CAR1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000050 urea cycle	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Arginase executes the arginine-to-ornithine-and-urea reaction shared by catabolism and the urea-cycle topology. Reason: GO:0000050 defines ornithine-to-arginine synthesis followed by arginine hydrolysis to urea and regenerated ornithine; it does not require ureotelic excretion. These yeasts possess the relevant OTC/ASS/ASL and arginase reactions. Retain the existing annotation as contextual participation in that network, distinct from the principal nitrogen-source catabolic role. This does not assert a measured net steady-state cycle flux or simultaneous maximal operation of anabolic and catabolic enzymes. The substrate-triggered CAR1-ARG3 inhibitory complex (PMID:12679340) constrains simultaneous cycling; it does not eliminate the inherited reaction or redefine the GO term. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000144386 SUPPORTS TRANSFER The node-level inherited urea-cycle reaction is compatible with native fungal reaction topology. Neither donor taxonomy nor absence of ureotelic excretion establishes a phylogenetic failure. Supporting Evidence: PMID:12679340 In the presence of ornithine and arginine, ornithine carbamoyltransferase (OTCase) and arginase form a one-to-one enzyme complex in which the activity of OTCase is inhibited whereas arginase remains catalytically active
GO:0000050 urea cycle	IDA PMID:2404017 The purification and characterization of arginase from Sacch...	KEEP AS NON CORE	Summary: Arginase executes the arginine-to-ornithine-and-urea reaction shared by catabolism and the urea-cycle topology. Reason: GO:0000050 defines ornithine-to-arginine synthesis followed by arginine hydrolysis to urea and regenerated ornithine; it does not require ureotelic excretion. These yeasts possess the relevant OTC/ASS/ASL and arginase reactions. Retain the existing annotation as contextual participation in that network, distinct from the principal nitrogen-source catabolic role. This does not assert a measured net steady-state cycle flux or simultaneous maximal operation of anabolic and catabolic enzymes. The substrate-triggered CAR1-ARG3 inhibitory complex (PMID:12679340) constrains simultaneous cycling; it does not eliminate the inherited reaction or redefine the GO term. Supporting Evidence: PMID:2404017 The purified enzyme has a specific activity of 885 mumol urea min-1 mg-1 and a Km for arginine of 15.7 mM.
GO:0000050 urea cycle	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: Arginase executes the arginine-to-ornithine-and-urea reaction shared by catabolism and the urea-cycle topology. Reason: GO:0000050 defines ornithine-to-arginine synthesis followed by arginine hydrolysis to urea and regenerated ornithine; it does not require ureotelic excretion. These yeasts possess the relevant OTC/ASS/ASL and arginase reactions. Retain the existing annotation as contextual participation in that network, distinct from the principal nitrogen-source catabolic role. This does not assert a measured net steady-state cycle flux or simultaneous maximal operation of anabolic and catabolic enzymes. The substrate-triggered CAR1-ARG3 inhibitory complex (PMID:12679340) constrains simultaneous cycling; it does not eliminate the inherited reaction or redefine the GO term.
GO:0000050 urea cycle	IMP PMID:14582193 Isolation of the CAR1 gene from Saccharomyces cerevisiae and...	KEEP AS NON CORE	Summary: Arginase executes the arginine-to-ornithine-and-urea reaction shared by catabolism and the urea-cycle topology. Reason: GO:0000050 defines ornithine-to-arginine synthesis followed by arginine hydrolysis to urea and regenerated ornithine; it does not require ureotelic excretion. These yeasts possess the relevant OTC/ASS/ASL and arginase reactions. Retain the existing annotation as contextual participation in that network, distinct from the principal nitrogen-source catabolic role. This does not assert a measured net steady-state cycle flux or simultaneous maximal operation of anabolic and catabolic enzymes. The substrate-triggered CAR1-ARG3 inhibitory complex (PMID:12679340) constrains simultaneous cycling; it does not eliminate the inherited reaction or redefine the GO term. Supporting Evidence: PMID:14582193 arginase production is probably controlled at the level of gene expression
