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Protein

Nuclear receptor ROR-alpha

Gene

Rora

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

Functioni

Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4+ T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.15 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi73 – 138Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
Zinc fingeri73 – 93NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri109 – 133NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • cellular response to interleukin-1 Source: MGI
  • cellular response to sterol Source: UniProtKB
  • cellular response to tumor necrosis factor Source: MGI
  • cerebellar granule cell precursor proliferation Source: UniProtKB
  • cerebellar Purkinje cell differentiation Source: MGI
  • cGMP metabolic process Source: MGI
  • circadian regulation of gene expression Source: UniProtKB
  • circadian rhythm Source: Reactome
  • intracellular receptor signaling pathway Source: UniProtKB
  • muscle cell differentiation Source: UniProtKB
  • negative regulation of fat cell differentiation Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of inflammatory response Source: UniProtKB
  • nitric oxide biosynthetic process Source: MGI
  • positive regulation of circadian rhythm Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of vascular endothelial growth factor production Source: UniProtKB
  • regulation of cholesterol homeostasis Source: UniProtKB
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of glucose metabolic process Source: UniProtKB
  • regulation of macrophage activation Source: MGI
  • regulation of smoothened signaling pathway Source: UniProtKB
  • regulation of steroid metabolic process Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription involved in cell fate commitment Source: UniProtKB
  • T-helper 17 cell differentiation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • triglyceride homeostasis Source: UniProtKB
  • xenobiotic metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1368082. RORA activates gene expression.
R-MMU-1368092. Rora activates gene expression.
R-MMU-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-MMU-1368110. Bmal1:Clock,Npas2 activates circadian gene expression.
R-MMU-383280. Nuclear Receptor transcription pathway.
R-MMU-400253. Circadian Clock.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor ROR-alpha
Alternative name(s):
Nuclear receptor RZR-alpha
Nuclear receptor subfamily 1 group F member 1
RAR-related orphan receptor A
Retinoid-related orphan receptor-alpha
Gene namesi
Name:Rora
Synonyms:Nr1f1, Rzra
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:104661. Rora.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation2 Publications

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Defects in Rora are the cause of the staggerer (SG) mutant phenotype which is characterized by disturbance of Purkinje cell development and immune system functioning. This phenotype exhibits lower body weight, reduced adiposity, decreased plasma cholesterol, triglyceride and apolipoprotein CIII levels, and is resistant to diet-induced obesity. Also has abnormal circadian rhythms.

Keywords - Diseasei

Disease mutation

Chemistry databases

ChEMBLiCHEMBL3217403.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535131 – 523Nuclear receptor ROR-alphaAdd BLAST523

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38N6-methyllysineBy similarity1
Modified residuei183Phosphothreonine; by MAPK1By similarity1
Cross-linki240Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Phosphorylation by conventional PKCs in neurons inhibits transcriptional activity. Phosphorylated on Thr-183 by MAPK1/ERK1 in vitro.By similarity
Sumoylated by SENP1 and SENP2. Sumoylation, promoted by PIAS2, PIAS3, PIAS4 but not PIAS1, enhances the transcriptional activity. Desumoylated by SENP1.By similarity
Ubiquitinated, leading to its degradation by the proteasome. Proteasomal degradation is required for efficient transcriptional activity and is prevented by HR.By similarity
Isoform 1: monomethylated at Lys-38 by EZH2, this creates a degron recognized by a DCX (DDB1-DCAF1/VPRBP-CUL4A-RBX1) E3 ubiquitin ligase complex.By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP51448.
PeptideAtlasiP51448.
PRIDEiP51448.

PTM databases

iPTMnetiP51448.
PhosphoSitePlusiP51448.

Expressioni

Tissue specificityi

Expressed in cerebellum, heart, liver, lung, kidney, retina and brown and white adipose tissues. Expressed in the subset of mature Th17 cells.4 Publications

Developmental stagei

In cerebellum, expression begins at E12.5. In the developing retina, first expressed at E17 in the ganglion cell layer. At P3, expressed in the inner border of the neuroblasitic border (presumptive amacrine cells). By P6, levels increase in developing cones. Expression found in the presumptive bipolar cells by P9. During adipocyte differentiation, expression gradually increases.3 Publications

Inductioni

In T(H) cells, induced upon antigen receptor ligation in the presence of IL6 and TGB1 (via STAT3). Oscillates diurnally in central nervous system. In liver, Isoform 1 oscillates diurnally but not isoform 4.4 Publications

Gene expression databases

BgeeiENSMUSG00000032238.
CleanExiMM_RORA.
ExpressionAtlasiP51448. baseline and differential.
GenevisibleiP51448. MM.

