RefGenome Electronic Jamboree 2009-02 CPS1

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Contents

Orthoset

Ortholog set at PPOD

EcoliWiki has included the carA gene product annotations. The CarA gene product is a subunit of the E. coli carbamoyl phosphate synthetase, but was not included in the ortholog set.

Participants

NameGroupOrganism(s)/Genome(s)Notes

Rama Balakrishnan

SGD

S. cerevisiae

Ruth Lovering

BHF-UCL

Human

Harold Drabkin

MGI

Mouse

Very few papers on mouse enzyme

Susan Tweedie

flyBase

D. melanogaster

No fly ortholog for CPS1.

Stan Laulederkind

RGD

Rat

Donghui Li

TAIR

A. thaliana

Varsha Khodiyar

BHF-UCL

Human

Rachael Huntley

GOA

Human

CPS1 (P31327)

Kimberly Van Auken

WormBase

C. elegans

C. elegans annotations on CAD page.

Val Wood

other

S. pombe

There is only one paper for pombe (annotated, although the experimental annotations are not visible in the annotations below)?????

Lakshmi Pillai

AgBase

G. gallus

CPS1 (Q5KTI9) Two papers but no experimental annotations. Only ISS.

Petra Fey

dictyBase

D. discoideum

Noticed that Dicty annotations belong to CAD (enzyme has CPSase, ATCase and DHOase activity)

edit table

CPS1

CategoryIDTermHumanMouseRatChickenZfishFlyWormDictyDicotYeastPombeEcoli
Molecular FunctionGO:0004087carbamoyl-phosphate synthase (ammonia) activityIMPIMPIDAXXXXXXXXX
Molecular FunctionGO:0005524ATP bindingXXIDAXXXXXXXXIMP
Molecular FunctionGO:0032403protein complex bindingXXIDAXXXXXXXXX
Molecular FunctionGO:0004088carbamoyl-phosphate synthase (glutamine-hydrolyzing) activityXXXXXXXXXIDA IMPXIMP IDA IGI
Molecular FunctionGO:0005515protein bindingXXXXXXXXXXXIMP IDA
Molecular FunctionGO:0004070aspartate carbamoyltransferase activityXXXXXXXXXIDA IMPXX
Molecular FunctionGO:0004086carbamoyl-phosphate synthase activityXXXXXXXXXXXIDA
Molecular FunctionGO:0046872metal ion bindingXXXXXXXXXXXIDA
Molecular FunctionGO:0000166nucleotide bindingXXXXXXXXXXXIMP IDA IPI
Molecular FunctionGO:0016597amino acid bindingXXXXXXXXXXXIDA IPI
Biological ProcessGO:0000050urea cycleXICXXXXXXXXXX
Biological ProcessGO:0051591response to cAMPXXIEPXXXXXXXXX
Biological ProcessGO:0051384response to glucocorticoid stimulusXXIEPXXXXXXXXX
Biological ProcessGO:0033762response to glucagon stimulusXXIEPXXXXXXXXX
Biological ProcessGO:0042493response to drugXXIEPXXXXXXXXX
Biological ProcessGO:0032496response to lipopolysaccharideIDAXIEPXXXXXXXXX
Biological ProcessGO:0019433triglyceride catabolic processIMPXXXXXXXXXXX
Biological ProcessGO:0034201response to oleateXXIEPXXXXXXXXX
Biological ProcessGO:0042594response to starvationXXIEPXXXXXXXXX
Biological ProcessGO:0045909positive regulation of vasodilationIMPXXXXXXXXXXX
Biological ProcessGO:0046209nitric oxide metabolic processIMPXXXXXXXXXXX
Biological ProcessGO:0005980glycogen catabolic processIMPXXXXXXXXXXX
Biological ProcessGO:0006207'de novo' pyrimidine base biosynthetic processXXXXXXXXXIMPXIMP
Biological ProcessGO:0006526arginine biosynthetic processXXXXXXXXXIMPXIMP
Biological ProcessGO:0006541glutamine metabolic processXXXXXXXXXIDAXIMP
Biological ProcessGO:0019856pyrimidine base biosynthetic processXXXXXXXXXIDAXIMP
Biological ProcessGO:0008652amino acid biosynthetic processXXXXXXXXXXXIMP
Biological ProcessGO:0070409carbamoyl phosphate biosynthetic processIMPXXXXXXXXXXX
Cellular ComponentGO:0005739mitochondrionXIDAXXXXXXXXXX
Cellular ComponentGO:0005737cytoplasmXXIDAXXXXXXIDAXIDA
Cellular ComponentGO:0005743mitochondrial inner membraneXXIDAXXXXXXXXX
Cellular ComponentGO:0043234protein complexXXIDAXXXXXXXXX
Cellular ComponentGO:0042645mitochondrial nucleoidIDAXXXXXXXXXXX
Cellular ComponentGO:0009570chloroplast stromaXXXXXXXXIDAXXX
Cellular ComponentGO:0009507chloroplastXXXXXXXXIDAXXX
Cellular ComponentGO:0016020membraneXXXXXXXXIDAXXX
Cellular ComponentGO:0016021integral to membraneXXXXXXXXXIDAXX
Cellular ComponentGO:0005951carbamoyl-phosphate synthase complexXXXXXXXXXIDAXX

