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Protein

Macrophage colony-stimulating factor 1

Gene

CSF1

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

Functioni

Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.4 Publications

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • growth factor activity Source: UniProtKB
  • macrophage colony-stimulating factor receptor binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • branching involved in mammary gland duct morphogenesis Source: Ensembl
  • cell differentiation Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • developmental process involved in reproduction Source: BHF-UCL
  • hemopoiesis Source: UniProtKB
  • homeostasis of number of cells within a tissue Source: Ensembl
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • macrophage colony-stimulating factor signaling pathway Source: Ensembl
  • macrophage differentiation Source: UniProtKB
  • mammary duct terminal end bud growth Source: Ensembl
  • mammary gland fat development Source: Ensembl
  • monocyte activation Source: BHF-UCL
  • odontogenesis Source: Ensembl
  • ossification Source: Ensembl
  • osteoclast differentiation Source: BHF-UCL
  • osteoclast proliferation Source: Ensembl
  • positive regulation of cell-matrix adhesion Source: BHF-UCL
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cellular protein metabolic process Source: BHF-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of macrophage chemotaxis Source: BHF-UCL
  • positive regulation of macrophage colony-stimulating factor signaling pathway Source: BHF-UCL
  • positive regulation of macrophage derived foam cell differentiation Source: BHF-UCL
  • positive regulation of macrophage differentiation Source: BHF-UCL
  • positive regulation of microglial cell migration Source: BHF-UCL
  • positive regulation of monocyte differentiation Source: BHF-UCL
  • positive regulation of mononuclear cell proliferation Source: BHF-UCL
  • positive regulation of multicellular organism growth Source: Ensembl
  • positive regulation of odontogenesis of dentin-containing tooth Source: Ensembl
  • positive regulation of osteoclast differentiation Source: BHF-UCL
  • positive regulation of protein kinase activity Source: BHF-UCL
  • positive regulation of Ras protein signal transduction Source: Ensembl
  • regulation of macrophage derived foam cell differentiation Source: BHF-UCL
  • regulation of ossification Source: Ensembl
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

SignaLinkiP09603.
SIGNORiP09603.

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage colony-stimulating factor 1
Short name:
CSF-1
Short name:
M-CSF
Short name:
MCSF
Alternative name(s):
Lanimostim
Cleaved into the following chain:
Gene namesi
Name:CSF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:2432. CSF1.

Subcellular locationi

  • Cell membrane 2 Publications; Single-pass type I membrane protein 2 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 496464LumenalSequence analysisAdd
BLAST
Transmembranei497 – 51721HelicalSequence analysisAdd
BLAST
Topological domaini518 – 55437CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • CSF1-CSF1R complex Source: BHF-UCL
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: BHF-UCL
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • perinuclear region of cytoplasm Source: BHF-UCL
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.

Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi489 – 55466Missing : Produces biologically active protein which is secreted. 1 PublicationAdd
BLAST

Organism-specific databases

PharmGKBiPA26935.

Polymorphism and mutation databases

BioMutaiCSF1.
DMDMi311033367.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 32321 PublicationAdd
BLAST
Chaini33 – 554522Macrophage colony-stimulating factor 1PRO_0000005857Add
BLAST
Chaini33 – 450418Processed macrophage colony-stimulating factor 1By similarityPRO_0000296231Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi39 ↔ 1221 Publication
Disulfide bondi63 – 63Interchain1 Publication
Disulfide bondi80 ↔ 1711 Publication
Disulfide bondi134 ↔ 1781 Publication
Glycosylationi154 – 1541N-linked (GlcNAc...)Sequence analysis
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence analysis
Disulfide bondi189 – 189Interchain1 Publication
Disulfide bondi191 – 191Interchain1 Publication
Modified residuei266 – 2661Phosphothreonine; by FAM20C1 Publication
Glycosylationi363 – 3631O-linked (GalNAc...)1 Publication
Glycosylationi365 – 3651O-linked (GalNAc...)1 Publication

Post-translational modificationi

N- and O-glycosylated. Glycosylation and proteolytic cleavage yield different soluble forms. One high molecular weight soluble form is a proteoglycan containing chondroitin sulfate. O-glycosylated with core 1 or possibly core 8 glycans. Isoform 1 is N- and O-glycosylated. Isoform 3 is only N-glycosylated.4 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Proteoglycan

Proteomic databases

MaxQBiP09603.
PaxDbiP09603.
PeptideAtlasiP09603.
PRIDEiP09603.

