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Identification
HMDB Protein ID HMDBP00359
Secondary Accession Numbers
  • 5595
  • HMDBP04249
Name Carbamoyl-phosphate synthase [ammonia], mitochondrial
Synonyms
  1. CPSase I
  2. Carbamoyl-phosphate synthetase I
Gene Name CPS1
Protein Type Enzyme
Biological Properties
General Function Involved in catalytic activity
Specific Function Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.
Pathways
  • 2-Hydroxyglutric Aciduria (D And L Form)
  • 4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency
  • Alanine, aspartate and glutamate metabolism
  • Ammonia Recycling
  • Arginine and Proline Metabolism
  • Arginine and proline metabolism
  • Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency)
  • Argininemia
  • Argininosuccinic Aciduria
  • Carbamoyl Phosphate Synthetase Deficiency
  • Citrullinemia Type I
  • Creatine deficiency, guanidinoacetate methyltransferase deficiency
  • Glutamate Metabolism
  • Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency)
  • Homocarnosinosis
  • Hyperinsulinism-Hyperammonemia Syndrome
  • Hyperornithinemia with gyrate atrophy (HOGA)
  • Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]
  • Hyperprolinemia Type I
  • Hyperprolinemia Type II
  • L-arginine:glycine amidinotransferase deficiency
  • Ornithine Aminotransferase Deficiency (OAT Deficiency)
  • Ornithine Transcarbamylase Deficiency (OTC Deficiency)
  • Prolidase Deficiency (PD)
  • Prolinemia Type II
  • Succinic semialdehyde dehydrogenase deficiency
  • Urea Cycle
Reactions
Adenosine triphosphate + Ammonia + CO(2) + Water → ADP + Phosphoric acid + Carbamoyl phosphate details
Adenosine triphosphate + Ammonia + Carbon dioxide + Water → ADP + Phosphoric acid + Carbamoyl phosphate details
GO Classification
Biological Process
response to zinc ion
response to amino acid stimulus
cellular response to fibroblast growth factor stimulus
response to lipopolysaccharide
positive regulation of vasodilation
cellular response to cAMP
cellular response to oleic acid
response to growth hormone stimulus
response to drug
hepatocyte differentiation
response to starvation
response to food
triglyceride catabolic process
anion homeostasis
carbamoyl phosphate biosynthetic process
citrulline biosynthetic process
midgut development
glutamine catabolic process
glycogen catabolic process
homocysteine metabolic process
nitric oxide metabolic process
response to dexamethasone stimulus
response to amine stimulus
