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PAICS phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase [ Homo sapiens (human) ]

Gene ID: 10606, updated on 3-Nov-2024

Summary

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Official Symbol
PAICSprovided by HGNC
Official Full Name
phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthaseprovided by HGNC
Primary source
HGNC:HGNC:8587
See related
Ensembl:ENSG00000128050 MIM:172439; AllianceGenome:HGNC:8587
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ADE2; AIRC; PAIS; ADE2H1; PAICSD
Summary
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]
Expression
Ubiquitous expression in placenta (RPKM 25.9), appendix (RPKM 25.5) and 25 other tissues See more
Orthologs
all
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Genomic context

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See PAICS in Genome Data Viewer
Location:
4q12
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (56410507..56464578)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (59898501..59952584)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (57276673..57330744)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene RNA, 5S ribosomal pseudogene 162 Neighboring gene aminoadipate-semialdehyde dehydrogenase Neighboring gene ribosomal protein L7a pseudogene 31 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:57253075-57253582 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:57253583-57254089 Neighboring gene phosphoribosyl pyrophosphate amidotransferase Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:57291569-57292254 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15449 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21579 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15450 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:57302513-57303396 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:57325164-57326363 Neighboring gene uncharacterized LOC124900706 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21580 Neighboring gene signal recognition particle 72 Neighboring gene uncharacterized LOC105377665 Neighboring gene ARF like GTPase 9

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Mapping of a locus correcting lack of phosphoribosylaminoimidazole carboxylase activity in Chinese hamster ovary cell Ade-D mutants to human chromosome 4. Barton JW, et al. Genomics, 1991 Feb. PMID 2004782
  2. [Testing the activity of enzymes responsible for biosynthesis of purine nucleotides AIR-carboxylase and SAICAR-synthetase in human cell extracts]. Alenin VV, et al. Vopr Med Khim, 1990 Nov-Dec. PMID 2075724
  3. Multienzyme interactions of the de novo purine biosynthetic protein PAICS facilitate purinosome formation and metabolic channeling. He J, et al. J Biol Chem, 2022 May. PMID 35331738, Free PMC Article
  4. Cloning and sequencing of a human cDNA coding for a multifunctional polypeptide of the purine pathway by complementation of the ade2-101 mutant in Saccharomyces cerevisiae. Minet M, et al. Curr Genet, 1990 Nov. PMID 2253271
  5. PAICS deficiency, a new defect of de novo purine synthesis resulting in multiple congenital anomalies and fatal outcome. Pelet A, et al. Hum Mol Genet, 2019 Nov 15. PMID 31600779

See all (183) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.
    Title: PAICS ubiquitination recruits UBAP2 to trigger phase separation for purinosome assembly.
  2. Multienzyme interactions of the de novo purine biosynthetic protein PAICS facilitate purinosome formation and metabolic channeling.
    Title: Multienzyme interactions of the de novo purine biosynthetic protein PAICS facilitate purinosome formation and metabolic channeling.
  3. Evidence Supporting Substrate Channeling between Domains of Human PAICS: A Time-Course Analysis of (13)C-Bicarbonate Incorporation.
    Title: Evidence Supporting Substrate Channeling between Domains of Human PAICS: A Time-Course Analysis of (13)C-Bicarbonate Incorporation.
  4. PAICS is related to glioma grade and can promote glioma growth and migration.
    Title: PAICS is related to glioma grade and can promote glioma growth and migration.
  5. Regulating COX10-AS1 / miR-142-5p / PAICS axis inhibits the proliferation of non-small cell lung cancer.
    Title: Regulating COX10-AS1 / miR-142-5p / PAICS axis inhibits the proliferation of non-small cell lung cancer.
  6. PAICS contributes to gastric carcinogenesis and participates in DNA damage response by interacting with histone deacetylase 1/2.
    Title: PAICS contributes to gastric carcinogenesis and participates in DNA damage response by interacting with histone deacetylase 1/2.
  7. Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.
    Title: Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.
  8. Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy.
    Title: Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy.
  9. PAICS is hypomethylated in the lung adenocarcinoma tissues.PAICS is highly expressed in the lung adenocarcinoma tissues.
    Title: Roles of highly expressed PAICS in lung adenocarcinoma.
  10. we show that PAICS, which catalyzes a critical step in purine biosynthetic pathway, is overexpressed and plays a role in BLCA cell proliferation, colony formation, and 3D spheroid invasion, suggesting a role in oncogenesis.
    Title: A Role for De Novo Purine Metabolic Enzyme PAICS in Bladder Cancer Progression.
Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Phosphoribosylaminoimidazole carboxylase deficiency
MedGen: C1291561 OMIM: 619859 GeneReviews: Not available
not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat 47-59 peptide upregulates gene expression of phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) in U-937 macrophages PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC1343, MGC5024, FLJ42646, DKFZp781N1372

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables cadherin binding HDA PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables phosphoribosylaminoimidazole carboxylase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphoribosylaminoimidazole carboxylase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables phosphoribosylaminoimidazolesuccinocarboxamide synthase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables phosphoribosylaminoimidazolesuccinocarboxamide synthase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphoribosylaminoimidazolesuccinocarboxamide synthase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in 'de novo' AMP biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in 'de novo' IMP biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in 'de novo' IMP biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in 'de novo' IMP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in 'de novo' XMP biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in GMP biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in purine nucleobase biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in membrane HDA PubMed 

