CAD
Multifunctional protein CAD
Also known as: GATD4, PYR1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P27708
- Gene
- CAD
- Ensembl
- ENSG00000084774
- Chromosome
- 2
- Canonical length
- 2225 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins
- Subcellular location
- Cytosol
- Quaternary structure
- Homohexamer
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
2225 residues, UniProt reviewed canonical sequence.
>P27708|CAD
1 MAALVLEDGS VLRGQPFGAA VSTAGEVVFQ TGMVGYPEAL TDPSYKAQIL VLTYPLIGNY
61 GIPPDEMDEF GLCKWFESSG IHVAALVVGE CCPTPSHWSA TRTLHEWLQQ HGIPGLQGVD
121 TRELTKKLRE QGSLLGKLVQ NGTEPSSLPF LDPNARPLVP EVSIKTPRVF NTGGAPRILA
181 LDCGLKYNQI RCLCQRGAEV TVVPWDHALD SQEYEGLFLS NGPGDPASYP SVVSTLSRVL
241 SEPNPRPVFG ICLGHQLLAL AIGAKTYKMR YGNRGHNQPC LLVGSGRCFL TSQNHGFAVE
301 TDSLPADWAP LFTNANDGSN EGIVHNSLPF FSVQFHPEHQ AGPSDMELLF DIFLETVKEA
361 TAGNPGGQTV RERLTERLCP PGIPTPGSGL PPPRKVLILG SGGLSIGQAG EFDYSGSQAI
421 KALKEENIQT LLINPNIATV QTSQGLADKV YFLPITPHYV TQVIRNERPD GVLLTFGGQT
481 ALNCGVELTK AGVLARYGVR VLGTPVETIE LTEDRRAFAA RMAEIGEHVA PSEAANSLEQ
541 AQAAAERLGY PVLVRAAFAL GGLGSGFASN REELSALVAP AFAHTSQVLV DKSLKGWKEI
601 EYEVVRDAYG NCVTVCNMEN LDPLGIHTGE SIVVAPSQTL NDREYQLLRQ TAIKVTQHLG
661 IVGECNVQYA LNPESEQYYI IEVNARLSRS SALASKATGY PLAYVAAKLA LGIPLPELRN
721 SVTGGTAAFE PSVDYCVVKI PRWDLSKFLR VSTKIGSCMK SVGEVMGIGR SFEEAFQKAL
781 RMVDENCVGF DHTVKPVSDM ELETPTDKRI FVVAAALWAG YSVDRLYELT RIDRWFLHRM
841 KRIIAHAQLL EQHRGQPLPP DLLQQAKCLG FSDKQIALAV LSTELAVRKL RQELGICPAV
901 KQIDTVAAEW PAQTNYLYLT YWGTTHDLTF RTPHVLVLGS GVYRIGSSVE FDWCAVGCIQ
961 QLRKMGYKTI MVNYNPETVS TDYDMCDRLY FDEISFEVVM DIYELENPEG VILSMGGQLP
1021 NNMAMALHRQ QCRVLGTSPE AIDSAENRFK FSRLLDTIGI SQPQWRELSD LESARQFCQT
1081 VGYPCVVRPS YVLSGAAMNV AYTDGDLERF LSSAAAVSKE HPVVISKFIQ EAKEIDVDAV
1141 ASDGVVAAIA ISEHVENAGV HSGDATLVTP PQDITAKTLE RIKAIVHAVG QELQVTGPFN
1201 LQLIAKDDQL KVIECNVRVS RSFPFVSKTL GVDLVALATR VIMGEEVEPV GLMTGSGVVG
1261 VKVPQFSFSR LAGADVVLGV EMTSTGEVAG FGESRCEAYL KAMLSTGFKI PKKNILLTIG
1321 SYKNKSELLP TVRLLESLGY SLYASLGTAD FYTEHGVKVT AVDWHFEEAV DGECPPQRSI
1381 LEQLAEKNFE LVINLSMRGA GGRRLSSFVT KGYRTRRLAA DFSVPLIIDI KCTKLFVEAL
1441 GQIGPAPPLK VHVDCMTSQK LVRLPGLIDV HVHLREPGGT HKEDFASGTA AALAGGITMV
1501 CAMPNTRPPI IDAPALALAQ KLAEAGARCD FALFLGASSE NAGTLGTVAG SAAGLKLYLN
1561 ETFSELRLDS VVQWMEHFET WPSHLPIVAH AEQQTVAAVL MVAQLTQRSV HICHVARKEE
1621 ILLIKAAKAR GLPVTCEVAP HHLFLSHDDL ERLGPGKGEV RPELGSRQDV EALWENMAVI
1681 DCFASDHAPH TLEEKCGSRP PPGFPGLETM LPLLLTAVSE GRLSLDDLLQ RLHHNPRRIF
1741 HLPPQEDTYV EVDLEHEWTI PSHMPFSKAH WTPFEGQKVK GTVRRVVLRG EVAYIDGQVL
1801 VPPGYGQDVR KWPQGAVPQL PPSAPATSEM TTTPERPRRG IPGLPDGRFH LPPRIHRASD
1861 PGLPAEEPKE KSSRKVAEPE LMGTPDGTCY PPPPVPRQAS PQNLGTPGLL HPQTSPLLHS
1921 LVGQHILSVQ QFTKDQMSHL FNVAHTLRMM VQKERSLDIL KGKVMASMFY EVSTRTSSSF
1981 AAAMARLGGA VLSFSEATSS VQKGESLADS VQTMSCYADV VVLRHPQPGA VELAAKHCRR
2041 PVINAGDGVG EHPTQALLDI FTIREELGTV NGMTITMVGD LKHGRTVHSL ACLLTQYRVS
2101 LRYVAPPSLR MPPTVRAFVA SRGTKQEEFE SIEEALPDTD VLYMTRIQKE RFGSTQEYEA
2161 CFGQFILTPH IMTRAKKKMV VMHPMPRVNE ISVEVDSDPR AAYFRQAENG MYIRMALLAT
2221 VLGRFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CAD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.22
- Highest tissue expression
- 27 nTPM
Expression across tissuesHPA
Tissue
- liver: 27 nTPM
- endometrium: 23 nTPM
- ovary: 22 nTPM
- pancreas: 22 nTPM
- testis: 22 nTPM
- cervix: 21 nTPM
Single-cell type
- megakaryocyte progenitors: 34 nCPM
- erythrocyte progenitors: 34 nCPM
- sertoli cells: 31 nCPM
- differentiating spermatogonia: 29 nCPM
- retinal ganglion cells: 23 nCPM
- megakaryocyte-erythroid progenitors: 23 nCPM
Immune cell
- T-reg: 5.9 nTPM
- memory CD8 T-cell: 5.2 nTPM
- memory CD4 T-cell: 4.4 nTPM
- memory B-cell: 3.4 nTPM
- plasmacytoid DC: 3.4 nTPM
- naive B-cell: 3.2 nTPM
Brain region
- white matter: 20 nTPM