PTM databases

iPTMnetiP09603.
PhosphoSiteiP09603.

Miscellaneous databases

PMAP-CutDBP09603.

Expressioni

Gene expression databases

BgeeiENSG00000184371.
CleanExiHS_CSF1.
ExpressionAtlasiP09603. baseline and differential.
GenevisibleiP09603. HS.

Interactioni

Subunit structurei

Homodimer or heterodimer; disulfide-linked. Interacts with CSF1R.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FHL3Q136433EBI-2872294,EBI-741101
NOTCH2NLQ7Z3S93EBI-2872294,EBI-945833
SGTAO437653EBI-2872294,EBI-347996

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • growth factor activity Source: UniProtKB
  • macrophage colony-stimulating factor receptor binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi107822. 6 interactions.
DIPiDIP-41860N.
IntActiP09603. 5 interactions.
MINTiMINT-196477.
STRINGi9606.ENSP00000327513.

Structurei

Secondary structure

1
554
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi37 – 415Combined sources
Helixi45 – 5713Combined sources
Beta strandi65 – 706Combined sources
Turni72 – 743Combined sources
Helixi78 – 9619Combined sources
Helixi104 – 11815Combined sources
Beta strandi119 – 1235Combined sources
Helixi128 – 1303Combined sources
Beta strandi135 – 1406Combined sources
Helixi142 – 16221Combined sources
Helixi166 – 1683Combined sources
Helixi172 – 1765Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HMCX-ray2.50A/B36-181[»]
3UEZX-ray3.41E/F/G/H33-181[»]
3UF2X-ray2.75A/B/C/D/E/F/G/H/I/J33-181[»]
4ADFX-ray4.40G/H/I/J/K/L/S/T/U/V/W/X33-181[»]
4FA8X-ray2.20E/F/G36-180[»]
4WRLX-ray2.80B/D33-181[»]
4WRMX-ray6.85B33-181[»]
ProteinModelPortaliP09603.
SMRiP09603. Positions 36-180.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09603.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni406 – 42621O-glycosylated at one siteAdd
BLAST

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410II8R. Eukaryota.
ENOG410Z5Q9. LUCA.
GeneTreeiENSGT00390000015805.
HOVERGENiHBG005410.
InParanoidiP09603.
KOiK05453.
OMAiDTGHERQ.
OrthoDBiEOG091G0TMC.
PhylomeDBiP09603.
TreeFamiTF337718.

Family and domain databases

InterProiIPR009079. 4_helix_cytokine-like_core.
IPR008001. MCSF-1.
[Graphical view]
PANTHERiPTHR10058. PTHR10058. 1 hit.
PfamiPF05337. CSF-1. 1 hit.
[Graphical view]
PIRSFiPIRSF001948. MCSF-1. 1 hit.
SUPFAMiSSF47266. SSF47266. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P09603-1) [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
MTAPGAAGRC PPTTWLGSLL LLVCLLASRS ITEEVSEYCS HMIGSGHLQS
60 70 80 90 100
LQRLIDSQME TSCQITFEFV DQEQLKDPVC YLKKAFLLVQ DIMEDTMRFR
110 120 130 140 150
DNTPNAIAIV QLQELSLRLK SCFTKDYEEH DKACVRTFYE TPLQLLEKVK
160 170 180 190 200
NVFNETKNLL DKDWNIFSKN CNNSFAECSS QDVVTKPDCN CLYPKAIPSS
210 220 230 240 250
DPASVSPHQP LAPSMAPVAG LTWEDSEGTE GSSLLPGEQP LHTVDPGSAK
260 270 280 290 300
QRPPRSTCQS FEPPETPVVK DSTIGGSPQP RPSVGAFNPG MEDILDSAMG
310 320 330 340 350
TNWVPEEASG EASEIPVPQG TELSPSRPGG GSMQTEPARP SNFLSASSPL
360 370 380 390 400
PASAKGQQPA DVTGTALPRV GPVRPTGQDW NHTPQKTDHP SALLRDPPEP
410 420 430 440 450
GSPRISSLRP QGLSNPSTLS AQPQLSRSHS SGSVLPLGEL EGRRSTRDRR
460 470 480 490 500
SPAEPEGGPA SEGAARPLPR FNSVPLTDTG HERQSEGSFS PQLQESVFHL
510 520 530 540 550
LVPSVILVLL AVGGLLFYRW RRRSHQEPQR ADSPLEQPEG SPLTQDDRQV

ELPV
Length:554
Mass (Da):60,179
Last modified:November 2, 2010 - v2
Checksum:i656B0894F9255AED
GO
Isoform 2 (identifier: P09603-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     365-480: Missing.