urea cycle
cellular response to glucagon stimulus
Cellular Component
nucleolus
mitochondrial nucleoid
mitochondrial inner membrane
protein complex
Function
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
ligase activity
carbamoyl-phosphate synthase activity
ligase activity, forming carbon-nitrogen bonds
Molecular Function
endopeptidase activity
phospholipid binding
ATP binding
calcium ion binding
carbamoyl-phosphate synthase (ammonia) activity
glutamate binding
modified amino acid binding
Process
metabolic process
nitrogen compound metabolic process
cellular metabolic process
glutamine metabolic process
glutamine family amino acid metabolic process
cellular amino acid and derivative metabolic process
cellular amino acid metabolic process
Cellular Location
  1. Mitochondrion
Gene Properties
Chromosome Location 2
Locus 2q35
SNPs CPS1
Gene Sequence
>4503 bp
ATGACGAGGATTTTGACAGCTTTCAAAGTGGTGAGGACACTGAAGACTGGTTTTGGCTTT
ACCAATGTGACTGCACACCAAAAATGGAAATTTTCAAGACCTGGCATCAGGCTCCTTTCT
GTCAAGGCACAGACAGCACACATTGTCCTGGAAGATGGAACTAAGATGAAAGGTTACTCC
TTTGGCCATCCATCCTCTGTTGCTGGTGAAGTGGTTTTTAATACTGGCCTGGGAGGGTAC
CCAGAAGCTATTACTGACCCTGCCTACAAAGGACAGATTCTCACAATGGCCAACCCTATT
ATTGGGAATGGTGGAGCTCCTGATACTACTGCTCTGGATGAACTGGGACTTAGCAAATAT
TTGGAGTCTAATGGAATCAAGGTTTCAGGTTTGCTGGTGCTGGATTATAGTAAAGACTAC
AACCACTGGCTGGCTACCAAGAGTTTAGGGCAATGGCTACAGGAAGAAAAGGTTCCTGCA
ATTTATGGAGTGGACACAAGAATGCTGACTAAAATAATTCGGGATAAGGGTACCATGCTT
GGGAAGATTGAATTTGAAGGTCAGCCTGTGGATTTTGTGGATCCAAATAAACAGAATTTG
ATTGCTGAGGTTTCAACCAAGGATGTCAAAGTGTACGGCAAAGGAAACCCCACAAAAGTG
GTAGCTGTAGACTGTGGGATTAAAAACAATGTAATCCGCCTGCTAGTAAAGCGAGGAGCT
GAAGTGCACTTAGTTCCCTGGAACCATGATTTCACCAAGATGGAGTATGATGGGATTTTG
ATCGCGGGAGGACCGGGGAACCCAGCTCTTGCAGAACCACTAATTCAGAATGTCAGAAAG
ATTTTGGAGAGTGATCGCAAGGAGCCATTGTTTGGAATCAGTACAGGAAACTTAATAACA
GGATTGGCTGCTGGTGCCAAAACCTACAAGATGTCCATGGCCAACAGAGGGCAGAATCAG
CCTGTTTTGAATATCACAAACAAACAGGCTTTCATTACTGCTCAGAATCATGGCTATGCC
TTGGACAACACCCTCCCTGCTGGCTGGAAACCACTTTTTGTGAATGTCAACGATCAAACA
AATGAGGGGATTATGCATGAGAGCAAACCCTTCTTCGCTGTGCAGTTCCACCCAGAGGTC
ACCCCGGGGCCAATAGACACTGAGTACCTGTTTGATTCCTTTTTCTCACTGATAAAGAAA
GGAAAAGCTACCACCATTACATCAGTCTTACCGAAGCCAGCACTAGTTGCATCTCGGGTT
GAGGTTTCCAAAGTCCTTATTCTAGGATCAGGAGGTCTGTCCATTGGTCAGGCTGGAGAA
TTTGATTACTCAGGATCTCAAGCTGTAAAAGCCATGAAGGAAGAAAATGTCAAAACTGTT
CTGATGAACCCAAACATTGCATCAGTCCAGACCAATGAGGTGGGCTTAAAGCAAGCGGAT
ACTGTCTACTTTCTTCCCATCACCCCTCAGTTTGTCACAGAGGTCATCAAGGCAGAACAG
CCAGATGGGTTAATTCTGGGCATGGGTGGCCAGACAGCTCTGAACTGTGGAGTGGAACTA
TTCAAGAGAGGTGTGCTCAAGGAATATGGTGTGAAAGTCCTGGGAACTTCAGTTGAGTCC
