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Protein

Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2

Gene

Inppl1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking. Confers resistance to dietary obesity. May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling. Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (By similarity). Regulates cell adhesion and cell spreading. Required for HGF-mediated lamellipodium formation, cell scattering and spreading. Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation. Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth. Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Involved in EGF signaling pathway. Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3. Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity. Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1. In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling. May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (By similarity).By similarity4 Publications

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 3,4-diphosphate + phosphate.

Enzyme regulationi

Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane. Enzymatic activity is enhanced in the presence of phosphatidylserine (By similarity).By similarity

GO - Molecular functioni

  • inositol-polyphosphate 5-phosphatase activity Source: RGD
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: RGD

GO - Biological processi

  • brain development Source: RGD
  • cell adhesion Source: UniProtKB-KW
  • endochondral ossification Source: UniProtKB
  • immune system process Source: UniProtKB-KW
  • inositol trisphosphate metabolic process Source: RGD
  • negative regulation of DNA replication Source: RGD
  • negative regulation of insulin-like growth factor receptor signaling pathway Source: RGD
  • negative regulation of insulin receptor signaling pathway Source: RGD
  • negative regulation of MAP kinase activity Source: RGD
  • negative regulation of neuron projection development Source: RGD
  • negative regulation of platelet-derived growth factor receptor signaling pathway Source: RGD
  • phosphatidylinositol dephosphorylation Source: InterPro
  • response to drug Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cell adhesion, Immunity

Keywords - Ligandi

Actin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 (EC:3.1.3.86)
Alternative name(s):
Inositol polyphosphate phosphatase-like protein 1
Short name:
INPPL-1
SH2 domain-containing inositol 5'-phosphatase 2
Short name:
SH2 domain-containing inositol phosphatase 2
Short name:
SHIP-2
Gene namesi
Name:Inppl1
Synonyms:Ship2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi68396. Inppl1.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • Cytoplasmcytoskeleton By similarity
  • Membrane 1 Publication; Peripheral membrane protein 1 Publication
  • Cell projectionfilopodium By similarity
  • Cell projectionlamellipodium By similarity

  • Note: Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type. Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B). Tyrosine phosphorylation may also participate in membrane localization. Insulin specifically stimulates its redistribution from the cytosol to the plasma membrane. Recruited to the membrane following M-CSF stimulation. In activated spreading platelets, localizes with actin at filopodia, lamellipodia and the central actin ring.

GO - Cellular componenti

  • cytoskeleton Source: UniProtKB-SubCell
  • cytosol Source: UniProtKB-SubCell
  • filopodium Source: UniProtKB-SubCell
  • lamellipodium Source: RGD
  • membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi987 – 9871Y → F: Loss of phosphorylation following insulin stimulation. 1 Publication

Chemistry

ChEMBLiCHEMBL2331062.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12571257Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2PRO_0000302872Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei132 – 1321PhosphoserineCombined sources
Modified residuei165 – 1651PhosphothreonineBy similarity
Modified residuei241 – 2411PhosphoserineBy similarity
Modified residuei987 – 9871PhosphotyrosineBy similarity
Modified residuei1136 – 11361PhosphotyrosineBy similarity
Modified residuei1161 – 11611PhosphotyrosineBy similarity

Post-translational modificationi

Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as insulin, growth factors such as EGF or PDGF, chemokines, integrin ligands and hypertonic and oxidative stress. May be phosphorylated upon IgG receptor FCGR2B-binding. Phosphorylated at Tyr-987 following cell attachment and spreading. Phosphorylated at Tyr-1161 following EGF signaling pathway stimulation (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9WVR3.
PRIDEiQ9WVR3.

PTM databases

PhosphoSiteiQ9WVR3.

Interactioni

Subunit structurei

Interacts with tyrosine phosphorylated form of SHC1, Interacts with EGFR. Upon stimulation by the EGF signaling pathway, it forms a complex with SHC1 and EGFR. Interacts with cytoskeletal protein SORBS3/vinexin, promoting its localization to the periphery of cells. Forms a complex with filamin (FLNA or FLNB), actin, GPIb (GP1BA or GP1BB) that regulates cortical and submembraneous actin. Interacts with c-Met/MET, when c-Met/MET is phosphorylated on 'Tyr-1356'. Interacts with p130Cas/BCAR1. Interacts with CENTD3/ARAP3 via its SAM domain. Interacts with c-Cbl/CBL and CAP/SORBS1. Interacts with activated EPHA2 receptor. Interacts with receptors FCGR2A and FCGR2B. Interacts with tyrosine kinases ABL1 and TEC. Interacts with CSF1R. Interacts (via N-terminus) with SH3YL1 (via SH3 domain).By similarity

Protein-protein interaction databases

IntActiQ9WVR3. 1 interaction.
STRINGi10116.ENSRNOP00000061371.

