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Protein

Mitogen-activated protein kinase kinase kinase 9

Gene

MAP3K9

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

Functioni

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Plays also a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Homodimerization via the leucine zipper domains is required for autophosphorylation of multiple sites in the activation loop and subsequent activation. Autophosphorylation at Thr-312 is the key step in activation of MAP3K9/MLK1 and is required for full phosphorylation. Autophosphorylation at Thr-304 and Ser-308 have been shown to be of secondary importance in the activation of MAP3K9/MLK1. CEP-1347 and many indolocarbazole analogs have been shown to act as inhibitors of MAP3K9/MLK1 activity.3 Publications

Kineticsi

  1. KM=62 µM for ATP1 Publication
  2. KM=7 µM for myelin basic protein (MBP) as substrate1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei171ATP1
    Active sitei268Proton acceptorPROSITE-ProRule annotation1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi150 – 158ATPPROSITE-ProRule annotation9

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • JUN kinase kinase kinase activity Source: UniProtKB
    • MAP kinase kinase activity Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB
    • protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    • activation of JUN kinase activity Source: UniProtKB
    • apoptotic process Source: UniProtKB-KW
    • positive regulation of apoptotic process Source: Ensembl
    • protein autophosphorylation Source: UniProtKB
    • protein phosphorylation Source: UniProtKB
    • regulation of transcription, DNA-templated Source: UniProtKB-KW
    • transcription, DNA-templated Source: UniProtKB-KW
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Stress response, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS00177-MONOMER.
    SignaLinkiP80192.
    SIGNORiP80192.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 9 (EC:2.7.11.25)
    Alternative name(s):
    Mixed lineage kinase 1
    Gene namesi
    Name:MAP3K9
    Synonyms:MLK1, PRKE1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:6861. MAP3K9.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    Involvement in diseasei

    May play a role in esophageal cancer susceptibility and/or development.

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi171K → A: Loss of kinase activity and threonine phosphorylation. 1 Publication1
    Mutagenesisi304T → A: Reduces threonine phosphorylation. Impairs JNK activation. 1 Publication1
    Mutagenesisi305T → A: Little effect on threonine phosphorylation. Mildly impairs JNK activation. 1 Publication1
    Mutagenesisi308S → A: Impairs JNK activation. 1 Publication1
    Mutagenesisi312T → A: Loss of threonine phosphorylation. Strongly impairs JNK activation. 1 Publication1

    Organism-specific databases

    DisGeNETi4293.
    OpenTargetsiENSG00000006432.
    PharmGKBiPA30607.

    Chemistry databases

    ChEMBLiCHEMBL2872.
    GuidetoPHARMACOLOGYi2084.

    Polymorphism and mutation databases

    DMDMi116242625.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000862581 – 1104Mitogen-activated protein kinase kinase kinase 9Add BLAST1104

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei304Phosphothreonine; by autocatalysis1 Publication1
    Modified residuei305Phosphothreonine; by autocatalysis1 Publication1
    Modified residuei308Phosphoserine; by autocatalysis1 Publication1
    Modified residuei312Phosphothreonine; by autocatalysis1 Publication1
    Modified residuei533PhosphoserineCombined sources1

    Post-translational modificationi

    Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-312 is likely to be the main autophosphorylation site. Autophosphorylation also occurs on Thr-304 and Ser-308.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP80192.
    PeptideAtlasiP80192.
    PRIDEiP80192.

    PTM databases

    iPTMnetiP80192.
    PhosphoSitePlusiP80192.

    Expressioni

    Tissue specificityi

    Expressed in epithelial tumor cell lines of colonic, breast and esophageal origin.1 Publication

    Gene expression databases

    BgeeiENSG00000006432.
    CleanExiHS_MAP3K9.
    ExpressionAtlasiP80192. baseline and differential.
    GenevisibleiP80192. HS.

