PAICS

Protein identityUniProt · HPA

UniProt accession

P22234

Gene

PAICS

Ensembl

ENSG00000128050

Chromosome

4

Canonical length

425 aa

Protein class

Disease related genes, Enzymes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

Quaternary structure

Homooctamer

OverviewNCBI Gene

This gene encodes a bifunctional enzyme containing phosphoribosylaminoimidazole carboxylase activity in its N-terminal region and phosphoribosylaminoimidazole succinocarboxamide synthetase in its C-terminal region. It catalyzes steps 6 and 7 of purine biosynthesis. The gene is closely linked and divergently transcribed with a locus that encodes an enzyme in the same pathway, and transcription of the two genes is coordinately regulated. The human genome contains several pseudogenes of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

425 residues, UniProt reviewed canonical sequence.

>P22234|PAICS
     1  MATAEVLNIG KKLYEGKTKE VYELLDSPGK VLLQSKDQIT AGNAARKNHL EGKAAISNKI
    61  TSCIFQLLQE AGIKTAFTRK CGETAFIAPQ CEMIPIEWVC RRIATGSFLK RNPGVKEGYK
   121  FYPPKVELFF KDDANNDPQW SEEQLIAAKF CFAGLLIGQT EVDIMSHATQ AIFEILEKSW
   181  LPQNCTLVDM KIEFGVDVTT KEIVLADVID NDSWRLWPSG DRSQQKDKQS YRDLKEVTPE
   241  GLQMVKKNFE WVAERVELLL KSESQCRVVV LMGSTSDLGH CEKIKKACGN FGIPCELRVT
   301  SAHKGPDETL RIKAEYEGDG IPTVFVAVAG RSNGLGPVMS GNTAYPVISC PPLTPDWGVQ
   361  DVWSSLRLPS GLGCSTVLSP EGSAQFAAQI FGLSNHLVWS KLRASILNTW ISLKQADKKI
   421  RECNL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PAICS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

103 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PAICS.

Disease | AllUniProt

Conditions PAICS is implicated in, by any mechanism.

• Phosphoribosylaminoimidazole carboxylase deficiency (PAICSD) MIM:619859

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 55 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Phosphoribosylaminoimidazole carboxylase deficiency
• Fetal anomalies with a likely genetic cause

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.83

gnomAD pLI

0

gnomAD missense Z

1.13

DepMap mean gene effect

-0.62

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• 'de novo' AMP biosynthetic process
• 'de novo' IMP biosynthetic process
• 'de novo' XMP biosynthetic process
• GMP biosynthetic process
• purine nucleobase biosynthetic process

Molecular functions

• ATP binding
• cadherin binding
• identical protein binding
• phosphoribosylaminoimidazole carboxylase activity
• phosphoribosylaminoimidazolesuccinocarboxamide synthase activity

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• membrane

Protein domainsUniProt · Pfam · InterPro

• PurE domain
• SAICAR synthetase, conserved site
• SAICAR synthetase/ADE2, N-terminal
• Class II PurE
• AIR carboxylase
• SAICAR synthetase

KeywordsUniProt

• Acetylation
• ATP-binding
• Decarboxylase
• Ligase
• Lyase
• Multifunctional enzyme
• Nucleotide-binding
• Phosphoprotein
• Purine biosynthesis

InteractionsUniProt · HPA

Protein binding partners of PAICS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ACTR2
• FXR2