Structurei

3D structure databases

ProteinModelPortaliQ9WVR3.
SMRiQ9WVR3. Positions 18-119.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 11797SH2PROSITE-ProRule annotationAdd
BLAST
Domaini1195 – 125763SAMPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi945 – 9506SH3-binding
Motifi984 – 9874NPXY motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi936 – 1106171Pro-richAdd
BLAST

Domaini

The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or FCGR2A. It also mediates the interaction with p130Cas/BCAR1 (By similarity).By similarity
The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.By similarity

Sequence similaritiesi

Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3-binding

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
KOG4384. Eukaryota.
COG5411. LUCA.
HOGENOMiHOG000004836.
HOVERGENiHBG106726.
InParanoidiQ9WVR3.
KOiK15909.
PhylomeDBiQ9WVR3.
TreeFamiTF323475.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
3.30.505.10. 1 hit.
3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR000980. SH2.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
PF00536. SAM_1. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00128. IPPc. 1 hit.
SM00454. SAM. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56219. SSF56219. 1 hit.
PROSITEiPS50105. SAM_DOMAIN. 1 hit.
PS50001. SH2. 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: Q9WVR3-1) [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
MASVCGAPSP GGALGSQAPA WYHRDLSRAA AEELLARAGR DGSFLVRDSE
60 70 80 90 100
SVAGAFALCV LYQKHVHTYR ILPDGEDFLA VQTSQGVPVR RFQTLGELIG
110 120 130 140 150
LYAQPNQGLV CALLLPVEGE REPDPPDDRD ASDVEDEKPP LPPRSGSTSI
160 170 180 190 200
SVPAGPSSPL PAPETPTTPA AESTPNGLST VSHEYLKGSY GLDLEAVRGG
210 220 230 240 250
ASNLPHLTRT LVTSCRRLHS EVDKVLSGLE ILSKVFDQQS SPMVTRLLQQ
260 270 280 290 300
QSLPQTGEQE LESLVLKLSV LKDFLSGIQK KALKALQDMS STAPPAPLQP
310 320 330 340 350
SIRKAKTIPV QAFEVKLDVT LGDLTKIGKS QKFTLSVDVE GGRLVLLRRQ
360 370 380 390 400
RDSQEDWTTF THDRIRQLIK SQRVQNKLGV VFEKEKDRTQ RKDFIFVSAR
410 420 430 440 450
KREAFCQLLQ LMKNKHSKQD EPDMISVFIG TWNMGSVPPP KNVTSWFTSK
460 470 480 490 500
GLGKALDEVT VTIPHDIYVF GTQENSVGDR EWLDLLRGGL KELTDLDYRP
510 520 530 540 550
IAMQSLWNIK VAVLVKPEHE NRISHVSTSS VKTGIANTLG NKGAVGVSFM
560 570 580 590 600
FNGTSFGFVN CHLTSGNEKT TRRNQNYLDI LRLLSLGDRQ LSAFDISLRF
610 620 630 640 650
THLFWFGDLN YRLDMDIQEI LNYISRREFE PLLRVDQLNL EREKHKVFLR
660 670 680 690 700
FSEEEISFPP TYRYERGSRD TYAWHKQKPT GVRTNVPSWC DRILWKSYPE
710 720 730 740 750
THIICNSYGC TDDIVTSDHS PVFGTFEVGV TSQFISKKGL SKTSDQAYIE
760 770 780 790 800
FESIEAIVKT ASRTKFFIEF YSTCLEEYKK SFENDAQSSD NINFLKVQWS
810 820 830 840 850
SRQLPTLKPI LADIEYLQDQ HLLLTVKSMD GYESYGECVV ALKSMIGSTA
860 870 880 890 900
QQFLTFLSHR GEETGNIRGS MKVRVPTERL GTRERLYEWI SIDKDDTGAK
910 920 930 940 950
SKAPSVLRGS QEHRSGSRKP TSTEASCPLS KLFEEPEKPP PTGRPPAPPR
960 970 980 990 1000
AVPREESLNP RLKSEGTPEQ EGVAAPPPKN SFNNPAYYVL EGVPHQLLPL
1010 1020 1030 1040 1050
EPTSFARAPI PPTTKNKVAI TVPAPQLGRH RTPRVGEGSS SDEDSGGTLP
1060 1070 1080 1090 1100
PPDFPPPPLP DSAIFLPPNL DPLSMPVVRG RSVGEARGPP PPKAHPRPPL
1110 1120 1130 1140 1150
PPGTSPASTF LEEVASADDR SCSVLQMAKT LSEVDYSPGP GRSALLPNPL
1160 1170 1180 1190 1200
ELQLPRGPSD YGRPLSFPPP RIRESIQEDL AEEAPCPQGG RASGLGEAGM
1210 1220 1230 1240 1250
GAWLRAIGLE RYEEGLVHNG WDDLEFLSDI TEEDLEEAGV QDPAHKRLLL

DTLQLSK
Length:1,257
Mass (Da):139,143
Last modified:November 1, 1999 - v1
Checksum:i3A994C8E52940083
GO
Isoform 2 (identifier: Q9WVR3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1184-1257: Missing.