Show »
Length:438
Mass (Da):47,903
Checksum:i1B6A3CDBE1C06775
GO
Isoform 3 (identifier: P09603-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-479: Missing.

Show »
Length:256
Mass (Da):29,215
Checksum:i0656D858DE1A4086
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti69 – 691F → S AA sequence (PubMed:3498652).Curated
Sequence conflicti91 – 911D → Y in AAB59527 (PubMed:2996129).Curated
Sequence conflicti91 – 911D → Y in AAA59572 (PubMed:2460758).Curated
Sequence conflicti91 – 911D → Y in AAA64849 (PubMed:2460758).Curated
Sequence conflicti91 – 911D → Y in AAA52120 (PubMed:1791839).Curated
Sequence conflicti104 – 1063PNA → ANP in AAA52117 (PubMed:3493529).Curated
Sequence conflicti364 – 3641G → A in AAA52117 (PubMed:3493529).Curated
Sequence conflicti374 – 3741R → M in AAA52117 (PubMed:3493529).Curated
Sequence conflicti412 – 4121G → A in AAA52117 (PubMed:3493529).Curated
Sequence conflicti450 – 4501R → T in AAA52117 (PubMed:3493529).Curated
Sequence conflicti457 – 4582GG → AA in AAA52117 (PubMed:3493529).Curated
Sequence conflicti480 – 4801Missing in AAA59573 (PubMed:2660794).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti341 – 3411S → N.
Corresponds to variant rs12565736 [ dbSNP | Ensembl ].
VAR_048810
Natural varianti408 – 4081L → P.1 Publication
Corresponds to variant rs1058885 [ dbSNP | Ensembl ].
VAR_020454
Natural varianti438 – 4381G → R.
Corresponds to variant rs2229165 [ dbSNP | Ensembl ].
VAR_029320
Natural varianti489 – 4891F → S.9 Publications
Corresponds to variant rs333971 [ dbSNP | Ensembl ].
VAR_048811
Natural varianti496 – 4961S → F.
Corresponds to variant rs12721516 [ dbSNP | Ensembl ].
VAR_020455
Natural varianti531 – 5311A → V.
Corresponds to variant rs2229167 [ dbSNP | Ensembl ].
VAR_022146

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei182 – 479298Missing in isoform 3. 1 PublicationVSP_001187Add
BLAST
Alternative sequencei365 – 480116Missing in isoform 2. CuratedVSP_001188Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11296, M11038, M11295 Genomic DNA. Translation: AAB59527.1.
M37435 mRNA. Translation: AAA52117.1.
M64592 mRNA. Translation: AAA59572.1.
U22386 mRNA. Translation: AAA64849.1.
M27087 mRNA. Translation: AAA59573.1.
AK291660 mRNA. Translation: BAF84349.1.
AL450468 Genomic DNA. Translation: CAH71146.1.
AL450468 Genomic DNA. Translation: CAH71147.1.
CH471122 Genomic DNA. Translation: EAW56416.1.
BC021117 mRNA. Translation: AAH21117.1.
X05825 mRNA. Translation: CAA29265.1.
X06106 Genomic DNA. Translation: CAA29479.1.
M76453 mRNA. Translation: AAA52120.2.
CCDSiCCDS30797.1. [P09603-3]
CCDS816.1. [P09603-1]
CCDS817.1. [P09603-2]
PIRiA47583. FQHUMP.
RefSeqiNP_000748.3. NM_000757.5.
NP_757349.1. NM_172210.2.
NP_757350.1. NM_172211.3.
NP_757351.1. NM_172212.2.
UniGeneiHs.173894.

