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:HS03870-MONOMER.
BRENDAi3.4.21.108. 2681.
SIGNORiO43464.

Protein family/group databases

MEROPSiS01.278.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease HTRA2, mitochondrial (EC:3.4.21.108)
Alternative name(s):
High temperature requirement protein A2
Short name:
HtrA2
Omi stress-regulated endoprotease
Serine protease 25
Serine proteinase OMI
Gene namesi
Name:HTRA2
Synonyms:OMI, PRSS25
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:14348. HTRA2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei105 – 125HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • CD40 receptor complex Source: BHF-UCL
  • chromatin Source: ParkinsonsUK-UCL
  • cytoplasmic side of plasma membrane Source: BHF-UCL
  • cytoskeleton Source: ParkinsonsUK-UCL
  • cytosol Source: ParkinsonsUK-UCL
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • membrane Source: ParkinsonsUK-UCL
  • mitochondrial intermembrane space Source: MGI
  • mitochondrial membrane Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Parkinson disease 13 (PARK13)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
See also OMIM:610297
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046135404R → W in PARK13. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi134A → M: Loss of interaction with XIAP. Loss of inhibition of XIAP activity. 1 Publication1
Mutagenesisi306S → A: Loss of protease activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNETi27429.
MalaCardsiHTRA2.
MIMi168600. phenotype.
610297. phenotype.
OpenTargetsiENSG00000115317.
Orphaneti2828. Young adult-onset Parkinsonism.
PharmGKBiPA33836.

Polymorphism and mutation databases

BioMutaiHTRA2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 31MitochondrionAdd BLAST31
PropeptideiPRO_000002694532 – 1331 PublicationAdd BLAST102
ChainiPRO_0000026946134 – 458Serine protease HTRA2, mitochondrialAdd BLAST325

Post-translational modificationi

Autoproteolytically activated.

Keywords - PTMi

Autocatalytic cleavage, Zymogen

Proteomic databases

EPDiO43464.
MaxQBiO43464.
PaxDbiO43464.
PeptideAtlasiO43464.
PRIDEiO43464.
TopDownProteomicsiO43464-2. [O43464-2]

2D gel databases

OGPiO43464.

PTM databases

iPTMnetiO43464.
PhosphoSitePlusiO43464.

Miscellaneous databases

PMAP-CutDBO43464.

Expressioni

Tissue specificityi

Isoform 1 is ubiquitous. Isoform 2 is expressed predominantly in the kidney, colon and thyroid.

Gene expression databases

BgeeiENSG00000115317.
CleanExiHS_HTRA2.
ExpressionAtlasiO43464. baseline and differential.
GenevisibleiO43464. HS.

Organism-specific databases

HPAiCAB004004.
HPA027366.

Interactioni

Subunit structurei

Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with BIRC6/bruce.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BIRC7Q96CA52EBI-517086,EBI-517623
CSN2P026665EBI-517086,EBI-5260183From a different organism.
NDUFA13Q9P0J06EBI-517086,EBI-372742
Ripk1Q608552EBI-517086,EBI-529119From a different organism.
XIAPP9817018EBI-517086,EBI-517127

GO - Molecular functioni

  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118165. 64 interactors.
IntActiO43464. 42 interactors.
MINTiMINT-216075.
STRINGi9606.ENSP00000258080.

Structurei

Secondary structure

1458
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi143 – 147Combined sources5
Helixi149 – 157Combined sources9
Helixi158 – 160Combined sources3
Beta strandi161 – 170Combined sources10
Turni171 – 174Combined sources4
Beta strandi175 – 188Combined sources14
Turni189 – 191Combined sources3
Beta strandi192 – 195Combined sources4
Helixi197 – 200Combined sources4
Beta strandi204 – 209Combined sources6
Beta strandi215 – 224Combined sources10
Turni225 – 228Combined sources4
Beta strandi229 – 233Combined sources5
Helixi248 – 250Combined sources3
Beta strandi256 – 259Combined sources4
Beta strandi265 – 268Combined sources4
Beta strandi271 – 275Combined sources5
Beta strandi295 – 299Combined sources5
Turni303 – 307Combined sources5
Beta strandi308 – 312Combined sources5
Beta strandi317 – 326Combined sources10
Beta strandi329 – 334Combined sources6
Helixi335 – 343Combined sources9
Beta strandi359 – 361Combined sources3
Beta strandi364 – 368Combined sources5
Helixi371 – 380Combined sources10
Beta strandi391 – 396Combined sources6
Helixi401 – 405Combined sources5
Beta strandi412 – 416Combined sources5
Helixi424 – 433Combined sources10
Beta strandi435 – 443Combined sources9
Beta strandi446 – 452Combined sources7
Beta strandi455 – 457Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LCYX-ray2.00A134-458[»]
2PZDX-ray2.75A/B359-458[»]
5FHTX-ray1.95A134-458[»]
DisProtiDP00315.
ProteinModelPortaliO43464.
SMRiO43464.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43464.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini364 – 445PDZPROSITE-ProRule annotationAdd BLAST82

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 342Serine proteaseAdd BLAST177

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi134 – 137IAP-binding motif4

Domaini

The mature N-terminus is involved in the interaction with XIAP.
The PDZ domain mediates interaction with MXI2.

