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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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