GO:0004053 arginase activity	IBA GO_REF:0000033	ACCEPT	Summary: Arginase activity IBA from PTN000144386, seeded by many arginases including SGD:S000006032 (CAR1 itself, which has its own experimental activity data). Core function. Supporting Evidence: PMID:2404017 The purified enzyme has a specific activity of 885 mumol urea min-1 mg-1
GO:0004053 arginase activity	IDA PMID:2404017 The purification and characterization of arginase from Sacch...	ACCEPT	Summary: Direct assay of purified, overproduced yeast arginase (specific activity and Km for arginine determined; Mn2+-dependent heat activation). Core function. Supporting Evidence: PMID:2404017 The purified enzyme has a specific activity of 885 mumol urea min-1 mg-1 and a Km for arginine of 15.7 mM.
GO:0004053 arginase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated assignment via EC 3.5.3.1 / RHEA:20569 and the arginase InterPro family (IPR014033); correct for CAR1 and consistent with direct biochemistry.
GO:0004053 arginase activity	IMP PMID:14582193 Isolation of the CAR1 gene from Saccharomyces cerevisiae and...	ACCEPT	Summary: Curator IMP from the CAR1 cloning paper (abstract-only in cache); the cloned gene and regulatory mutants were related to arginase levels. Consistent with direct biochemical evidence; defer to curator. Supporting Evidence: PMID:14582193 qualitative correlation between the steady-state levels of CAR1-specific, polyadenylated RNA and the degree of arginase induction and repression
GO:0004053 arginase activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS transfer from human ARG1 (P05089). Correct but redundant with direct experimental evidence for the yeast enzyme.
GO:0004053 arginase activity	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways ARG-PRO-PWY (arginine degradation via the arginase pathway) assigns the arginase step to CAR1; correct.
GO:0004053 arginase activity	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways ARGDEG-YEAST-PWY (arginine degradation) assigns the arginase step to CAR1; correct.
GO:0005515 protein binding	IPI PMID:12679340 Yeast epiarginase regulation, an enzyme-enzyme activity cont...	MODIFY	Summary: Functional CAR1-ARG3 binding is resolved as ornithine carbamoyltransferase inhibitor activity. Reason: PMID:12679340 directly establishes the consequence of this interaction: CAR1 inhibits ARG3 in the substrate-triggered epiarginase complex. Replace generic protein binding with the supported inhibitor molecular function, already present in this review, under the current binding policy. Proposed replacements: ornithine carbamoyltransferase inhibitor activity Supporting Evidence: PMID:12679340 In arginase, two cysteines at the C terminus of the protein are crucial for its epiarginase function but not for its catalytic activity and trimeric structure.
GO:0005634 nucleus	HDA PMID:14562095 Global analysis of protein localization in budding yeast.	KEEP AS NON CORE	Summary: The curated genome-wide GFP screen records a nuclear localization in addition to the established cytosolic enzyme pool. Reason: Retain this specific experimental location as non-core while distinguishing localization from any proposed nuclear catalytic or regulatory function. No passive-diffusion mechanism is inferred.
GO:0005737 cytoplasm	HDA PMID:14562095 Global analysis of protein localization in budding yeast.	MODIFY	Summary: Cytoplasmic GFP localisation from the global screen; consistent with fractionation showing arginase in the soluble fraction. Reason: Cytoplasm is correct but broader than the supported cytosolic enzyme location already represented in this review. Refine to cytosol; this does not deny separate context-specific nuclear observations. Proposed replacements: cytosol Supporting Evidence: PMID:205532 the two first catabolic enzymes, arginase and ornithine aminotransferase, were in the "soluble" fraction of the cell
GO:0005737 cytoplasm	IBA GO_REF:0000033	MODIFY	Summary: Cytoplasm IBA from PTN000144386 including CAR1 itself; consistent with fractionation data. Reason: Cytoplasm is correct but broader than the supported cytosolic enzyme location already represented in this review. Refine to cytosol; this does not deny separate context-specific nuclear observations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000144386 SUPPORTS TRANSFER The inherited claim remains true; this review refines the term using the independently supported target function or compartment, without alleging incorrect node placement. Proposed replacements: cytosol