- medulla oblongata: 19 nTPM
- cerebral cortex: 19 nTPM
- thalamus: 19 nTPM
- basal ganglia: 19 nTPM
- pons: 18 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CAD.
Disease | AllUniProt
Conditions CAD is implicated in, by any mechanism.
- Developmental and epileptic encephalopathy 50 (DEE50) MIM:616457
Disease | GeneticClinVar
97 pathogenic / likely-pathogenic of 2,366 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Developmental and epileptic encephalopathy, 50
- Infantile epileptic dyskinetic encephalopathy
- Ovarian serous cystadenocarcinoma
- Pancreatic adenocarcinoma
- Melanoma
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.25
- gnomAD pLI
- 1
- gnomAD missense Z
- 4.34
- DepMap mean gene effect
- -0.44
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- 'de novo' pyrimidine nucleobase biosynthetic process
- 'de novo' UMP biosynthetic process
- animal organ regeneration
- cellular response to epidermal growth factor stimulus
- citrulline biosynthetic process
- female pregnancy
- glutamine metabolic process
- heart development
- lactation
- liver development
- response to amine
- response to caffeine
- response to cortisol
- response to insulin
- response to starvation
- response to testosterone
- UDP biosynthetic process
- UTP biosynthetic process
- xenobiotic metabolic process
Molecular functions
- ATP binding
- carbamoyl-phosphate synthase (ammonia) activity
- carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
- dihydroorotase activity
- enzyme binding
- glutaminase activity
- identical protein binding
- protein kinase activity
- zinc ion binding
- aspartate binding
- aspartate carbamoyltransferase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Dihydroorotase, conserved site
- Carbamoyl-phosphate synthase small subunit, N-terminal domain
- Carbamoyl phosphate synthase, ATP-binding domain
- Carbamoyl-phosphate synthetase, large subunit oligomerisation domain
- Carbamoyl phosphate synthase, CPSase domain
- Aspartate/ornithine carbamoyltransferase
- Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain
- Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding
- Carbamoyl-phosphate synthase, small subunit
- Carbamoyl-phosphate synthase, large subunit
- Amidohydrolase-related
- Metal-dependent hydrolase, composite domain superfamily
- Methylglyoxal synthase-like domain
- ATP-grasp fold
- ATP-grasp fold, subdomain 1
- Pre-ATP-grasp domain superfamily
- Glutamine amidotransferase
- Class I glutamine amidotransferase-like
- Metal-dependent hydrolase
- Carbamoyl-phosphate synthase small subunit, GATase1 domain
- Carbamoyl-phosphate synthase small subunit, N-terminal domain superfamily
- Carbamoyl-phosphate synthetase, large subunit oligomerisation domain superfamily
- Aspartate/ornithine carbamoyltransferase superfamily
- Methylglyoxal synthase-like domain superfamily
- Carbamoyl phosphate synthase, preATP-grasp domain
- Glutamine amidotransferase class-I
- Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain
- Carbamoyl-phosphate synthase small chain, CPSase domain
- Amidohydrolase family
- MGS-like domain
- Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding domain
- Carbamoyl-phosphate synthase L chain, ATP binding domain
- Carbamoyl-phosphate synthetase large chain, oligomerisation domain
- Carbamoyl phosphate synthase preATP-grasp domain
- Aspartate carbamoyltransferase
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CAD in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CAD as an antibody target. Whether an autoantibody or antibody against CAD could matter depends on whether native CAD is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CAD is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CAD as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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