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GroupOrganismGeneQualifierGO IDGO term nameReference(s)Evidence Codewith/fromAspectNotesStatus

MGI

Mouse

Cps1

GO:0004087

carbamoyl-phosphate synthase (ammonia) activity

PMID:9862865[1]

IMP: Inferred from Mutant Phenotype

MGI:2386969

F

evidence:ECO:0000005; inferred from enzyme assay anatomy:MA:0000358; liver Difference between mt and wt in crude preps Annotated to (ammonia) because the assay used ammonium bicarbonate as ammonia source rather than glutamine). Maybe this too granular (just to cps activity?)

complete

MGI

Mouse

Cps1

GO:0000050

urea cycle

PMID:9862865[1]

IC: Inferred by Curator

GO:0004087

P

evidence:ECO:0000005; inferred from enzyme assay anatomy:MA:0000358; liver

text:based on how assay was done: they coupled it with citrulline conversion, which is two steps removed downstream. I'm clutching straws here.

complete

MGI

Mouse

Cps1

GO:0005739

mitochondrion

PMID:6200105[2]

IDA: Inferred from Direct Assay

C

evidence:ECO:0000004; inferred from cell fractionation|ECO:0000005;inferred from enzyme assay anatomy:MA:0000358; live text:enzyme puirfied to homogeneity from liver

complete

RGD

Rat

Cps1

GO:0005524

ATP binding

PMID:11577071[3]

IDA: Inferred from Direct Assay

F

complete

RGD

Rat

Cps1

GO:0004087

carbamoyl-phosphate synthase (ammonia) activity

PMID:11577071[3]

IDA: Inferred from Direct Assay

F

complete

RGD

Rat

Cps1

GO:0032403

protein complex binding

PMID:17669278[4]

IDA: Inferred from Direct Assay

F

complete

RGD

Rat

Cps1

GO:0051591

response to cAMP

PMID:6092398[5]

IEP: Inferred from Expression Pattern

P

complete

RGD

Rat

Cps1

GO:0051384

response to glucocorticoid stimulus

PMID:8985169[6]

IEP: Inferred from Expression Pattern

P

complete

RGD

Rat

Cps1

GO:0033762

response to glucagon stimulus

PMID:3754512[7]

IEP: Inferred from Expression Pattern

P

complete

RGD

Rat

Cps1

GO:0042493

response to drug

PMID:19135993[8]

IEP: Inferred from Expression Pattern

P

complete

RGD

Rat

Cps1

GO:0032496

response to lipopolysaccharide

PMID:17539997[9]

IEP: Inferred from Expression Pattern

P

complete

BHF-UCL

Human

CPS1

GO:0019433

triglyceride catabolic process

PMID:9711878[10]

