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

Cullin-4A

Gene

CUL4A

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

Functioni

Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. DCX(DTL) directs autoubiquitination of DTL.8 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair, Host-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139842-MONOMER.
ReactomeiR-HSA-110314. Recognition of DNA damage by PCNA-containing replication complex.
R-HSA-5696394. DNA Damage Recognition in GG-NER.
R-HSA-5696395. Formation of Incision Complex in GG-NER.
R-HSA-5696400. Dual Incision in GG-NER.
R-HSA-6781823. Formation of TC-NER Pre-Incision Complex.
R-HSA-6781827. Transcription-Coupled Nucleotide Excision Repair (TC-NER).
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
SIGNORiQ13619.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-4A
Short name:
CUL-4A
Gene namesi
Name:CUL4A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:2554. CUL4A.

Subcellular locationi

GO - Cellular componenti

  • Cul4A-RING E3 ubiquitin ligase complex Source: UniProtKB
  • Cul4-RING E3 ubiquitin ligase complex Source: UniProtKB
  • nucleoplasm Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi86 – 90LYQAV → AAAAA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. 2 Publications5
Mutagenesisi139 – 142WQDH → AADA: Largely reduces interaction with DDB1; abolishes interaction with DDB2. 2 Publications4

Organism-specific databases

DisGeNETi8451.
OpenTargetsiENSG00000139842.
PharmGKBiPA27050.

Polymorphism and mutation databases

BioMutaiCUL4A.
DMDMi108936013.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001197951 – 759Cullin-4AAdd BLAST759

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineCombined sources1
Cross-linki33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-linki705Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)By similarity

Post-translational modificationi

Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.3 Publications
(Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13619.
MaxQBiQ13619.
PaxDbiQ13619.
PeptideAtlasiQ13619.
PRIDEiQ13619.

PTM databases

iPTMnetiQ13619.
PhosphoSitePlusiQ13619.

Expressioni

Gene expression databases

BgeeiENSG00000139842.
CleanExiHS_CUL4A.
ExpressionAtlasiQ13619. baseline and differential.
GenevisibleiQ13619. HS.

Organism-specific databases

HPAiHPA058979.

Interactioni

Subunit structurei

Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to consist of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the CSA complex (DCX(ERCC8) complex) containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Component of the DCX(DET1-COP1) complex with the substrate recognition component DET1 and COP1. Component of the DCX(DDB2) complex with the substrate recognition component DDB2. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Interacts with DDB1, RBX1, RNF7, CTD1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9. Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually exclusive. Interacts with VPRBP, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, RFWD2, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5, LRWD1 and DCAF8. May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5. Can self-associate. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655).18 Publications
(Microbial infection) Interacts with Epstein-Barr virus BPLF1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CAND1Q86VP63EBI-456106,EBI-456077
DDB1Q165314EBI-456106,EBI-350322
DDB2Q924663EBI-456106,EBI-1176171
RBBP5Q152913EBI-456106,EBI-592823

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114029. 298 interactors.
DIPiDIP-31610N.
IntActiQ13619. 46 interactors.
MINTiMINT-4532640.
STRINGi9606.ENSP00000364589.

Structurei

Secondary structure

1759
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni58 – 61Combined sources4
Helixi62 – 71Combined sources10
Helixi83 – 93Combined sources11
Turni96 – 98Combined sources3
Helixi99 – 121Combined sources23
Helixi130 – 152Combined sources23
Helixi154 – 157Combined sources4
Turni158 – 162Combined sources5
Beta strandi165 – 167Combined sources3
Helixi170 – 180Combined sources11
Turni181 – 183Combined sources3
Beta strandi184 – 186Combined sources3
Helixi189 – 191Combined sources3
Helixi193 – 201Combined sources9
Turni202 – 206Combined sources5
Helixi211 – 223Combined sources13
Turni227 – 231Combined sources5
Helixi232 – 253Combined sources22
Helixi256 – 269Combined sources14
Helixi271 – 274Combined sources4
Turni275 – 277Combined sources3
Turni280 – 282Combined sources3
Helixi283 – 294Combined sources12
Turni295 – 297Combined sources3
Helixi300 – 304Combined sources5
Helixi307 – 311Combined sources5
Turni312 – 314Combined sources3
Helixi316 – 328Combined sources13
Helixi332 – 352Combined sources21
Helixi355 – 357Combined sources3
Turni358 – 360Combined sources3
Helixi361 – 377Combined sources17
Turni378 – 382Combined sources5
Helixi384 – 398Combined sources15
Helixi404 – 417Combined sources14
Helixi421 – 423Combined sources3
Helixi429 – 440Combined sources12
Helixi446 – 462Combined sources17
Helixi469 – 480Combined sources12
Turni481 – 483Combined sources3
Turni485 – 488Combined sources4
Helixi489 – 513Combined sources25
Beta strandi522 – 529Combined sources8
Turni530 – 532Combined sources3
Helixi545 – 559Combined sources15
Beta strandi564 – 566Combined sources3
Helixi571 – 573Combined sources3
Beta strandi575 – 579Combined sources5
Beta strandi588 – 592Combined sources5
Helixi593 – 601Combined sources9
Helixi610 – 616Combined sources7
Helixi621 – 629Combined sources9
Turni630 – 636Combined sources7
Beta strandi638 – 641Combined sources4
Beta strandi645 – 647Combined sources3
Beta strandi653 – 656Combined sources4
Beta strandi665 – 668Combined sources4
Helixi670 – 674Combined sources5
Helixi678 – 706Combined sources29
Beta strandi707 – 711Combined sources5
Helixi713 – 722Combined sources10
Beta strandi723 – 725Combined sources3
Helixi729 – 741Combined sources13
Beta strandi754 – 756Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HYEX-ray3.10C1-759[»]
4A0KX-ray5.93A38-759[»]
ProteinModelPortaliQ13619.
SMRiQ13619.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13619.

