Human Gene CAD (ENST00000264705.9_4) from GENCODE V47lift37
  Description: carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, transcript variant 1 (from RefSeq NM_004341.5)
Gencode Transcript: ENST00000264705.9_4
Gencode Gene: ENSG00000084774.14_11
Transcript (Including UTRs)
   Position: hg19 chr2:27,440,237-27,466,811 Size: 26,575 Total Exon Count: 44 Strand: +
Coding Region
   Position: hg19 chr2:27,440,420-27,466,386 Size: 25,967 Coding Exon Count: 44 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:27,440,237-27,466,811)mRNA (may differ from genome)Protein (2225 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGeneCardsHGNC
MalacardsMGIOMIMPubMedReactomeUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PYR1_HUMAN
DESCRIPTION: RecName: Full=CAD protein; Includes: RecName: Full=Glutamine-dependent carbamoyl-phosphate synthase; EC=6.3.5.5; Includes: RecName: Full=Aspartate carbamoyltransferase; EC=2.1.3.2; Includes: RecName: Full=Dihydroorotase; EC=3.5.2.3;
FUNCTION: This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
CATALYTIC ACTIVITY: 2 ATP + L-glutamine + HCO(3)(-) + H(2)O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate.
CATALYTIC ACTIVITY: Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate.
CATALYTIC ACTIVITY: (S)-dihydroorotate + H(2)O = N-carbamoyl-L- aspartate.
COFACTOR: Binds 1 zinc ion per subunit (for dihydroorotase activity) (Potential).
ENZYME REGULATION: Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate is an activator while UMP is an inhibitor of the CPSase reaction.
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3.
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3.
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3.
SUBUNIT: Homohexamer.
SUBCELLULAR LOCATION: Cytoplasm.
MISCELLANEOUS: GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine- dependent CPSase (GD-CPSase) (EC 6.3.5.5).
SIMILARITY: In the central section; belongs to the DHOase family.
SIMILARITY: Contains 2 ATP-grasp domains.
SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain.
WEB RESOURCE: Name=Wikipedia; Note=Aspartate carbamoyltransferase entry; URL="http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: CAD
Diseases sorted by gene-association score: epileptic encephalopathy, early infantile, 50* (1580)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 17.09 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 341.35 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -53.50183-0.292 Picture PostScript Text
3' UTR -152.00425-0.358 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006132 - Asp/Orn_carbamoyltranf_P-bd
IPR006130 - Asp/Orn_carbamoylTrfase
IPR002082 - Asp_carbamoyltransf
IPR006131 - Asp_carbamoyltransf_Asp/Orn-bd
IPR011761 - ATP-grasp
IPR013815 - ATP_grasp_subdomain_1
IPR013816 - ATP_grasp_subdomain_2
IPR006275 - CarbamoylP_synth_lsu
IPR005481 - CarbamoylP_synth_lsu_N
IPR005480 - CarbamoylP_synth_lsu_oligo
IPR006274 - CarbamoylP_synth_ssu
IPR002474 - CarbamoylP_synth_ssu_N
IPR005479 - CbamoylP_synth_lsu-like_ATP-bd
IPR005483 - CbamoylP_synth_lsu_CPSase_dom
IPR002195 - Dihydroorotase_CS
IPR017926 - GATASE_1
IPR011059 - Metal-dep_hydrolase_composite
IPR011607 - MGS-like_dom
IPR016185 - PreATP-grasp_fold

Pfam Domains:
PF00117 - Glutamine amidotransferase class-I
PF00185 - Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain
PF00988 - Carbamoyl-phosphate synthase small chain, CPSase domain
PF01979 - Amidohydrolase family
PF02142 - MGS-like domain
PF02222 - ATP-grasp domain
PF02729 - Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain
PF02786 - Carbamoyl-phosphate synthase L chain, ATP binding domain
PF02787 - Carbamoyl-phosphate synthetase large chain, oligomerisation domain
PF07478 - D-ala D-ala ligase C-terminus

SCOP Domains:
48108 - Carbamoyl phosphate synthetase, large subunit connection domain
51338 - Composite domain of metallo-dependent hydrolases
51556 - Metallo-dependent hydrolases
51735 - NAD(P)-binding Rossmann-fold domains
52317 - Class I glutamine amidotransferase-like
52335 - Methylglyoxal synthase-like
52440 - PreATP-grasp domain
51984 - MurCD N-terminal domain
53671 - Aspartate/ornithine carbamoyltransferase
52021 - Carbamoyl phosphate synthetase, small subunit N-terminal domain
56059 - Glutathione synthetase ATP-binding domain-like

ModBase Predicted Comparative 3D Structure on P27708
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologGenome BrowserGenome Browser
Gene DetailsGene Details Gene DetailsGene DetailsGene Details
Gene SorterGene Sorter Gene SorterGene SorterGene Sorter
 RGDEnsembl WormBaseSGD
    Protein SequenceProtein Sequence
    AlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0004070 aspartate carbamoyltransferase activity
GO:0004087 carbamoyl-phosphate synthase (ammonia) activity
GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
GO:0004151 dihydroorotase activity
GO:0004672 protein kinase activity
GO:0005524 ATP binding
GO:0008270 zinc ion binding
GO:0016597 amino acid binding
GO:0016740 transferase activity
GO:0016743 carboxyl- or carbamoyltransferase activity
GO:0016787 hydrolase activity
GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
GO:0016812 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides
GO:0016874 ligase activity
GO:0019899 enzyme binding
GO:0042802 identical protein binding
GO:0046872 metal ion binding
GO:0070335 aspartate binding