IMP

P

complete

RGD

Rat

Cps1

GO:0034201

response to oleate

PMID:8985169[6]

IEP: Inferred from Expression Pattern

P

complete

RGD

Rat

Cps1

GO:0042594

response to starvation

PMID:1979948[11]

IEP: Inferred from Expression Pattern

P

complete

BHF-UCL

Human

CPS1

GO:0045909

positive regulation of vasodilation

PMID:14718356[12]

IMP

P

complete

RGD

Rat

Cps1

GO:0005737

cytoplasm

PMID:3527129[13]

IDA: Inferred from Direct Assay

C

complete

BHF-UCL

Human

CPS1

GO:0046209

nitric oxide metabolic process

PMID:14718356[12]

IMP

P

complete

RGD

Rat

Cps1

GO:0005743

mitochondrial inner membrane

PMID:3680220[14]

IDA: Inferred from Direct Assay

C

complete

BHF-UCL

Human

CPS1

GO:0005980

glycogen catabolic process

PMID:9711878[10]

IMP

P

complete

RGD

Rat

Cps1

GO:0043234

protein complex

PMID:17669278[4]

IDA: Inferred from Direct Assay

C

complete

RGD

Rat

Cps1

GO:0005743

mitochondrial inner membrane

PMID:3680220[14]

IDA: Inferred from Direct Assay

C

complete

BHF-UCL

Human

CPS1

GO:0004087

carbamoyl-phosphate synthase (ammonia) activity

PMID:9711878[10]

IMP

F

complete

BHF-UCL

Human

CPS1

GO:0004087

carbamoyl-phosphate synthase (ammonia) activity

PMID:8486760[15]

IMP

F

complete

BHF-UCL

Human

CPS1

GO:0042645

mitochondrial nucleoid

PMID:18063578[16]

IDA

C

complete

GOA

Human

CPS1

GO:0032496

response to lipopolysaccharide

PMID:15897806[17]

IDA: Inferred from Direct Assay

P

complete

TAIR

Arabidopsis

AT1g29900

GO:0009570

chloroplast stroma

PMID:16207701[18]

IDA: Inferred from Direct Assay

C

large scale proteomic experiments (mass spec)

complete

TAIR

Arabidopsis

AT1g29900

GO:0009507

chloroplast

PMID:15028209[19]

IDA: Inferred from Direct Assay

C

large scale proteomic experiments (mass spec)

complete

TAIR

Arabidopsis

AT1g29900

GO:0016020

membrane

PMID:17432890[20]

IDA: Inferred from Direct Assay

C

large scale proteomic experiments (mass spec)

complete

GOA

Human

CPS1

GO:0004087

carbamoyl-phosphate synthase (ammonia) activity

PMID:7416778[21]

IMP: Inferred from Mutant Phenotype

F

complete

EcoliWiki

E. coli

carA

GO:0006207

'de novo' pyrimidine base biosynthetic process

PMID:5319709[22]

IMP: Inferred from Mutant Phenotype

P

complete

EcoliWiki

E. coli

carA

GO:0006526

arginine biosynthetic process

PMID:5319709[22]

IMP: Inferred from Mutant Phenotype

P

complete

EcoliWiki

E. coli

carA

GO:0006541

glutamine metabolic process

PMID:1827118[23]

IMP: Inferred from Mutant Phenotype

P

complete

EcoliWiki

E. coli

carA

Contributes to

GO:0004088

carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity

PMID:1827118[23]

IMP: Inferred from Mutant Phenotype

F

complete

EcoliWiki

E. coli

carA

GO:0005737

cytoplasm

PMID:2682645[24]

IDA: Inferred from Direct Assay

C

complete

EcoliWiki

E. coli

carA

GO:0005515

protein binding

PMID:2682645[24]

IMP: Inferred from Mutant Phenotype

F

complete

EcoliWiki

E. coli

carB

GO:0005524

ATP binding

PMID:14718657[25]

IMP: Inferred from Mutant Phenotype

F

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0004070

aspartate carbamoyltransferase activity

PMID:10446140[26]