ATTATGGCTACGGAAGACAGGCAGCTGTTTTCAGATAAACTAAATGAGATCAATGAAAAG
ATTGCTCCAAGTTTTGCAGTGGAATCGATTGAGGATGCACTGAAGGCAGCAGACACCATT
GGCTACCCAGTGATGATCCGTTCCGCCTATGCACTGGGTGGGTTAGGCTCAGGCATCTGT
CCCAACAGAGAGACTTTGATGGACCTCAGCACAAAGGCCTTTGCTATGACCAACCAAATT
CTGGTGGAGAAGTCAGTGACAGGTTGGAAAGAAATAGAATATGAAGTGGTTCGAGATGCT
GATGACAATTGTGTCACTGTCTGTAACATGGAAAATGTTGATGCCATGGGTGTTCACACA
GGTGACTCAGTTGTTGTGGCTCCTGCCCAGACACTCTCCAATGCCGAGTTTCAGATGTTG
AGACGTACTTCAATCAATGTTGTTCGCCACTTGGGCATTGTGGGTGAATGCAACATTCAG
TTTGCCCTTCATCCTACCTCAATGGAATACTGCATCATTGAAGTGAATGCCAGACTGTCC
CGAAGCTCTGCTCTGGCCTCAAAAGCCACTGGCTACCCATTGGCATTCATTGCTGCAAAG
ATTGCCCTAGGAATCCCACTTCCAGAAATTAAGAACGTCGTATCCGGGAAGACATCAGCC
TGTTTTGAACCTAGCCTGGATTACATGGTCACCAAGATTCCCCGCTGGGATCTTGACCGT
TTTCATGGAACATCTAGCCGAATTGGTAGCTCTATGAAAAGTGTAGGAGAGGTCATGGCT
ATTGGTCGTACCTTTGAGGAGAGTTTCCAGAAAGCTTTACGGATGTGCCACCCATCTATA
GAAGGTTTCACTCCCCGTCTCCCAATGAACAAAGAATGGCCATCTAATTTAGATCTTAGA
AAAGAGTTGTCTGAACCAAGCAGCACGCGTATCTATGCCATTGCCAAGGCCATTGATGAC
AACATGTCCCTTGATGAGATTGAGAAGCTCACATACATTGACAAGTGGTTTTTGTATAAG
ATGCGTGATATTTTAAACATGGAAAAGACACTGAAAGGGCTCAACAGTGAGTCCATGACA
GAAGAAACCCTGAAAAGGGCAAAGGAGATTGGGTTCTCAGATAAGCAGATTTCAAAATGC
CTTGGGCTCACTGAGGCCCAGACAAGGGAGCTGAGGTTAAAGAAAAACATCCACCCTTGG
GTTAAACAGATTGATACACTGGCTGCAGAATACCCATCAGTAACAAACTATCTCTATGTT
ACCTACAATGGTCAGGAGCATGATGTCAATTTTGATGACCATGGAATGATGGTGCTAGGC
TGTGGTCCATATCACATTGGCAGCAGTGTGGAATTTGATTGGTGTGCTGTCTCTAGTATC
CGCACACTGCGTCAACTTGGCAAGAAGACGGTGGTGGTGAATTGCAATCCTGAGACTGTG
AGCACAGACTTTGATGAGTGTGACAAACTGTACTTTGAAGAGTTGTCCTTGGAGAGAATC
CTAGACATCTACCATCAGGAGGCATGTGGTGGCTGCATCATATCAGTTGGAGGCCAGATT
CCAAACAACCTGGCAGTTCCTCTATACAAGAATGGTGTCAAGATCATGGGCACAAGCCCC
CTGCAGATCGACAGGGCTGAGGATCGCTCCATCTTCTCAGCTGTCTTGGATGAGCTGAAG
GTGGCTCAGGCACCTTGGAAAGCTGTTAATACTTTGAATGAAGCACTGGAATTTGCAAAG
TCTGTGGACTACCCCTGCTTGTTGAGGCCTTCCTATGTTTTGAGTGGGTCTGCTATGAAT
GTGGTATTCTCTGAGGATGAGATGAAAAAATTCCTAGAAGAGGCGACTAGAGTTTCTCAG
GAGCACCCAGTGGTCCTGACAAAATTTGTTGAAGGGGCCCGAGAAGTAGAAATGGACGCT
GTTGGCAAAGATGGAAGGGTTATCTCTCATGCCATCTCTGAACATGTTGAAGATGCAGGT
GTCCACTCGGGAGATGCCACTCTGATGCTGCCCACACAAACCATCAGCCAAGGGGCCATT
GAAAAGGTGAAGGATGCTACCCGGAAGATTGCAAAGGCTTTTGCCATCTCTGGTCCATTC
AACGTCCAATTTCTTGTCAAAGGAAATGATGTCTTGGTGATTGAGTGTAACTTGAGAGCT
TCTCGATCCTTCCCCTTTGTTTCCAAGACTCTTGGGGTTGACTTCATTGATGTGGCCACC
AAGGTGATGATTGGAGAGAATGTTGATGAGAAACATCTTCCAACATTGGACCATCCCATA
ATTCCTGCTGACTATGTTGCAATTAAGGCTCCCATGTTTTCCTGGCCCCGGTTGAGGGAT
GCTGACCCCATTCTGAGATGTGAGATGGCTTCCACTGGAGAGGTGGCTTGCTTTGGTGAA
