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Protein

Ras-related protein Rab-7a

Gene

RAB7A

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

Functioni

Key regulator in endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in the fusion of phagosomes with lysosomes. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA (PubMed:11179213, PubMed:12944476, PubMed:14617358, PubMed:20028791, PubMed:21255211). Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation. Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway (By similarity). Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).By similarity5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 22GTP2 Publications8
Nucleotide bindingi34 – 40GTP2 Publications7
Nucleotide bindingi63 – 67GTP2 Publications5
Nucleotide bindingi125 – 128GTP2 Publications4
Nucleotide bindingi156 – 157GTP2 Publications2

GO - Molecular functioni

  • GDP binding Source: BHF-UCL
  • GTPase activity Source: BHF-UCL
  • GTP binding Source: BHF-UCL
  • retromer complex binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
  • bone resorption Source: Ensembl
  • early endosome to late endosome transport Source: UniProtKB
  • endocytosis Source: ProtInc
  • endosome to lysosome transport Source: BHF-UCL
  • epidermal growth factor catabolic process Source: BHF-UCL
  • lipophagy Source: GO_Central
  • multi-organism intracellular transport Source: ParkinsonsUK-UCL
  • negative regulation of exosomal secretion Source: ParkinsonsUK-UCL
  • negative regulation of intralumenal vesicle formation Source: ParkinsonsUK-UCL
  • phagosome acidification Source: UniProtKB
  • phagosome-lysosome fusion Source: UniProtKB
  • phagosome maturation Source: UniProtKB
  • positive regulation of exosomal secretion Source: UniProtKB
  • positive regulation of protein catabolic process Source: CACAO
  • positive regulation of viral process Source: CACAO
  • protein targeting to lysosome Source: BHF-UCL
  • protein to membrane docking Source: UniProtKB
  • protein transport Source: UniProtKB
  • regulation of autophagosome assembly Source: UniProtKB
  • retrograde transport, endosome to Golgi Source: UniProtKB
  • small GTPase mediated signal transduction Source: InterPro
  • viral release from host cell Source: CACAO
Complete GO annotation...

Keywords - Biological processi

Autophagy, Lipid degradation, Lipid metabolism, Protein transport, Transport

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000075785-MONOMER.
ReactomeiR-HSA-2132295. MHC class II antigen presentation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
SignaLinkiP51149.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related protein Rab-7a
Gene namesi
Name:RAB7A
Synonyms:RAB7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:9788. RAB7A.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Lipid droplet, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 2B (CMT2B)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.
See also OMIM:600882
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_018722129L → F in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant rs121909078dbSNPEnsembl.1
Natural variantiVAR_037887157K → N in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant rs121909081dbSNPEnsembl.1
Natural variantiVAR_037888161N → T in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant rs121909080dbSNPEnsembl.1
Natural variantiVAR_018723162V → M in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant rs121909079dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi8L → A: Abolishes interaction with RILP and reduces its localization to late endosomal/lysosomal compartments. 1 Publication1
Mutagenesisi10K → A: Abolishes interaction with RILP and localization to late endosomal/lysosomal compartments. 1 Publication1
Mutagenesisi22T → N: Abolishes localization on late endosomes, lysosomes and phagosomes and reduces phagosomal fusions. Abolishes association of RILP with the phagosomes. No loss of interaction with CLN5. 2 Publications1
Mutagenesisi67Q → L: Does not abolish localization on late endosomes, lysosomes and phagosomes and does not reduce phagosomal fusions. No loss of interaction with CLN5. 2 Publications1
Mutagenesisi180V → A: Abolishes interaction with RILP and localization to late endosomal/lysosomal compartments. 1 Publication1
Mutagenesisi182L → A: Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments. Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments; when associated with A-183. 1 Publication1
Mutagenesisi183Y → A: Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments. Does not abolish interaction with RILP and localization to late endosomal/lysosomal compartments; when associated with A-182. 1 Publication1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi7879.
MalaCardsiRAB7A.
MIMi600882. phenotype.
OpenTargetsiENSG00000075785.
Orphaneti99936. Autosomal dominant Charcot-Marie-Tooth disease type 2B.
PharmGKBiPA162400619.

Polymorphism and mutation databases

BioMutaiRAB7A.
DMDMi1709999.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001211212 – 207Ras-related protein Rab-7aAdd BLAST206

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonineCombined sources1
Modified residuei72PhosphoserineCombined sources1
Lipidationi205S-geranylgeranyl cysteineBy similarity1
Modified residuei207Cysteine methyl esterBy similarity1
Lipidationi207S-geranylgeranyl cysteineBy similarity1

Keywords - PTMi

Acetylation, Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

EPDiP51149.
MaxQBiP51149.
PaxDbiP51149.
PeptideAtlasiP51149.
PRIDEiP51149.
TopDownProteomicsiP51149.

