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Protein

Apoptosis regulator Bcl-2

Gene

Bcl2

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

Functioni

Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).1 Publication

GO - Molecular functioni

GO - Biological processi

  • actin filament organization Source: MGI
  • animal organ morphogenesis Source: MGI
  • apoptotic mitochondrial changes Source: MGI
  • apoptotic process Source: MGI
  • axonogenesis Source: MGI
  • axon regeneration Source: MGI
  • B cell differentiation Source: MGI
  • B cell homeostasis Source: MGI
  • B cell lineage commitment Source: MGI
  • B cell proliferation Source: MGI
  • B cell receptor signaling pathway Source: MGI
  • behavioral fear response Source: MGI
  • branching involved in ureteric bud morphogenesis Source: MGI
  • CD8-positive, alpha-beta T cell lineage commitment Source: MGI
  • cell aging Source: MGI
  • cell growth Source: MGI
  • cell morphogenesis Source: MGI
  • cell proliferation Source: MGI
  • cellular calcium ion homeostasis Source: MGI
  • cellular response to DNA damage stimulus Source: MGI
  • cellular response to glucose starvation Source: MGI
  • cellular response to hypoxia Source: MGI
  • cellular response to organic substance Source: MGI
  • cochlear nucleus development Source: MGI
  • defense response to virus Source: MGI
  • developmental growth Source: MGI
  • developmental pigmentation Source: MGI
  • digestive tract morphogenesis Source: MGI
  • ear development Source: MGI
  • endoplasmic reticulum calcium ion homeostasis Source: MGI
  • extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  • focal adhesion assembly Source: MGI
  • gland morphogenesis Source: MGI
  • glomerulus development Source: MGI
  • growth Source: MGI
  • hair follicle morphogenesis Source: UniProtKB
  • hemopoiesis Source: MGI
  • homeostasis of number of cells within a tissue Source: MGI
  • immune system development Source: MGI
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: MGI
  • intrinsic apoptotic signaling pathway in response to oxidative stress Source: MGI
  • kidney development Source: MGI
  • leukocyte homeostasis Source: MGI
  • lymphocyte homeostasis Source: MGI
  • lymphoid progenitor cell differentiation Source: MGI
  • male gonad development Source: MGI
  • melanin metabolic process Source: MGI
  • melanocyte differentiation Source: MGI
  • mesenchymal cell development Source: MGI
  • metanephros development Source: MGI
  • negative regulation of anoikis Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of apoptotic signaling pathway Source: MGI
  • negative regulation of autophagy Source: ParkinsonsUK-UCL
  • negative regulation of calcium ion transport into cytosol Source: MGI
  • negative regulation of cell growth Source: MGI
  • negative regulation of cell migration Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of cellular pH reduction Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • negative regulation of G1/S transition of mitotic cell cycle Source: MGI
  • negative regulation of intrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of mitotic cell cycle Source: MGI
  • negative regulation of myeloid cell apoptotic process Source: MGI
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of ossification Source: MGI
  • negative regulation of osteoblast proliferation Source: MGI
  • negative regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
  • negative regulation of retinal cell programmed cell death Source: MGI
  • neuron apoptotic process Source: MGI
  • oocyte development Source: MGI
  • organ growth Source: MGI
  • ossification Source: MGI
  • ovarian follicle development Source: MGI
  • peptidyl-serine phosphorylation Source: MGI
  • peptidyl-threonine phosphorylation Source: MGI
  • pigmentation Source: UniProtKB
  • pigment granule organization Source: MGI
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of catalytic activity Source: MGI
  • positive regulation of cell growth Source: MGI
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of developmental pigmentation Source: MGI
  • positive regulation of melanocyte differentiation Source: MGI
  • positive regulation of multicellular organism growth Source: MGI
  • positive regulation of neuron maturation Source: MGI
  • positive regulation of peptidyl-serine phosphorylation Source: MGI
  • positive regulation of skeletal muscle fiber development Source: MGI
  • positive regulation of smooth muscle cell migration Source: MGI
  • post-embryonic development Source: MGI
  • protein dephosphorylation Source: MGI
  • protein polyubiquitination Source: MGI
  • reactive oxygen species metabolic process Source: MGI
  • regulation of apoptotic process Source: MGI
  • regulation of autophagy Source: CACAO
  • regulation of calcium ion transport Source: MGI
  • regulation of catalytic activity Source: MGI
  • regulation of cell cycle Source: MGI
  • regulation of cell-matrix adhesion Source: MGI
  • regulation of developmental pigmentation Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of glycoprotein biosynthetic process Source: MGI
  • regulation of mitochondrial membrane permeability Source: HGNC
  • regulation of mitochondrial membrane potential Source: HGNC
  • regulation of nitrogen utilization Source: MGI
  • regulation of programmed cell death Source: MGI
  • regulation of protein heterodimerization activity Source: MGI
  • regulation of protein homodimerization activity Source: MGI
  • regulation of protein localization Source: MGI
  • regulation of protein stability Source: MGI
  • regulation of transmembrane transporter activity Source: MGI
  • regulation of viral genome replication Source: UniProtKB
  • release of cytochrome c from mitochondria Source: HGNC
  • renal system process Source: MGI
  • response to cytokine Source: MGI
  • response to drug Source: MGI
  • response to gamma radiation Source: MGI
  • response to glucocorticoid Source: MGI
  • response to hydrogen peroxide Source: MGI
  • response to iron ion Source: MGI
  • response to ischemia Source: MGI
  • response to nicotine Source: MGI
  • response to oxidative stress Source: MGI
  • response to steroid hormone Source: MGI
  • response to toxic substance Source: MGI
  • response to UV-B Source: MGI
  • single organismal cell-cell adhesion Source: MGI
  • spleen development Source: MGI
  • T cell differentiation Source: MGI
  • T cell differentiation in thymus Source: MGI
  • T cell homeostasis Source: MGI
  • T cell lineage commitment Source: MGI
  • thymus development Source: MGI
  • ureteric bud development Source: MGI
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-MMU-111447. Activation of BAD and translocation to mitochondria.
R-MMU-111453. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
R-MMU-844455. The NLRP1 inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis regulator Bcl-2
Gene namesi
Name:Bcl2
Synonyms:Bcl-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:88138. Bcl2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei209 – 230HelicalSequence analysisAdd BLAST22

