Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Guanine nucleotide-binding protein G(t) subunit alpha-3

Gene

Gnat3

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

Functioni

Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. Transduction by this alpha subunit involves coupling of specific cell-surface receptors with a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. Indeed, denatonium and strychnine induce transient reduction in cAMP and cGMP in taste tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. GNAT3 can functionally couple to taste receptors to transmit intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act as bitter sensors. Functions also as lumenal sugar sensors in the gut to control the expression of the Na+-glucose transporter SGLT1 in response to dietaty sugar, as well as the secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to absorb sugars, with implications in malabsorption syndromes and diet-related disorders including diabetes and obesity.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi47 – 471MagnesiumBy similarity
Metal bindingi181 – 1811MagnesiumBy similarity
Binding sitei326 – 3261GTP; via amide nitrogenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi40 – 478GTPBy similarity
Nucleotide bindingi175 – 1817GTPBy similarity
Nucleotide bindingi200 – 2045GTPBy similarity
Nucleotide bindingi269 – 2724GTPBy similarity

GO - Molecular functioni

  1. G-protein beta/gamma-subunit complex binding Source: GO_Central
  2. G-protein coupled photoreceptor activity Source: GO_Central
  3. G-protein coupled receptor binding Source: GO_Central
  4. GTPase activity Source: MGI
  5. GTP binding Source: UniProtKB-KW
  6. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: GO_Central
  2. detection of chemical stimulus involved in sensory perception of bitter taste Source: GO_Central
  3. detection of visible light Source: GOC
  4. G-protein coupled receptor signaling pathway Source: MGI
  5. GTP catabolic process Source: InterPro
  6. response to nicotine Source: Ensembl
  7. sensory perception of bitter taste Source: MGI
  8. sensory perception of sweet taste Source: MGI
  9. sensory perception of taste Source: MGI
  10. sensory perception of umami taste Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_205726. G-protein activation.
REACT_222824. Adenylate cyclase inhibitory pathway.
REACT_232481. ADP signalling through P2Y purinoceptor 12.
REACT_242871. G alpha (s) signalling events.
REACT_250376. G alpha (i) signalling events.
REACT_253342. PLC beta mediated events.
REACT_258013. G alpha (z) signalling events.
REACT_259776. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide-binding protein G(t) subunit alpha-3
Alternative name(s):
Gustducin alpha-3 chain
Gene namesi
Name:Gnat3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:3588268. Gnat3.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. acrosomal vesicle Source: Ensembl
  2. apical plasma membrane Source: Ensembl
  3. axoneme Source: Ensembl
  4. cytoplasm Source: MGI
  5. photoreceptor inner segment Source: GO_Central
  6. photoreceptor outer segment Source: GO_Central
  7. protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice are not affected in their tasting ability for salty (NaCl) and sour (HCl) stimuli, which are known not to be mediated by G proteins; but, they exhibit a significant reduction in the ability to taste the bitter compounds denatonium and quinine as well as the sweet compounds sucrose and SC45647, a guanidine sweetener. The incidence of cells responding to bitter stimulus is also reduced by seventy per cent. The residual behavioral response to bitter and sweet taste in these deficient mice suggests that there is alternative mechanism to compensate. However, transgenic expression of Gnat3 in these deficient mice restores responsiveness to both bitter and sweet compounds, whereas expression of mutated 'Gly-352' transgene do not. Furthermore, in wild-type mice, this mutated transgene acts as dominant-negative by inhibition of endogenous Gnat3 interactions with taste receptors. Mice show less preference for acesulfame-K, dulcin, fructose, D-phenylalanine, L-proline, D-tryptophan, saccharin, sweetener SC45647 and sucrose; Furthermore, in their gut, sugar or sweeteners do not increase SGLT1 expression and glucose-absorptive capacity compared to wild-type mice and the ingestion of glucose reveals deficiencies in secretion of GLP-1 and regulation of plasma insulin and glucose. Mice lacking GNAT3 show less preference for umami compounds such as monosodium glutamate (MSG) and no preference for inosine monophosphate (IMP) whereas wild-type mice strongly prefer IMP. The response to umami signals implicates the anteriorly placed taste buds of the tongue, and not the posterior part.8 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed
Chaini2 – 354353Guanine nucleotide-binding protein G(t) subunit alpha-3PRO_0000342672Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity

Post-translational modificationi

Potential N-myristoylation may anchor alpha-subunit to the inner surface of plasma membrane.By similarity

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

MaxQBiQ3V3I2.
PaxDbiQ3V3I2.
PRIDEiQ3V3I2.