Show »
Length:1,183
Mass (Da):131,114
Checksum:i327D87FFF1FA497D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti910 – 9101S → N in BAA81818 (PubMed:10381377).Curated
Sequence conflicti1009 – 10091P → L in BAA81818 (PubMed:10381377).Curated

Polymorphismi

Variant Cys-1142 found in diabetic GK strain may be a cause of diabete in this strain. Genetic variations in Inppl1 may also be a cause of susceptibility to hypertension.1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1142 – 11421R → C in strain: GK. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1184 – 125774Missing in isoform 2. 1 PublicationVSP_027986Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011439 mRNA. Translation: BAA81818.1.
AB025794 mRNA. Translation: BAA82308.1.
RefSeqiNP_001257772.1. NM_001270843.1. [Q9WVR3-2]
NP_075233.1. NM_022944.2. [Q9WVR3-1]
UniGeneiRn.42902.

Genome annotation databases

GeneIDi65038.
KEGGirno:65038.
UCSCiRGD:68396. rat. [Q9WVR3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011439 mRNA. Translation: BAA81818.1.
AB025794 mRNA. Translation: BAA82308.1.
RefSeqiNP_001257772.1. NM_001270843.1. [Q9WVR3-2]
NP_075233.1. NM_022944.2. [Q9WVR3-1]
UniGeneiRn.42902.

3D structure databases

ProteinModelPortaliQ9WVR3.
SMRiQ9WVR3. Positions 18-119.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9WVR3. 1 interaction.
STRINGi10116.ENSRNOP00000061371.

Chemistry

ChEMBLiCHEMBL2331062.

PTM databases

PhosphoSiteiQ9WVR3.

Proteomic databases

PaxDbiQ9WVR3.
PRIDEiQ9WVR3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi65038.
KEGGirno:65038.
UCSCiRGD:68396. rat. [Q9WVR3-1]

Organism-specific databases

CTDi3636.
RGDi68396. Inppl1.

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
KOG4384. Eukaryota.
COG5411. LUCA.
HOGENOMiHOG000004836.
HOVERGENiHBG106726.
InParanoidiQ9WVR3.
KOiK15909.
PhylomeDBiQ9WVR3.
TreeFamiTF323475.

Miscellaneous databases

NextBioi613848.
PROiQ9WVR3.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
3.30.505.10. 1 hit.
3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR000300. IPPc.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR000980. SH2.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
PF00536. SAM_1. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00128. IPPc. 1 hit.
SM00454. SAM. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56219. SSF56219. 1 hit.
PROSITEiPS50105. SAM_DOMAIN. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of rat SH2-containing inositol phosphatase 2 (SHIP2) and its role in the regulation of insulin signaling."
    Ishihara H., Sasaoka T., Hori H., Wada T., Hirai H., Haruta T., Kobayashi M.
    Biochem. Biophys. Res. Commun. 260:265-272(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, PHOSPHORYLATION.
    Strain: Sprague-Dawley.
  2. "Localization of mRNA for SHIP2, SH2 domain-containing inositol polyphosphate 5-phosphatase, in the brain of developing and mature rats."
    Kudo M., Saito S., Owada Y., Suzaki H., Kondo H.
    Brain Res. Mol. Brain Res. 75:172-177(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  3. "Overexpression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'-phosphatase catalytic activity."
    Wada T., Sasaoka T., Funaki M., Hori H., Murakami S., Ishiki M., Haruta T., Asano T., Ogawa W., Ishihara H., Kobayashi M.
    Mol. Cell. Biol. 21:1633-1646(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "Membrane localization of Src homology 2-containing inositol 5'-phosphatase 2 via Shc association is required for the negative regulation of insulin signaling in Rat1 fibroblasts overexpressing insulin receptors."
    Ishihara H., Sasaoka T., Ishiki M., Wada T., Hori H., Kagawa S., Kobayashi M.
    Mol. Endocrinol. 16:2371-2381(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-987.
  5. "An essential role for the SHIP2-dependent negative feedback loop in neuritogenesis of nerve growth factor-stimulated PC12 cells."
    Aoki K., Nakamura T., Inoue T., Meyer T., Matsuda M.
    J. Cell Biol. 177:817-827(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "The gene INPPL1, encoding the lipid phosphatase SHIP2, is a candidate for type 2 diabetes in rat and man."
    Marion E., Kaisaki P.J., Pouillon V., Gueydan C., Levy J.C., Bodson A., Krzentowski G., Daubresse J.-C., Mockel J., Behrends J., Servais G., Szpirer C., Kruys V., Gauguier D., Schurmans S.
    Diabetes 51:2012-2017(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CYS-1142, POLYMORPHISM.

Entry informationi

Entry nameiSHIP2_RAT
AccessioniPrimary (citable) accession number: Q9WVR3
Secondary accession number(s): Q9R1V2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: November 1, 1999
Last modified: January 20, 2016
This is version 105 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. 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.