CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase)

Gene

• Entrez ID: 790
• Gene name: Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
• Gene symbol: CAD
• Synonyms: CDG1Z, DEE50, EIEE50, GATD4
• Chromosome: 2
• Chromosome location: 2p23.3
• 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. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs62130681	C>A,T	Pathogenic	Coding sequence variant, stop gained, synonymous variant
rs139332887	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs202227357	A>G	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs751610198	T>G	Pathogenic, likely-pathogenic	Genic upstream transcript variant, coding sequence variant, missense variant
rs763410987	G>A	Pathogenic	Coding sequence variant, missense variant
rs769567624	G>A	Pathogenic	Intron variant, splice acceptor variant
rs1019263242	TTCTCCAAGGCCC>-	Pathogenic	Frameshift variant, coding sequence variant
rs1057519262	C>T	Likely-pathogenic	Intron variant
rs1085307810	GACA>-	Pathogenic	Coding sequence variant, frameshift variant
rs1572423883	C>T	Pathogenic	Coding sequence variant, genic upstream transcript variant, stop gained
rs1572426165	TG>-	Likely-pathogenic	Coding sequence variant, upstream transcript variant, frameshift variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023598	hsa-miR-1-3p	Proteomics	18668040
MIRT025309	hsa-miR-34a-5p	Proteomics	21566225
MIRT028960	hsa-miR-26b-5p	Microarray	19088304
MIRT037845	hsa-miR-455-3p	CLASH	23622248
MIRT037845	hsa-miR-455-3p	PAR-CLIP	27292025
MIRT037941	hsa-miR-505-5p	CLASH	23622248
MIRT040681	hsa-miR-92b-3p	CLASH	23622248
MIRT040681	hsa-miR-92b-3p	PAR-CLIP	27292025
MIRT043489	hsa-miR-331-3p	CLASH	23622248
MIRT044218	hsa-miR-301a-3p	CLASH	23622248
MIRT045293	hsa-miR-186-5p	CLASH	23622248
MIRT049353	hsa-miR-92a-3p	CLASH	23622248
MIRT049353	hsa-miR-92a-3p	PAR-CLIP	27292025
MIRT052821	hsa-miR-3200-3p	CLASH	23622248
MIRT480192	hsa-miR-7856-5p	PAR-CLIP	23592263
MIRT480193	hsa-miR-4477b	PAR-CLIP	23592263
MIRT480194	hsa-let-7g-3p	PAR-CLIP	23592263
MIRT480195	hsa-let-7a-2-3p	PAR-CLIP	23592263
MIRT480196	hsa-miR-943	PAR-CLIP	23592263
MIRT480197	hsa-miR-486-3p	PAR-CLIP	23592263
MIRT480198	hsa-miR-4722-5p	PAR-CLIP	23592263
MIRT480199	hsa-miR-1286	PAR-CLIP	23592263
MIRT480200	hsa-miR-873-5p	PAR-CLIP	23592263
MIRT480201	hsa-miR-4771	PAR-CLIP	23592263
MIRT480202	hsa-miR-4699-5p	PAR-CLIP	23592263
MIRT480203	hsa-miR-4494	PAR-CLIP	23592263
MIRT480204	hsa-miR-4463	PAR-CLIP	23592263
MIRT480205	hsa-miR-3675-5p	PAR-CLIP	23592263
MIRT480206	hsa-miR-552-3p	PAR-CLIP	23592263
MIRT480207	hsa-miR-4735-3p	PAR-CLIP	23592263
MIRT480208	hsa-miR-18b-5p	PAR-CLIP	23592263
MIRT480209	hsa-miR-18a-5p	PAR-CLIP	23592263
MIRT480210	hsa-miR-4662b	PAR-CLIP	23592263
MIRT480211	hsa-miR-4647	PAR-CLIP	23592263
MIRT480212	hsa-miR-4426	PAR-CLIP	23592263
MIRT484452	hsa-miR-874-5p	PAR-CLIP	23592263
MIRT484453	hsa-miR-4758-3p	PAR-CLIP	23592263
MIRT484454	hsa-miR-5008-5p	PAR-CLIP	23592263
MIRT484455	hsa-miR-6089	PAR-CLIP	23592263
MIRT484456	hsa-miR-7162-3p	PAR-CLIP	23592263
MIRT484457	hsa-miR-4649-3p	PAR-CLIP	23592263
MIRT484458	hsa-miR-6872-3p	PAR-CLIP	23592263
MIRT484459	hsa-miR-3200-5p	PAR-CLIP	23592263
MIRT761915	hsa-miR-1273g-3p	PAR-CLIP	27292025
MIRT762190	hsa-miR-1285-3p	PAR-CLIP	27292025
MIRT763485	hsa-miR-196a-3p	PAR-CLIP	27292025
MIRT764162	hsa-miR-25-3p	PAR-CLIP	27292025
MIRT765293	hsa-miR-3187-5p	PAR-CLIP	27292025
MIRT765576	hsa-miR-32-5p	PAR-CLIP	27292025
MIRT766181	hsa-miR-363-3p	PAR-CLIP	27292025
MIRT766620	hsa-miR-367-3p	PAR-CLIP	27292025
MIRT772367	hsa-miR-4793-3p	PAR-CLIP	27292025
MIRT772967	hsa-miR-500a-3p	PAR-CLIP	27292025
MIRT773127	hsa-miR-508-5p	PAR-CLIP	27292025
MIRT773543	hsa-miR-5189-5p	PAR-CLIP	27292025
MIRT775834	hsa-miR-612	PAR-CLIP	27292025
MIRT776214	hsa-miR-6499-3p	PAR-CLIP	27292025
MIRT776881	hsa-miR-6512-3p	PAR-CLIP	27292025
MIRT777077	hsa-miR-6516-5p	PAR-CLIP	27292025
MIRT777408	hsa-miR-661	PAR-CLIP	27292025
MIRT777727	hsa-miR-6720-5p	PAR-CLIP	27292025
MIRT779558	hsa-miR-6807-5p	PAR-CLIP	27292025
MIRT780542	hsa-miR-6860	PAR-CLIP	27292025
MIRT781834	hsa-miR-766-3p	PAR-CLIP	27292025
MIRT781940	hsa-miR-767-5p	PAR-CLIP	27292025
MIRT781983	hsa-miR-7703	PAR-CLIP	27292025
MIRT782788	hsa-miR-939-3p	PAR-CLIP	27292025

