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Protein

Protein arginine N-methyltransferase 5

Gene

Prmt5

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

Functioni

Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Methylates SUPT5H. Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. Plays a role in the assembly of snRNP core particles. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. May regulate the SUPT5H transcriptional elongation properties. May be part of a pathway that is connected to a chloride current, possibly through cytoskeletal rearrangement. Methylates histone H2A and H4 'Arg-3' during germ cell development. Methylates histone H3 'Arg-8', which may repress transcription. Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage. Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity. Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation. Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter.5 Publications

Catalytic activityi

S-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone].

Enzyme regulationi

Activity is increased by EGF, HGF, FGF1 or FGF2 treatments, and slightly decreased by NGF treatment.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei304 – 3041Peptide substrateBy similarity
Binding sitei307 – 3071Peptide substrateBy similarity
Binding sitei324 – 3241S-adenosyl-L-methionineBy similarity
Sitei327 – 3271Critical for specifying symmetric addition of methyl groupsBy similarity
Binding sitei392 – 3921S-adenosyl-L-methionineBy similarity
Active sitei435 – 4351Proton donor/acceptorBy similarity
Active sitei444 – 4441Proton donor/acceptorBy similarity

GO - Molecular functioni

  1. chromatin binding Source: MGI
  2. core promoter sequence-specific DNA binding Source: UniProtKB
  3. histone-arginine N-methyltransferase activity Source: GO_Central
  4. methyltransferase activity Source: MGI
  5. protein-arginine omega-N symmetric methyltransferase activity Source: UniProtKB
  6. protein heterodimerization activity Source: MGI
  7. ribonucleoprotein complex binding Source: MGI
  8. transcription corepressor activity Source: UniProtKB

GO - Biological processi

  1. circadian regulation of gene expression Source: UniProtKB
  2. endothelial cell activation Source: MGI
  3. histone arginine methylation Source: GO_Central
  4. histone H4-R3 methylation Source: UniProtKB
  5. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  6. peptidyl-arginine methylation Source: UniProtKB
  7. peptidyl-arginine methylation, to symmetrical-dimethyl arginine Source: MGI
  8. peptidyl-arginine N-methylation Source: MGI
  9. spliceosomal snRNP assembly Source: UniProtKB
  10. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiREACT_319868. RMTs methylate histone arginines.
REACT_333207. snRNP Assembly.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein arginine N-methyltransferase 5 (EC:2.1.1.-)
Alternative name(s):
Histone-arginine N-methyltransferase PRMT5 (EC:2.1.1.125)
Jak-binding protein 1
Shk1 kinase-binding protein 1 homolog
Short name:
SKB1 homolog
Gene namesi
Name:Prmt5
Synonyms:Jbp1, Skb1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1351645. Prmt5.

Subcellular locationi

Cytoplasm By similarity. Nucleus 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. cytosol Source: UniProtKB
  3. methylosome Source: UniProtKB
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 637636Protein arginine N-methyltransferase 5PRO_0000212344Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ8CIG8.
PaxDbiQ8CIG8.
PRIDEiQ8CIG8.

PTM databases

PhosphoSiteiQ8CIG8.

Expressioni

Gene expression databases

BgeeiQ8CIG8.
CleanExiMM_PRMT5.
ExpressionAtlasiQ8CIG8. baseline and differential.
GenevestigatoriQ8CIG8.

Interactioni

Subunit structurei

Forms, at least, homodimers and homotetramers. Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1 and WDR77/MEP50. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Also interacts with Sm proteins, JAK2 and SSTR1. Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with LSM11, PRMT7 and SNRPD3. Interacts with COPRS; promoting its recruitment on histone H4 (By similarity). Interacts with PRDM1. Interacts with RPS10. Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation (By similarity). Interacts with BRAF and with active RAF1 (By similarity). Interacts with HOXA9 (By similarity). Interacts with SRGAP2. Interacts with EPB41L3; this modulates methylation of target proteins (By similarity). Found in a complex with COPRS, RUNX1 and CBFB. Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1. Interacts with IWS1 (By similarity). Interacts with CRY1.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ccnd1P253225EBI-2527009,EBI-847243
ChtopQ9CY574EBI-2527009,EBI-6393116