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Cytosol IBA from PTN000144387 (fungal arginase subclade, seeded by S. pombe and CAR1). Correct.
GO:0005829 cytosol	IDA PMID:205532 Arginine metabolism in Saccharomyces cerevisiae: subcellular...	ACCEPT	Summary: Subcellular fractionation placed arginase in the soluble (cytosolic) fraction together with OTCase, with which it forms the epiarginase complex. Supporting Evidence: PMID:205532 the two first catabolic enzymes, arginase and ornithine aminotransferase, were in the "soluble" fraction of the cell
GO:0005829 cytosol	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways (ARG-PRO-PWY) places the arginase step in the cytosol; consistent with fractionation.
GO:0005829 cytosol	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways (ARGDEG-YEAST-PWY) places the arginase step in the cytosol; consistent with fractionation.
GO:0006525 arginine metabolic process	IBA GO_REF:0000033	MODIFY	Summary: Arginine metabolic process IBA; correct but general parent of the catabolic process that arginase actually performs in yeast. Reason: Arginase directly hydrolyzes L-arginine. Refine the broad metabolic term to its supported catabolic descendant, already present in this review; the broad inherited claim is true. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000144386 SUPPORTS TRANSFER The inherited claim remains true; this review refines the term using the independently supported target function or compartment, without alleging incorrect node placement. Proposed replacements: L-arginine catabolic process
GO:0006525 arginine metabolic process	IEA GO_REF:0000002	MODIFY	Summary: InterPro arginase family (IPR014033) mapping to arginine metabolic process; correct, general. Reason: Arginase directly hydrolyzes L-arginine. Refine the broad metabolic term to its supported catabolic descendant, already present in this review; the broad inherited claim is true. Proposed replacements: L-arginine catabolic process
GO:0006527 L-arginine catabolic process	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways arginine degradation (arginase pathway); arginase performs the first step of arginine catabolism. Core process. Supporting Evidence: PMID:14582193 A 1.25-kilobase CAR1-specific RNA species was markedly increased, however, in wild-type cells grown in the presence of inducer
GO:0006527 L-arginine catabolic process	RCA GO_REF:0000123	ACCEPT	Summary: YeastPathways aerobic arginine degradation; same catabolic step as above. Core process.
GO:0008270 zinc ion binding	IDA PMID:1939179 Roles of metal ions in the maintenance of the tertiary and q...	ACCEPT	Summary: Metal analysis of purified yeast arginase identified a tightly bound structural Zn2+ that stabilises the trimer (removal lowers thermal stability). Real, but a structural cofactor rather than the catalytic function. Reason: Binding of the structural zinc site stabilizes the native arginase fold and oligomer. Structural cofactor binding is a core biochemical property, not peripheral merely because it is distinct from catalysis. PMID:1939179 directly measured the metal and stability effects; the proteome survey is corroborative. Supporting Evidence: PMID:1939179 Both the loosely associated catalytic Mn2+ ion and the more tightly associated structural Zn2+ ion confer stability to the enzyme.
GO:0008270 zinc ion binding	RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr...	ACCEPT	Summary: Zinc-proteome survey (bioinformatic prediction plus proteomics) listing CAR1 as a zinc protein. Consistent with the biochemically identified structural Zn2+ site. Reason: Binding of the structural zinc site stabilizes the native arginase fold and oligomer. Structural cofactor binding is a core biochemical property, not peripheral merely because it is distinct from catalysis. PMID:1939179 directly measured the metal and stability effects; the proteome survey is corroborative.
GO:0016813 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines	IEA GO_REF:0000002	MODIFY	Summary: InterPro ureohydrolase Mn-binding site (IPR020855) mapping to hydrolase acting on linear amidines; correct parent of arginase activity. Reason: The broad amidine hydrolase activity is true, and the specific arginase reaction is independently supported and already annotated. Refine to that activity. Proposed replacements: arginase activity