Family & Domainsi

Sequence similaritiesi

Belongs to the cullin family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2167. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOVERGENiHBG003619.
InParanoidiQ13619.
KOiK10609.
OMAiFQRNERF.
OrthoDBiEOG091G02DP.
PhylomeDBiQ13619.
TreeFamiTF101153.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 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: Q13619-1) [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
MADEAPRKGS FSALVGRTNG LTKPAALAAA PAKPGGAGGS KKLVIKNFRD
60 70 80 90 100
RPRLPDNYTQ DTWRKLHEAV RAVQSSTSIR YNLEELYQAV ENLCSHKVSP
110 120 130 140 150
MLYKQLRQAC EDHVQAQILP FREDSLDSVL FLKKINTCWQ DHCRQMIMIR
160 170 180 190 200
SIFLFLDRTY VLQNSTLPSI WDMGLELFRT HIISDKMVQS KTIDGILLLI
210 220 230 240 250
ERERSGEAVD RSLLRSLLGM LSDLQVYKDS FELKFLEETN CLYAAEGQRL
260 270 280 290 300
MQEREVPEYL NHVSKRLEEE GDRVITYLDH STQKPLIACV EKQLLGEHLT
310 320 330 340 350
AILQKGLDHL LDENRVPDLA QMYQLFSRVR GGQQALLQHW SEYIKTFGTA
360 370 380 390 400
IVINPEKDKD MVQDLLDFKD KVDHVIEVCF QKNERFVNLM KESFETFINK
410 420 430 440 450
RPNKPAELIA KHVDSKLRAG NKEATDEELE RTLDKIMILF RFIHGKDVFE
460 470 480 490 500
AFYKKDLAKR LLVGKSASVD AEKSMLSKLK HECGAAFTSK LEGMFKDMEL
510 520 530 540 550
SKDIMVHFKQ HMQNQSDSGP IDLTVNILTM GYWPTYTPME VHLTPEMIKL
560 570 580 590 600
QEVFKAFYLG KHSGRKLQWQ TTLGHAVLKA EFKEGKKEFQ VSLFQTLVLL
610 620 630 640 650
MFNEGDGFSF EEIKMATGIE DSELRRTLQS LACGKARVLI KSPKGKEVED
660 670 680 690 700
GDKFIFNGEF KHKLFRIKIN QIQMKETVEE QVSTTERVFQ DRQYQIDAAI
710 720 730 740 750
VRIMKMRKTL GHNLLVSELY NQLKFPVKPG DLKKRIESLI DRDYMERDKD

NPNQYHYVA
Length:759
Mass (Da):87,680
Last modified:May 30, 2006 - v3
Checksum:i3C4C6A1BBD94D51B
GO
Isoform 2 (identifier: Q13619-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Show »
Length:659
Mass (Da):76,821
Checksum:i56D4D196BB1074CB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti281S → T in BAD93235 (PubMed:15811626).Curated1
Sequence conflicti339 – 346HWSEYIKT → NSARARAA in AAC50547 (PubMed:8681378).Curated8
Sequence conflicti496K → R in BAD93235 (PubMed:15811626).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020341644K → R.Corresponds to variant rs2302757dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0185771 – 100Missing in isoform 2. 1 PublicationAdd BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077188 mRNA. Translation: AAD45191.1.
AY365124 mRNA. Translation: AAR13072.1.
AB178950 mRNA. Translation: BAD93235.1.
AL136221 Genomic DNA. Translation: CAM18410.1.
AL136221 Genomic DNA. Translation: CAI13795.1.
BC008308 mRNA. Translation: AAH08308.2.
AB012193 mRNA. Translation: BAA33146.1.
U58090 mRNA. Translation: AAC50547.1.
CCDSiCCDS41908.1. [Q13619-1]
CCDS9533.1. [Q13619-2]
RefSeqiNP_001008895.1. NM_001008895.2. [Q13619-1]
NP_001265442.1. NM_001278513.1. [Q13619-2]
NP_003580.1. NM_003589.2. [Q13619-2]
XP_011535825.1. XM_011537523.2. [Q13619-2]
UniGeneiHs.339735.

