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Protein

G protein-coupled receptor kinase 4

Gene

GRK4

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

Functioni

Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2.2 Publications

Catalytic activityi

ATP + [G-protein-coupled receptor] = ADP + [G-protein-coupled receptor] phosphate.

Enzyme regulationi

Inhibited by heparin.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei216ATPPROSITE-ProRule annotation1
Active sitei312Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi193 – 201ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS04880-MONOMER.
BRENDAi2.7.11.16. 2681.
ReactomeiR-HSA-2514859. Inactivation, recovery and regulation of the phototransduction cascade.
SignaLinkiP32298.
SIGNORiP32298.

Names & Taxonomyi

Protein namesi
Recommended name:
G protein-coupled receptor kinase 4 (EC:2.7.11.16)
Alternative name(s):
G protein-coupled receptor kinase GRK4
ITI1
Gene namesi
Name:GRK4
Synonyms:GPRK2L, GPRK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4543. GRK4.

Subcellular locationi

  • Cytoplasm
  • Cytoplasmcell cortex

  • Note: Both at the cell surface and dispersed in the cytoplasm under basal conditions. Receptor stimulation results in the internalization of GRK4 to the perinuclear area, where colocalization with DRD3 is observed strongly at 5 and 15 minutes. DRD3 and GRK4 colocalize in lipid rafts of renal proximal tubule cells.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi2868.
OpenTargetsiENSG00000125388.
PharmGKBiPA28941.

Chemistry databases

ChEMBLiCHEMBL5861.
GuidetoPHARMACOLOGYi1468.

Polymorphism and mutation databases

BioMutaiGRK4.
DMDMi143811400.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859671 – 578G protein-coupled receptor kinase 4Add BLAST578

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei485PhosphoserineBy similarity1

Post-translational modificationi

Palmitoylated.1 Publication

Keywords - PTMi

Acetylation, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiP32298.
PaxDbiP32298.
PeptideAtlasiP32298.
PRIDEiP32298.

PTM databases

iPTMnetiP32298.
PhosphoSitePlusiP32298.

Expressioni

Tissue specificityi

Isoform 1, isoform 2, isoform 3, and isoform 4 are expressed in testis. Isoform 4 is expressed in myometrium.2 Publications

Gene expression databases

BgeeiENSG00000125388.
ExpressionAtlasiP32298. baseline and differential.
GenevisibleiP32298. HS.

Organism-specific databases

HPAiHPA028737.
HPA057023.

Interactioni

Subunit structurei

Interacts with DRD3.1 Publication

Protein-protein interaction databases

BioGridi109126. 5 interactors.
IntActiP32298. 2 interactors.
STRINGi9606.ENSP00000381129.

Chemistry databases

BindingDBiP32298.

Structurei

Secondary structure

1578
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi30 – 33Combined sources4
Turni39 – 42Combined sources4
Helixi43 – 48Combined sources6
Helixi53 – 57Combined sources5
Helixi61 – 71Combined sources11
Helixi75 – 91Combined sources17
Turni95 – 97Combined sources3
Helixi98 – 109Combined sources12
Beta strandi113 – 115Combined sources3
Helixi123 – 132Combined sources10
Beta strandi135 – 137Combined sources3
Turni140 – 143Combined sources4
Helixi144 – 154Combined sources11
Helixi157 – 162Combined sources6
Helixi166 – 178Combined sources13
Helixi184 – 186Combined sources3
Beta strandi187 – 195Combined sources9
Beta strandi197 – 206Combined sources10
Turni207 – 209Combined sources3
Beta strandi212 – 219Combined sources8
Helixi220 – 226Combined sources7
Helixi229 – 241Combined sources13
Beta strandi250 – 255Combined sources6
Beta strandi257 – 264Combined sources8
Helixi272 – 276Combined sources5
Turni277 – 279Combined sources3
Beta strandi280 – 283Combined sources4
Helixi286 – 304Combined sources19
Turni305 – 307Combined sources3
Helixi315 – 317Combined sources3
Beta strandi318 – 320Combined sources3
Beta strandi326 – 328Combined sources3
Beta strandi341 – 343Combined sources3
Turni350 – 352Combined sources3
Helixi355 – 358Combined sources4
Beta strandi363 – 365Combined sources3
Helixi366 – 381Combined sources16
Beta strandi382 – 384Combined sources3
Helixi395 – 403Combined sources9
Helixi415 – 424Combined sources10
Helixi429 – 431Combined sources3
Turni433 – 438Combined sources6
Helixi439 – 444Combined sources6
Helixi447 – 449Combined sources3
Helixi454 – 458Combined sources5
Helixi494 – 500Combined sources7
Beta strandi505 – 507Combined sources3
Helixi509 – 518Combined sources10
Turni519 – 524Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YHJX-ray2.60A/B1-578[»]
ProteinModelPortaliP32298.
SMRiP32298.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini52 – 172RGSPROSITE-ProRule annotationAdd BLAST121
Domaini187 – 449Protein kinasePROSITE-ProRule annotationAdd BLAST263
Domaini450 – 515AGC-kinase C-terminalAdd BLAST66