Interactioni

Subunit structurei

Monomer. Interacts (via the DNA-binding domain) with HIF1A; the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interacts with CEBPB; the interaction disrupts the interaction CEBPB:EP300. Interacts with the coactivators NCOA2, PPARGC1A (via LXXLL motif), EP300 and MED1. Interacts with the corepressor NCOR1. Interacts with MAGED1 and CTNNB1. Interacts with CRY1 and PER2. Interacts (via AF-2 motif) with PROX1. Interacts with NRIP1. Isoform 4 interacts (via AF-2 motif) with isoform 1 of FOXP3 (via LXXLL motif) (By similarity).By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Atxn1P542543EBI-1169722,EBI-1169713
Maged1Q9QYH65EBI-1169722,EBI-1801274

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • transcription coactivator binding Source: UniProtKB
  • transcription corepressor binding Source: MGI
  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi202956. 1 interactor.
DIPiDIP-35351N.
IntActiP51448. 2 interactors.
STRINGi10090.ENSMUSP00000034766.

Structurei

3D structure databases

ProteinModelPortaliP51448.
SMRiP51448.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni139 – 271HingeAdd BLAST133
Regioni272 – 523Ligand-bindingAdd BLAST252

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi506 – 511AF-26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi101 – 175Gln-richAdd BLAST75

Domaini

The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs.By similarity

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri73 – 93NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri109 – 133NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4216. Eukaryota.
ENOG410XUGR. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000010200.
HOVERGENiHBG106848.
InParanoidiP51448.
KOiK08532.
OMAiNKPREVM.
OrthoDBiEOG091G0649.
PhylomeDBiP51448.
TreeFamiTF319910.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR003079. ROR_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01293. RORNUCRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform 1 (identifier: P51448-1) [UniParc]FASTAAdd to basket
Also known as: Alpha-1

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
MESAPAAPDP AASEPGSSGS EAAAGSRETP LTQDTGRKSE APGAGRRQSY
60 70 80 90 100
ASSSRGISVT KKTHTSQIEI IPCKICGDKS SGIHYGVITC EGCKGFFRRS
110 120 130 140 150
QQSNATYSCP RQKNCLIDRT SRNRCQHCRL QKCLAVGMSR DAVKFGRMSK
160 170 180 190 200
KQRDSLYAEV QKHRMQQQQR DHQQQPGEAE PLTPTYNISA NGLTELHDDL
210 220 230 240 250
STYMDGHTPE GSKADSAVSS FYLDIQPSPD QSGLDINGIK PEPICDYTPA
260 270 280 290 300
SGFFPYCSFT NGETSPTVSM AELEHLAQNI SKSHLETCQY LREELQQITW
310 320 330 340 350
QTFLQEEIEN YQNKQREVMW QLCAIKITEA IQYVVEFAKR IDGFMELCQN
360 370 380 390 400
DQIVLLKAGS LEVVFIRMCR AFDSQNNTVY FDGKYASPDV FKSLGCEDFI
410 420 430 440 450
SFVFEFGKSL CSMHLTEDEI ALFSAFVLMS ADRSWLQEKV KIEKLQQKIQ
460 470 480 490 500
LALQHVLQKN HREDGILTKL ICKVSTLRAL CGRHTEKLMA FKAIYPDIVR
510 520
LHFPPLYKEL FTSEFEPAMQ IDG
Length:523
Mass (Da):58,845
Last modified:October 1, 1996 - v1
Checksum:iA194E02E4D9D177E
GO
Isoform 2 (identifier: P51448-3)
Also known as: Alpha-2
Sequence is not available
Length:
Mass (Da):
Isoform 3 (identifier: P51448-4)
Also known as: Alpha-3
Sequence is not available
Length:
Mass (Da):
Isoform 4 (identifier: P51448-2) [UniParc]FASTAAdd to basket
Also known as: Alpha-4

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: MESAPAAPDP...ISVTKKTHTS → MYFVIAAMKA