GGTATTCATACAGCCTTCCTAAAGGCAATGCTTTCCACAGGATTTAAGATACCCCAGAAA
GGCATCCTGATAGGCATCCAGCAATCATTCCGGCCAAGATTCCTTGGTGTGGCTGAACAA
TTACACAATGAAGGTTTCAAGCTGTTTGCCACGGAAGCCACATCAGACTGGCTCAACGCC
AACAATGTCCCTGCCACCCCAGTGGCATGGCCGTCTCAAGAAGGACAGAATCCCAGCCTC
TCTTCCATCAGAAAATTGATTAGAGATGGCAGCATTGACCTAGTGATTAACCTTCCCAAC
AACAACACTAAATTTGTCCATGATAATTATGTGATTCGGAGGACAGCTGTTGATAGTGGA
ATCCCTCTCCTCACTAATTTTCAGGTGACCAAACTTTTTGCTGAAGCTGTGCAGAAATCT
CGCAAGGTGGACTCCAAGAGTCTTTTCCACTACAGGCAGTACAGTGCTGGAAAAGCAGCA
TAG
Protein Properties
Number of Residues 1500
Molecular Weight 165649.075
Theoretical pI 6.79
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Carbamoyl-phosphate synthase [ammonia], mitochondrial
MTRILTAFKVVRTLKTGFGFTNVTAHQKWKFSRPGIRLLSVKAQTAHIVLEDGTKMKGYS
FGHPSSVAGEVVFNTGLGGYPEAITDPAYKGQILTMANPIIGNGGAPDTTALDELGLSKY
LESNGIKVSGLLVLDYSKDYNHWLATKSLGQWLQEEKVPAIYGVDTRMLTKIIRDKGTML
GKIEFEGQPVDFVDPNKQNLIAEVSTKDVKVYGKGNPTKVVAVDCGIKNNVIRLLVKRGA
EVHLVPWNHDFTKMEYDGILIAGGPGNPALAEPLIQNVRKILESDRKEPLFGISTGNLIT
GLAAGAKTYKMSMANRGQNQPVLNITNKQAFITAQNHGYALDNTLPAGWKPLFVNVNDQT
NEGIMHESKPFFAVQFHPEVTPGPIDTEYLFDSFFSLIKKGKATTITSVLPKPALVASRV
EVSKVLILGSGGLSIGQAGEFDYSGSQAVKAMKEENVKTVLMNPNIASVQTNEVGLKQAD
TVYFLPITPQFVTEVIKAEQPDGLILGMGGQTALNCGVELFKRGVLKEYGVKVLGTSVES
IMATEDRQLFSDKLNEINEKIAPSFAVESIEDALKAADTIGYPVMIRSAYALGGLGSGIC
PNRETLMDLSTKAFAMTNQILVEKSVTGWKEIEYEVVRDADDNCVTVCNMENVDAMGVHT
GDSVVVAPAQTLSNAEFQMLRRTSINVVRHLGIVGECNIQFALHPTSMEYCIIEVNARLS
RSSALASKATGYPLAFIAAKIALGIPLPEIKNVVSGKTSACFEPSLDYMVTKIPRWDLDR
FHGTSSRIGSSMKSVGEVMAIGRTFEESFQKALRMCHPSIEGFTPRLPMNKEWPSNLDLR
KELSEPSSTRIYAIAKAIDDNMSLDEIEKLTYIDKWFLYKMRDILNMEKTLKGLNSESMT
EETLKRAKEIGFSDKQISKCLGLTEAQTRELRLKKNIHPWVKQIDTLAAEYPSVTNYLYV
TYNGQEHDVNFDDHGMMVLGCGPYHIGSSVEFDWCAVSSIRTLRQLGKKTVVVNCNPETV
STDFDECDKLYFEELSLERILDIYHQEACGGCIISVGGQIPNNLAVPLYKNGVKIMGTSP
LQIDRAEDRSIFSAVLDELKVAQAPWKAVNTLNEALEFAKSVDYPCLLRPSYVLSGSAMN
VVFSEDEMKKFLEEATRVSQEHPVVLTKFVEGAREVEMDAVGKDGRVISHAISEHVEDAG
VHSGDATLMLPTQTISQGAIEKVKDATRKIAKAFAISGPFNVQFLVKGNDVLVIECNLRA
SRSFPFVSKTLGVDFIDVATKVMIGENVDEKHLPTLDHPIIPADYVAIKAPMFSWPRLRD
ADPILRCEMASTGEVACFGEGIHTAFLKAMLSTGFKIPQKGILIGIQQSFRPRFLGVAEQ
LHNEGFKLFATEATSDWLNANNVPATPVAWPSQEGQNPSLSSIRKLIRDGSIDLVINLPN
NNTKFVHDNYVIRRTAVDSGIPLLTNFQVTKLFAEAVQKSRKVDSKSLFHYRQYSAGKAA
GenBank ID Protein 5020420
UniProtKB/Swiss-Prot ID P31327
UniProtKB/Swiss-Prot Entry Name CPSM_HUMAN
PDB IDs
GenBank Gene ID AF154830
GeneCard ID CPS1
GenAtlas ID CPS1
HGNC ID HGNC:2323