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • endoplasmic reticulum Source: MGI
  • endoplasmic reticulum membrane Source: MGI
  • intracellular Source: MGI
  • membrane Source: MGI
  • mitochondrial membrane Source: MGI
  • mitochondrial outer membrane Source: MGI
  • mitochondrion Source: MGI
  • myelin sheath Source: MGI
  • nuclear membrane Source: MGI
  • nucleus Source: MGI
  • pore complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

In response to intraperitoneal injection of muramyl dipeptide (MDP), knockout animals show lower serum IL1B levels than wild type. Mutant macrophages release 30% less IL1B than the wild-type cells.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi70S → A: Loss of phosphorylation. Unable to suppress apoptosis. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001430491 – 236Apoptosis regulator Bcl-2Add BLAST236

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei69Phosphothreonine; by MAPK8By similarity1
Modified residuei70Phosphoserine; by MAPK8 and PKC1 Publication1
Modified residuei84Phosphoserine; by MAPK8By similarity1

Post-translational modificationi

Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-84, wich stimulates starvation-induced autophagy (By similarity). Dephosphorylated by protein phosphatase 2A (PP2A).By similarity1 Publication
Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity.
Monoubiquitinated by PARK2, leading to increase its stability. Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei34 – 35Cleavage; by caspasesBy similarity2

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP10417.
PeptideAtlasiP10417.
PRIDEiP10417.

PTM databases

iPTMnetiP10417.
PhosphoSitePlusiP10417.

Expressioni

Tissue specificityi

Expressed in a variety of tissues.

Gene expression databases

BgeeiENSMUSG00000057329.
CleanExiMM_BCL2.
ExpressionAtlasiP10417. baseline and differential.
GenevisibleiP10417. MM.

