CPS1

Protein identityUniProt · HPA

UniProt accession

P31327

Gene

CPS1

Ensembl

ENSG00000021826

Chromosome

2

Canonical length

1500 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoli,Nucleoli rim,Mid piece,Principal piece

Quaternary structure

Homooligomer

OverviewNCBI Gene

The mitochondrial enzyme encoded by this gene catalyzes synthesis of carbamoyl phosphate from ammonia and bicarbonate. This reaction is the first committed step of the urea cycle, which is important in the removal of excess urea from cells. The encoded protein may also represent a core mitochondrial nucleoid protein. Three transcript variants encoding different isoforms have been found for this gene. The shortest isoform may not be localized to the mitochondrion. Mutations in this gene have been associated with carbamoyl phosphate synthetase deficiency, susceptibility to persistent pulmonary hypertension, and susceptibility to venoocclusive disease after bone marrow transplantation.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

1500 residues, UniProt reviewed canonical sequence.

>P31327|CPS1
     1  MTRILTAFKV VRTLKTGFGF TNVTAHQKWK FSRPGIRLLS VKAQTAHIVL EDGTKMKGYS
    61  FGHPSSVAGE VVFNTGLGGY PEAITDPAYK GQILTMANPI IGNGGAPDTT ALDELGLSKY
   121  LESNGIKVSG LLVLDYSKDY NHWLATKSLG QWLQEEKVPA IYGVDTRMLT KIIRDKGTML
   181  GKIEFEGQPV DFVDPNKQNL IAEVSTKDVK VYGKGNPTKV VAVDCGIKNN VIRLLVKRGA
   241  EVHLVPWNHD FTKMEYDGIL IAGGPGNPAL AEPLIQNVRK ILESDRKEPL FGISTGNLIT
   301  GLAAGAKTYK MSMANRGQNQ PVLNITNKQA FITAQNHGYA LDNTLPAGWK PLFVNVNDQT
   361  NEGIMHESKP FFAVQFHPEV TPGPIDTEYL FDSFFSLIKK GKATTITSVL PKPALVASRV
   421  EVSKVLILGS GGLSIGQAGE FDYSGSQAVK AMKEENVKTV LMNPNIASVQ TNEVGLKQAD
   481  TVYFLPITPQ FVTEVIKAEQ PDGLILGMGG QTALNCGVEL FKRGVLKEYG VKVLGTSVES
   541  IMATEDRQLF SDKLNEINEK IAPSFAVESI EDALKAADTI GYPVMIRSAY ALGGLGSGIC
   601  PNRETLMDLS TKAFAMTNQI LVEKSVTGWK EIEYEVVRDA DDNCVTVCNM ENVDAMGVHT
   661  GDSVVVAPAQ TLSNAEFQML RRTSINVVRH LGIVGECNIQ FALHPTSMEY CIIEVNARLS
   721  RSSALASKAT GYPLAFIAAK IALGIPLPEI KNVVSGKTSA CFEPSLDYMV TKIPRWDLDR
   781  FHGTSSRIGS SMKSVGEVMA IGRTFEESFQ KALRMCHPSI EGFTPRLPMN KEWPSNLDLR
   841  KELSEPSSTR IYAIAKAIDD NMSLDEIEKL TYIDKWFLYK MRDILNMEKT LKGLNSESMT
   901  EETLKRAKEI GFSDKQISKC LGLTEAQTRE LRLKKNIHPW VKQIDTLAAE YPSVTNYLYV
   961  TYNGQEHDVN FDDHGMMVLG CGPYHIGSSV EFDWCAVSSI RTLRQLGKKT VVVNCNPETV
  1021  STDFDECDKL YFEELSLERI LDIYHQEACG GCIISVGGQI PNNLAVPLYK NGVKIMGTSP
  1081  LQIDRAEDRS IFSAVLDELK VAQAPWKAVN TLNEALEFAK SVDYPCLLRP SYVLSGSAMN
  1141  VVFSEDEMKK FLEEATRVSQ EHPVVLTKFV EGAREVEMDA VGKDGRVISH AISEHVEDAG
  1201  VHSGDATLML PTQTISQGAI EKVKDATRKI AKAFAISGPF NVQFLVKGND VLVIECNLRA
  1261  SRSFPFVSKT LGVDFIDVAT KVMIGENVDE KHLPTLDHPI IPADYVAIKA PMFSWPRLRD
  1321  ADPILRCEMA STGEVACFGE GIHTAFLKAM LSTGFKIPQK GILIGIQQSF RPRFLGVAEQ
  1381  LHNEGFKLFA TEATSDWLNA NNVPATPVAW PSQEGQNPSL SSIRKLIRDG SIDLVINLPN
  1441  NNTKFVHDNY VIRRTAVDSG IPLLTNFQVT KLFAEAVQKS RKVDSKSLFH YRQYSAGKAA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CPS1 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.19