Biological Process:
GO:0000050 urea cycle
GO:0001889 liver development
GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
GO:0006221 pyrimidine nucleotide biosynthetic process
GO:0006228 UTP biosynthetic process
GO:0006520 cellular amino acid metabolic process
GO:0006526 arginine biosynthetic process
GO:0006541 glutamine metabolic process
GO:0006807 nitrogen compound metabolic process
GO:0007507 heart development
GO:0007565 female pregnancy
GO:0007595 lactation
GO:0008152 metabolic process
GO:0014075 response to amine
GO:0017144 drug metabolic process
GO:0018107 peptidyl-threonine phosphorylation
GO:0019240 citrulline biosynthetic process
GO:0031000 response to caffeine
GO:0031100 animal organ regeneration
GO:0032868 response to insulin
GO:0033574 response to testosterone
GO:0035690 cellular response to drug
GO:0042594 response to starvation
GO:0044205 'de novo' UMP biosynthetic process
GO:0046134 pyrimidine nucleoside biosynthetic process
GO:0046777 protein autophosphorylation
GO:0051414 response to cortisol
GO:0071364 cellular response to epidermal growth factor stimulus

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016020 membrane
GO:0016363 nuclear matrix
GO:0032991 macromolecular complex
GO:0042995 cell projection
GO:0043025 neuronal cell body
GO:0043195 terminal bouton
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  BC065510 - Homo sapiens carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, mRNA (cDNA clone MGC:74758 IMAGE:5551082), complete cds.
AK226105 - Homo sapiens mRNA for carbamoylphosphate synthetase 2/aspartate transcarbamylase/dihydroorotase variant, clone: ha00950.
AB621827 - Homo sapiens CAD mRNA for CAD protein, partial cds, clone: HP08891-RBdS015C14.
JD405736 - Sequence 386760 from Patent EP1572962.
D78586 - Homo sapiens CAD mRNA for multifunctional protein CAD, complete cds.
AB384768 - Synthetic construct DNA, clone: pF1KB3244, Homo sapiens CAD gene for CAD protein, complete cds, without stop codon, in Flexi system.
BC014178 - Homo sapiens carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase, mRNA (cDNA clone IMAGE:4580779), partial cds.
JD289704 - Sequence 270728 from Patent EP1572962.
JD326438 - Sequence 307462 from Patent EP1572962.
JD162979 - Sequence 144003 from Patent EP1572962.
JD475782 - Sequence 456806 from Patent EP1572962.
JD459873 - Sequence 440897 from Patent EP1572962.
AL832309 - Homo sapiens mRNA; cDNA DKFZp667L1519 (from clone DKFZp667L1519).
JD064864 - Sequence 45888 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-4984 - urea cycle
PWY-5686 - UMP biosynthesis
PWY-5921 - glutaminyl-tRNAgln biosynthesis via transamidation
PWY-7211 - superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis
PWY0-162 - superpathway of pyrimidine ribonucleotides de novo biosynthesis

BioCarta from NCI Cancer Genome Anatomy Project
h_setPathway - Granzyme A mediated Apoptosis Pathway
h_caspasePathway - Caspase Cascade in Apoptosis
h_mitochondriaPathway - Role of Mitochondria in Apoptotic Signaling
h_deathPathway - Induction of apoptosis through DR3 and DR4/5 Death Receptors
h_tnfr1Pathway - TNFR1 Signaling Pathway
h_fasPathway - FAS signaling pathway ( CD95 )
h_DNAfragmentPathway - Apoptotic DNA fragmentation and tissue homeostasis
h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF

Reactome (by CSHL, EBI, and GO)

Protein P27708 (Reactome details) participates in the following event(s):

R-HSA-73577 L-glutamine + 2 ATP + HCO3- + H2O => carbamoyl phosphate + L-glutamate + 2 ADP + orthophosphate
R-HSA-73573 carbamoyl phosphate + L-aspartate <=> N-carbamoyl L-aspartate + orthophosphate
R-HSA-73571 N-carbamoyl L-aspartate + H+ <=> (S)-dihydroorotate + H2O
R-HSA-500753 Pyrimidine biosynthesis
R-HSA-8956320 Nucleobase biosynthesis
R-HSA-15869 Metabolism of nucleotides
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: CAD , D6W552, ENST00000264705.1, ENST00000264705.2, ENST00000264705.3, ENST00000264705.4, ENST00000264705.5, ENST00000264705.6, ENST00000264705.7, ENST00000264705.8, NM_004341, P27708, PYR1_HUMAN, Q6P0Q0, Q96CK3, uc317huq.1, uc317huq.2
UCSC ID: ENST00000264705.9_4
RefSeq Accession: NM_004341.5
Protein: P27708 (aka PYR1_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.