Genome annotation databases

EnsembliENST00000375440; ENSP00000364589; ENSG00000139842. [Q13619-1]
ENST00000375441; ENSP00000364590; ENSG00000139842. [Q13619-2]
ENST00000451881; ENSP00000389118; ENSG00000139842. [Q13619-2]
ENST00000617546; ENSP00000481782; ENSG00000139842. [Q13619-2]
GeneIDi8451.
KEGGihsa:8451.
UCSCiuc021rmu.2. human. [Q13619-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077188 mRNA. Translation: AAD45191.1.
AY365124 mRNA. Translation: AAR13072.1.
AB178950 mRNA. Translation: BAD93235.1.
AL136221 Genomic DNA. Translation: CAM18410.1.
AL136221 Genomic DNA. Translation: CAI13795.1.
BC008308 mRNA. Translation: AAH08308.2.
AB012193 mRNA. Translation: BAA33146.1.
U58090 mRNA. Translation: AAC50547.1.
CCDSiCCDS41908.1. [Q13619-1]
CCDS9533.1. [Q13619-2]
RefSeqiNP_001008895.1. NM_001008895.2. [Q13619-1]
NP_001265442.1. NM_001278513.1. [Q13619-2]
NP_003580.1. NM_003589.2. [Q13619-2]
XP_011535825.1. XM_011537523.2. [Q13619-2]
UniGeneiHs.339735.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HYEX-ray3.10C1-759[»]
4A0KX-ray5.93A38-759[»]
ProteinModelPortaliQ13619.
SMRiQ13619.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114029. 298 interactors.
DIPiDIP-31610N.
IntActiQ13619. 46 interactors.
MINTiMINT-4532640.
STRINGi9606.ENSP00000364589.

PTM databases

iPTMnetiQ13619.
PhosphoSitePlusiQ13619.

Polymorphism and mutation databases

BioMutaiCUL4A.
DMDMi108936013.

Proteomic databases

EPDiQ13619.
MaxQBiQ13619.
PaxDbiQ13619.
PeptideAtlasiQ13619.
PRIDEiQ13619.

Protocols and materials databases

DNASUi8451.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375440; ENSP00000364589; ENSG00000139842. [Q13619-1]
ENST00000375441; ENSP00000364590; ENSG00000139842. [Q13619-2]
ENST00000451881; ENSP00000389118; ENSG00000139842. [Q13619-2]
ENST00000617546; ENSP00000481782; ENSG00000139842. [Q13619-2]
GeneIDi8451.
KEGGihsa:8451.
UCSCiuc021rmu.2. human. [Q13619-1]

Organism-specific databases

CTDi8451.
DisGeNETi8451.
GeneCardsiCUL4A.
HGNCiHGNC:2554. CUL4A.
HPAiHPA058979.
MIMi603137. gene.
neXtProtiNX_Q13619.
OpenTargetsiENSG00000139842.
PharmGKBiPA27050.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2167. Eukaryota.
COG5647. LUCA.
GeneTreeiENSGT00760000119212.
HOVERGENiHBG003619.
InParanoidiQ13619.
KOiK10609.
OMAiFQRNERF.
OrthoDBiEOG091G02DP.
PhylomeDBiQ13619.
TreeFamiTF101153.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000139842-MONOMER.
ReactomeiR-HSA-110314. Recognition of DNA damage by PCNA-containing replication complex.
R-HSA-5696394. DNA Damage Recognition in GG-NER.
R-HSA-5696395. Formation of Incision Complex in GG-NER.
R-HSA-5696400. Dual Incision in GG-NER.
R-HSA-6781823. Formation of TC-NER Pre-Incision Complex.
R-HSA-6781827. Transcription-Coupled Nucleotide Excision Repair (TC-NER).
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
SIGNORiQ13619.

Miscellaneous databases

ChiTaRSiCUL4A. human.
EvolutionaryTraceiQ13619.
GeneWikiiCUL4A.
GenomeRNAii8451.
PROiQ13619.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139842.
CleanExiHS_CUL4A.
ExpressionAtlasiQ13619. baseline and differential.
GenevisibleiQ13619. HS.

Family and domain databases

Gene3Di1.10.10.10. 2 hits.
InterProiIPR016157. Cullin_CS.
IPR016158. Cullin_homology.
IPR001373. Cullin_N.
IPR019559. Cullin_neddylation_domain.
IPR016159. Cullin_repeat-like_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00888. Cullin. 1 hit.
PF10557. Cullin_Nedd8. 1 hit.
[Graphical view]
SMARTiSM00182. CULLIN. 1 hit.
SM00884. Cullin_Nedd8. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF74788. SSF74788. 1 hit.
SSF75632. SSF75632. 1 hit.
PROSITEiPS01256. CULLIN_1. 1 hit.
PS50069. CULLIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCUL4A_HUMAN
AccessioniPrimary (citable) accession number: Q13619
Secondary accession number(s): A2A2W2
, O75834, Q589T6, Q5TC62, Q6UP08, Q9UP17
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2006
Last modified: November 30, 2016
This is version 159 of the entry and version 3 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 13
    Human chromosome 13: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.