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 154N-terminalAdd BLAST154

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RGS domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
GeneTreeiENSGT00860000133699.
HOVERGENiHBG004532.
InParanoidiP32298.
KOiK08291.
OMAiHSIEKDY.
OrthoDBiEOG091G062G.
PhylomeDBiP32298.
TreeFamiTF313940.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P32298-1) [UniParc]FASTAAdd to basket
Also known as: GRK4-alpha, GRK4D

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
MELENIVANS LLLKARQGGY GKKSGRSKKW KEILTLPPVS QCSELRHSIE
60 70 80 90 100
KDYSSLCDKQ PIGRRLFRQF CDTKPTLKRH IEFLDAVAEY EVADDEDRSD
110 120 130 140 150
CGLSILDRFF NDKLAAPLPE IPPDVVTECR LGLKEENPSK KAFEECTRVA
160 170 180 190 200
HNYLRGEPFE EYQESSYFSQ FLQWKWLERQ PVTKNTFRHY RVLGKGGFGE
210 220 230 240 250
VCACQVRATG KMYACKKLQK KRIKKRKGEA MALNEKRILE KVQSRFVVSL
260 270 280 290 300
AYAYETKDAL CLVLTIMNGG DLKFHIYNLG NPGFDEQRAV FYAAELCCGL
310 320 330 340 350
EDLQRERIVY RDLKPENILL DDRGHIRISD LGLATEIPEG QRVRGRVGTV
360 370 380 390 400
GYMAPEVVNN EKYTFSPDWW GLGCLIYEMI QGHSPFKKYK EKVKWEEVDQ
410 420 430 440 450
RIKNDTEEYS EKFSEDAKSI CRMLLTKNPS KRLGCRGEGA AGVKQHPVFK
460 470 480 490 500
DINFRRLEAN MLEPPFCPDP HAVYCKDVLD IEQFSVVKGI YLDTADEDFY
510 520 530 540 550
ARFATGCVSI PWQNEMIESG CFKDINKSES EEALPLDLDK NIHTPVSRPN
560 570
RGFFYRLFRR GGCLTMVPSE KEVEPKQC
Length:578
Mass (Da):66,583
Last modified:April 3, 2007 - v3
Checksum:i72FCF94ED551F2D0
GO
Isoform 2 (identifier: P32298-2) [UniParc]FASTAAdd to basket
Also known as: GRK4-beta, GRK4C

The sequence of this isoform differs from the canonical sequence as follows:
     18-49: Missing.

Show »
Length:546
Mass (Da):63,030
Checksum:iAD60D125A5839CA3
GO
Isoform 3 (identifier: P32298-3) [UniParc]FASTAAdd to basket
Also known as: GRK4-delta, GRK4A

The sequence of this isoform differs from the canonical sequence as follows:
     18-49: Missing.
     516-561: Missing.

Show »
Length:500
Mass (Da):57,663
Checksum:i6AF0953E8D1F7A06
GO
Isoform 4 (identifier: P32298-4) [UniParc]FASTAAdd to basket
Also known as: GRK4-gamma, GRK4B

The sequence of this isoform differs from the canonical sequence as follows:
     516-561: Missing.