Highest tissue expression

995 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CPS1.

Disease | AllUniProt

Conditions CPS1 is implicated in, by any mechanism.

• Carbamoyl phosphate synthetase 1 deficiency (CPS1D) MIM:237300

Disease | GeneticClinVar

402 pathogenic / likely-pathogenic of 2,250 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital hyperammonemia, type I
• Pulmonary hypertension, neonatal, susceptibility to
• CPS1-related disorder
• Inborn genetic diseases
• Uterine corpus endometrial carcinoma

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)

0.52

gnomAD pLI

0

gnomAD missense Z

1.46

DepMap mean gene effect

0.15

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% 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
• cellular response to ammonium ion
• cellular response to cAMP
• cellular response to fibroblast growth factor stimulus
• cellular response to glucagon stimulus
• cellular response to oleic acid
• citrulline biosynthetic process
• glutamine metabolic process
• hepatocyte differentiation
• homocysteine metabolic process
• midgut development
• monoatomic anion homeostasis
• nitric oxide metabolic process
• response to alcohol
• response to amine
• response to amino acid
• response to dexamethasone
• response to food
• response to growth hormone
• response to lipopolysaccharide
• response to starvation
• response to toxic substance
• response to xenobiotic stimulus
• response to zinc ion
• triglyceride catabolic process
• urea cycle
• vasodilation
• carbamoyl phosphate biosynthetic process

Molecular functions

• ATP binding
• calcium ion binding
• carbamoyl-phosphate synthase (ammonia) activity
• carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
• endopeptidase activity
• glutamate binding
• metal ion binding
• modified amino acid binding
• phospholipid binding
• potassium ion binding
• protein-containing complex binding
• small molecule binding

Cellular components

• cytoplasm
• cytosol
• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrial nucleoid
• mitochondrion
• nucleolus
• plasma membrane
• protein-containing complex
• sperm midpiece
• sperm principal piece

Protein domainsUniProt · Pfam · InterPro

• 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
• Carbamoyl-phosphate synthase, small subunit
• Carbamoyl-phosphate synthase, large subunit
• Methylglyoxal synthase-like domain
• ATP-grasp fold
• ATP-grasp fold, subdomain 1
• Pre-ATP-grasp domain superfamily
• Glutamine amidotransferase
• Class I glutamine amidotransferase-like
• Carbamoyl-phosphate synthase small subunit, GATase1 domain
• Carbamoyl-phosphate synthase small subunit, N-terminal domain superfamily
• Carbamoyl-phosphate synthetase, large subunit oligomerisation domain superfamily
• Methylglyoxal synthase-like domain superfamily
• Carbamoyl phosphate synthase, preATP-grasp domain
• Glutamine amidotransferase class-I
• Carbamoyl-phosphate synthase small chain, CPSase domain
• MGS-like domain
• Carbamoyl-phosphate synthase L chain, ATP binding domain
• Carbamoyl-phosphate synthetase large chain, oligomerisation domain
• Carbamoyl phosphate synthase preATP-grasp domain

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• ATP-binding
• Cell membrane
• Glycoprotein
• Ligase
• Membrane
• Mitochondrion
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Repeat
• Transit peptide
• Urea cycle

InteractionsUniProt · HPA

Protein binding partners of CPS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SIRT5