    Organism-specific databases

    HPAiHPA000942.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HSP90AB1P082382EBI-3951604,EBI-352572

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi110439. 1 interactor.
    IntActiP80192. 1 interactor.
    STRINGi9606.ENSP00000451263.

    Chemistry databases

    BindingDBiP80192.

    Structurei

    Secondary structure

    11104
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi143 – 153Combined sources11
    Beta strandi156 – 163Combined sources8
    Beta strandi166 – 172Combined sources7
    Helixi185 – 197Combined sources13
    Beta strandi206 – 210Combined sources5
    Beta strandi217 – 221Combined sources5
    Helixi228 – 232Combined sources5
    Helixi239 – 258Combined sources20
    Beta strandi259 – 262Combined sources4
    Helixi271 – 273Combined sources3
    Beta strandi274 – 278Combined sources5
    Beta strandi281 – 283Combined sources3
    Beta strandi290 – 292Combined sources3
    Helixi299 – 301Combined sources3
    Helixi313 – 315Combined sources3
    Helixi318 – 323Combined sources6
    Helixi328 – 344Combined sources17
    Turni348 – 351Combined sources4
    Helixi354 – 362Combined sources9
    Helixi376 – 385Combined sources10
    Helixi390 – 392Combined sources3
    Helixi396 – 404Combined sources9
    Helixi410 – 412Combined sources3
    Helixi418 – 439Combined sources22
    Helixi441 – 444Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3DTCX-ray2.60A136-406[»]
    4UY9X-ray2.81A/B135-456[»]
    ProteinModelPortaliP80192.
    SMRiP80192.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP80192.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini52 – 116SH3PROSITE-ProRule annotationAdd BLAST65
    Domaini144 – 412Protein kinasePROSITE-ProRule annotationAdd BLAST269

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni430 – 451Leucine-zipper 1Add BLAST22
    Regioni465 – 486Leucine-zipper 2Add BLAST22

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi12 – 42Ala-richAdd BLAST31
    Compositional biasi30 – 38Poly-Glu9
    Compositional biasi495 – 509Arg/Lys-rich (basic)Add BLAST15
    Compositional biasi863 – 972Pro-richAdd BLAST110
    Compositional biasi1011 – 1041Ser-richAdd BLAST31