Interactioni

Subunit structurei

Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2 (By similarity). Interacts with EI24. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with PPIF; the interaction is impaired by CsA (By similarity). Interacts with BOP (By similarity). Interacts with the SCF(FBXO10) complex (By similarity). Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats) (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
BaxQ078132EBI-526314,EBI-700711
Bcl2l11O54918-12EBI-526314,EBI-526076
Becn1O885974EBI-526314,EBI-643716

GO - Molecular functioni

  • BH3 domain binding Source: MGI
  • protease binding Source: MGI
  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • protein phosphatase 2A binding Source: MGI
  • protein phosphatase binding Source: MGI
  • transcription factor binding Source: MGI
  • ubiquitin protein ligase binding Source: MGI

Protein-protein interaction databases

BioGridi198318. 31 interactors.
DIPiDIP-1065N.
IntActiP10417. 8 interactors.
MINTiMINT-209615.
STRINGi10090.ENSMUSP00000108371.

Chemistry databases

BindingDBiP10417.

Structurei

3D structure databases

ProteinModelPortaliP10417.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi10 – 30BH4Add BLAST21
Motifi90 – 104BH3Add BLAST15
Motifi133 – 152BH1Add BLAST20
Motifi184 – 199BH2Add BLAST16

Domaini

The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity.By similarity
The loop between motifs BH4 and BH3 is required for the interaction with NLRP1.By similarity

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4728. Eukaryota.
ENOG41123S0. LUCA.
GeneTreeiENSGT00530000062935.
HOGENOMiHOG000056452.
HOVERGENiHBG004472.
InParanoidiP10417.
KOiK02161.
OMAiIVLKYIH.
OrthoDBiEOG091G0OCU.
TreeFamiTF315834.

Family and domain databases

InterProiIPR013278. Apop_reg_Bcl2.
IPR002475. Bcl2-like.
IPR004725. Bcl2/BclX.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR020728. Bcl2_BH3_motif_CS.
IPR003093. Bcl2_BH4.
IPR020731. Bcl2_BH4_motif_CS.
IPR026298. Blc2_fam.
[Graphical view]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSiPR01863. APOPREGBCL2.
PR01862. BCL2FAMILY.
SMARTiSM00265. BH4. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00865. bcl-2. 1 hit.
PROSITEiPS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01259. BH3. 1 hit.
PS01260. BH4_1. 1 hit.
PS50063. BH4_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform Alpha (identifier: P10417-1) [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
MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDADAAPL GAAPTPGIFS
60 70 80 90 100
FQPESNPMPA VHRDMAARTS PLRPLVATAG PALSPVPPVV HLTLRRAGDD
110 120 130 140 150
FSRRYRRDFA EMSSQLHLTP FTARGRFATV VEELFRDGVN WGRIVAFFEF
160 170 180 190 200
GGVMCVESVN REMSPLVDNI ALWMTEYLNR HLHTWIQDNG GWDAFVELYG
210 220 230
PSMRPLFDFS WLSLKTLLSL ALVGACITLG AYLGHK
Length:236
Mass (Da):26,407
Last modified:October 3, 2012 - v3
Checksum:i80FDCFE78C735092
GO
Isoform Beta (identifier: P10417-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     193-236: DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK → VGACLVE

Show »
Length:199
Mass (Da):22,281
Checksum:iF13C8037262BA955
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti64D → E in AAA37281 (PubMed:3032455).Curated1
Sequence conflicti64D → E in AAA37282 (PubMed:3032455).Curated1
Sequence conflicti89V → C in AAA37281 (PubMed:3032455).Curated1
Sequence conflicti89V → C in AAA37282 (PubMed:3032455).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000513193 – 236DAFVE…YLGHK → VGACLVE in isoform Beta. CuratedAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L31532, M16506 Genomic DNA. Translation: AAA37282.1.
M16506 Genomic DNA. Translation: AAA37281.1.
AC122842 Genomic DNA. No translation available.
AC162916 Genomic DNA. No translation available.
CH466520 Genomic DNA. Translation: EDL39862.1.
BC095964 mRNA. Translation: AAH95964.1.
CCDSiCCDS15209.1. [P10417-1]
CCDS78667.1. [P10417-2]
PIRiA25960. TVMSA1.
B25960. TVMSB1.
RefSeqiNP_033871.2. NM_009741.5. [P10417-1]
UniGeneiMm.257460.

