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Protein

Bifunctional purine biosynthesis protein PURH

Gene

ATIC

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

Functioni

Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.1 Publication
Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).1 Publication

Catalytic activityi

10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.
IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.

Pathwayi: IMP biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route).
Proteins known to be involved in this subpathway in this organism are:
  1. Bifunctional purine biosynthesis protein PURH (ATIC)
This subpathway is part of the pathway IMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route), the pathway IMP biosynthesis via de novo pathway and in Purine metabolism.

Pathwayi: IMP biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide.
Proteins known to be involved in this subpathway in this organism are:
  1. Bifunctional purine biosynthesis protein PURH (ATIC)
This subpathway is part of the pathway IMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes IMP from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, the pathway IMP biosynthesis via de novo pathway and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei137Proton acceptorSequence analysis1
Sitei266Transition state stabilizerSequence analysis1
Active sitei267Proton acceptorCurated1
Binding sitei316AICAR; via carbonyl oxygen1 Publication1
Binding sitei339AICAR1 Publication1
Binding sitei431AICAR; shared with dimeric partner1 Publication1
Binding sitei451AICAR; shared with dimeric partner1 Publication1
Binding sitei541AICAR; via carbonyl oxygen; shared with dimeric partner1 Publication1
Binding sitei588AICAR; shared with dimeric partner1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 14IMP3
Nucleotide bindingi34 – 37IMP4
Nucleotide bindingi64 – 67IMP4
Nucleotide bindingi101 – 104IMP4
Nucleotide bindingi125 – 127IMP3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Keywords - Biological processi

Purine biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS06490-MONOMER.
ZFISH:HS06490-MONOMER.
BRENDAi2.1.2.3. 2681.
3.5.4.10. 2681.
ReactomeiR-HSA-73817. Purine ribonucleoside monophosphate biosynthesis.
SABIO-RKP31939.
UniPathwayiUPA00074; UER00133.
UPA00074; UER00135.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional purine biosynthesis protein PURH
Cleaved into the following chain:
Including the following 2 domains:
Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC:2.1.2.3)
Alternative name(s):
5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase
AICAR transformylase
IMP cyclohydrolase (EC:3.5.4.10)
Alternative name(s):
ATIC
IMP synthase
Inosinicase
Gene namesi
Name:ATIC
Synonyms:PURH
ORF Names:OK/SW-cl.86
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:794. ATIC.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
  • mitochondrion Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

AICAR transformylase/IMP cyclohydrolase deficiency (AICAR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurologically devastating inborn error of purine biosynthesis. Patients excrete massive amounts of AICA-riboside in the urine and accumulate AICA-ribotide and its derivatives in erythrocytes and fibroblasts. AICAR causes profound mental retardation, epilepsy, dysmorphic features and congenital blindness.
See also OMIM:608688
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019307426K → R in AICAR; loss of transformylase activity. 1 PublicationCorresponds to variant rs121434478dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi471.
MalaCardsiATIC.
MIMi608688. phenotype.
OpenTargetsiENSG00000138363.
Orphaneti250977. AICA-ribosiduria.
PharmGKBiPA25094.

Chemistry databases

ChEMBLiCHEMBL2518.
DrugBankiDB00563. Methotrexate.
DB00642. Pemetrexed.
DB00116. Tetrahydrofolic acid.

Polymorphism and mutation databases

BioMutaiATIC.
DMDMi23831360.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001921561 – 592Bifunctional purine biosynthesis protein PURHAdd BLAST592
Initiator methionineiRemoved; alternateCombined sources
ChainiPRO_00004343762 – 592Bifunctional purine biosynthesis protein PURH, N-terminally processedAdd BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei199N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP31939.
PaxDbiP31939.
PeptideAtlasiP31939.
PRIDEiP31939.

2D gel databases

REPRODUCTION-2DPAGEIPI00289499.
UCD-2DPAGEP31939.

PTM databases

iPTMnetiP31939.
PhosphoSitePlusiP31939.
SwissPalmiP31939.

Expressioni

Gene expression databases

BgeeiENSG00000138363.
CleanExiHS_ATIC.
ExpressionAtlasiP31939. baseline and differential.
GenevisibleiP31939. HS.

Organism-specific databases

HPAiCAB013462.
HPA021012.

