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Protein

Multifunctional protein ADE2

Gene

PAICS

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

Functioni

Catalytic activityi

ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate + (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate.
5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate = 5-amino-1-(5-phospho-D-ribosyl)imidazole + CO2.

Pathwayi: IMP biosynthesis via de novo pathway

This protein is involved in step 1 of the subpathway that synthesizes 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Multifunctional protein ADE2 (PAICS)
  2. Adenylosuccinate lyase (ADSL), Adenylosuccinate lyase (ADSL), Adenylosuccinate lyase (ADSL), Adenylosuccinate lyase, Adenylosuccinate lyase (ADSL), Adenylosuccinate lyase, Adenylosuccinate lyase, Adenylosuccinate lyase (ADSL)
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-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate, 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 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate from 5-amino-1-(5-phospho-D-ribosyl)imidazole (carboxylase route).
Proteins known to be involved in this subpathway in this organism are:
  1. Multifunctional protein ADE2 (PAICS)
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-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate from 5-amino-1-(5-phospho-D-ribosyl)imidazole (carboxylase route), the pathway IMP biosynthesis via de novo pathway and in Purine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei101For SAICAR synthetase activity1 Publication1
Active sitei107For SAICAR synthetase activity1 Publication1
Active sitei215For SAICAR synthetase activity1 Publication1
Active sitei303For AIR carboxylase activity1 Publication1
Active sitei332For AIR carboxylase activity1 Publication1
Sitei334Essential for AIR carboxylase activity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Decarboxylase, Ligase, Lyase

Keywords - Biological processi

Purine biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS05155-MONOMER.
ZFISH:HS05155-MONOMER.
ReactomeiR-HSA-73817. Purine ribonucleoside monophosphate biosynthesis.
UniPathwayiUPA00074; UER00130.
UPA00074; UER00131.

Names & Taxonomyi

Protein namesi
Recommended name:
Multifunctional protein ADE2
Including the following 2 domains:
Phosphoribosylaminoimidazole-succinocarboxamide synthase (EC:6.3.2.6)
Alternative name(s):
SAICAR synthetase
Phosphoribosylaminoimidazole carboxylase (EC:4.1.1.21)
Alternative name(s):
AIR carboxylase
Short name:
AIRC
Gene namesi
Name:PAICS
Synonyms:ADE2, AIRC, PAIS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:8587. PAICS.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytoplasm Source: BHF-UCL
  • cytosol Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • membrane Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi303H → Y: Loss of AIR carboxylase activity. 1 Publication1
Mutagenesisi332S → A: Loss of AIR carboxylase activity. 1 Publication1
Mutagenesisi334G → A: Loss of AIR carboxylase activity. 1 Publication1
Mutagenesisi400S → A: No change of AIR carboxylase activity. 1

Organism-specific databases

DisGeNETi10606.
OpenTargetsiENSG00000128050.
PharmGKBiPA32914.

Chemistry databases

ChEMBLiCHEMBL5922.
DrugBankiDB00128. L-Aspartic Acid.

Polymorphism and mutation databases

BioMutaiPAICS.
DMDMi131628.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000750302 – 425Multifunctional protein ADE2Add BLAST424

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei22PhosphotyrosineBy similarity1
Modified residuei27PhosphoserineCombined sources1
Modified residuei36N6-acetyllysineBy similarity1
Modified residuei107PhosphoserineCombined sources1
Modified residuei238PhosphothreonineCombined sources1
Modified residuei247N6-acetyllysineCombined sources1
Modified residuei274PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP22234.
MaxQBiP22234.
PaxDbiP22234.
PeptideAtlasiP22234.
PRIDEiP22234.

PTM databases

iPTMnetiP22234.
PhosphoSitePlusiP22234.
SwissPalmiP22234.

Expressioni

Gene expression databases

BgeeiENSG00000128050.
CleanExiHS_PAICS.
ExpressionAtlasiP22234. baseline and differential.
GenevisibleiP22234. HS.

Organism-specific databases

HPAiHPA035895.
HPA041538.

Interactioni

Subunit structurei

Homooctamer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself6EBI-712261,EBI-712261
FXR2P511163EBI-712261,EBI-740459
L3MBTL2Q969R53EBI-712261,EBI-739909
LNX1Q8TBB13EBI-712261,EBI-739832
NUDT18Q6ZVK83EBI-712261,EBI-740486

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi115852. 82 interactors.
IntActiP22234. 28 interactors.
MINTiMINT-5006326.
STRINGi9606.ENSP00000382595.

