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    CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase [ Homo sapiens (human) ]

    Gene ID: 790, updated on 27-Nov-2024

    Summary

    Official Symbol
    CADprovided by HGNC
    Official Full Name
    carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotaseprovided by HGNC
    Primary source
    HGNC:HGNC:1424
    See related
    Ensembl:ENSG00000084774 MIM:114010; AllianceGenome:HGNC:1424
    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
    CDG1Z; DEE50; GATD4; EIEE50
    Summary
    The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II), aspartate transcarbamoylase, and dihydroorotase. This protein is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of the MAPK cascade and de novo biosynthesis of pyrimidine nucleotides. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
    Expression
    Ubiquitous expression in testis (RPKM 7.3), ovary (RPKM 6.7) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CAD in Genome Data Viewer
    Location:
    2p23.3
    Exon count:
    45
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (27217369..27243943)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (27259008..27285579)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (27440237..27466811)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15492 Neighboring gene transcription factor 23 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15493 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11288 Neighboring gene Sharpr-MPRA regulatory region 2640 Neighboring gene MPRA-validated peak3631 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:27432993-27433790 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11289 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11290 Neighboring gene solute carrier family 5 member 6 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11291 Neighboring gene all-trans retinoic acid induced differentiation factor Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:27454350-27455549 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:27465505-27466704 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:27472326-27473120 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:27473121-27473914 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11292 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11293 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11294 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11295 Neighboring gene solute carrier family 30 member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11296 Neighboring gene DnaJ heat shock protein family (Hsp40) member C5 gamma Neighboring gene tripartite motif containing 54 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:27524348-27524553 Neighboring gene urocortin

    Genomic regions, transcripts, and products

    Expression

    • Project title: 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify carbamoyl-phosphate synthetase 2 (CAD), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify carbamoyl-phosphate synthetase 2 (CAD), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Nef nef Tandem affinity purification and mass spectrometry analysis identify carbamoyl-phosphate synthetase 2 (CAD), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Pr55(Gag) gag Tandem affinity purification and mass spectrometry analysis identify carbamoyl-phosphate synthetase 2 (CAD), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Vif vif HIV-1 Vif interacts with CAD; interaction predicted to be relevant to purine pyrimidine biosynthesis PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables aspartate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables aspartate carbamoyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables aspartate carbamoyltransferase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables carbamoyl-phosphate synthase (ammonia) activity IEA
    Inferred from Electronic Annotation
    more info
     
    contributes_to carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables dihydroorotase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables dihydroorotase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables dihydroorotase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables glutaminase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables identical protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in 'de novo' UMP biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in 'de novo' UMP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in 'de novo' pyrimidine nucleobase biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in 'de novo' pyrimidine nucleobase biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in 'de novo' pyrimidine nucleobase biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in UDP biosynthetic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in UTP biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in animal organ regeneration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to epidermal growth factor stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in citrulline biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in female pregnancy IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in glutamine metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in glutamine metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in heart development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in lactation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in liver development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in peptidyl-threonine phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in protein autophosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to amine IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to caffeine IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to cortisol IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to insulin IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to starvation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to testosterone IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in xenobiotic metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in cell projection ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol 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 
    located_in neuronal cell body ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in nuclear matrix IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of protein-containing complex IEA
    Inferred from Electronic Annotation
    more info
     
    located_in terminal bouton ISS
    Inferred from Sequence or Structural Similarity
    more info
     

    General protein information

    Preferred Names
    multifunctional protein CAD
    Names
    CAD trifunctional protein
    carbamoyl phosphate synthetase 2-aspartate transcarbamylase-dihydroorotase
    NP_001293008.1
    NP_004332.2
    XP_006712164.1
    XP_047301759.1
    XP_054199815.1
    XP_054199816.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_046394.1 RefSeqGene

      Range
      4980..31554
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001306079.2NP_001293008.1  multifunctional protein CAD isoform 2

      See identical proteins and their annotated locations for NP_001293008.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. It encodes isoform 2 which is shorter than isoform 1.
      Source sequence(s)
      AC013403, AC013413, AK226105, BC065510, BG766243, BQ447516
      Consensus CDS
      CCDS77396.1
      UniProtKB/TrEMBL
      F8VPD4, Q53SY7
      Related
      ENSP00000384510.1, ENST00000403525.5
      Conserved Domains (4) summary
      PRK00856
      Location:18572161
      pyrB; aspartate carbamoyltransferase catalytic subunit
      PRK12564
      Location:1355
      PRK12564; carbamoyl-phosphate synthase small subunit
      cd01316
      Location:13971743
      CAD_DHOase; The eukaryotic CAD protein is a trifunctional enzyme of carbamoylphosphate synthetase-aspartate transcarbamoylase-dihydroorotase, which catalyzes the first three steps of de novo pyrimidine nucleotide biosynthesis. Dihydroorotase (DHOase) catalyzes the ...
      TIGR01369
      Location:3911377
      CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit
    2. NM_004341.5NP_004332.2  multifunctional protein CAD isoform 1