Protein-protein interaction databases

BioGridi205181. 14 interactions.
IntActiQ8CIG8. 7 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ8CIG8.
SMRiQ8CIG8. Positions 13-637.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini308 – 615308SAM-dependent MTase PRMT-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni13 – 292280TIM barrelBy similarityAdd
BLAST
Regioni333 – 3342S-adenosyl-L-methionine bindingBy similarity
Regioni419 – 4202S-adenosyl-L-methionine bindingBy similarity
Regioni465 – 637173Beta barrelBy similarityAdd
BLAST
Regioni488 – 4947DimerizationBy similarity

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.PROSITE-ProRule annotation
Contains 1 SAM-dependent MTase PRMT-type domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG291156.
HOGENOMiHOG000175933.
HOVERGENiHBG057083.
InParanoidiQ8CIG8.
KOiK02516.
OrthoDBiEOG7X6KZR.
PhylomeDBiQ8CIG8.
TreeFamiTF300626.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025799. Arg_MeTrfase.
IPR007857. Arg_MeTrfase_PRMT5.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR10738. PTHR10738. 1 hit.
PfamiPF05185. PRMT5. 1 hit.
[Graphical view]
PIRSFiPIRSF015894. Skb1_MeTrfase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8CIG8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAMAVGGAG GSRVSSGRDL NCVPEIADTL GAVAKQGFDF LCMPVFHPRF
60 70 80 90 100
KREFIQEPAK NRPGPQTRSD LLLSGRDWNT LIVGKLSPWI HPDSKVEKIR
110 120 130 140 150
RNSEAAMLQE LNFGAYLGLP AFLLPLNQED NTNLARVLTN HIHTGHHSSM
160 170 180 190 200
FWMRVPLVAP EDLRDDVIAN APTTHTEEYS GEEKTWMWWH NFRTLCDYSK
210 220 230 240 250
RIAVALEIGA DLPSNHVIDR WLGEPIKAAI LPTSIFLTNK KGFPVLSKVQ
260 270 280 290 300
QRLIFRLLKL EVQFIITGTN HHSEKEFCSY LQYLEYLSQN RPPPNAYELF
310 320 330 340 350
AKGYEDYLQS PLQPLMDNLE SQTYEVFEKD PIKYSQYQQA IYKCLLDRVP
360 370 380 390 400
EEEKETNVQV LMVLGAGRGP LVNASLRAAK QAERRIRLYA VEKNPNAVVT
410 420 430 440 450
LENWQFEEWG SQVTVVSSDM REWVAPEKAD IIVSELLGSF ADNELSPECL
460 470 480 490 500
DGAQHFLKDD GVSIPGEYTS FLAPISSSKL YNEVRACREK DRDPEAQFEM
510 520 530 540 550
PYVVRLHNFH QLSAPKPCFT FSHPNRDPMI DNNRYCTLEF PVEVNTVLHG
560 570 580 590 600
FAGYFETVLY RDITLSIRPE THSPGMFSWF PIFFPIKQPI TVHEGQNICV
610 620 630
RFWRCSNSKK VWYEWAVTAP VCSSIHNPTG RSYTIGL
Length:637
Mass (Da):72,680
Last modified:January 22, 2007 - v3
Checksum:iE8014CA172B30543
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti169 – 1691A → E in BAE21155 (PubMed:16141072).Curated
Sequence conflicti169 – 1691A → E in BAE38057 (PubMed:16141072).Curated
Sequence conflicti376 – 3761L → F in AAF04503 (PubMed:10531356).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK132414 mRNA. Translation: BAE21155.1.
AK165165 mRNA. Translation: BAE38057.1.
BC023905 mRNA. Translation: AAH23905.1.
AF167573 mRNA. Translation: AAF04503.1.
CCDSiCCDS27091.1.
RefSeqiNP_038796.2. NM_013768.3.
UniGeneiMm.196585.

Genome annotation databases

GeneIDi27374.
KEGGimmu:27374.
UCSCiuc007twf.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK132414 mRNA. Translation: BAE21155.1.
AK165165 mRNA. Translation: BAE38057.1.
BC023905 mRNA. Translation: AAH23905.1.
AF167573 mRNA. Translation: AAF04503.1.
CCDSiCCDS27091.1.
RefSeqiNP_038796.2. NM_013768.3.
UniGeneiMm.196585.