IDA: Inferred from Direct Assay

F

complete

EcoliWiki

E. coli

carB

Contributes to

GO:0004088

carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity

PMID:14718657[25]

IDA: Inferred from Direct Assay

F

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0004070

aspartate carbamoyltransferase activity

PMID:4550660[27]

IMP: Inferred from Mutant Phenotype

F

complete

EcoliWiki

E. coli

carB

GO:0005515

protein binding

PMID:4358555[28]

IDA: Inferred from Direct Assay

F

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0004088

carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity

PMID:5776390[29]

IDA: Inferred from Direct Assay

F

complete

EcoliWiki

E. coli

carB

GO:0004086

carbamoyl-phosphate synthase activity

PMID:3549732[30]

IDA: Inferred from Direct Assay

F

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0006207

'de novo' pyrimidine base biosynthetic process

PMID:4550660[27]

IMP: Inferred from Mutant Phenotype

P

complete

EcoliWiki

E. coli

carB

GO:0046872

metal ion binding

PMID:229896[31]

IDA: Inferred from Direct Assay

F

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0006541

glutamine metabolic process

PMID:5651325[32]


IDA: Inferred from Direct Assay

P

complete

EcoliWiki

E. coli

carB

GO:0019856

pyrimidine base biosynthetic process

PMID:1737023[33]

IMP: Inferred from Mutant Phenotype

P

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0019856

pyrimidine base biosynthetic process

PMID:181668[34]

IDA: Inferred from Direct Assay

P

complete

EcoliWiki

E. coli

carB

GO:0008652

amino acid biosynthetic process

PMID:1737023[33]

IMP: Inferred from Mutant Phenotype

P

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0005737

cytoplasm

PMID:11015727[35]

IDA: Inferred from Direct Assay

C

complete

EcoliWiki

E. coli

carB

GO:0004088

carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity

PMID:1737023[33]

IGI: Inferred from Genetic Interaction

EcoliWiki:carA

F

complete

SGD

S. cerevisiae

URA2|S000003666

GO:0016021

integral to membrane

PMID:11921093[36]

IDA: Inferred from Direct Assay

C

complete

EcoliWiki

E. coli

carB

GO:0000166

nucleotide binding

PMID:10843852[37]

IMP: Inferred from Mutant Phenotype

F

complete

SGD

S. cerevisiae

CPA2|S000003870

GO:0004088

carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity

PMID:6358221[38]

IMP: Inferred from Mutant Phenotype

F

complete

EcoliWiki

E. coli

carB

GO:0000166

nucleotide binding

PMID:7648201[39]

IDA: Inferred from Direct Assay

F

complete

SGD

S. cerevisiae

CPA2|S000003870

GO:0006526

arginine biosynthetic process

PMID:8626695[40]

IMP: Inferred from Mutant Phenotype

P

complete

EcoliWiki

E. coli

carB

GO:0016597

amino acid binding

PMID:7648201[39]

IDA: Inferred from Direct Assay

F

complete

SGD

S. cerevisiae

CPA2|S000003870

GO:0005951

carbamoyl-phosphate synthase complex

PMID:206535[41]

IDA: Inferred from Direct Assay

C

complex was purified in this paper. But named later.

complete

EcoliWiki

E. coli

carB

GO:0000166

nucleotide binding

PMID:15322282[42]

IPI: Inferred from Physical Interaction

F

complete

EcoliWiki

E. coli

carB

GO:0016597

amino acid binding

PMID:10047492[43]

IPI: Inferred from Physical Interaction

F

complete

GOA

Human

CPS1

GO:0070409

carbamoyl phosphate biosynthetic process

PMID:7416778[21]

IMP: Inferred from Mutant Phenotype

P

New term carbomyl phosphate biosynthetic process

complete

edit table

Notes

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New terms requested;
carbomyl phosphate biosynthetic process GO:0070409

There are 3 carbamoyl phosphate synthetases - CPSI, II, & III. Prokaryotes have only 1 type, usually type II. CPSII can utilize glutamine as the nitrogen donor.[44] CPSI is the only carbamoyl phosphate synthetase that cannot use glutamine. [44]