Show »
Length:467
Mass (Da):53,414
Checksum:i5621E275EC282A54
GO

Sequence cautioni

The sequence AAH03757 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA69930 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti163H → R in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti180 – 181EP → T in CAA69930 (PubMed:7935491).Curated2
Sequence conflicti182L → I in AAB46801 (PubMed:8750880).Curated1
Sequence conflicti182L → I in BAA22970 (PubMed:8750880).Curated1
Sequence conflicti193 – 194LT → SA in CAA69930 (PubMed:7935491).Curated2
Sequence conflicti304L → W in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti315Missing in AAB46801 (PubMed:8750880).Curated1
Sequence conflicti315Missing in BAA22970 (PubMed:8750880).Curated1
Sequence conflicti362E → G in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti433R → P in CAA69930 (PubMed:7935491).Curated1
Sequence conflicti450 – 451QL → HM in CAA69930 (PubMed:7935491).Curated2
Sequence conflicti487K → N in AAB46801 (PubMed:8750880).Curated1
Sequence conflicti487K → N in BAA22970 (PubMed:8750880).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti275 – 314Missing in SG; disturbance of Purkinje cell and muscle development, lipid metabolism, circadian behavior and immune system functioning. 1 PublicationAdd BLAST40

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0036581 – 66MESAP…KTHTS → MYFVIAAMKA in isoform 4. 4 PublicationsAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53228 mRNA. Translation: AAC52513.1.
Y08640 mRNA. Translation: CAA69930.1. Different initiation.
Z82994 mRNA. Translation: CAB05396.1.
S82720 mRNA. Translation: AAB46801.2.
D45910 mRNA. Translation: BAA22970.1.
BC003757 mRNA. Translation: AAH03757.2. Different initiation.
CCDSiCCDS23314.1. [P51448-1]
CCDS72268.1. [P51448-2]
PIRiS68517.
RefSeqiNP_001276845.1. NM_001289916.1. [P51448-2]
NP_038674.1. NM_013646.2. [P51448-1]
UniGeneiMm.378450.
Mm.391890.
Mm.427266.
Mm.445802.
Mm.491288.

Genome annotation databases

EnsembliENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238. [P51448-1]
ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238. [P51448-2]
GeneIDi19883.
KEGGimmu:19883.
UCSCiuc009qmx.2. mouse. [P51448-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53228 mRNA. Translation: AAC52513.1.
Y08640 mRNA. Translation: CAA69930.1. Different initiation.
Z82994 mRNA. Translation: CAB05396.1.
S82720 mRNA. Translation: AAB46801.2.
D45910 mRNA. Translation: BAA22970.1.
BC003757 mRNA. Translation: AAH03757.2. Different initiation.
CCDSiCCDS23314.1. [P51448-1]
CCDS72268.1. [P51448-2]
PIRiS68517.
RefSeqiNP_001276845.1. NM_001289916.1. [P51448-2]
NP_038674.1. NM_013646.2. [P51448-1]
UniGeneiMm.378450.
Mm.391890.
Mm.427266.
Mm.445802.
Mm.491288.

3D structure databases

ProteinModelPortaliP51448.
SMRiP51448.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202956. 1 interactor.
DIPiDIP-35351N.
IntActiP51448. 2 interactors.
STRINGi10090.ENSMUSP00000034766.

Chemistry databases

ChEMBLiCHEMBL3217403.

PTM databases

iPTMnetiP51448.
PhosphoSitePlusiP51448.

Proteomic databases

PaxDbiP51448.
PeptideAtlasiP51448.
PRIDEiP51448.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238. [P51448-1]
ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238. [P51448-2]
GeneIDi19883.
KEGGimmu:19883.
UCSCiuc009qmx.2. mouse. [P51448-1]

Organism-specific databases

CTDi6095.
MGIiMGI:104661. Rora.

Phylogenomic databases

eggNOGiKOG4216. Eukaryota.
ENOG410XUGR. LUCA.
GeneTreeiENSGT00850000132242.
HOGENOMiHOG000010200.
HOVERGENiHBG106848.
InParanoidiP51448.
KOiK08532.
OMAiNKPREVM.
OrthoDBiEOG091G0649.
PhylomeDBiP51448.
TreeFamiTF319910.

Enzyme and pathway databases

ReactomeiR-MMU-1368082. RORA activates gene expression.
R-MMU-1368092. Rora activates gene expression.
R-MMU-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-MMU-1368110. Bmal1:Clock,Npas2 activates circadian gene expression.
R-MMU-383280. Nuclear Receptor transcription pathway.
R-MMU-400253. Circadian Clock.

Miscellaneous databases

ChiTaRSiRora. mouse.
PROiP51448.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032238.
CleanExiMM_RORA.
ExpressionAtlasiP51448. baseline and differential.
GenevisibleiP51448. MM.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR003079. ROR_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01293. RORNUCRECPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRORA_MOUSE
AccessioniPrimary (citable) accession number: P51448
Secondary accession number(s): P70283
, P97741, P97773, Q923G1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 165 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, Direct protein sequencing, 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.