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FLASH GENE

Symbol

CAD

contributors: mct - updated : 15-01-2019

HGNC name	carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
HGNC id	1424

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node       highly Visual eye       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly

cell lineage
cell lines	cell lines deficient in MLH1 or MSH6
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains

conjugated

PhosphoP

mono polymer

homomer , hexamer

HOMOLOGY

interspecies

homolog to C.elegans D2085.1

Homologene

FAMILY

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	nuclear import of CAD appears to promote optimal cell growth

basic FUNCTION	catalyzing the first steps of the pyrimidine de novo biosynthesis among them, Cpsase is the rate-limiting step in this pathway
	multifunctional protein that initiates and regulates de novo pyrimidine biosynthesis
	aspartate transcarbamylase (atcase)
	dihydroorotase (dhoase)
	glutamine amidotransferase (gatase)
	gatase and cpsase form together the glutamine-dependent cpase activity (gd-cpasase)
	required for de novo pyrimidine nucleotide synthesis
	multifunctional polypeptide that catalyzes the first three reactions of de novo pyrimidine biosynthesis: glutamine-dependent carbamyl phosphate synthetase, aspartate transcarbamylase and dihydroorotase (DHO)
	CAD enzymatic activity decreased in the cells depleted of amino acids and serum, in which the mTOR activity is suppressed
	up-regulation of CAD is essential for normal and tumour cell proliferation
	CAD is a downstream effector of RHEB, suggesting a possible role of RHEB in regulating de novo pyrimidine nucleotide synthesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

purine/pyrimidine

signaling

pyrimidine nucleotide metabolism

a component

INTERACTION

DNA

RNA

small molecule	cofactor,
	zinc Zn2+ for dhoase activity

protein	NOD2-interacting protein (negative regulator of NOD2)
	MLST8 bridges between CAD and MTOR, and plays a role in the signaling mechanism where CAD is regulated in the MTOR pathway through the association with MLST8
	RHEB proteins binds to CAD protein (RHEB and RHEBL1 binds CAD in a GTP- and effector domain-dependent manner)

cell & other

REGULATION

activated by	EGF-dependent and phosphorylation
	PRPP for Cpsase activity

inhibited by

UMP for Cpsase activity

repressed by	12-O-tetradecanoylphorbol-13-acetate and trans-retinoic acid and dibutyrol cyclic AMP
		by HIF-1alpha, which represents a functional link between hypoxia and cell-cycle arrest

Other	regulated by mitogen-activated protein kinase (MAPK) cascade
	regulated by allostery

ASSOCIATED DISORDERS

corresponding disease(s)

EIEE50

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in the intestinal epithelium of patients with Crohn disease compared with controls

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	potential predictive marker of prostate cancer relapse
Therapy target
	System Type Disorder Pubmed immunology inflammatory   potential therapeutic target for Crohn disease

ANIMAL & CELL MODELS