Transcription factors

Transcription factor	Regulation	Reference
HDAC2	Unknown	14559996
MYC	Unknown	10931841;17706770
SMARCA4	Unknown	14559996

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001889	Process	Liver development	IEA
GO:0004070	Function	Aspartate carbamoyltransferase activity	IBA	21873635
GO:0004070	Function	Aspartate carbamoyltransferase activity	ISS
GO:0004088	Function	Carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity	ISS
GO:0004151	Function	Dihydroorotase activity	IBA	21873635
GO:0004151	Function	Dihydroorotase activity	IDA	24332717
GO:0004151	Function	Dihydroorotase activity	ISS
GO:0004672	Function	Protein kinase activity	ISS
GO:0005524	Function	ATP binding	ISS
GO:0005634	Component	Nucleus	IDA	15890648
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	IDA	15890648
GO:0005829	Component	Cytosol	TAS
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	IBA	21873635
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	IDA	24332717
GO:0006207	Process	'de novo' pyrimidine nucleobase biosynthetic process	ISS
GO:0006228	Process	UTP biosynthetic process	IBA	21873635
GO:0006541	Process	Glutamine metabolic process	IBA	21873635
GO:0006541	Process	Glutamine metabolic process	ISS
GO:0006807	Process	Nitrogen compound metabolic process	IBA	21873635
GO:0007507	Process	Heart development	IEA
GO:0007565	Process	Female pregnancy	IEA
GO:0007595	Process	Lactation	IEA
GO:0008270	Function	Zinc ion binding	IDA	24332717
GO:0014075	Process	Response to amine	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016363	Component	Nuclear matrix	IDA	9525610
GO:0017144	Process	Drug metabolic process	ISS
GO:0018107	Process	Peptidyl-threonine phosphorylation	ISS
GO:0019240	Process	Citrulline biosynthetic process	IBA	21873635
GO:0019899	Function	Enzyme binding	IPI	15326225
GO:0031000	Process	Response to caffeine	IEA
GO:0031100	Process	Animal organ regeneration	IEA
GO:0032868	Process	Response to insulin	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0033574	Process	Response to testosterone	IEA
GO:0035690	Process	Cellular response to drug	IEA
GO:0042594	Process	Response to starvation	IEA
GO:0042802	Function	Identical protein binding	IPI	24332717
GO:0042802	Function	Identical protein binding	ISS
GO:0042995	Component	Cell projection	ISS
GO:0043025	Component	Neuronal cell body	ISS
GO:0043195	Component	Terminal bouton	ISS
GO:0044205	Process	'de novo' UMP biosynthetic process	IEA
GO:0046134	Process	Pyrimidine nucleoside biosynthetic process	TAS
GO:0046777	Process	Protein autophosphorylation	ISS
GO:0051414	Process	Response to cortisol	IEA
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0070335	Function	Aspartate binding	ISS
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	IEA