PTM databases

PhosphoSiteiQ3V3I2.

Expressioni

Tissue specificityi

Expressed in taste buds (sensory organs of clustered epithelial cells) of the circumvallate and fungiform papillae of the tongue as well as in palatal taste buds at protein level. Expressed in enteroendocrine cells of the gut, such as in subsets of enteroendocrine cells in the midjejunum and brush cells. Detected also in spermatozoa.5 Publications

Developmental stagei

From week 1 to 7, the number of cells expressing GNAT3 in single taste buds increases within fungiform papilla; by week 7, the number reached the value found in adults. Expressed in cell bodies and axons of facial motor neurons at E10.5.2 Publications

Gene expression databases

BgeeiQ3V3I2.
ExpressionAtlasiQ3V3I2. baseline.
GenevestigatoriQ3V3I2.

Interactioni

Subunit structurei

G proteins are composed of 3 units; alpha, beta and gamma, respectively GNAT3, GNB1 and GNG13 for Gustducin heterotrimer for bitter taste transduction. The alpha chain contains the guanine nucleotide binding site. Gustducin heterotrimer may also be composed of GNAT3, GNB3 and GNG13.1 Publication

Structurei

3D structure databases

ProteinModelPortaliQ3V3I2.
SMRiQ3V3I2. Positions 14-354.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-alpha family. G(i/o/t/z) subfamily.Curated

Phylogenomic databases

eggNOGiNOG322962.
GeneTreeiENSGT00760000118851.
HOGENOMiHOG000038730.
HOVERGENiHBG063184.
InParanoidiQ3V3I2.
KOiK04631.
OMAiLCAMANT.
OrthoDBiEOG72C50B.
PhylomeDBiQ3V3I2.
TreeFamiTF300673.

Family and domain databases

Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 1 hit.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00441. GPROTEINAI.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.

Sequencei

Sequence statusi: Complete.

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

Q3V3I2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSGISSESK ESARRSKELE KKLQEDAERD ARTVKLLLLG AGESGKSTIV
60 70 80 90 100
KQMKIIHKNG YSKQECMEFK AVIYSNTLQS ILAIVKAMAT LGIDYVNPRS
110 120 130 140 150
REDQEQLHSM ANTLEDGDMT PQLAEIIKRL WGDPGIQACF ERASEYQLND
160 170 180 190 200
SAAYYLNDLD RLTAPGYVPN EQDVLHSRVK TTGIIETQFS FKDLNFRMFD
210 220 230 240 250
VGGQRSERKK WIHCFEGVTC IIFCAALSAY DMVLVEDEEV NRMHESLHLF
260 270 280 290 300
NSICNHKYFA TTSIVLFLNK KDLFQEKVAK VHLSICFPEY TGPNTFEDAG
310 320 330 340 350
NYIKNQFLDL NLKKEDKEIY SHMTCATDTQ NVKFVFDAVT DIIIKENLKD

CGLF
Length:354
Mass (Da):40,316
Last modified:July 1, 2008 - v2
Checksum:i05DBC95DAC356CEF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC129572 Genomic DNA. No translation available.
AK040065 mRNA. Translation: BAE20568.1.
CCDSiCCDS39017.1.
RefSeqiNP_001074612.1. NM_001081143.1.
UniGeneiMm.332230.

Genome annotation databases

EnsembliENSMUST00000030561; ENSMUSP00000030561; ENSMUSG00000028777.
GeneIDi242851.
KEGGimmu:242851.
UCSCiuc008wnr.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC129572 Genomic DNA. No translation available.
AK040065 mRNA. Translation: BAE20568.1.
CCDSiCCDS39017.1.
RefSeqiNP_001074612.1. NM_001081143.1.
UniGeneiMm.332230.

3D structure databases

ProteinModelPortaliQ3V3I2.
SMRiQ3V3I2. Positions 14-354.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiQ3V3I2.

Proteomic databases

MaxQBiQ3V3I2.
PaxDbiQ3V3I2.
PRIDEiQ3V3I2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030561; ENSMUSP00000030561; ENSMUSG00000028777.
GeneIDi242851.
KEGGimmu:242851.
UCSCiuc008wnr.1. mouse.

Organism-specific databases

CTDi346562.
MGIiMGI:3588268. Gnat3.

Phylogenomic databases

eggNOGiNOG322962.
GeneTreeiENSGT00760000118851.
HOGENOMiHOG000038730.
HOVERGENiHBG063184.
InParanoidiQ3V3I2.
KOiK04631.
OMAiLCAMANT.
OrthoDBiEOG72C50B.
PhylomeDBiQ3V3I2.
TreeFamiTF300673.