Genome annotation databases

EnsembliENSMUST00000112751; ENSMUSP00000108371; ENSMUSG00000057329. [P10417-1]
ENSMUST00000189999; ENSMUSP00000139856; ENSMUSG00000057329. [P10417-2]
GeneIDi12043.
KEGGimmu:12043.
UCSCiuc007cgw.2. mouse. [P10417-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L31532, M16506 Genomic DNA. Translation: AAA37282.1.
M16506 Genomic DNA. Translation: AAA37281.1.
AC122842 Genomic DNA. No translation available.
AC162916 Genomic DNA. No translation available.
CH466520 Genomic DNA. Translation: EDL39862.1.
BC095964 mRNA. Translation: AAH95964.1.
CCDSiCCDS15209.1. [P10417-1]
CCDS78667.1. [P10417-2]
PIRiA25960. TVMSA1.
B25960. TVMSB1.
RefSeqiNP_033871.2. NM_009741.5. [P10417-1]
UniGeneiMm.257460.

3D structure databases

ProteinModelPortaliP10417.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198318. 31 interactors.
DIPiDIP-1065N.
IntActiP10417. 8 interactors.
MINTiMINT-209615.
STRINGi10090.ENSMUSP00000108371.

Chemistry databases

BindingDBiP10417.

PTM databases

iPTMnetiP10417.
PhosphoSitePlusiP10417.

Proteomic databases

PaxDbiP10417.
PeptideAtlasiP10417.
PRIDEiP10417.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000112751; ENSMUSP00000108371; ENSMUSG00000057329. [P10417-1]
ENSMUST00000189999; ENSMUSP00000139856; ENSMUSG00000057329. [P10417-2]
GeneIDi12043.
KEGGimmu:12043.
UCSCiuc007cgw.2. mouse. [P10417-1]

Organism-specific databases

CTDi596.
MGIiMGI:88138. Bcl2.

Phylogenomic databases

eggNOGiKOG4728. Eukaryota.
ENOG41123S0. LUCA.
GeneTreeiENSGT00530000062935.
HOGENOMiHOG000056452.
HOVERGENiHBG004472.
InParanoidiP10417.
KOiK02161.
OMAiIVLKYIH.
OrthoDBiEOG091G0OCU.
TreeFamiTF315834.

Enzyme and pathway databases

ReactomeiR-MMU-111447. Activation of BAD and translocation to mitochondria.
R-MMU-111453. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
R-MMU-844455. The NLRP1 inflammasome.

Miscellaneous databases

ChiTaRSiBcl2. mouse.
PROiP10417.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000057329.
CleanExiMM_BCL2.
ExpressionAtlasiP10417. baseline and differential.
GenevisibleiP10417. MM.

Family and domain databases

InterProiIPR013278. Apop_reg_Bcl2.
IPR002475. Bcl2-like.
IPR004725. Bcl2/BclX.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR020728. Bcl2_BH3_motif_CS.
IPR003093. Bcl2_BH4.
IPR020731. Bcl2_BH4_motif_CS.
IPR026298. Blc2_fam.
[Graphical view]
PANTHERiPTHR11256. PTHR11256. 1 hit.
PTHR11256:SF11. PTHR11256:SF11. 1 hit.
PfamiPF00452. Bcl-2. 1 hit.
PF02180. BH4. 1 hit.
[Graphical view]
PRINTSiPR01863. APOPREGBCL2.
PR01862. BCL2FAMILY.
SMARTiSM00265. BH4. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00865. bcl-2. 1 hit.
PROSITEiPS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01259. BH3. 1 hit.
PS01260. BH4_1. 1 hit.
PS50063. BH4_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBCL2_MOUSE
AccessioniPrimary (citable) accession number: P10417
Secondary accession number(s): P10418, Q4VBF6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 3, 2012
Last modified: November 30, 2016
This is version 177 of the entry and version 3 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.