Sequence similaritiesi

Belongs to the peptidase S1C family.Curated
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1320. Eukaryota.
COG0265. LUCA.
GeneTreeiENSGT00510000046315.
HOGENOMiHOG000223641.
HOVERGENiHBG052044.
InParanoidiO43464.
KOiK08669.
OMAiEINGQAT.
OrthoDBiEOG091G0LXR.
PhylomeDBiO43464.
TreeFamiTF323480.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
InterProiIPR001478. PDZ.
IPR009003. Peptidase_S1_PA.
IPR001940. Peptidase_S1C.
[Graphical view]
PfamiPF13180. PDZ_2. 1 hit.
[Graphical view]
PRINTSiPR00834. PROTEASES2C.
SMARTiSM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43464-1) [UniParc]FASTAAdd to basket
Also known as: 13B

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
MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV
60 70 80 90 100
TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG
110 120 130 140 150
TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI
160 170 180 190 200
ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV
210 220 230 240 250
ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD
260 270 280 290 300
VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA
310 320 330 340 350
IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS
360 370 380 390 400
SSGISGSQRR YIGVMMLTLS PSILAELQLR EPSFPDVQHG VLIHKVILGS
410 420 430 440 450
PAHRAGLRPG DVILAIGEQM VQNAEDVYEA VRTQSQLAVQ IRRGRETLTL

YVTPEVTE
Length:458
Mass (Da):48,841
Last modified:May 1, 2000 - v2
Checksum:iCEA955A7D0DD8C0D
GO
Isoform 2 (identifier: O43464-2) [UniParc]FASTAAdd to basket
Also known as: D-Omi

The sequence of this isoform differs from the canonical sequence as follows:
     238-302: Missing.
     372-403: Missing.

Show »
Length:361
Mass (Da):38,493
Checksum:iBD0824D4308140D7
GO
Isoform 3 (identifier: O43464-3) [UniParc]FASTAAdd to basket
Also known as: p7

The sequence of this isoform differs from the canonical sequence as follows:
     313-313: L → LARELGAVSLQ
     372-403: Missing.

Show »
Length:436
Mass (Da):46,382
Checksum:iB48266A8EB7E4EE8
GO
Isoform 4 (identifier: O43464-4) [UniParc]FASTAAdd to basket
Also known as: p4

The sequence of this isoform differs from the canonical sequence as follows:
     314-458: DGEVIGVNTM...TLYVTPEVTE → VSETSFLPRI...FGCPHPLLFV

Show »
Length:377
Mass (Da):39,914
Checksum:i14D0982E08A58FB2
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07696712W → C.1 Publication1
Natural variantiVAR_04613472L → P.1 PublicationCorresponds to variant rs150047108dbSNPEnsembl.1
Natural variantiVAR_076968128P → L.1 Publication1
Natural variantiVAR_027349141A → S Polymorphism; may be a risk factor for Parkinson disease; reduced protease activity. 3 PublicationsCorresponds to variant rs72470544dbSNPEnsembl.1
Natural variantiVAR_076969227A → S.1 Publication1
Natural variantiVAR_027350399G → S Polymorphism; may be a risk factor for Parkinson disease reduced protease activity. 4 PublicationsCorresponds to variant rs72470545dbSNPEnsembl.1
Natural variantiVAR_046135404R → W in PARK13. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005359238 – 302Missing in isoform 2. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_005360313L → LARELGAVSLQ in isoform 3. 1 Publication1
Alternative sequenceiVSP_005362314 – 458DGEVI…PEVTE → VSETSFLPRIPAPGQCGKGR FPLIQGCLVKFLSSSLLAIS QYPTRSPQHLLVLLFGCPHP LLFV in isoform 4. 1 PublicationAdd BLAST145
Alternative sequenceiVSP_005361372 – 403Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020760 mRNA. Translation: AAB94569.2.
AF141305 mRNA. Translation: AAF66596.1.
AF141306 mRNA. Translation: AAF66597.1.
AF141307 mRNA. Translation: AAF66598.1.
AF184911 mRNA. Translation: AAG13126.1.
AC006544 Genomic DNA. No translation available.
BC000096 mRNA. Translation: AAH00096.1.
CCDSiCCDS1951.1. [O43464-1]
CCDS1952.1. [O43464-2]
RefSeqiNP_001308656.1. NM_001321727.1. [O43464-3]
NP_037379.1. NM_013247.4. [O43464-1]
NP_659540.1. NM_145074.2. [O43464-2]
UniGeneiHs.469045.
Hs.744841.