Show »
Length:532
Mass (Da):61,216
Checksum:i1DD49402FCB381E5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti562G → D in CAA66468 (PubMed:1338872).Curated1
Sequence conflicti562G → D in CAA66802 (PubMed:1338872).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02457365R → L.1 PublicationCorresponds to variant rs2960306dbSNPEnsembl.1
Natural variantiVAR_05162195D → H.Corresponds to variant rs13305979dbSNPEnsembl.1
Natural variantiVAR_046043116A → T.1 PublicationCorresponds to variant rs34857805dbSNPEnsembl.1
Natural variantiVAR_024574142A → V.1 PublicationCorresponds to variant rs1024323dbSNPEnsembl.1
Natural variantiVAR_051622183T → R.Corresponds to variant rs45538934dbSNPEnsembl.1
Natural variantiVAR_007806247V → I.1 PublicationCorresponds to variant rs35605687dbSNPEnsembl.1
Natural variantiVAR_046044383H → Q.1 PublicationCorresponds to variant rs55852353dbSNPEnsembl.1
Natural variantiVAR_040516425L → P.1 Publication1
Natural variantiVAR_051623440A → V.Corresponds to variant rs1801058dbSNPEnsembl.1
Natural variantiVAR_046045473V → I.1 PublicationCorresponds to variant rs35024854dbSNPEnsembl.1
Natural variantiVAR_024575486V → A.6 PublicationsCorresponds to variant rs1801058dbSNPEnsembl.1
Natural variantiVAR_046046495A → T.1 PublicationCorresponds to variant rs35463176dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00493618 – 49Missing in isoform 2 and isoform 3. 3 PublicationsAdd BLAST32
Alternative sequenceiVSP_004937516 – 561Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L03718 Genomic DNA. Translation: AAB04045.1.
X97879 mRNA. Translation: CAA66468.1.
X97880 mRNA. Translation: CAA66469.1.
X97881 mRNA. Translation: CAA66470.1.
U33054 mRNA. Translation: AAC50406.1.
U33055 mRNA. Translation: AAC50407.1.
U33056 mRNA. Translation: AAC50408.1.
U33168
, U33153, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166, U33167 Genomic DNA. Translation: AAC50409.1.
U33168
, U33153, U33154, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166, U33167 Genomic DNA. Translation: AAC50410.1.
U33168
, U33153, U33154, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166 Genomic DNA. Translation: AAC50411.1.
U33168
, U33153, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166 Genomic DNA. Translation: AAC50412.1.
AK223581 mRNA. Translation: BAD97301.1.
X98118 mRNA. Translation: CAA66802.1.
X75897 mRNA. Translation: CAA53506.1.
Z68192 Genomic DNA. Translation: CAA92341.1.
BC117320 mRNA. Translation: AAI17321.1.
CCDSiCCDS33946.1. [P32298-1]
CCDS33947.1. [P32298-4]
CCDS47002.1. [P32298-2]
CCDS68656.1. [P32298-3]
PIRiI54326.
JC2127.
RefSeqiNP_001004056.1. NM_001004056.1. [P32298-2]
NP_001004057.1. NM_001004057.1. [P32298-4]
NP_005298.2. NM_005307.2. [P32298-3]
NP_892027.2. NM_182982.2. [P32298-1]
UniGeneiHs.32959.