Minutes

CAD activity is separate for genes that have both CPS and CAD. CAD annotations on a separate page RefGenome_Electronic_Jamboree_2009-02_CAD

CPS1

  • Issue with Process annotation:

MGI (Harold): CPS1 is involved in the urea cycle from textbooks, but there is no mouse paper directly testing that. In one paper they assayed one step, inferred by testing two steps down, but only possible if there is a urea cycle. Harold extended it to process 'urea cycle' by IC based on the function annotation (carbamoyl-phosphate synthase (ammonia) activity, GO:0004087). Would not have done it if they only had assayed synthesis of.. They knock out the gene and assay for carbamoyl Particulary step is in urea cycle Also tested ammonia, indicative of urea cycle (but no term for it)

  • Poll: would you have annotated to urea cycle using IC from evidence from the molecular function carbamoyl-phosphate synthase (ammonia) activity ?
    • 67% yes, 33% Unsure
    • Karen: For IC, it's not experimental, and so we don't need to discuss, as IC is inferred by knowledge of curator. Question is, is the assay good enough for the experimental function to infer the process
    • Note: (Suzi) Anything that's IC will not be used for inference in the Ref Genome.
    • Pascale: How does a Process annotation ever get an IDA? (or an experimental evidence).
  • Rama SGD: CPS1 process: Should this be annotated to 'Glutamine metabolic biosynthesis'?

general agreement: If the function term says it's hydrolyzing glutamine it is metabolizing glutamine and the process can be annotated! This is a general principle that applies to all substrates in reactions.

  • How does one distinguish between salvage and de novo' pyrimidine base biosynthetic process:

Harold: from the ground up, if you know it's synthesized from scratch. This reaction is only in de novo. Pyrimidine is synthesized from scratch, by definition. (Pascale: Is this then an IC?)

  • Rama: carbamoyl-phosphate synthase complex. As yeast has the complex, it's ok to annotate, even though the paper does not call it 'carbamoyl-phosphate synthase complex',

since the description of the complex in that older paper fits the definition of the term.

References

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See Help:References for how to manage references in GONUTS.