Interactioni

Subunit structurei

Homodimer (PubMed:14756553, PubMed:14966129). Associates with internalized INSR complexes on Golgi/endosomal membranes. Interacts with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (PubMed:25687571).3 Publications

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi106961. 69 interactors.
IntActiP31939. 9 interactors.
MINTiMINT-4999053.
STRINGi9606.ENSP00000236959.

Chemistry databases

BindingDBiP31939.

Structurei

Secondary structure

1592
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 10Combined sources5
Helixi17 – 25Combined sources9
Turni26 – 28Combined sources3
Beta strandi30 – 33Combined sources4
Helixi35 – 42Combined sources8
Turni43 – 45Combined sources3
Helixi51 – 55Combined sources5
Turni61 – 64Combined sources4
Beta strandi65 – 67Combined sources3
Helixi70 – 77Combined sources8
Helixi82 – 91Combined sources10
Beta strandi96 – 101Combined sources6
Helixi106 – 111Combined sources6
Helixi117 – 122Combined sources6
Helixi127 – 137Combined sources11
Turni138 – 141Combined sources4
Beta strandi143 – 145Combined sources3
Helixi148 – 150Combined sources3
Helixi151 – 160Combined sources10
Beta strandi161 – 165Combined sources5
Helixi168 – 197Combined sources30
Turni200 – 202Combined sources3
Beta strandi203 – 207Combined sources5
Beta strandi209 – 211Combined sources3
Beta strandi217 – 220Combined sources4
Beta strandi222 – 225Combined sources4
Beta strandi227 – 233Combined sources7
Helixi237 – 257Combined sources21
Beta strandi261 – 266Combined sources6
Beta strandi269 – 275Combined sources7
Helixi281 – 286Combined sources6
Helixi290 – 295Combined sources6
Helixi298 – 308Combined sources11
Turni311 – 316Combined sources6
Beta strandi317 – 323Combined sources7
Helixi327 – 334Combined sources8
Beta strandi338 – 344Combined sources7
Helixi348 – 360Combined sources13
Beta strandi363 – 367Combined sources5
Beta strandi375 – 381Combined sources7
Beta strandi384 – 389Combined sources6
Helixi397 – 400Combined sources4
Helixi412 – 426Combined sources15
Beta strandi433 – 437Combined sources5
Beta strandi440 – 445Combined sources6
Helixi451 – 467Combined sources17
Helixi471 – 474Combined sources4
Helixi486 – 496Combined sources11
Helixi503 – 509Combined sources7
Beta strandi512 – 514Combined sources3
Helixi521 – 528Combined sources8
Beta strandi534 – 540Combined sources7
Beta strandi543 – 545Combined sources3
Helixi546 – 552Combined sources7
Turni553 – 555Combined sources3
Beta strandi556 – 562Combined sources7
Helixi568 – 578Combined sources11
Beta strandi581 – 586Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P4RX-ray2.55A/B1-592[»]
1PKXX-ray1.90A/B/C/D1-592[»]
1PL0X-ray2.60A/B/C/D1-592[»]
ProteinModelPortaliP31939.
SMRiP31939.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP31939.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni207 – 208AICAR binding2

Domaini

The IMP cyclohydrolase activity resides in the N-terminal region.

Sequence similaritiesi

Belongs to the PurH family.Curated

Phylogenomic databases

eggNOGiKOG2555. Eukaryota.
COG0138. LUCA.
GeneTreeiENSGT00390000004553.
HOGENOMiHOG000230372.
HOVERGENiHBG006912.
InParanoidiP31939.
KOiK00602.
OMAiPCGVAEG.
OrthoDBiEOG091G03H4.
PhylomeDBiP31939.
TreeFamiTF105642.

