Seroatlas · Human Serome Atlas

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  VLGRF

LocalizationUniProt · 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.

Disease | GeneticClinVar

97 pathogenic / likely-pathogenic of 2,366 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

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.

Canonical record: https://seroatlas.com/gene/CAD. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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