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

Gene ID: 790, updated on 9-Feb-2020

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
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; 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

Genomic context

See CAD in Genome Data Viewer
Location:
2p23.3
Exon count:
45
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (27217369..27243943)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (27440258..27466660)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene transcription factor 23 Neighboring gene solute carrier family 5 member 6 Neighboring gene all-trans retinoic acid induced differentiation factor Neighboring gene solute carrier family 30 member 3 Neighboring gene DnaJ heat shock protein family (Hsp40) member C5 gamma Neighboring gene tripartite motif containing 54 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

Homology

Gene Ontology Provided by GOA

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

General protein information

Preferred Names
CAD protein
Names
CAD trifunctional protein
multifunctional protein CAD
NP_001293008.1
NP_004332.2
XP_006712164.1
XP_024308899.1

NCBI Reference Sequences (RefSeq)

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_001306079.1NP_001293008.1  CAD protein 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)
    AK226105, BC065510, BG766243, BQ447516
    Consensus CDS
    CCDS77396.1
    UniProtKB/Swiss-Prot
    P27708
    UniProtKB/TrEMBL
    F8VPD4
    Related
    ENSP00000384510.1, ENST00000403525.5
    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:18572161
    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:20092158
    OTCace; Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain
    pfam00988
    Location:2138
    CPSase_sm_chain; Carbamoyl-phosphate synthase small chain, CPSase domain
    pfam02729
    Location:18622002
    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
  2. NM_004341.5NP_004332.2  CAD protein 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
    P27708
    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: Homo sapiens Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

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

mRNA and Protein(s)

  1. XM_006712101.3XP_006712164.1  CAD protein isoform X1

    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
  2. XM_024453131.1XP_024308899.1  CAD protein isoform X2

    Conserved Domains (4) summary
    PRK00856
    Location:11791483
    pyrB; aspartate carbamoyltransferase catalytic subunit; Provisional
    cd01316
    Location:7021048
    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 ...
    pfam16612
    Location:10541166
    RGS12_usC; C-terminal unstructured region of RGS12
    cl27719
    Location:1682
    Biotin_carb_N; Biotin carboxylase, N-terminal domain
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