Structurei

Secondary structure

1425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi20 – 22Combined sources3
Beta strandi32 – 35Combined sources4
Helixi54 – 71Combined sources18
Beta strandi82 – 88Combined sources7
Beta strandi91 – 93Combined sources3
Beta strandi97 – 103Combined sources7
Helixi106 – 111Combined sources6
Beta strandi126 – 130Combined sources5
Helixi142 – 146Combined sources5
Turni147 – 149Combined sources3
Helixi159 – 180Combined sources22
Helixi181 – 183Combined sources3
Beta strandi186 – 192Combined sources7
Beta strandi194 – 197Combined sources4
Turni198 – 200Combined sources3
Beta strandi203 – 205Combined sources3
Beta strandi213 – 217Combined sources5
Beta strandi241 – 243Combined sources3
Helixi249 – 253Combined sources5
Helixi256 – 260Combined sources5
Beta strandi267 – 273Combined sources7
Helixi275 – 277Combined sources3
Helixi278 – 290Combined sources13
Beta strandi295 – 299Combined sources5
Turni302 – 304Combined sources3
Helixi306 – 317Combined sources12
Beta strandi323 – 328Combined sources6
Helixi335 – 342Combined sources8
Beta strandi347 – 349Combined sources3
Turni355 – 357Combined sources3
Helixi358 – 361Combined sources4
Helixi362 – 364Combined sources3
Helixi380 – 392Combined sources13
Helixi396 – 421Combined sources26

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H31X-ray2.80A1-425[»]
ProteinModelPortaliP22234.
SMRiP22234.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22234.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 260SAICAR synthetaseAdd BLAST259
Regioni261 – 266Linker6
Regioni267 – 425AIR carboxylaseAdd BLAST159

Sequence similaritiesi

In the N-terminal section; belongs to the SAICAR synthetase family.Curated
In the C-terminal section; belongs to the AIR carboxylase family. Class II subfamily.Curated

Phylogenomic databases

eggNOGiKOG2835. Eukaryota.
COG0041. LUCA.
COG0152. LUCA.
GeneTreeiENSGT00390000010172.
HOGENOMiHOG000082628.
HOVERGENiHBG008335.
InParanoidiP22234.
KOiK01587.
OMAiWQTKNCA.
OrthoDBiEOG091G08DN.
PhylomeDBiP22234.
TreeFamiTF106384.

Family and domain databases

Gene3Di3.30.470.20. 1 hit.
3.40.50.7700. 1 hit.
HAMAPiMF_02045. PurE_classII. 1 hit.
MF_00137. SAICAR_synth. 1 hit.
InterProiIPR013816. ATP_grasp_subdomain_2.
IPR033626. PurE_classII.
IPR000031. PurE_dom.
IPR028923. SAICAR_synt/ADE2_N.
IPR018236. SAICAR_synthetase_CS.
[Graphical view]
PfamiPF00731. AIRC. 1 hit.
PF01259. SAICAR_synt. 1 hit.
[Graphical view]
SMARTiSM01001. AIRC. 1 hit.
[Graphical view]
SUPFAMiSSF52255. SSF52255. 1 hit.
TIGRFAMsiTIGR01162. purE. 1 hit.
PROSITEiPS01057. SAICAR_SYNTHETASE_1. 1 hit.
PS01058. SAICAR_SYNTHETASE_2. 1 hit.
[Graphical view]

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: P22234-1) [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
MATAEVLNIG KKLYEGKTKE VYELLDSPGK VLLQSKDQIT AGNAARKNHL
60 70 80 90 100
EGKAAISNKI TSCIFQLLQE AGIKTAFTRK CGETAFIAPQ CEMIPIEWVC
110 120 130 140 150
RRIATGSFLK RNPGVKEGYK FYPPKVELFF KDDANNDPQW SEEQLIAAKF
160 170 180 190 200
CFAGLLIGQT EVDIMSHATQ AIFEILEKSW LPQNCTLVDM KIEFGVDVTT
210 220 230 240 250
KEIVLADVID NDSWRLWPSG DRSQQKDKQS YRDLKEVTPE GLQMVKKNFE
260 270 280 290 300
WVAERVELLL KSESQCRVVV LMGSTSDLGH CEKIKKACGN FGIPCELRVT
310 320 330 340 350
SAHKGPDETL RIKAEYEGDG IPTVFVAVAG RSNGLGPVMS GNTAYPVISC
360 370 380 390 400
PPLTPDWGVQ DVWSSLRLPS GLGCSTVLSP EGSAQFAAQI FGLSNHLVWS
410 420
KLRASILNTW ISLKQADKKI RECNL
Length:425
Mass (Da):47,079
Last modified:January 23, 2007 - v3
Checksum:iE08CF19BC8898F29
GO
Isoform 2 (identifier: P22234-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     72-72: G → VTSYKSNR

Show »
Length:432
Mass (Da):47,958
Checksum:i1F8F3B240AD1C137
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti217W → R in CAH18683 (PubMed:17974005).Curated1
Sequence conflicti340S → T in CAH18683 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051884201K → N.Corresponds to variant rs11549976dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04126572G → VTSYKSNR in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53793 mRNA. Translation: CAA37801.1.
BT006988 mRNA. Translation: AAP35634.1.
CR749824 mRNA. Translation: CAH18683.1.
AC068620 Genomic DNA. No translation available.
AC114766 Genomic DNA. No translation available.
BC010273 mRNA. Translation: AAH10273.1.
BC019255 mRNA. Translation: AAH19255.1.
CCDSiCCDS47060.1. [P22234-2]
CCDS47061.1. [P22234-1]
PIRiS14147.
RefSeqiNP_001072992.1. NM_001079524.1. [P22234-1]
NP_001072993.1. NM_001079525.1. [P22234-2]
NP_006443.1. NM_006452.3. [P22234-1]
UniGeneiHs.518774.
Hs.709570.