Family and domain databases

Gene3Di1.10.287.440. 1 hit.
3.40.140.20. 3 hits.
3.40.50.1380. 1 hit.
HAMAPiMF_00139. PurH. 1 hit.
InterProiIPR024051. AICAR_Tfase_dom.
IPR024050. AICAR_Tfase_insert_dom.
IPR002695. AICARFT_IMPCHas.
IPR016193. Cytidine_deaminase-like.
IPR011607. MGS-like_dom.
[Graphical view]
PANTHERiPTHR11692. PTHR11692. 1 hit.
PfamiPF01808. AICARFT_IMPCHas. 1 hit.
PF02142. MGS. 1 hit.
[Graphical view]
PIRSFiPIRSF000414. AICARFT_IMPCHas. 1 hit.
SMARTiSM00798. AICARFT_IMPCHas. 1 hit.
SM00851. MGS. 1 hit.
[Graphical view]
SUPFAMiSSF52335. SSF52335. 1 hit.
SSF53927. SSF53927. 1 hit.
TIGRFAMsiTIGR00355. purH. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P31939-1) [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
MAPGQLALFS VSDKTGLVEF ARNLTALGLN LVASGGTAKA LRDAGLAVRD
60 70 80 90 100
VSELTGFPEM LGGRVKTLHP AVHAGILARN IPEDNADMAR LDFNLIRVVA
110 120 130 140 150
CNLYPFVKTV ASPGVTVEEA VEQIDIGGVT LLRAAAKNHA RVTVVCEPED
160 170 180 190 200
YVVVSTEMQS SESKDTSLET RRQLALKAFT HTAQYDEAIS DYFRKQYSKG
210 220 230 240 250
VSQMPLRYGM NPHQTPAQLY TLQPKLPITV LNGAPGFINL CDALNAWQLV
260 270 280 290 300
KELKEALGIP AAASFKHVSP AGAAVGIPLS EDEAKVCMVY DLYKTLTPIS
310 320 330 340 350
AAYARARGAD RMSSFGDFVA LSDVCDVPTA KIISREVSDG IIAPGYEEEA
360 370 380 390 400
LTILSKKKNG NYCVLQMDQS YKPDENEVRT LFGLHLSQKR NNGVVDKSLF
410 420 430 440 450
SNVVTKNKDL PESALRDLIV ATIAVKYTQS NSVCYAKNGQ VIGIGAGQQS
460 470 480 490 500
RIHCTRLAGD KANYWWLRHH PQVLSMKFKT GVKRAEISNA IDQYVTGTIG
510 520 530 540 550
EDEDLIKWKA LFEEVPELLT EAEKKEWVEK LTEVSISSDA FFPFRDNVDR
560 570 580 590
AKRSGVAYIA APSGSAADKV VIEACDELGI ILAHTNLRLF HH
Length:592
Mass (Da):64,616
Last modified:October 10, 2002 - v3
Checksum:iAD778892021F0888
GO
Isoform 2 (identifier: P31939-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MAPGQL → MSSLS

Show »
Length:591
Mass (Da):64,524
Checksum:i372861CF93D74887
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti165D → G in AAA97405 (PubMed:8567683).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019306116T → S.2 PublicationsCorresponds to variant rs2372536dbSNPEnsembl.1
Natural variantiVAR_019307426K → R in AICAR; loss of transformylase activity. 1 PublicationCorresponds to variant rs121434478dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0534951 – 6MAPGQL → MSSLS in isoform 2. 2 Publications6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37436 mRNA. Translation: AAA97405.1.
D82348 mRNA. Translation: BAA11559.1.
D89976 mRNA. Translation: BAA21762.1.
AB062403 mRNA. Translation: BAB93490.1.
AK290067 mRNA. Translation: BAF82756.1.
AC073284 Genomic DNA. Translation: AAY24062.1.
CH471063 Genomic DNA. Translation: EAW70529.1.
BC008879 mRNA. Translation: AAH08879.1.
CCDSiCCDS2398.1. [P31939-1]
PIRiJC4642.
RefSeqiNP_004035.2. NM_004044.6. [P31939-1]
UniGeneiHs.90280.

Genome annotation databases

EnsembliENST00000236959; ENSP00000236959; ENSG00000138363. [P31939-1]
ENST00000435675; ENSP00000415935; ENSG00000138363. [P31939-2]
GeneIDi471.
KEGGihsa:471.
UCSCiuc002vey.5. human. [P31939-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37436 mRNA. Translation: AAA97405.1.
D82348 mRNA. Translation: BAA11559.1.
D89976 mRNA. Translation: BAA21762.1.
AB062403 mRNA. Translation: BAB93490.1.
AK290067 mRNA. Translation: BAF82756.1.
AC073284 Genomic DNA. Translation: AAY24062.1.
CH471063 Genomic DNA. Translation: EAW70529.1.
BC008879 mRNA. Translation: AAH08879.1.
CCDSiCCDS2398.1. [P31939-1]
PIRiJC4642.
RefSeqiNP_004035.2. NM_004044.6. [P31939-1]
UniGeneiHs.90280.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P4RX-ray2.55A/B1-592[»]
1PKXX-ray1.90A/B/C/D1-592[»]
1PL0X-ray2.60A/B/C/D1-592[»]
ProteinModelPortaliP31939.
SMRiP31939.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106961. 69 interactors.
IntActiP31939. 9 interactors.
MINTiMINT-4999053.
STRINGi9606.ENSP00000236959.