Other IDs

• MIM: 114010
• HGNC: 1424
• e!Ensembl: ENSG00000084774

Protein

• UniProt ID: P27708
• Protein name: 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)]
• Protein function: This protein is a 'fusion' protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
• PDB: 4BY3, 4C6B, 4C6C, 4C6D, 4C6E, 4C6F, 4C6I, 4C6J, 4C6K, 4C6L, 4C6M, 4C6N, 4C6O, 4C6P, 4C6Q, 5G1N, 5G1O, 5G1P, 5YNZ, 6HFD, 6HFE, 6HFF, 6HFH, 6HFI, 6HFJ, 6HFK, 6HFL, 6HFN, 6HFP, 6HFQ, 6HFR, 6HFS, 6HFU, 6HG1
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00988	CPSase_sm_chain	1 → 138	Carbamoyl-phosphate synthase small chain, CPSase domain	Domain
  PF00117	GATase	179 → 356	Glutamine amidotransferase class-I	Domain
  PF02786	CPSase_L_D2	514 → 718	Carbamoyl-phosphate synthase L chain, ATP binding domain	Domain
  PF02787	CPSase_L_D3	800 → 881	Carbamoyl-phosphate synthetase large chain, oligomerisation domain	Domain
  PF02786	CPSase_L_D2	1047 → 1250	Carbamoyl-phosphate synthase L chain, ATP binding domain	Domain
  PF02142	MGS	1327 → 1428	MGS-like domain	Domain
  PF01979	Amidohydro_1	1462 → 1745	Amidohydrolase family	Domain
  PF02729	OTCace_N	1924 → 2065	Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain	Domain
  PF00185	OTCace	2071 → 2221	Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain	Domain

• Sequence:

