CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase [Homo sapiens] - Gene

Help top of page

Summary

Official Symbol: CADprovided by HGNC
Official Full Name: carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotaseprovided by HGNC
Primary source: HGNC:1424
See related: Ensembl:ENSG00000084774; HPRD:06437; MIM:114010; Vega:OTTHUMG00000097070
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
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. [provided by RefSeq, Jul 2008]

Help top of page

Genomic context

Location :: 2p22-p21

Sequence :: Chromosome: 2; NC_000002.11 (27440258..27466654)

See CAD in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

findings show that in prostate tumor cells, CAD fosters androgen receptor translocation into the nucleus and stimulates its transcriptional activity; in radical prostatectomy specimens, CAD expression was not correlated with proliferation markers, but ...
Title: Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
hCPS_DeltaA was not able to fully assume the catalytically competent conformation, with specific activity of CP formation decreased 700-fold.
Title: Human carbamoyl-phosphate synthetase: insight into N-acetylglutamate interaction and the functional effects of a common single nucleotide polymorphism.
Observational study of gene-disease association. (HuGE Navigator)
Title: Candidate genes associated with ageing and life expectancy in the Jerusalem longitudinal study.
the cad gene is regulated by a nonclassical ERalpha/Sp1-mediated pathway.
Title: Estrogen receptor/Sp1 complexes are required for induction of cad gene expression by 17beta-estradiol in breast cancer cells.
the nuclear import of CAD appears to promote optimal cell growth
Title: Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD.
Data show that PRMT5 can be found in association with hSWI/SNF complexes and is involved in regulating the expression of carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase.
Title: mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad.
cad gene expression is repressed by hypoxia-inducible factor-1alpha, which represents a functional link between hypoxia and cell-cycle arrest.
Title: Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha.

Submit: New GeneRIF Correction

Help top of page

Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Help top of page

Products	Interactant	Other Gene	Source	Pubs	Description
P27708	P27708	CAD	HPRD	PubMed
P27708	P42574	CASP3	HPRD	PubMed
P27708	P28482	MAPK1	HPRD	PubMed
P27708	P62136	PPP1CA	HPRD	PubMed
P27708	Protein phosphatase 2A, catalytic subunit, alpha isoform	PPP2CA	HPRD	PubMed
P27708	P17612	PRKACA	HPRD	PubMed
P27708	P61981	YWHAG	HPRD	PubMed
BioGRID:107243	BioGRID:971788	EBNA-LP	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107243	BioGRID:115331	HDAC5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107243	BioGRID:115761	NCOA2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107243	BioGRID:110811	NEDD4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107243	BioGRID:111822	RAD21	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107243	BioGRID:113188	SUMO1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107243	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107243	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

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	ISS Inferred from Sequence or Structural Similarity more info
aspartate carbamoyltransferase activity	TAS Traceable Author Statement more info
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity	ISS Inferred from Sequence or Structural Similarity more info
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity	TAS Traceable Author Statement more info
dihydroorotase activity	ISS Inferred from Sequence or Structural Similarity more info
dihydroorotase activity	TAS Traceable Author Statement more info
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
ligase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
'de novo' pyrimidine base biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
carbamoyl phosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
cellular amino acid metabolic process	IEA Inferred from Electronic Annotation more info
drug metabolic process	ISS Inferred from Sequence or Structural Similarity more info
embryo development	IEA Inferred from Electronic Annotation more info
female pregnancy	IEA Inferred from Electronic Annotation more info
glutamine catabolic process	IEA Inferred from Electronic Annotation more info
glutamine metabolic process	ISS Inferred from Sequence or Structural Similarity more info
nitrogen compound metabolic process	IEA Inferred from Electronic Annotation more info
nucleobase-containing small molecule metabolic process	TAS Traceable Author Statement more info
organ regeneration	IEA Inferred from Electronic Annotation more info
peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
pyrimidine base metabolic process	TAS Traceable Author Statement more info
pyrimidine nucleoside biosynthetic process	TAS Traceable Author Statement more info
pyrimidine nucleotide biosynthetic process	IEA Inferred from Electronic Annotation more info
response to amine stimulus	IEA Inferred from Electronic Annotation more info
response to caffeine	IEA Inferred from Electronic Annotation more info
response to testosterone stimulus	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cell projection	ISS Inferred from Sequence or Structural Similarity more info
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
nuclear matrix	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
protein complex	IEA Inferred from Electronic Annotation more info
soluble fraction	IEA Inferred from Electronic Annotation more info
terminal button	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Preferred Names: CAD protein