Chemistry databases

BindingDBiP31939.
ChEMBLiCHEMBL2518.
DrugBankiDB00563. Methotrexate.
DB00642. Pemetrexed.
DB00116. Tetrahydrofolic acid.

PTM databases

iPTMnetiP31939.
PhosphoSitePlusiP31939.
SwissPalmiP31939.

Polymorphism and mutation databases

BioMutaiATIC.
DMDMi23831360.

2D gel databases

REPRODUCTION-2DPAGEIPI00289499.
UCD-2DPAGEP31939.

Proteomic databases

EPDiP31939.
PaxDbiP31939.
PeptideAtlasiP31939.
PRIDEiP31939.

Protocols and materials databases

DNASUi471.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000236959; ENSP00000236959; ENSG00000138363. [P31939-1]
ENST00000435675; ENSP00000415935; ENSG00000138363. [P31939-2]
GeneIDi471.
KEGGihsa:471.
UCSCiuc002vey.5. human. [P31939-1]

Organism-specific databases

CTDi471.
DisGeNETi471.
GeneCardsiATIC.
HGNCiHGNC:794. ATIC.
HPAiCAB013462.
HPA021012.
MalaCardsiATIC.
MIMi601731. gene.
608688. phenotype.
neXtProtiNX_P31939.
OpenTargetsiENSG00000138363.
Orphaneti250977. AICA-ribosiduria.
PharmGKBiPA25094.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2555. Eukaryota.
COG0138. LUCA.
GeneTreeiENSGT00390000004553.
HOGENOMiHOG000230372.
HOVERGENiHBG006912.
InParanoidiP31939.
KOiK00602.
OMAiPCGVAEG.
OrthoDBiEOG091G03H4.
PhylomeDBiP31939.
TreeFamiTF105642.

Enzyme and pathway databases

UniPathwayiUPA00074; UER00133.
UPA00074; UER00135.
BioCyciMetaCyc:HS06490-MONOMER.
ZFISH:HS06490-MONOMER.
BRENDAi2.1.2.3. 2681.
3.5.4.10. 2681.
ReactomeiR-HSA-73817. Purine ribonucleoside monophosphate biosynthesis.
SABIO-RKP31939.

Miscellaneous databases

ChiTaRSiATIC. human.
EvolutionaryTraceiP31939.
GeneWikiiInosine_monophosphate_synthase.
GenomeRNAii471.
PROiP31939.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138363.
CleanExiHS_ATIC.
ExpressionAtlasiP31939. baseline and differential.
GenevisibleiP31939. HS.

Family and domain databases

Gene3Di1.10.287.440. 1 hit.
3.40.140.20. 3 hits.
3.40.50.1380. 1 hit.
HAMAPiMF_00139. PurH. 1 hit.
InterProiIPR024051. AICAR_Tfase_dom.
IPR024050. AICAR_Tfase_insert_dom.
IPR002695. AICARFT_IMPCHas.
IPR016193. Cytidine_deaminase-like.
IPR011607. MGS-like_dom.
[Graphical view]
PANTHERiPTHR11692. PTHR11692. 1 hit.
PfamiPF01808. AICARFT_IMPCHas. 1 hit.
PF02142. MGS. 1 hit.
[Graphical view]
PIRSFiPIRSF000414. AICARFT_IMPCHas. 1 hit.
SMARTiSM00798. AICARFT_IMPCHas. 1 hit.
SM00851. MGS. 1 hit.
[Graphical view]
SUPFAMiSSF52335. SSF52335. 1 hit.
SSF53927. SSF53927. 1 hit.
TIGRFAMsiTIGR00355. purH. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPUR9_HUMAN
AccessioniPrimary (citable) accession number: P31939
Secondary accession number(s): A8K202
, E9PBU3, Q13856, Q53S28
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 10, 2002
Last modified: November 2, 2016
This is version 175 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, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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.