Genome annotation databases

EnsembliENST00000264221; ENSP00000264221; ENSG00000128050. [P22234-1]
ENST00000399688; ENSP00000382595; ENSG00000128050. [P22234-2]
ENST00000512576; ENSP00000421096; ENSG00000128050. [P22234-1]
GeneIDi10606.
KEGGihsa:10606.
UCSCiuc003hbs.1. human. [P22234-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53793 mRNA. Translation: CAA37801.1.
BT006988 mRNA. Translation: AAP35634.1.
CR749824 mRNA. Translation: CAH18683.1.
AC068620 Genomic DNA. No translation available.
AC114766 Genomic DNA. No translation available.
BC010273 mRNA. Translation: AAH10273.1.
BC019255 mRNA. Translation: AAH19255.1.
CCDSiCCDS47060.1. [P22234-2]
CCDS47061.1. [P22234-1]
PIRiS14147.
RefSeqiNP_001072992.1. NM_001079524.1. [P22234-1]
NP_001072993.1. NM_001079525.1. [P22234-2]
NP_006443.1. NM_006452.3. [P22234-1]
UniGeneiHs.518774.
Hs.709570.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H31X-ray2.80A1-425[»]
ProteinModelPortaliP22234.
SMRiP22234.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115852. 82 interactors.
IntActiP22234. 28 interactors.
MINTiMINT-5006326.
STRINGi9606.ENSP00000382595.

Chemistry databases

ChEMBLiCHEMBL5922.
DrugBankiDB00128. L-Aspartic Acid.

PTM databases

iPTMnetiP22234.
PhosphoSitePlusiP22234.
SwissPalmiP22234.

Polymorphism and mutation databases

BioMutaiPAICS.
DMDMi131628.

Proteomic databases

EPDiP22234.
MaxQBiP22234.
PaxDbiP22234.
PeptideAtlasiP22234.
PRIDEiP22234.

Protocols and materials databases

DNASUi10606.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264221; ENSP00000264221; ENSG00000128050. [P22234-1]
ENST00000399688; ENSP00000382595; ENSG00000128050. [P22234-2]
ENST00000512576; ENSP00000421096; ENSG00000128050. [P22234-1]
GeneIDi10606.
KEGGihsa:10606.
UCSCiuc003hbs.1. human. [P22234-1]

Organism-specific databases

CTDi10606.
DisGeNETi10606.
GeneCardsiPAICS.
HGNCiHGNC:8587. PAICS.
HPAiHPA035895.
HPA041538.
MIMi172439. gene.
neXtProtiNX_P22234.
OpenTargetsiENSG00000128050.
PharmGKBiPA32914.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2835. Eukaryota.
COG0041. LUCA.
COG0152. LUCA.
GeneTreeiENSGT00390000010172.
HOGENOMiHOG000082628.
HOVERGENiHBG008335.
InParanoidiP22234.
KOiK01587.
OMAiWQTKNCA.
OrthoDBiEOG091G08DN.
PhylomeDBiP22234.
TreeFamiTF106384.

Enzyme and pathway databases

UniPathwayiUPA00074; UER00130.
UPA00074; UER00131.
BioCyciMetaCyc:HS05155-MONOMER.
ZFISH:HS05155-MONOMER.
ReactomeiR-HSA-73817. Purine ribonucleoside monophosphate biosynthesis.

Miscellaneous databases

ChiTaRSiPAICS. human.
EvolutionaryTraceiP22234.
GenomeRNAii10606.
PROiP22234.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128050.
CleanExiHS_PAICS.
ExpressionAtlasiP22234. baseline and differential.
GenevisibleiP22234. HS.

Family and domain databases

Gene3Di3.30.470.20. 1 hit.
3.40.50.7700. 1 hit.
HAMAPiMF_02045. PurE_classII. 1 hit.
MF_00137. SAICAR_synth. 1 hit.
InterProiIPR013816. ATP_grasp_subdomain_2.
IPR033626. PurE_classII.
IPR000031. PurE_dom.
IPR028923. SAICAR_synt/ADE2_N.
IPR018236. SAICAR_synthetase_CS.
[Graphical view]
PfamiPF00731. AIRC. 1 hit.
PF01259. SAICAR_synt. 1 hit.
[Graphical view]
SMARTiSM01001. AIRC. 1 hit.
[Graphical view]
SUPFAMiSSF52255. SSF52255. 1 hit.
TIGRFAMsiTIGR01162. purE. 1 hit.
PROSITEiPS01057. SAICAR_SYNTHETASE_1. 1 hit.
PS01058. SAICAR_SYNTHETASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPUR6_HUMAN
AccessioniPrimary (citable) accession number: P22234
Secondary accession number(s): E9PDH9, Q68CQ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 180 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 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. 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.