Enzyme and pathway databases

ReactomeiREACT_205726. G-protein activation.
REACT_222824. Adenylate cyclase inhibitory pathway.
REACT_232481. ADP signalling through P2Y purinoceptor 12.
REACT_242871. G alpha (s) signalling events.
REACT_250376. G alpha (i) signalling events.
REACT_253342. PLC beta mediated events.
REACT_258013. G alpha (z) signalling events.
REACT_259776. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).

Miscellaneous databases

NextBioi385586.
PROiQ3V3I2.
SOURCEiSearch...

Gene expression databases

BgeeiQ3V3I2.
ExpressionAtlasiQ3V3I2. baseline.
GenevestigatoriQ3V3I2.

Family and domain databases

Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR001408. Gprotein_alpha_I.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 1 hit.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00441. GPROTEINAI.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-310.
    Strain: C57BL/6J.
    Tissue: Thymus.
  3. "Transduction of bitter and sweet taste by gustducin."
    Wong G.T., Gannon K.S., Margolskee R.F.
    Nature 381:796-800(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  4. "Directing gene expression to gustducin-positive taste receptor cells."
    Wong G.T., Ruiz-Avila L., Margolskee R.F.
    J. Neurosci. 19:5802-5809(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, TRANSGENE.
  5. "Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium."
    Huang L., Shanker Y.G., Dubauskaite J., Zheng J.Z., Yan W., Rosenzweig S., Spielman A.I., Max M., Margolskee R.F.
    Nat. Neurosci. 2:1055-1062(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT.
  6. "Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides."
    Yan W., Sunavala G., Rosenzweig S., Dasso M., Brand J.G., Spielman A.I.
    Am. J. Physiol. 280:C742-C751(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Dominant loss of responsiveness to sweet and bitter compounds caused by a single mutation in alpha-gustducin."
    Ruiz-Avila L., Wong G.T., Damak S., Margolskee R.F.
    Proc. Natl. Acad. Sci. U.S.A. 98:8868-8873(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, TRANSGENE.
  8. "Regional expression patterns of taste receptors and gustducin in the mouse tongue."
    Kim M.-R., Kusakabe Y., Miura H., Shindo Y., Ninomiya Y., Hino A.
    Biochem. Biophys. Res. Commun. 312:500-506(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  9. "Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli."
    Caicedo A., Pereira E., Margolskee R.F., Roper S.D.
    J. Neurosci. 23:9947-9952(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  10. "Dynamic expression of RGS4 in the developing nervous system and regulation by the neural type-specific transcription factor Phox2b."
    Grillet N., Dubreuil V., Dufour H.D., Brunet J.-F.
    J. Neurosci. 23:10613-10621(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  11. "Umami taste responses are mediated by alpha-transducin and alpha-gustducin."
    He W., Yasumatsu K., Varadarajan V., Yamada A., Lem J., Ninomiya Y., Margolskee R.F., Damak S.
    J. Neurosci. 24:7674-7680(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  12. "Developmental change of alpha-gustducin expression in the mouse fungiform papilla."
    Zhang G.-H., Deng S.-P., Li L.-L., Li H.-T.
    Anat. Embryol. (Berl.) 211:625-630(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  13. "Taste responses to sweet stimuli in alpha-gustducin knockout and wild-type mice."
    Danilova V., Damak S., Margolskee R.F., Hellekant G.
    Chem. Senses 31:573-580(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  14. "Phenotypic characterization of taste cells of the mouse small intestine."
    Sutherland K., Young R.L., Cooper N.J., Horowitz M., Blackshaw L.A.
    Am. J. Physiol. 292:G1420-G1428(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  15. "Expression of T1Rs and gustducin in palatal taste buds of mice."
    Stone L.M., Barrows J., Finger T.E., Kinnamon S.C.
    Chem. Senses 32:255-262(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  16. "Expression of the G-protein alpha-subunit gustducin in mammalian spermatozoa."
    Fehr J., Meyer D., Widmayer P., Borth H.C., Ackermann F., Wilhelm B., Gudermann T., Boekhoff I.
    J. Comp. Physiol. A 193:21-34(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  17. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  18. Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiGNAT3_MOUSE
AccessioniPrimary (citable) accession number: Q3V3I2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 2008
Last sequence update: July 1, 2008
Last modified: March 4, 2015
This is version 89 of the entry and version 2 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

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.