      See identical proteins and their annotated locations for NP_004332.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC013403, AC013413, BC065510, BM927624, BQ447516, BU541191, BU558264, D78586
      Consensus CDS
      CCDS1742.1
      UniProtKB/Swiss-Prot
      D6W552, P27708, Q6P0Q0, Q96CK3
      UniProtKB/TrEMBL
      Q53SY7
      Related
      ENSP00000264705.3, ENST00000264705.9
      Conserved Domains (13) summary
      cd01744
      Location:178354
      GATase1_CPSase; Small chain of the glutamine-dependent form of carbamoyl phosphate synthase, CPSase II
      PRK09060
      Location:14291810
      PRK09060; dihydroorotase; Validated
      PRK00856
      Location:19202224
      pyrB; aspartate carbamoyltransferase catalytic subunit; Provisional
      PRK12564
      Location:1355
      PRK12564; carbamoyl phosphate synthase small subunit; Reviewed
      cd01316
      Location:14601806
      CAD_DHOase; The eukaryotic CAD protein is a trifunctional enzyme of carbamoylphosphate synthetase-aspartate transcarbamoylase-dihydroorotase, which catalyzes the first three steps of de novo pyrimidine nucleotide biosynthesis. Dihydroorotase (DHOase) catalyzes the ...
      cd01423
      Location:13131438
      MGS_CPS_I_III; Methylglyoxal synthase-like domain found in pyr1 and URA1-like carbamoyl phosphate synthetases (CPS), including ammonia-dependent CPS Type I, and glutamine-dependent CPS Type III. These are multidomain proteins, in which MGS is the C-terminal domain.
      TIGR01369
      Location:3911440
      CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit
      pfam00185
      Location:20722221
      OTCace; Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain
      pfam00988
      Location:2138
      CPSase_sm_chain; Carbamoyl-phosphate synthase small chain, CPSase domain
      pfam02729
      Location:19252065
      OTCace_N; Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain
      pfam02786
      Location:514716
      CPSase_L_D2; Carbamoyl-phosphate synthase L chain, ATP binding domain
      pfam02787
      Location:801921
      CPSase_L_D3; Carbamoyl-phosphate synthetase large chain, oligomerization domain
      cl17255
      Location:10481245
      ATP-grasp_4; ATP-grasp domain

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      27217369..27243943
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047445803.1XP_047301759.1  multifunctional protein CAD isoform X1

    2. XM_006712101.4XP_006712164.1  multifunctional protein CAD isoform X2

      UniProtKB/TrEMBL
      Q53SY7
      Conserved Domains (12) summary
      cd01744
      Location:178354
      GATase1_CPSase; Small chain of the glutamine-dependent form of carbamoyl phosphate synthase, CPSase II
      PRK09060
      Location:13661747
      PRK09060; dihydroorotase; Validated
      PRK00856
      Location:18742178
      pyrB; aspartate carbamoyltransferase catalytic subunit; Provisional
      PRK12564
      Location:1355
      PRK12564; carbamoyl phosphate synthase small subunit; Reviewed
      cd01316
      Location:13971743
      CAD_DHOase; The eukaryotic CAD protein is a trifunctional enzyme of carbamoylphosphate synthetase-aspartate transcarbamoylase-dihydroorotase, which catalyzes the first three steps of de novo pyrimidine nucleotide biosynthesis. Dihydroorotase (DHOase) catalyzes the ...
      cd01423
      Location:12501375
      MGS_CPS_I_III; Methylglyoxal synthase-like domain found in pyr1 and URA1-like carbamoyl phosphate synthetases (CPS), including ammonia-dependent CPS Type I, and glutamine-dependent CPS Type III. These are multidomain proteins, in which MGS is the C-terminal domain.
      TIGR01369
      Location:3911377
      CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit
      pfam00185
      Location:20262175
      OTCace; Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain
      pfam00988
      Location:2138
      CPSase_sm_chain; Carbamoyl-phosphate synthase small chain, CPSase domain
      pfam02729
      Location:18792019
      OTCace_N; Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain
      pfam02787
      Location:738858
      CPSase_L_D3; Carbamoyl-phosphate synthetase large chain, oligomerization domain
      cl17255
      Location:514653
      ATP-grasp_4; ATP-grasp domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      27259008..27285579
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343840.1XP_054199815.1  multifunctional protein CAD isoform X1

    2. XM_054343841.1XP_054199816.1  multifunctional protein CAD isoform X2