  1. 1.0 1.1 Schofield JP et al. (1999) Mice deficient in the urea-cycle enzyme, carbamoyl phosphate synthetase I, die during the early neonatal period from hyperammonemia. Hepatology 29: 181-5 PubMed GONUTS page
  2. Bhat NK & Avadhani NG (1984) The transport and processing of carbamyl phosphate synthetase-I in mouse hepatic mitochondria. Biochem Biophys Res Commun 118: 514-22 PubMed GONUTS page
  3. 3.0 3.1 Corvi MM et al. (2001) Regulation of mitochondrial carbamoyl-phosphate synthetase 1 activity by active site fatty acylation. J Biol Chem 276: 45704-12 PubMed GONUTS page
  4. 4.0 4.1 Kim HS et al. (2007) Rat liver 10-formyltetrahydrofolate dehydrogenase, carbamoyl phosphate synthetase 1 and betaine homocysteine S-methytransferase were co-purified on Kunitz-type soybean trypsin inhibitor-coupled sepharose CL-4B. J Biochem Mol Biol 40: 604-9 PubMed GONUTS page
  5. Goss SJ (1984) Arginine synthesis by hepatomas in vitro. II. Isolation and characterization of Morris hepatoma variants unable to convert ornithine to arginine, and modulation of urea-cycle enzymes by dexamethasone and cyclic-AMP. J Cell Sci 68: 305-19 PubMed GONUTS page
  6. 6.0 6.1 Tomomura M et al. (1996) Long-chain fatty acids suppress the induction of urea cycle enzyme genes by glucocorticoid action. FEBS Lett 399: 310-2 PubMed GONUTS page
  7. Ryall JC et al. (1986) Rat liver and intestinal mucosa differ in the developmental pattern and hormonal regulation of carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase gene expression. Eur J Biochem 156: 453-8 PubMed GONUTS page
  8. Gelosa P et al. (2009) S 35171 exerts protective effects in spontaneously hypertensive stroke-prone rats by preserving mitochondrial function. Eur J Pharmacol 604: 117-24 PubMed GONUTS page
  9. Nielsen SS et al. (2007) Cirrhosis and endotoxin decrease urea synthesis in rats. Hepatol Res 37: 540-7 PubMed GONUTS page
  10. 10.0 10.1 10.2 Finckh U et al. (1998) Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat 12: 206-11 PubMed GONUTS page
  11. Moorman AF et al. (1990) Diet- and hormone-induced reversal of the carbamoylphosphate synthetase mRNA gradient in the rat liver lobulus. FEBS Lett 276: 9-13 PubMed GONUTS page
  12. 12.0 12.1 Summar ML et al. (2004) Relationship between carbamoyl-phosphate synthetase genotype and systemic vascular function. Hypertension 43: 186-91 PubMed GONUTS page
  13. Brands R & Hoogenraad N (1986) Import of carbamylphosphate synthetase and ornithine transcarbamylase into mitochondria of rat liver: detection of aggregates of enzyme in cytoplasm and mitochondria using immunoelectron microscopy with the protein A-gold method. Aust J Exp Biol Med Sci 64 ( Pt 2): 165-73 PubMed GONUTS page
  14. 14.0 14.1 Powers-Lee SG et al. (1987) The interaction of rat liver carbamoyl phosphate synthetase and ornithine transcarbamoylase with inner mitochondrial membranes. J Biol Chem 262: 15683-8 PubMed GONUTS page
  15. Hoshide R et al. (1993) Carbamyl phosphate synthetase I deficiency. One base substitution in an exon of the CPS I gene causes a 9-basepair deletion due to aberrant splicing. J Clin Invest 91: 1884-7 PubMed GONUTS page
  16. Bogenhagen DF et al. (2008) The layered structure of human mitochondrial DNA nucleoids. J Biol Chem 283: 3665-75 PubMed GONUTS page
  17. Struck J et al. (2005) Release of the mitochondrial enzyme carbamoyl phosphate synthase under septic conditions. Shock 23: 533-8 PubMed GONUTS page
  18. Peltier JB et al. (2006) The oligomeric stromal proteome of Arabidopsis thaliana chloroplasts. Mol Cell Proteomics 5: 114-33 PubMed GONUTS page
  19. Kleffmann T et al. (2004) The Arabidopsis thaliana chloroplast proteome reveals pathway abundance and novel protein functions. Curr Biol 14: 354-62 PubMed GONUTS page
  20. Mitra SK et al. (2007) Membrane proteomic analysis of Arabidopsis thaliana using alternative solubilization techniques. J Proteome Res 6: 1933-50 PubMed GONUTS page
  21. 21.0 21.1 Hoogenraad NJ et al. (1980) Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples. Arch Dis Child 55: 292-5 PubMed GONUTS page
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  36. Vorisek J et al. (2002) Enzymatic activities of Ura2 and Ura1 proteins (aspartate carbamoyltransferase and dihydro-orotate dehydrogenase) are present in both isolated membranes and cytoplasm of Saccharomyces cerevisiae. Yeast 19: 449-57 PubMed GONUTS page
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  42. Thoden JB et al. (2004) Long-range allosteric transitions in carbamoyl phosphate synthetase. Protein Sci 13: 2398-405 PubMed GONUTS page
  43. Delannay S et al. (1999) Serine 948 and threonine 1042 are crucial residues for allosteric regulation of Escherichia coli carbamoylphosphate synthetase and illustrate coupling effects of activation and inhibition pathways. J Mol Biol 286: 1217-28 PubMed GONUTS page
  44. 44.0 44.1 Hong J et al. (1994) Carbamyl phosphate synthetase III, an evolutionary intermediate in the transition between glutamine-dependent and ammonia-dependent carbamyl phosphate synthetases. J Mol Biol 243: 131-40 PubMed GONUTS page