General protein information

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Preferred Names
bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase
Names
AIR carboxylase
SAICAR synthetase
multifunctional protein ADE2
multifunctional protein ADE2H1
phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase
phosphoribosylaminoimidazole carboxylase; phosphoribosylaminoimidazolesuccinocarboxamide synthase
NP_001072992.1
NP_001072993.1
NP_001378939.1
NP_001378940.1
NP_001378941.1
NP_006443.1
XP_047305483.1
XP_047305484.1
XP_047305485.1
XP_047305486.1
XP_054204749.1
XP_054204750.1
XP_054204751.1
XP_054204752.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001079524.2 → NP_001072992.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform 2

    See identical proteins and their annotated locations for NP_001072992.1

    Status: REVIEWED

    Source sequence(s)
    AA669362, AC114766, BC019255
    Consensus CDS
    CCDS47061.1
    UniProtKB/Swiss-Prot
    E9PDH9, P22234, Q68CQ5
    UniProtKB/TrEMBL
    E9PBS1
    Related
    ENSP00000421096.1, ENST00000512576.3
    Conserved Domains (2) summary
    cd01416
    Location:7 → 258
    SAICAR_synt_Ade5; Ade5_like 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) synthase
    TIGR01162
    Location:268 → 421
    purE; phosphoribosylaminoimidazole carboxylase, PurE protein

  2. NM_001079525.2 → NP_001072993.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform 1

    Status: REVIEWED

    Source sequence(s)
    AA669362, AC068620, AC114766, BM807012, CR749824
    Consensus CDS
    CCDS47060.1
    UniProtKB/TrEMBL
    E9PBS1
    Related
    ENSP00000382595.3, ENST00000399688.7
    Conserved Domains (2) summary
    cd01416
    Location:7 → 265
    SAICAR_synt_Ade5; Ade5_like 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) synthase
    TIGR01162
    Location:275 → 428
    purE; phosphoribosylaminoimidazole carboxylase, PurE protein

  3. NM_001392010.1 → NP_001378939.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC068620, AC114766
    Conserved Domains (3) summary
    cd01416
    Location:389 → 647
    SAICAR_synt_Ade5; Ade5_like 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) synthase
    TIGR01162
    Location:657 → 810
    purE; phosphoribosylaminoimidazole carboxylase, PurE protein
    pfam13837
    Location:151 → 235
    Myb_DNA-bind_4; Myb/SANT-like DNA-binding domain

  4. NM_001392011.1 → NP_001378940.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC068620, AC114766
    Conserved Domains (3) summary
    cd01416
    Location:361 → 619
    SAICAR_synt_Ade5; Ade5_like 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) synthase
    TIGR01162
    Location:629 → 782
    purE; phosphoribosylaminoimidazole carboxylase, PurE protein
    pfam13837
    Location:151 → 235
    Myb_DNA-bind_4; Myb/SANT-like DNA-binding domain

  5. NM_001392012.1 → NP_001378941.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC068620, AC114766
    Conserved Domains (3) summary
    cd01416
    Location:216 → 467
    SAICAR_synt_Ade5; Ade5_like 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) synthase
    TIGR01162
    Location:477 → 630
    purE; phosphoribosylaminoimidazole carboxylase, PurE protein
    pfam13837
    Location:6 → 91
    Myb_DNA-bind_4; Myb/SANT-like DNA-binding domain

  6. NM_006452.4 → NP_006443.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform 2

    See identical proteins and their annotated locations for NP_006443.1

    Status: REVIEWED

    Source sequence(s)
    AA669362, AC114766, BC010273, CN337183
    Consensus CDS
    CCDS47061.1
    UniProtKB/Swiss-Prot
    E9PDH9, P22234, Q68CQ5
    UniProtKB/TrEMBL
    E9PBS1
    Related
    ENSP00000264221.2, ENST00000264221.6
    Conserved Domains (2) summary
    cd01416
    Location:7 → 258
    SAICAR_synt_Ade5; Ade5_like 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide (SAICAR) synthase
    TIGR01162
    Location:268 → 421
    purE; phosphoribosylaminoimidazole carboxylase, PurE protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    56410507..56464578
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047449527.1 → XP_047305483.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X1

  2. XM_047449528.1 → XP_047305484.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X2

  3. XM_047449530.1 → XP_047305486.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X4

  4. XM_047449529.1 → XP_047305485.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X3

    UniProtKB/Swiss-Prot
    E9PDH9, P22234, Q68CQ5
    Related
    ENSP00000424053.1, ENST00000505164.5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    59898501..59952584
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054348774.1 → XP_054204749.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X1

  2. XM_054348775.1 → XP_054204750.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X2

  3. XM_054348777.1 → XP_054204752.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X4

  4. XM_054348776.1 → XP_054204751.1  bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase isoform X3

    UniProtKB/Swiss-Prot
    E9PDH9, P22234, Q68CQ5
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P22234.3 GenPept UniProtKB/Swiss-Prot:P22234

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