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH3 domain

    Phylogenomic databases

    eggNOGiKOG0192. Eukaryota.
    COG0515. LUCA.
    GeneTreeiENSGT00760000118807.
    HOGENOMiHOG000060081.
    HOVERGENiHBG067662.
    InParanoidiP80192.
    KOiK04417.
    OMAiHHRRCEV.
    OrthoDBiEOG091G0JNI.
    PhylomeDBiP80192.
    TreeFamiTF105118.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR016231. MLK1/MLK2/MLK4.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000556. MAPKKK9_11. 1 hit.
    PRINTSiPR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00220. S_TKc. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    Isoform 1 (identifier: P80192-1) [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
    MEPSRALLGC LASAAAAAPP GEDGAGAGAE EEEEEEEEAA AAVGPGELGC
    60 70 80 90 100
    DAPLPYWTAV FEYEAAGEDE LTLRLGDVVE VLSKDSQVSG DEGWWTGQLN
    110 120 130 140 150
    QRVGIFPSNY VTPRSAFSSR CQPGGEDPSC YPPIQLLEID FAELTLEEII
    160 170 180 190 200
    GIGGFGKVYR AFWIGDEVAV KAARHDPDED ISQTIENVRQ EAKLFAMLKH
    210 220 230 240 250
    PNIIALRGVC LKEPNLCLVM EFARGGPLNR VLSGKRIPPD ILVNWAVQIA
    260 270 280 290 300
    RGMNYLHDEA IVPIIHRDLK SSNILILQKV ENGDLSNKIL KITDFGLARE
    310 320 330 340 350
    WHRTTKMSAA GTYAWMAPEV IRASMFSKGS DVWSYGVLLW ELLTGEVPFR
    360 370 380 390 400
    GIDGLAVAYG VAMNKLALPI PSTCPEPFAK LMEDCWNPDP HSRPSFTNIL
    410 420 430 440 450
    DQLTTIEESG FFEMPKDSFH CLQDNWKHEI QEMFDQLRAK EKELRTWEEE
    460 470 480 490 500
    LTRAALQQKN QEELLRRREQ ELAEREIDIL ERELNIIIHQ LCQEKPRVKK
    510 520 530 540 550
    RKGKFRKSRL KLKDGNRISL PSDFQHKFTV QASPTMDKRK SLINSRSSPP
    560 570 580 590 600
    ASPTIIPRLR AIQLTPGESS KTWGRSSVVP KEEGEEEEKR APKKKGRTWG
    610 620 630 640 650
    PGTLGQKELA SGDEGSPQRR EKANGLSTPS ESPHFHLGLK SLVDGYKQWS
    660 670 680 690 700
    SSAPNLVKGP RSSPALPGFT SLMEMEDEDS EGPGSGESRL QHSPSQSYLC
    710 720 730 740 750
    IPFPRGEDGD GPSSDGIHEE PTPVNSATST PQLTPTNSLK RGGAHHRRCE
    760 770 780 790 800
    VALLGCGAVL AATGLGFDLL EAGKCQLLPL EEPEPPAREE KKRREGLFQR
    810 820 830 840 850
    SSRPRRSTSP PSRKLFKKEE PMLLLGDPSA SLTLLSLSSI SECNSTRSLL
    860 870 880 890 900
    RSDSDEIVVY EMPVSPVEAP PLSPCTHNPL VNVRVERFKR DPNQSLTPTH
    910 920 930 940 950
    VTLTTPSQPS SHRRTPSDGA LKPETLLASR SPSSNGLSPS PGAGMLKTPS
    960 970 980 990 1000
    PSRDPGEFPR LPDPNVVFPP TPRRWNTQQD STLERPKTLE FLPRPRPSAN
    1010 1020 1030 1040 1050
    RQRLDPWWFV SPSHARSTSP ANSSSTETPS NLDSCFASSS STVEERPGLP
    1060 1070 1080 1090 1100
    ALLPFQAGPL PPTERTLLDL DAEGQSQDST VPLCRAELNT HRPAPYEIQQ

    EFWS
    Length:1,104
    Mass (Da):121,895
    Last modified:October 17, 2006 - v3
    Checksum:i0F059C867FCE7276
    GO
    Isoform 2 (identifier: P80192-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         675-675: M → MALLAASWVVPIDIE

    Show »
    Length:1,118
    Mass (Da):123,373
    Checksum:i608E5BDC00DC09B8
    GO

    Sequence cautioni

    The sequence AAI11408 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti356A → R (PubMed:8477742).Curated1
    Sequence conflicti433M → T in AAQ23054 (PubMed:15610029).Curated1
    Sequence conflicti511 – 535KLKDG…QASPT → AQPVLPFPHGHSRCPGGTGS SWGGQ (PubMed:8477742).CuratedAdd BLAST25

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_040698246A → V in a metastatic melanoma sample; somatic mutation. 1 Publication1
    Natural variantiVAR_040699467R → C in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs773256562dbSNPEnsembl.1
    Natural variantiVAR_040700497R → Q.1 PublicationCorresponds to variant rs56196343dbSNPEnsembl.1
    Natural variantiVAR_040701646Y → C.1 PublicationCorresponds to variant rs34322726dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_013765675M → MALLAASWVVPIDIE in isoform 2. 1 Publication1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY327900 mRNA. Translation: AAQ23054.1.
    BC111407 mRNA. Translation: AAI11408.1. Different initiation.
    BC133706 mRNA. Translation: AAI33707.1.
    AF251442 mRNA. Translation: AAG44591.1.
    CCDSiCCDS32112.1. [P80192-4]
    CCDS61488.1. [P80192-1]
    PIRiS32467. JU0229.
    RefSeqiNP_001271159.1. NM_001284230.1. [P80192-1]
    NP_149132.2. NM_033141.3. [P80192-4]
    UniGeneiHs.445496.
    Hs.593542.