PTM databases

iPTMnetiP51149.
PhosphoSitePlusiP51149.
SwissPalmiP51149.

Expressioni

Tissue specificityi

Widely expressed; high expression found in skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000075785.
CleanExiHS_RAB7A.
ExpressionAtlasiP51149. baseline and differential.
GenevisibleiP51149. HS.

Organism-specific databases

HPAiCAB037131.
HPA006964.

Interactioni

Subunit structurei

The GTP-bound form interacts with RAC1 (By similarity). Interacts with NTRK1/TRKA (By similarity). Interacts with C9orf72 (By similarity). Interacts with CHM, the substrate-binding subunit of the Rab geranylgeranyltransferase complex (By similarity). Interacts with RILP (PubMed:11179213, PubMed:14668488, PubMed:15933719, PubMed:20028791, PubMed:22431521). Interacts with PSMA7 (PubMed:14998988). Interacts with RNF115 (PubMed:16925951). Interacts with FYCO1 (PubMed:20100911). Interacts with the PIK3C3/VPS34-PIK3R4 complex (PubMed:14617358). The GTP-bound form interacts with OSBPL1A (PubMed:16176980). Interacts with CLN3 (PubMed:22261744). Does not interact with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and HPS4) (PubMed:20048159). Interacts with CLN5 (PubMed:22431521).By similarity12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RILPQ96NA22EBI-1056089,EBI-2856119

GO - Molecular functioni

  • retromer complex binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi113624. 170 interactors.
DIPiDIP-39879N.
IntActiP51149. 102 interactors.
MINTiMINT-4999676.
STRINGi9606.ENSP00000265062.

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 14Combined sources7
Helixi21 – 30Combined sources10
Beta strandi42 – 54Combined sources13
Beta strandi56 – 64Combined sources9
Helixi68 – 70Combined sources3
Beta strandi82 – 89Combined sources8
Helixi93 – 97Combined sources5
Helixi99 – 110Combined sources12
Helixi115 – 117Combined sources3
Beta strandi120 – 125Combined sources6
Helixi136 – 145Combined sources10
Beta strandi151 – 153Combined sources3
Turni156 – 159Combined sources4
Helixi162 – 181Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1T91X-ray1.90A/B/C/D1-207[»]
1YHNX-ray3.00A1-207[»]
3LAWX-ray2.80A/B/C/D/E1-207[»]
ProteinModelPortaliP51149.
SMRiP51149.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51149.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi37 – 45Effector regionBy similarity9

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rab family.Curated

Phylogenomic databases

eggNOGiKOG0394. Eukaryota.
ENOG410XNZV. LUCA.
GeneTreeiENSGT00760000119125.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP51149.
KOiK07897.
OMAiDYPDPIK.
OrthoDBiEOG091G0JIV.
PhylomeDBiP51149.
TreeFamiTF105605.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P51149-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTSRKKVLLK VIILGDSGVG KTSLMNQYVN KKFSNQYKAT IGADFLTKEV
60 70 80 90 100
MVDDRLVTMQ IWDTAGQERF QSLGVAFYRG ADCCVLVFDV TAPNTFKTLD
110 120 130 140 150
SWRDEFLIQA SPRDPENFPF VVLGNKIDLE NRQVATKRAQ AWCYSKNNIP
160 170 180 190 200
YFETSAKEAI NVEQAFQTIA RNALKQETEV ELYNEFPEPI KLDKNDRAKA

SAESCSC
Length:207
Mass (Da):23,490
Last modified:October 1, 1996 - v1
Checksum:iA2AF33B16A672971
GO

