CAD
entrez
790
canonical
uniprot
P27708
canonical
ensembl
ENSG00000084774
resolver
ensp
ENSP00000264705
resolver
ensp
ENSP00000384510
resolver
enst
ENST00000264705
resolver
enst
ENST00000403525
resolver
genesymbol
CAD
resolver
hgnc
HGNC:1424
resolver
uniprot
D6W552
resolver
uniprot
F8VPD4
resolver
uniprot
Q6P0Q0
resolver
uniprot
Q96CK3
resolver
uniprot_entry
F8VPD4_HUMAN
resolver
uniprot_entry
PYR1_HUMAN
resolver
uniprot_sec
D6W552
resolver
uniprot_sec
Q6P0Q0
resolver
uniprot_sec
Q96CK3
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:11872754}.
uniprot
proteins
amino_acid_sequence
MAALVLEDGSVLRGQPFGAAVSTAGEVVFQTGMVGYPEALTDPSYKAQILVLTYPLIGNYGIPPDEMDEFGLCKWFESSGIHVAALVVGECCPTPSHWSATRTLHEWLQQHGIPGLQGVDTRELTKKLREQGSLLGKLVQNGTEPSSLPFLDPNARPLVPEVSIKTPRVFNTGGAPRILALDCGLKYNQIRCLCQRGAEVTVVPWDHALDSQEYEGLFLSNGPGDPASYPSVVSTLSRVLSEPNPRPVFGICLGHQLLALAIGAKTYKMRYGNRGHNQPCLLVGSGRCFLTSQNHGFAVETDSLPADWAPLFTNANDGSNEGIVHNSLPFFSVQFHPEHQAGPSDMELLFDIFLETVKEATAGNPGGQTVRERLTERLCPPGIPTPGSGLPPPRKVLILGSGGLSIGQAGEFDYSGSQAIKALKEENIQTLLINPNIATVQTSQGLADKVYFLPITPHYVTQVIRNERPDGVLLTFGGQTALNCGVELTKAGVLARYGVRVLGTPVETIELTEDRRAFAARMAEIGEHVAPSEAANSLEQAQAAAERLGYPVLVRAAFALGGLGSGFASNREELSALVAPAFAHTSQVLVDKSLKGWKEIEYEVVRDAYGNCVTVCNMENLDPLGIHTGESIVVAPSQTLNDREYQLLRQTAIKVTQHLGIVGECNVQYALNPESEQYYIIEVNARLSRSSALASKATGYPLAYVAAKLALGIPLPELRNSVTGGTAAFEPSVDYCVVKIPRWDLSKFLRVSTKIGSCMKSVGEVMGIGRSFEEAFQKALRMVDENCVGFDHTVKPVSDMELETPTDKRIFVVAAALWAGYSVDRLYELTRIDRWFLHRMKRIIAHAQLLEQHRGQPLPPDLLQQAKCLGFSDKQIALAVLSTELAVRKLRQELGICPAVKQIDTVAAEWPAQTNYLYLTYWGTTHDLTFRTPHVLVLGSGVYRIGSSVEFDWCAVGCIQQLRKMGYKTIMVNYNPETVSTDYDMCDRLYFDEISFEVVMDIYELENPEGVILSMGGQLPNNMAMALHRQQCRVLGTSPEAIDSAENRFKFSRLLDTIGISQPQWRELSDLESARQFCQTVGYPCVVRPSYVLSGAAMNVAYTDGDLERFLSSAAAVSKEHPVVISKFIQEAKEIDVDAVASDGVVAAIAISEHVENAGVHSGDATLVTPPQDITAKTLERIKAIVHAVGQELQVTGPFNLQLIAKDDQLKVIECNVRVSRSFPFVSKTLGVDLVALATRVIMGEEVEPVGLMTGSGVVGVKVPQFSFSRLAGADVVLGVEMTSTGEVAGFGESRCEAYLKAMLSTGFKIPKKNILLTIGSYKNKSELLPTVRLLESLGYSLYASLGTADFYTEHGVKVTAVDWHFEEAVDGECPPQRSILEQLAEKNFELVINLSMRGAGGRRLSSFVTKGYRTRRLAADFSVPLIIDIKCTKLFVEALGQIGPAPPLKVHVDCMTSQKLVRLPGLIDVHVHLREPGGTHKEDFASGTAAALAGGITMVCAMPNTRPPIIDAPALALAQKLAEAGARCDFALFLGASSENAGTLGTVAGSAAGLKLYLNETFSELRLDSVVQWMEHFETWPSHLPIVAHAEQQTVAAVLMVAQLTQRSVHICHVARKEEILLIKAAKARGLPVTCEVAPHHLFLSHDDLERLGPGKGEVRPELGSRQDVEALWENMAVIDCFASDHAPHTLEEKCGSRPPPGFPGLETMLPLLLTAVSEGRLSLDDLLQRLHHNPRRIFHLPPQEDTYVEVDLEHEWTIPSHMPFSKAHWTPFEGQKVKGTVRRVVLRGEVAYIDGQVLVPPGYGQDVRKWPQGAVPQLPPSAPATSEMTTTPERPRRGIPGLPDGRFHLPPRIHRASDPGLPAEEPKEKSSRKVAEPELMGTPDGTCYPPPPVPRQASPQNLGTPGLLHPQTSPLLHSLVGQHILSVQQFTKDQMSHLFNVAHTLRMMVQKERSLDILKGKVMASMFYEVSTRTSSSFAAAMARLGGAVLSFSEATSSVQKGESLADSVQTMSCYADVVVLRHPQPGAVELAAKHCRRPVINAGDGVGEHPTQALLDIFTIREELGTVNGMTITMVGDLKHGRTVHSLACLLTQYRVSLRYVAPPSLRMPPTVRAFVASRGTKQEEFESIEEALPDTDVLYMTRIQKERFGSTQEYEACFGQFILTPHIMTRAKKKMVVMHPMPRVNEISVEVDSDPRAAYFRQAENGMYIRMALLATVLGRF
uniprot
proteins
disease_involvement
DISEASE: Developmental and epileptic encephalopathy 50 (DEE50) [MIM:616457]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE50 is an autosomal recessive, progressive disease with onset in infancy and favorable response to treatment with oral uridine. {ECO:0000269|PubMed:25678555, ECO:0000269|PubMed:28087732}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.1.3.2
uniprot
proteins
ec_number
3.5.1.2
uniprot
proteins
ec_number
3.5.2.3
uniprot
proteins
ec_number
6.3.4.16
uniprot
proteins
ec_number
6.3.5.5
uniprot
proteins
function
FUNCTION: Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate. {ECO:0000269|PubMed:24332717}.