3D structure databases

ProteinModelPortaliQ8CIG8.
SMRiQ8CIG8. Positions 13-637.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205181. 14 interactions.
IntActiQ8CIG8. 7 interactions.

PTM databases

PhosphoSiteiQ8CIG8.

Proteomic databases

MaxQBiQ8CIG8.
PaxDbiQ8CIG8.
PRIDEiQ8CIG8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi27374.
KEGGimmu:27374.
UCSCiuc007twf.2. mouse.

Organism-specific databases

CTDi10419.
MGIiMGI:1351645. Prmt5.

Phylogenomic databases

eggNOGiNOG291156.
HOGENOMiHOG000175933.
HOVERGENiHBG057083.
InParanoidiQ8CIG8.
KOiK02516.
OrthoDBiEOG7X6KZR.
PhylomeDBiQ8CIG8.
TreeFamiTF300626.

Enzyme and pathway databases

ReactomeiREACT_319868. RMTs methylate histone arginines.
REACT_333207. snRNP Assembly.

Miscellaneous databases

NextBioi305288.
PROiQ8CIG8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8CIG8.
CleanExiMM_PRMT5.
ExpressionAtlasiQ8CIG8. baseline and differential.
GenevestigatoriQ8CIG8.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025799. Arg_MeTrfase.
IPR007857. Arg_MeTrfase_PRMT5.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PANTHERiPTHR10738. PTHR10738. 1 hit.
PfamiPF05185. PRMT5. 1 hit.
[Graphical view]
PIRSFiPIRSF015894. Skb1_MeTrfase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51678. SAM_MT_PRMT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Skin.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  3. "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity."
    Pollack B.P., Kotenko S.V., He W., Izotova L.S., Barnoski B.L., Pestka S.
    J. Biol. Chem. 274:31531-31542(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-637.
  4. "Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes."
    Pal S., Vishwanath S.N., Erdjument-Bromage H., Tempst P., Sif S.
    Mol. Cell. Biol. 24:9630-9645(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN METHYLATION OF HISTONE H3.
  5. "Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells."
    Ancelin K., Lange U.C., Hajkova P., Schneider R., Bannister A.J., Kouzarides T., Surani M.A.
    Nat. Cell Biol. 8:623-630(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PRDM1.
  6. "Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members."
    Vagin V.V., Wohlschlegel J., Qu J., Jonsson Z., Huang X., Chuma S., Girard A., Sachidanandam R., Hannon G.J., Aravin A.A.
    Genes Dev. 23:1749-1762(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN METHYLATION OF PIWI PROTEINS.
  7. Cited for: FUNCTION, INTERACTION WITH CHTOP.
  8. "Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF."
    Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M., Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G., Avila M.A., Recio J.A.
    Sci. Signal. 4:RA58-RA58(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN THE REGULATION OF MAPK1/MAPK3 SIGNALING PATHWAY, RAF1 METHYLATION.
  9. "Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to desumoylation."
    Fanis P., Gillemans N., Aghajanirefah A., Pourfarzad F., Demmers J., Esteghamat F., Vadlamudi R.K., Grosveld F., Philipsen S., van Dijk T.B.
    Mol. Cell. Proteomics 11:1263-1273(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CHTOP, SUBCELLULAR LOCATION.
  10. "The histone- and PRMT5-associated protein COPR5 is required for myogenic differentiation."
    Paul C., Sardet C., Fabbrizio E.
    Cell Death Differ. 19:900-908(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH COPRS, IDENTIFICATION IN A COMPLEX WITH PRMT5; RUNX1 AND CBFB.
  11. "Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene."
    Na J., Lee K., Kim H.G., Shin J.Y., Na W., Jeong H., Lee J.W., Cho S., Kim W.S., Ju B.G.
    PLoS ONE 7:E48152-E48152(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CRY1.

Entry informationi

Entry nameiANM5_MOUSE
AccessioniPrimary (citable) accession number: Q8CIG8
Secondary accession number(s): Q3TNN1, Q9QZS9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 19, 2003
Last sequence update: January 22, 2007
Last modified: March 31, 2015
This is version 109 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

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.