GO:0030145 manganese ion binding	IBA GO_REF:0000033	ACCEPT	Summary: Inherited manganese binding is independently supported by native yeast arginase biochemistry; the specific yeast preparation measured about one weakly bound catalytic Mn per subunit, with a separate tight predominantly Zn site. Reason: Accept manganese binding without replacing the target-specific metal measurements by a universal two-Mn stoichiometry. Supporting Evidence: PMID:2404017 Arginase has a weakly bound manganese responsible for the maintenance of the catalytic activity
GO:0030145 manganese ion binding	IDA PMID:1939179 Roles of metal ions in the maintenance of the tertiary and q...	ACCEPT	Summary: Atomic absorption showed ~1 Mn2+ per subunit in the catalytic site of the purified yeast enzyme. Supporting Evidence: PMID:1939179 there is a weakly associated Mn2+ that binds to the trimeric enzyme with a stoichiometry of 1.04 +/- 0.05 mol of Mn2+ bound per subunit
GO:0043332 mating projection tip	HDA PMID:19053807 Systematic definition of protein constituents along the majo...	KEEP AS NON CORE	Summary: The full primary text explicitly identifies Car1 among proteins recovered in the pheromone-induced shmoo-tip screen. Reason: Retain the observed context-specific localization as non-core; the screen does not establish a particular mating function for arginase. Supporting Evidence: PMID:19053807 Car1, an arginase that when deleted causes cells to undergo G1 cell cycle arrest upon starvation
GO:0046872 metal ion binding	IEA GO_REF:0000002	MODIFY	Summary: Generic metal ion binding from InterPro ureohydrolase signatures; correct but superseded by the specific Mn2+ and Zn2+ binding annotations. Reason: Refine general metal binding to the independently supported catalytic/cofactor metal. The general parent is true, not an over-annotation. PMID:1939179 directly measures both weak catalytic Mn and tightly bound predominantly structural Zn in purified yeast arginase. Proposed replacements: manganese ion binding zinc ion binding
GO:0090369 ornithine carbamoyltransferase inhibitor activity	IDA PMID:12679340 Yeast epiarginase regulation, an enzyme-enzyme activity cont...	ACCEPT	Summary: In the ornithine- and arginine-triggered epiarginase complex arginase inhibits OTCase (ARG3); arginase acts as a negative effector of OTCase. Genuine regulatory moonlighting function. Supporting Evidence: PMID:12679340 In the presence of ornithine and arginine, ornithine carbamoyltransferase (OTCase) and arginase form a one-to-one enzyme complex in which the activity of OTCase is inhibited whereas arginase remains catalytically active PMID:2404017 In this complex, arginase acts as a negative allosteric effector for ornithine transcarbamoylase.
GO:0090369 ornithine carbamoyltransferase inhibitor activity	IMP PMID:12679340 Yeast epiarginase regulation, an enzyme-enzyme activity cont...	ACCEPT	Summary: Mutations of two C-terminal cysteines abolish the epiarginase (OTCase-inhibitory) function without affecting catalysis, genetically separating the inhibitor activity from arginase activity. Supporting Evidence: PMID:12679340 In arginase, two cysteines at the C terminus of the protein are crucial for its epiarginase function but not for its catalytic activity and trimeric structure.
GO:1903269 ornithine carbamoyltransferase inhibitor complex	IPI PMID:12679340 Yeast epiarginase regulation, an enzyme-enzyme activity cont...	ACCEPT	Summary: Arginase is the inhibitory partner in the one-to-one OTCase-arginase complex. Supporting Evidence: PMID:12679340 In the presence of ornithine and arginine, ornithine carbamoyltransferase (OTCase) and arginase form a one-to-one enzyme complex

Gene Description

Existing Annotations Review

Core Functions

Mn2+-dependent hydrolysis of L-arginine to L-ornithine and urea (EC 3.5.3.1), the first step of arginine catabolism for nitrogen use, in the cytosol.

Epiarginase regulation - in the presence of ornithine and arginine, arginase binds OTCase (ARG3) one-to-one and inhibits it, preventing futile simultaneous arginine synthesis and degradation.

References

Deep Research

SGD

SGD gene description for CAR1 (yeast)

📚 Additional Documentation

Notes

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