Genome annotation databases

EnsembliENST00000345167; ENSP00000264764; ENSG00000125388. [P32298-2]
ENST00000398051; ENSP00000381128; ENSG00000125388. [P32298-3]
ENST00000398052; ENSP00000381129; ENSG00000125388. [P32298-1]
ENST00000504933; ENSP00000427445; ENSG00000125388. [P32298-4]
GeneIDi2868.
KEGGihsa:2868.
UCSCiuc003ggn.2. human. [P32298-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L03718 Genomic DNA. Translation: AAB04045.1.
X97879 mRNA. Translation: CAA66468.1.
X97880 mRNA. Translation: CAA66469.1.
X97881 mRNA. Translation: CAA66470.1.
U33054 mRNA. Translation: AAC50406.1.
U33055 mRNA. Translation: AAC50407.1.
U33056 mRNA. Translation: AAC50408.1.
U33168
, U33153, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166, U33167 Genomic DNA. Translation: AAC50409.1.
U33168
, U33153, U33154, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166, U33167 Genomic DNA. Translation: AAC50410.1.
U33168
, U33153, U33154, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166 Genomic DNA. Translation: AAC50411.1.
U33168
, U33153, U33155, U33156, U33157, U33158, U33159, U33160, U33161, U33162, U33163, U33164, U33165, U33166 Genomic DNA. Translation: AAC50412.1.
AK223581 mRNA. Translation: BAD97301.1.
X98118 mRNA. Translation: CAA66802.1.
X75897 mRNA. Translation: CAA53506.1.
Z68192 Genomic DNA. Translation: CAA92341.1.
BC117320 mRNA. Translation: AAI17321.1.
CCDSiCCDS33946.1. [P32298-1]
CCDS33947.1. [P32298-4]
CCDS47002.1. [P32298-2]
CCDS68656.1. [P32298-3]
PIRiI54326.
JC2127.
RefSeqiNP_001004056.1. NM_001004056.1. [P32298-2]
NP_001004057.1. NM_001004057.1. [P32298-4]
NP_005298.2. NM_005307.2. [P32298-3]
NP_892027.2. NM_182982.2. [P32298-1]
UniGeneiHs.32959.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YHJX-ray2.60A/B1-578[»]
ProteinModelPortaliP32298.
SMRiP32298.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109126. 5 interactors.
IntActiP32298. 2 interactors.
STRINGi9606.ENSP00000381129.

Chemistry databases

BindingDBiP32298.
ChEMBLiCHEMBL5861.
GuidetoPHARMACOLOGYi1468.

PTM databases

iPTMnetiP32298.
PhosphoSitePlusiP32298.

Polymorphism and mutation databases

BioMutaiGRK4.
DMDMi143811400.

Proteomic databases

MaxQBiP32298.
PaxDbiP32298.
PeptideAtlasiP32298.
PRIDEiP32298.

Protocols and materials databases

DNASUi2868.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345167; ENSP00000264764; ENSG00000125388. [P32298-2]
ENST00000398051; ENSP00000381128; ENSG00000125388. [P32298-3]
ENST00000398052; ENSP00000381129; ENSG00000125388. [P32298-1]
ENST00000504933; ENSP00000427445; ENSG00000125388. [P32298-4]
GeneIDi2868.
KEGGihsa:2868.
UCSCiuc003ggn.2. human. [P32298-1]

Organism-specific databases

CTDi2868.
DisGeNETi2868.
GeneCardsiGRK4.
HGNCiHGNC:4543. GRK4.
HPAiHPA028737.
HPA057023.
MIMi137026. gene.
neXtProtiNX_P32298.
OpenTargetsiENSG00000125388.
PharmGKBiPA28941.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0986. Eukaryota.
ENOG410YRQZ. LUCA.
GeneTreeiENSGT00860000133699.
HOVERGENiHBG004532.
InParanoidiP32298.
KOiK08291.
OMAiHSIEKDY.
OrthoDBiEOG091G062G.
PhylomeDBiP32298.
TreeFamiTF313940.

Enzyme and pathway databases

BioCyciZFISH:HS04880-MONOMER.
BRENDAi2.7.11.16. 2681.
ReactomeiR-HSA-2514859. Inactivation, recovery and regulation of the phototransduction cascade.
SignaLinkiP32298.
SIGNORiP32298.

Miscellaneous databases

ChiTaRSiGRK4. human.
GeneWikiiGRK4.
GenomeRNAii2868.
PROiP32298.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125388.
ExpressionAtlasiP32298. baseline and differential.
GenevisibleiP32298. HS.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR000239. GPCR_kinase.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016137. RGS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR00717. GPCRKINASE.
SMARTiSM00315. RGS. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGRK4_HUMAN
AccessioniPrimary (citable) accession number: P32298
Secondary accession number(s): O00641
, O00642, Q13293, Q13294, Q13295, Q14453, Q14725, Q15313, Q15314, Q15315, Q15316, Q17RH6, Q53EQ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: April 3, 2007
Last modified: November 30, 2016
This is version 167 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 4
    Human chromosome 4: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  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.