Names & Taxonomy
- Uniprot ID:
- P27708
- Entry Name:
- PYR1_HUMAN
- Status:
- reviewed
- Protein Names:
- CAD protein [Includes: Glutamine-dependent carbamoyl-phosphate synthase (EC 6.3.5.5); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)]
- Gene Names:
- CAD
- Gene Names Primary:
- CAD
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 2225
- Sequence:
- MAALVLEDGSVLRGQPFGAAVSTAGEVVFQTGMVGYPEALTDPSYKAQILVLTYPLIGNYGIPPDEMDEFGLCKWFESSGIHVAALVVGECCPTPSHWSATRTLHEWLQQHGIPGLQGVDTRELTKKLREQGSLLGKLVQNGTEPSSLPFLDPNARPLVPEVSIKTPRVFNTGGAPRILALDCGLKYNQIRCLCQRGAEVTVVPWDHALDSQEYEGLFLSNGPGDPASYPSVVSTLSRVLSEPNPRPVFGICLGHQLLALAIGAKTYKMRYGNRGHNQPCLLVGSGRCFLTSQNHGFAVETDSLPADWAPLFTNANDGSNEGIVHNSLPFFSVQFHPEHQAGPSDMELLFDIFLETVKEATAGNPGGQTVRERLTERLCPPGIPTPGSGLPPPRKVLILGSGGLSIGQAGEFDYSGSQAIKALKEENIQTLLINPNIATVQTSQGLADKVYFLPITPHYVTQVIRNERPDGVLLTFGGQTALNCGVELTKAGVLARYGVRVLGTPVETIELTEDRRAFAARMAEIGEHVAPSEAANSLEQAQAAAERLGYPVLVRAAFALGGLGSGFASNREELSALVAPAFAHTSQVLVDKSLKGWKEIEYEVVRDAYGNCVTVCNMENLDPLGIHTGESIVVAPSQTLNDREYQLLRQTAIKVTQHLGIVGECNVQYALNPESEQYYIIEVNARLSRSSALASKATGYPLAYVAAKLALGIPLPELRNSVTGGTAAFEPSVDYCVVKIPRWDLSKFLRVSTKIGSCMKSVGEVMGIGRSFEEAFQKALRMVDENCVGFDHTVKPVSDMELETPTDKRIFVVAAALWAGYSVDRLYELTRIDRWFLHRMKRIIAHAQLLEQHRGQPLPPDLLQQAKCLGFSDKQIALAVLSTELAVRKLRQELGICPAVKQIDTVAAEWPAQTNYLYLTYWGTTHDLTFRTPHVLVLGSGVYRIGSSVEFDWCAVGCIQQLRKMGYKTIMVNYNPETVSTDYDMCDRLYFDEISFEVVMDIYELENPEGVILSMGGQLPNNMAMALHRQQCRVLGTSPEAIDSAENRFKFSRLLDTIGISQPQWRELSDLESARQFCQTVGYPCVVRPSYVLSGAAMNVAYTDGDLERFLSSAAAVSKEHPVVISKFIQEAKEIDVDAVASDGVVAAIAISEHVENAGVHSGDATLVTPPQDITAKTLERIKAIVHAVGQELQVTGPFNLQLIAKDDQLKVIECNVRVSRSFPFVSKTLGVDLVALATRVIMGEEVEPVGLMTGSGVVGVKVPQFSFSRLAGADVVLGVEMTSTGEVAGFGESRCEAYLKAMLSTGFKIPKKNILLTIGSYKNKSELLPTVRLLESLGYSLYASLGTADFYTEHGVKVTAVDWHFEEAVDGECPPQRSILEQLAEKNFELVINLSMRGAGGRRLSSFVTKGYRTRRLAADFSVPLIIDIKCTKLFVEALGQIGPAPPLKVHVDCMTSQKLVRLPGLIDVHVHLREPGGTHKEDFASGTAAALAGGITMVCAMPNTRPPIIDAPALALAQKLAEAGARCDFALFLGASSENAGTLGTVAGSAAGLKLYLNETFSELRLDSVVQWMEHFETWPSHLPIVAHAEQQTVAAVLMVAQLTQRSVHICHVARKEEILLIKAAKARGLPVTCEVAPHHLFLSHDDLERLGPGKGEVRPELGSRQDVEALWENMAVIDCFASDHAPHTLEEKCGSRPPPGFPGLETMLPLLLTAVSEGRLSLDDLLQRLHHNPRRIFHLPPQEDTYVEVDLEHEWTIPSHMPFSKAHWTPFEGQKVKGTVRRVVLRGEVAYIDGQVLVPPGYGQDVRKWPQGAVPQLPPSAPATSEMTTTPERPRRGIPGLPDGRFHLPPRIHRASDPGLPAEEPKEKSSRKVAEPELMGTPDGTCYPPPPVPRQASPQNLGTPGLLHPQTSPLLHSLVGQHILSVQQFTKDQMSHLFNVAHTLRMMVQKERSLDILKGKVMASMFYEVSTRTSSSFAAAMARLGGAVLSFSEATSSVQKGESLADSVQTMSCYADVVVLRHPQPGAVELAAKHCRRPVINAGDGVGEHPTQALLDIFTIREELGTVNGMTITMVGDLKHGRTVHSLACLLTQYRVSLRYVAPPSLRMPPTVRAFVASRGTKQEEFESIEEALPDTDVLYMTRIQKERFGSTQEYEACFGQFILTPHIMTRAKKKMVVMHPMPRVNEISVEVDSDPRAAYFRQAENGMYIRMALLATVLGRF
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm
Function
- Function:
- This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
- Pathway:
- Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3.; Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3.; Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3.
- Catalytic Activity:
- 2 ATP + L-glutamine + HCO(3)(-) + H(2)O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate.