uniprot
proteins
mass_dalton
242984
uniprot
proteins
mutagenesis
MUTAGEN 1471; /note="H->A: No zinc-binding and no catalytic activity."; /evidence="ECO:0000269|PubMed:24332717, ECO:0000269|PubMed:7766613"; MUTAGEN 1471; /note="H->N: Abolishes dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717, ECO:0000269|PubMed:7766613"; MUTAGEN 1473; /note="H->A: No zinc-binding and no catalytic activity."; /evidence="ECO:0000269|PubMed:7766613"; MUTAGEN 1512; /note="D->N: No change in catalytic activity."; /evidence="ECO:0000269|PubMed:7766613"; MUTAGEN 1562; /note="T->A: Abolishes dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717"; MUTAGEN 1563; /note="F->A: Abolishes dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717"; MUTAGEN 1590; /note="H->A: Abolishes dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717, ECO:0000269|PubMed:7766613"; MUTAGEN 1590; /note="H->N: No catalytic activity."; /evidence="ECO:0000269|PubMed:24332717, ECO:0000269|PubMed:7766613"; MUTAGEN 1613; /note="C->S: Reduces dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717"; MUTAGEN 1614; /note="H->A: Abolishes dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717"; MUTAGEN 1637; /note="E->T: Abolishes dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717"; MUTAGEN 1642; /note="H->N: 11.5% of wild-type catalytic activity."; /evidence="ECO:0000269|PubMed:7766613"; MUTAGEN 1686; /note="D->N: Abolishes dihydroorotase activity."; /evidence="ECO:0000269|PubMed:24332717"; MUTAGEN 1690; /note="H->N: 3% of wild-type catalytic activity."; /evidence="ECO:0000269|PubMed:7766613"; MUTAGEN 1873; /note="S->A: Abolishes PMA-induced Thr-456 phosphorylation."; /evidence="ECO:0000269|PubMed:17485345
uniprot
proteins
pathway_participation
PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3. {ECO:0000269|PubMed:24332717}.; PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3. {ECO:0000269|PubMed:24332717}.; PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3. {ECO:0000269|PubMed:24332717}.
uniprot
proteins
post_translational_modification
PTM: Activated by MAP kinase (Erk1/2) phosphorylation just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. Phosphorylation at Ser-1859 by RPS6KB1 downstream of MTOR promotes oligomerization and stimulates dihydroorotase activity. Phosphorylation at Ser-1406 reduces sensitivity to feedback inhibition by UTP. {ECO:0000269|PubMed:17485345, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704}.
uniprot
proteins
protein_family
ATCase family
uniprot
proteins
protein_family
CAD subfamily; Aspartate/ornithine carbamoyltransferase superfamily
uniprot
proteins
protein_family
CarA family; CarB family; Metallo-dependent hydrolases superfamily
uniprot
proteins
protein_family
DHOase family
uniprot
proteins
pubmed
11872754
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15890648
uniprot
proteins
pubmed
16155188
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17485345
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
1979741
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23429703
uniprot
proteins
pubmed
23429704
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24332717
uniprot
proteins
pubmed
25678555
uniprot
proteins
pubmed
26657846
uniprot
proteins
pubmed
27265852
uniprot
proteins
pubmed
28087732
uniprot
proteins
pubmed
30268498
uniprot
proteins
pubmed
30315107
uniprot
proteins
pubmed
7766613
uniprot
proteins
pubmed
8619816
uniprot
proteins
sequence_length
2225
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15890648}. Nucleus {ECO:0000269|PubMed:15890648}. Note=Cytosolic and unphosphorylated in resting cells, translocates to the nucleus in response to EGF stimulation, nuclear import promotes optimal cell growth.
uniprot
proteins