Names: CAD protein; CAD trifunctional protein; multifunctional protein CAD

NP_004332.2

EC 2.1.3.2

EC 3.5.2.3

EC 6.3.5.5

Help top of page

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.

mRNA and Protein(s)

NM_004341.3 → NP_004332.2 CAD protein

Status: REVIEWED

Source sequence(s)

BC065510, BM927624, BU541191, BU558264, D78586

Consensus CDS

CCDS1742.1

UniProtKB/Swiss-Prot

P27708

Related

ENSP00000264705, OTTHUMP00000122585, ENST00000264705, OTTHUMT00000214186

Conserved Domains (13) summary

cd01423
Location:1313 – 1438
Blast Score: 349

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.

cd01316
Location:1460 – 1806
Blast Score: 1435

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 ...

COG0044
Location:1442 – 1804
Blast Score: 756

PyrC; Dihydroorotase and related cyclic amidohydrolases [Nucleotide transport and metabolism]

cd01744
Location:178 – 354
Blast Score: 783

GATase1_CPSase; Small chain of the glutamine-dependent form of carbamoyl phosphate synthase, CPSase II

TIGR01369
Location:391 – 1440
Blast Score: 4184

CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit

PRK00856
Location:1920 – 2224
Blast Score: 1020

pyrB; aspartate carbamoyltransferase catalytic subunit; Provisional

PRK12564
Location:1 – 355
Blast Score: 1264

PRK12564; carbamoyl phosphate synthase small subunit; Reviewed

cl03056
Location:2 – 138
Blast Score: 595

CPSase_sm_chain; Carbamoyl-phosphate synthase small chain, CPSase domain

pfam00289
Location:935 – 1041
Blast Score: 211

CPSase_L_chain; Carbamoyl-phosphate synthase L chain, N-terminal domain

pfam02729
Location:1924 – 2066
Blast Score: 484

OTCace_N; Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain

pfam02787
Location:801 – 921
Blast Score: 435

CPSase_L_D3; Carbamoyl-phosphate synthetase large chain, oligomerisation domain

cl03087
Location:1047 – 1223
Blast Score: 152

ATP-grasp_4; ATP-grasp domain

cl09931
Location:2071 – 2221
Blast Score: 431

NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p5 Primary Assembly

Range

27440258..27466654

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

27181964..27208360

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC013403.9	AAX93165.1
genomic	AC013413.6	AAY24293.1
genomic	CH471053.2	EAX00612.1
		EAX00613.1
		EAX00614.1
genomic	M38561.1	AAA51907.1
mRNA	AB621827.1	BAK64162.1
mRNA	AK226105.1	None
mRNA	BC014178.2	AAH14178.2
mRNA	BC065510.1	AAH65510.1
mRNA	BM927624.1	None
mRNA	BU541191.1	None
mRNA	BU558264.1	None
mRNA	D78586.1	BAA11423.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P27708.3	GenPept	UniProtKB/Swiss-Prot:P27708
Q53SY7	GenPept	UniProtKB/TrEMBL:Q53SY7
Q53SZ4	GenPept	UniProtKB/TrEMBL:Q53SZ4
Q96CK3	GenPept	UniProtKB/TrEMBL:Q96CK3