- Cofactor:
- COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=28 uM for dihydroorotate
- Enzyme Regulation:
- ENZYME REGULATION: Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction.
- Active Site:
- ACT_SITE 252 252 For GATase activity.
- Cross Reference Drug Bank:
- DB00128 DB00130
- Gene Ontology Go:
- cell projection
cytosol
extracellular exosome
membrane
neuronal cell body
nuclear matrix
nucleoplasm
nucleus
protein complex
terminal bouton
aspartate binding
aspartate carbamoyltransferase activity
ATP binding
carbamoyl-phosphate synthase (ammonia) activity
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
dihydroorotase activity
enzyme binding
identical protein binding
protein kinase activity
zinc ion binding
'de novo' pyrimidine nucleobase biosynthetic process
'de novo' UMP biosynthetic process
arginine biosynthetic process
cellular response to drug
cellular response to epidermal growth factor stimulus
drug metabolic process
female pregnancy
glutamine metabolic process
heart development
lactation
liver development
nucleobase-containing small molecule metabolic process
organ regeneration
peptidyl-threonine phosphorylation
protein autophosphorylation
pyrimidine nucleobase metabolic process
pyrimidine nucleoside biosynthetic process
response to amine
response to caffeine
response to cortisol
response to testosterone
small molecule metabolic process
urea cycle
UTP biosynthetic process - Gene Ontology Biological Process:
- 'de novo' pyrimidine nucleobase biosynthetic process
'de novo' UMP biosynthetic process
arginine biosynthetic process
cellular response to drug
cellular response to epidermal growth factor stimulus
drug metabolic process
female pregnancy
glutamine metabolic process
heart development
lactation
liver development
nucleobase-containing small molecule metabolic process
organ regeneration
peptidyl-threonine phosphorylation
protein autophosphorylation
pyrimidine nucleobase metabolic process
pyrimidine nucleoside biosynthetic process
response to amine
response to caffeine
response to cortisol
response to testosterone
small molecule metabolic process
urea cycle
UTP biosynthetic process - Gene Ontology Molecular Function:
- aspartate binding
aspartate carbamoyltransferase activity
ATP binding
carbamoyl-phosphate synthase (ammonia) activity
carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
dihydroorotase activity
enzyme binding
identical protein binding
protein kinase activity
zinc ion binding - Gene Ontology Cellular Component:
- cell projection
cytosol
extracellular exosome
membrane
neuronal cell body
nuclear matrix
nucleoplasm
nucleus
protein complex
terminal bouton - Keywords:
- 3D-structure
ATP-binding
Acetylation
Allosteric enzyme
Complete proteome
Congenital disorder of glycosylation
Cytoplasm
Direct protein sequencing
Disease mutation
Hydrolase
Ligase
Metal-binding
Multifunctional enzyme
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Pyrimidine biosynthesis
Reference proteome
Repeat
Transferase
Zinc