    Genome annotation databases

    EnsembliENST00000554752; ENSP00000451612; ENSG00000006432. [P80192-1]
    ENST00000555993; ENSP00000451263; ENSG00000006432. [P80192-4]
    GeneIDi4293.
    KEGGihsa:4293.
    UCSCiuc001xml.5. human. [P80192-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY327900 mRNA. Translation: AAQ23054.1.
    BC111407 mRNA. Translation: AAI11408.1. Different initiation.
    BC133706 mRNA. Translation: AAI33707.1.
    AF251442 mRNA. Translation: AAG44591.1.
    CCDSiCCDS32112.1. [P80192-4]
    CCDS61488.1. [P80192-1]
    PIRiS32467. JU0229.
    RefSeqiNP_001271159.1. NM_001284230.1. [P80192-1]
    NP_149132.2. NM_033141.3. [P80192-4]
    UniGeneiHs.445496.
    Hs.593542.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3DTCX-ray2.60A136-406[»]
    4UY9X-ray2.81A/B135-456[»]
    ProteinModelPortaliP80192.
    SMRiP80192.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi110439. 1 interactor.
    IntActiP80192. 1 interactor.
    STRINGi9606.ENSP00000451263.

    Chemistry databases

    BindingDBiP80192.
    ChEMBLiCHEMBL2872.
    GuidetoPHARMACOLOGYi2084.

    PTM databases

    iPTMnetiP80192.
    PhosphoSitePlusiP80192.

    Polymorphism and mutation databases

    DMDMi116242625.

    Proteomic databases

    PaxDbiP80192.
    PeptideAtlasiP80192.
    PRIDEiP80192.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000554752; ENSP00000451612; ENSG00000006432. [P80192-1]
    ENST00000555993; ENSP00000451263; ENSG00000006432. [P80192-4]
    GeneIDi4293.
    KEGGihsa:4293.
    UCSCiuc001xml.5. human. [P80192-1]

    Organism-specific databases

    CTDi4293.
    DisGeNETi4293.
    GeneCardsiMAP3K9.
    H-InvDBHIX0011779.
    HGNCiHGNC:6861. MAP3K9.
    HPAiHPA000942.
    MIMi600136. gene.
    neXtProtiNX_P80192.
    OpenTargetsiENSG00000006432.
    PharmGKBiPA30607.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0192. Eukaryota.
    COG0515. LUCA.
    GeneTreeiENSGT00760000118807.
    HOGENOMiHOG000060081.
    HOVERGENiHBG067662.
    InParanoidiP80192.
    KOiK04417.
    OMAiHHRRCEV.
    OrthoDBiEOG091G0JNI.
    PhylomeDBiP80192.
    TreeFamiTF105118.

    Enzyme and pathway databases

    BioCyciZFISH:HS00177-MONOMER.
    SignaLinkiP80192.
    SIGNORiP80192.

    Miscellaneous databases

    ChiTaRSiMAP3K9. human.
    EvolutionaryTraceiP80192.
    GeneWikiiMAP3K9.
    GenomeRNAii4293.
    PROiP80192.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000006432.
    CleanExiHS_MAP3K9.
    ExpressionAtlasiP80192. baseline and differential.
    GenevisibleiP80192. HS.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR016231. MLK1/MLK2/MLK4.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008271. Ser/Thr_kinase_AS.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000556. MAPKKK9_11. 1 hit.
    PRINTSiPR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00220. S_TKc. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiM3K9_HUMAN
    AccessioniPrimary (citable) accession number: P80192
    Secondary accession number(s): A3KN85
    , Q0D2G7, Q6EH31, Q9H2N5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: October 17, 2006
    Last modified: November 2, 2016
    This is version 165 of the entry and version 3 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 14
      Human chromosome 14: 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. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    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.