Genome annotation databases

EnsembliENST00000329608; ENSP00000327513; ENSG00000184371. [P09603-1]
ENST00000369801; ENSP00000358816; ENSG00000184371. [P09603-2]
ENST00000369802; ENSP00000358817; ENSG00000184371. [P09603-1]
ENST00000420111; ENSP00000407317; ENSG00000184371. [P09603-3]
GeneIDi1435.
KEGGihsa:1435.
UCSCiuc001dyt.3. human. [P09603-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11296, M11038, M11295 Genomic DNA. Translation: AAB59527.1.
M37435 mRNA. Translation: AAA52117.1.
M64592 mRNA. Translation: AAA59572.1.
U22386 mRNA. Translation: AAA64849.1.
M27087 mRNA. Translation: AAA59573.1.
AK291660 mRNA. Translation: BAF84349.1.
AL450468 Genomic DNA. Translation: CAH71146.1.
AL450468 Genomic DNA. Translation: CAH71147.1.
CH471122 Genomic DNA. Translation: EAW56416.1.
BC021117 mRNA. Translation: AAH21117.1.
X05825 mRNA. Translation: CAA29265.1.
X06106 Genomic DNA. Translation: CAA29479.1.
M76453 mRNA. Translation: AAA52120.2.
CCDSiCCDS30797.1. [P09603-3]
CCDS816.1. [P09603-1]
CCDS817.1. [P09603-2]
PIRiA47583. FQHUMP.
RefSeqiNP_000748.3. NM_000757.5.
NP_757349.1. NM_172210.2.
NP_757350.1. NM_172211.3.
NP_757351.1. NM_172212.2.
UniGeneiHs.173894.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HMCX-ray2.50A/B36-181[»]
3UEZX-ray3.41E/F/G/H33-181[»]
3UF2X-ray2.75A/B/C/D/E/F/G/H/I/J33-181[»]
4ADFX-ray4.40G/H/I/J/K/L/S/T/U/V/W/X33-181[»]
4FA8X-ray2.20E/F/G36-180[»]
4WRLX-ray2.80B/D33-181[»]
4WRMX-ray6.85B33-181[»]
ProteinModelPortaliP09603.
SMRiP09603. Positions 36-180.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107822. 6 interactions.
DIPiDIP-41860N.
IntActiP09603. 5 interactions.
MINTiMINT-196477.
STRINGi9606.ENSP00000327513.

PTM databases

iPTMnetiP09603.
PhosphoSiteiP09603.

Polymorphism and mutation databases

BioMutaiCSF1.
DMDMi311033367.

Proteomic databases

MaxQBiP09603.
PaxDbiP09603.
PeptideAtlasiP09603.
PRIDEiP09603.

Protocols and materials databases

DNASUi1435.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329608; ENSP00000327513; ENSG00000184371. [P09603-1]
ENST00000369801; ENSP00000358816; ENSG00000184371. [P09603-2]
ENST00000369802; ENSP00000358817; ENSG00000184371. [P09603-1]
ENST00000420111; ENSP00000407317; ENSG00000184371. [P09603-3]
GeneIDi1435.
KEGGihsa:1435.
UCSCiuc001dyt.3. human. [P09603-1]

Organism-specific databases

CTDi1435.
GeneCardsiCSF1.
HGNCiHGNC:2432. CSF1.
MIMi120420. gene.
neXtProtiNX_P09603.
PharmGKBiPA26935.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410II8R. Eukaryota.
ENOG410Z5Q9. LUCA.
GeneTreeiENSGT00390000015805.
HOVERGENiHBG005410.
InParanoidiP09603.
KOiK05453.
OMAiDTGHERQ.
OrthoDBiEOG091G0TMC.
PhylomeDBiP09603.
TreeFamiTF337718.

Enzyme and pathway databases

SignaLinkiP09603.
SIGNORiP09603.

Miscellaneous databases

ChiTaRSiCSF1. human.
EvolutionaryTraceiP09603.
GeneWikiiMacrophage_colony-stimulating_factor.
GenomeRNAii1435.
PMAP-CutDBP09603.
PROiP09603.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000184371.
CleanExiHS_CSF1.
ExpressionAtlasiP09603. baseline and differential.
GenevisibleiP09603. HS.

Family and domain databases

InterProiIPR009079. 4_helix_cytokine-like_core.
IPR008001. MCSF-1.
[Graphical view]
PANTHERiPTHR10058. PTHR10058. 1 hit.
PfamiPF05337. CSF-1. 1 hit.
[Graphical view]
PIRSFiPIRSF001948. MCSF-1. 1 hit.
SUPFAMiSSF47266. SSF47266. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCSF1_HUMAN
AccessioniPrimary (citable) accession number: P09603
Secondary accession number(s): A8K6J5
, Q13130, Q14086, Q14806, Q5VVF3, Q5VVF4, Q9UQR8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 2, 2010
Last modified: September 7, 2016
This is version 175 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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

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.