Sequence cautioni

The sequence BAA91390 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated
The sequence BAF83410 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated
The sequence EAW79303 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti47T → I in AAD02565 (Ref. 3) Curated1
Sequence conflicti108I → V in AAA86640 (PubMed:9126495).Curated1
Sequence conflicti127I → V in AAA86640 (PubMed:9126495).Curated1
Sequence conflicti180V → E in AAD02565 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03788632K → E.Corresponds to variant rs11549759dbSNPEnsembl.1
Natural variantiVAR_018722129L → F in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant rs121909078dbSNPEnsembl.1
Natural variantiVAR_037887157K → N in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant rs121909081dbSNPEnsembl.1
Natural variantiVAR_037888161N → T in CMT2B; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 2 PublicationsCorresponds to variant rs121909080dbSNPEnsembl.1
Natural variantiVAR_018723162V → M in CMT2B; increases GTP hydrolysis; decreases affinity for GTP and GDP; does not affect interaction with NTRK1; results in higher levels of NTRK1 and MAPK1/MAPK3 phosphorylation after NGF stimulation consistent with enhanced MAPK signaling. 3 PublicationsCorresponds to variant rs121909079dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93499 mRNA. Translation: CAA63763.1.
U44104 mRNA. Translation: AAA86640.1.
AF050175 Genomic DNA. Translation: AAD02565.1.
AF498942 mRNA. Translation: AAM21090.1.
AK000826 mRNA. Translation: BAA91390.1. Sequence problems.
AK290721 mRNA. Translation: BAF83410.1. Sequence problems.
BC008721 mRNA. Translation: AAH08721.2.
CH471052 Genomic DNA. Translation: EAW79303.1. Sequence problems.
CCDSiCCDS3052.1.
PIRiJC5268.
RefSeqiNP_004628.4. NM_004637.5.
UniGeneiHs.684374.
Hs.744853.

Genome annotation databases

EnsembliENST00000265062; ENSP00000265062; ENSG00000075785.
GeneIDi7879.
KEGGihsa:7879.
UCSCiuc003eks.2. human.

Cross-referencesi

Web resourcesi

Inherited peripheral neuropathies mutation db
Leiden Muscular Dystrophy pages RAB7A, member RAS oncogene family (RAB7A)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X93499 mRNA. Translation: CAA63763.1.
U44104 mRNA. Translation: AAA86640.1.
AF050175 Genomic DNA. Translation: AAD02565.1.
AF498942 mRNA. Translation: AAM21090.1.
AK000826 mRNA. Translation: BAA91390.1. Sequence problems.
AK290721 mRNA. Translation: BAF83410.1. Sequence problems.
BC008721 mRNA. Translation: AAH08721.2.
CH471052 Genomic DNA. Translation: EAW79303.1. Sequence problems.
CCDSiCCDS3052.1.
PIRiJC5268.
RefSeqiNP_004628.4. NM_004637.5.
UniGeneiHs.684374.
Hs.744853.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1T91X-ray1.90A/B/C/D1-207[»]
1YHNX-ray3.00A1-207[»]
3LAWX-ray2.80A/B/C/D/E1-207[»]
ProteinModelPortaliP51149.
SMRiP51149.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113624. 170 interactors.
DIPiDIP-39879N.
IntActiP51149. 102 interactors.
MINTiMINT-4999676.
STRINGi9606.ENSP00000265062.

PTM databases

iPTMnetiP51149.
PhosphoSitePlusiP51149.
SwissPalmiP51149.

Polymorphism and mutation databases

BioMutaiRAB7A.
DMDMi1709999.

Proteomic databases

EPDiP51149.
MaxQBiP51149.
PaxDbiP51149.
PeptideAtlasiP51149.
PRIDEiP51149.
TopDownProteomicsiP51149.

Protocols and materials databases

DNASUi7879.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265062; ENSP00000265062; ENSG00000075785.
GeneIDi7879.
KEGGihsa:7879.
UCSCiuc003eks.2. human.

Organism-specific databases

CTDi7879.
DisGeNETi7879.
GeneCardsiRAB7A.
GeneReviewsiRAB7A.
HGNCiHGNC:9788. RAB7A.
HPAiCAB037131.
HPA006964.
MalaCardsiRAB7A.
MIMi600882. phenotype.
602298. gene.
neXtProtiNX_P51149.
OpenTargetsiENSG00000075785.
Orphaneti99936. Autosomal dominant Charcot-Marie-Tooth disease type 2B.
PharmGKBiPA162400619.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0394. Eukaryota.
ENOG410XNZV. LUCA.
GeneTreeiENSGT00760000119125.
HOGENOMiHOG000233968.
HOVERGENiHBG009351.
InParanoidiP51149.
KOiK07897.
OMAiDYPDPIK.
OrthoDBiEOG091G0JIV.
PhylomeDBiP51149.
TreeFamiTF105605.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000075785-MONOMER.
ReactomeiR-HSA-2132295. MHC class II antigen presentation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
SignaLinkiP51149.

Miscellaneous databases

ChiTaRSiRAB7A. human.
EvolutionaryTraceiP51149.
GeneWikiiRAB7A.
GenomeRNAii7879.
PROiP51149.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000075785.
CleanExiHS_RAB7A.
ExpressionAtlasiP51149. baseline and differential.
GenevisibleiP51149. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRAB7A_HUMAN
AccessioniPrimary (citable) accession number: P51149
Secondary accession number(s): A8K3V6, Q9NWJ0, Q9UPB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 180 of the entry and version 1 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 3
    Human chromosome 3: 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. 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.