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  3. Haraguchi Y, Uchino T, Takiguchi M, Endo F, Mori M, Matsuda I: Cloning and sequence of a cDNA encoding human carbamyl phosphate synthetase I: molecular analysis of hyperammonemia. Gene. 1991 Nov 15;107(2):335-40. [PubMed:1840546 ]
  4. Finckh U, Kohlschutter A, Schafer H, Sperhake K, Colombo JP, Gal A: Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat. 1998;12(3):206-11. [PubMed:9711878 ]
  5. Summar ML, Hall LD, Eeds AM, Hutcheson HB, Kuo AN, Willis AS, Rubio V, Arvin MK, Schofield JP, Dawson EP: Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene. Gene. 2003 Jun 5;311:51-7. [PubMed:12853138 ]
  6. Funghini S, Donati MA, Pasquini E, Zammarchi E, Morrone A: Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesions. Hum Mutat. 2003 Oct;22(4):340-1. [PubMed:12955727 ]
  7. Haberle J, Schmidt E, Pauli S, Rapp B, Christensen E, Wermuth B, Koch HG: Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onset. Hum Mutat. 2003 Apr;21(4):444. [PubMed:12655559 ]
  8. Aoshima T, Kajita M, Sekido Y, Kikuchi S, Yasuda I, Saheki T, Watanabe K, Shimokata K, Niwa T: Novel mutations (H337R and 238-362del) in the CPS1 gene cause carbamoyl phosphate synthetase I deficiency. Hum Hered. 2001;52(2):99-101. [PubMed:11474210 ]
  9. Pearson DL, Dawling S, Walsh WF, Haines JL, Christman BW, Bazyk A, Scott N, Summar ML: Neonatal pulmonary hypertension--urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med. 2001 Jun 14;344(24):1832-8. [PubMed:11407344 ]
  10. Wakutani Y, Nakayasu H, Takeshima T, Adachi M, Kawataki M, Kihira K, Sawada H, Bonno M, Yamamoto H, Nakashima K: Mutational analysis of carbamoylphosphate synthetase I deficiency in three Japanese patients. J Inherit Metab Dis. 2004;27(6):787-8. [PubMed:15617192 ]
  11. Haberle J, Koch HG: Genetic approach to prenatal diagnosis in urea cycle defects. Prenat Diagn. 2004 May;24(5):378-83. [PubMed:15164414 ]
  12. Kurokawa K, Yorifuji T, Kawai M, Momoi T, Nagasaka H, Takayanagi M, Kobayashi K, Yoshino M, Kosho T, Adachi M, Otsuka H, Yamamoto S, Murata T, Suenaga A, Ishii T, Terada K, Shimura N, Kiwaki K, Shintaku H, Yamakawa M, Nakabayashi H, Wakutani Y, Nakahata T: Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency. J Hum Genet. 2007;52(4):349-54. Epub 2007 Feb 20. [PubMed:17310273 ]
  13. Moonen RM, Reyes I, Cavallaro G, Gonzalez-Luis G, Bakker JA, Villamor E: The T1405N carbamoyl phosphate synthetase polymorphism does not affect plasma arginine concentrations in preterm infants. PLoS One. 2010 May 25;5(5):e10792. doi: 10.1371/journal.pone.0010792. [PubMed:20520828 ]