Genome annotation databases

EnsembliENST00000258080; ENSP00000258080; ENSG00000115317. [O43464-1]
ENST00000352222; ENSP00000312893; ENSG00000115317. [O43464-2]
GeneIDi27429.
KEGGihsa:27429.
UCSCiuc002smi.2. human. [O43464-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020760 mRNA. Translation: AAB94569.2.
AF141305 mRNA. Translation: AAF66596.1.
AF141306 mRNA. Translation: AAF66597.1.
AF141307 mRNA. Translation: AAF66598.1.
AF184911 mRNA. Translation: AAG13126.1.
AC006544 Genomic DNA. No translation available.
BC000096 mRNA. Translation: AAH00096.1.
CCDSiCCDS1951.1. [O43464-1]
CCDS1952.1. [O43464-2]
RefSeqiNP_001308656.1. NM_001321727.1. [O43464-3]
NP_037379.1. NM_013247.4. [O43464-1]
NP_659540.1. NM_145074.2. [O43464-2]
UniGeneiHs.469045.
Hs.744841.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LCYX-ray2.00A134-458[»]
2PZDX-ray2.75A/B359-458[»]
5FHTX-ray1.95A134-458[»]
DisProtiDP00315.
ProteinModelPortaliO43464.
SMRiO43464.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118165. 64 interactors.
IntActiO43464. 42 interactors.
MINTiMINT-216075.
STRINGi9606.ENSP00000258080.

Protein family/group databases

MEROPSiS01.278.

PTM databases

iPTMnetiO43464.
PhosphoSitePlusiO43464.

Polymorphism and mutation databases

BioMutaiHTRA2.

2D gel databases

OGPiO43464.

Proteomic databases

EPDiO43464.
MaxQBiO43464.
PaxDbiO43464.
PeptideAtlasiO43464.
PRIDEiO43464.
TopDownProteomicsiO43464-2. [O43464-2]

Protocols and materials databases

DNASUi27429.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258080; ENSP00000258080; ENSG00000115317. [O43464-1]
ENST00000352222; ENSP00000312893; ENSG00000115317. [O43464-2]
GeneIDi27429.
KEGGihsa:27429.
UCSCiuc002smi.2. human. [O43464-1]

Organism-specific databases

CTDi27429.
DisGeNETi27429.
GeneCardsiHTRA2.
GeneReviewsiHTRA2.
HGNCiHGNC:14348. HTRA2.
HPAiCAB004004.
HPA027366.
MalaCardsiHTRA2.
MIMi168600. phenotype.
606441. gene.
610297. phenotype.
neXtProtiNX_O43464.
OpenTargetsiENSG00000115317.
Orphaneti2828. Young adult-onset Parkinsonism.
PharmGKBiPA33836.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1320. Eukaryota.
COG0265. LUCA.
GeneTreeiENSGT00510000046315.
HOGENOMiHOG000223641.
HOVERGENiHBG052044.
InParanoidiO43464.
KOiK08669.
OMAiEINGQAT.
OrthoDBiEOG091G0LXR.
PhylomeDBiO43464.
TreeFamiTF323480.

Enzyme and pathway databases

BioCyciZFISH:HS03870-MONOMER.
BRENDAi3.4.21.108. 2681.
SIGNORiO43464.

Miscellaneous databases

ChiTaRSiHTRA2. human.
EvolutionaryTraceiO43464.
GeneWikiiHtrA_serine_peptidase_2.
GenomeRNAii27429.
PMAP-CutDBO43464.
PROiO43464.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115317.
CleanExiHS_HTRA2.
ExpressionAtlasiO43464. baseline and differential.
GenevisibleiO43464. HS.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
InterProiIPR001478. PDZ.
IPR009003. Peptidase_S1_PA.
IPR001940. Peptidase_S1C.
[Graphical view]
PfamiPF13180. PDZ_2. 1 hit.
[Graphical view]
PRINTSiPR00834. PROTEASES2C.
SMARTiSM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHTRA2_HUMAN
AccessioniPrimary (citable) accession number: O43464
Secondary accession number(s): Q9HBZ4, Q9P0Y3, Q9P0Y4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 182 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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. Peptidase families
    Classification of peptidase families and list of 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.