  MAALVLEDGSVLRGQPFGAAVSTAGEVVFQTGMVGYPEALTDPSYKAQILVLTYPLIGNY
  GIPPDEMDEFGLCKWFESSGIHVAALVVGECCPTPSHWSATRTLHEWLQQHGIPGLQGVD
  TRELTKKLREQGSLLGKLVQNGTEPSSLPFLDPNARPLVPEVSIKTPRVFNTGGAPRILA
  LDCGLKYNQIRCLCQRGAEVTVVPWDHALDSQEYEGLFLSNGPGDPASYPSVVSTLSRVL
  SEPNPRPVFGICLGHQLLALAIGAKTYKMRYGNRGHNQPCLLVGSGRCFLTSQNHGFAVE
  TDSLPADWAPLFTNANDGSNEGIVHNSLPFFSVQFHPEHQAGPSDMELLFDIFLETVKEA
  TAGNPGGQTVRERLTERLCPPGIPTPGSGLPPPRKVLILGSGGLSIGQAGEFDYSGSQAI
  KALKEENIQTLLINPNIATVQTSQGLADKVYFLPITPHYVTQVIRNERPDGVLLTFGGQT
  ALNCGVELTKAGVLARYGVRVLGTPVETIELTEDRRAFAARMAEIGEHVAPSEAANSLEQ
  AQAAAERLGYPVLVRAAFALGGLGSGFASNREELSALVAPAFAHTSQVLVDKSLKGWKEI
  EYEVVRDAYGNCVTVCNMENLDPLGIHTGESIVVAPSQTLNDREYQLLRQTAIKVTQHLG
  IVGECNVQYALNPESEQYYIIEVNARLSRSSALASKATGYPLAYVAAKLALGIPLPELRN
  SVTGGTAAFEPSVDYCVVKIPRWDLSKFLRVSTKIGSCMKSVGEVMGIGRSFEEAFQKAL
  RMVDENCVGFDHTVKPVSDMELETPTDKRIFVVAAALWAGYSVDRLYELTRIDRWFLHRM
  KRIIAHAQLLEQHRGQPLPPDLLQQAKCLGFSDKQIALAVLSTELAVRKLRQELGICPAV
  KQIDTVAAEWPAQTNYLYLTYWGTTHDLTFRTPHVLVLGSGVYRIGSSVEFDWCAVGCIQ
  QLRKMGYKTIMVNYNPETVSTDYDMCDRLYFDEISFEVVMDIYELENPEGVILSMGGQLP
  NNMAMALHRQQCRVLGTSPEAIDSAENRFKFSRLLDTIGISQPQWRELSDLESARQFCQT
  VGYPCVVRPSYVLSGAAMNVAYTDGDLERFLSSAAAVSKEHPVVISKFIQEAKEIDVDAV
  ASDGVVAAIAISEHVENAGVHSGDATLVTPPQDITAKTLERIKAIVHAVGQELQVTGPFN
  LQLIAKDDQLKVIECNVRVSRSFPFVSKTLGVDLVALATRVIMGEEVEPVGLMTGSGVVG
  VKVPQFSFSRLAGADVVLGVEMTSTGEVAGFGESRCEAYLKAMLSTGFKIPKKNILLTIG
  SYKNKSELLPTVRLLESLGYSLYASLGTADFYTEHGVKVTAVDWHFEEAVDGECPPQRSI
  LEQLAEKNFELVINLSMRGAGGRRLSSFVTKGYRTRRLAADFSVPLIIDIKCTKLFVEAL
  GQIGPAPPLKVHVDCMTSQKLVRLPGLIDVHVHLREPGGTHKEDFASGTAAALAGGITMV
  CAMPNTRPPIIDAPALALAQKLAEAGARCDFALFLGASSENAGTLGTVAGSAAGLKLYLN
  ETFSELRLDSVVQWMEHFETWPSHLPIVAHAEQQTVAAVLMVAQLTQRSVHICHVARKEE
  ILLIKAAKARGLPVTCEVAPHHLFLSHDDLERLGPGKGEVRPELGSRQDVEALWENMAVI
  DCFASDHAPHTLEEKCGSRPPPGFPGLETMLPLLLTAVSEGRLSLDDLLQRLHHNPRRIF
  HLPPQEDTYVEVDLEHEWTIPSHMPFSKAHWTPFEGQKVKGTVRRVVLRGEVAYIDGQVL
  VPPGYGQDVRKWPQGAVPQLPPSAPATSEMTTTPERPRRGIPGLPDGRFHLPPRIHRASD
  PGLPAEEPKEKSSRKVAEPELMGTPDGTCYPPPPVPRQASPQNLGTPGLLHPQTSPLLHS
  LVGQHILSVQQFTKDQMSHLFNVAHTLRMMVQKERSLDILKGKVMASMFYEVSTRTSSSF
  AAAMARLGGAVLSFSEATSSVQKGESLADSVQTMSCYADVVVLRHPQPGAVELAAKHCRR
  PVINAGDGVGEHPTQALLDIFTIREELGTVNGMTITMVGDLKHGRTVHSLACLLTQYRVS
  LRYVAPPSLRMPPTVRAFVASRGTKQEEFESIEEALPDTDVLYMTRIQKERFGSTQEYEA
  CFGQFILTPHIMTRAKKKMVVMHPMPRVNEISVEVDSDPRAAYFRQAENGMYIRMALLAT
  VLGRF

• Sequence length: 2225