Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Cloning and site-directed mutagenesis of human ADP-ribosylarginine hydrolase.
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The human ADP-ribosylarginine hydrolase was cloned and expressed in E. coli, and site-directed mutants were assayed for hydrolase activity, establishing the human enzyme's activity and the residue basis of its dithiothreitol independence.
"Human hydrolase and rat C108S were DTT-independent; human S103C was, however, DTT-dependent."
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The paper frames the enzyme as the reversing half of an arginine ADP-ribosylation cycle, which is the biological process the GO rows record.
"Mono-ADP-ribosylation of arginine is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the opposing reactions in the cycle."
Cloning, expression, purification and crystallization as well as X-ray fluorescence and preliminary X-ray diffraction analyses of human ADP-ribosylhydrolase 1.
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A potassium ion is present in the hARH1 crystal used for the 1.9 A structure (PDB 3HFW), identified by X-ray fluorescence and then supplied deliberately as K-ADP.
"hARH1 has been cloned, expressed heterologously in Escherichia coli, purified and crystallized in complex with K(+) and ADP."
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The potassium originated from the crystallisation conditions and was pursued because it improved diffraction, not because a functional requirement was measured.
"A prerequisite for obtaining well diffracting crystals was the performance of X-ray fluorescence analysis on poorly diffracting apo hARH1 crystals, which revealed the presence of trace amounts of K(+) in the crystal."
(ADP-ribosyl)hydrolases: Structural Basis for Differential Substrate Recognition and Inhibition.
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ARH1 is specific for the arginine (N-glycosidic) linkage, whereas the paralog ARH3 handles serine-linked ADP-ribose and poly(ADP-ribose); this is the measurement that fixes the granularity of GO:0003875 for ADPRH.
"Whereas ARH1 is specific for the N-glycolytic linkage of mono(ADP-ribosylated) arginines, ARH3 specifically cleaves the O-glycolytic linkage of mono(ADP-ribosylated) serine and, at least in vitro, other linkages as well, such as those in poly(ADP-ribose) chains."
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The division of labour across the eraser families assigns arginine de-modification to ARH1 alone, with PARG/ARH3 on PAR, macrodomains on acidic residues and ARH3 on serine.
"Arginine de-modification is catalyzed by ARH1, PARylation is removed by PARG and to a lesser extend ARH3, MARylation on glutamate/aspartate residues is hydrolyzed by macrodomain proteins, whereas the terminal modification on serine residues is removed by ARH3."
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The poly(ADP-ribose), 1''-O-acetyl-ADP-ribose and DNA-end activities are attributed by these authors to ARH3, not to ARH1 - relevant because a paper titled for ARH3 (PMID:21498885) reports the same activities for ARH1 in passing.
"In addition, ARH3 can cleave PAR chains, 1″-O-acetyl-ADPr and ADPr at the phosphorylated DNA ends"
A proteome-scale map of the human interactome network.
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The ADPRH-TFCP2 pair comes from this systematic binary yeast two-hybrid map, with no orthogonal assay reported for the pair.
"Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions."
A reference map of the human binary protein interactome.
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The ADPRH-SPSB1 pair comes from HuRI, a systematic yeast two-hybrid reference map, with no orthogonal assay reported for the pair.
"Specifically, yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs."
Immunohistochemical localization of ADP-ribosylarginine hydrolase in rodent CNS.
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The sole experimental basis anywhere for an extracellular location of any ADPRH ortholog is one western blot of rat cerebrospinal fluid; the rest of the paper localises the enzyme inside neurons.
"On Western blot analysis of rat cerebrospinal fluid (CSF), the anti-AAH antibodies recognized a protein with a molecular mass of 38 kDa."
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The authors present the extracellular observation as a first report rather than an established localisation.
"the presence of extracellular AAH in rat CSF."
Molecular and immunological characterization of ADP-ribosylarginine hydrolases.
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The rat enzyme's hydrolase activity is Mg2+- and dithiothreitol-dependent and was demonstrated on purified and recombinant protein; this is the experimental annotation that the PAINT node's rat seed carries.
"A hydrolase fusion protein, synthesized in Escherichia coli, reacted with anti-39-kDa polyclonal antibodies and exhibited Mg(2+)- and dithiothreitol-dependent hydrolase activity."
The ARH and Macrodomain Families of α-ADP-ribose-acceptor Hydrolases Catalyze α-NAD(+) Hydrolysis.
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ARH1 hydrolyses the alpha anomer of NAD+ but not beta-NAD+, an activity shared with ARH3 and the macrodomain hydrolases; the stereospecificity is the substance of the result.
"Here, we report that ARH1, ARH3, and macrodomain proteins (i.e., MacroD1, MacroD2, C6orf130 (TARG1), Af1521, hydrolyzed α-NAD+ but not β-NAD+."
Enhanced sensitivity to cholera toxin in ADP-ribosylarginine hydrolase-deficient mice.
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Adprh-null mouse cells and intestinal loops accumulate more ADP-ribosylated Gs-alpha and more ADP-ribosylarginine after cholera-toxin challenge, and the defect is rescued by re-expressing wild-type ADPRH - identifying Gs-alpha as an in vivo substrate.
"Effects of intoxication on murine ADPRH-/- cells were greater than those on wild-type cells and were significantly reduced by overexpression of wild-type ADPRH in ADPRH-/- cells, as evidenced by both ADP-ribose-arginine content and Gsalpha modification."
Role of a TRIM72 ADP-ribosylation cycle in myocardial injury and membrane repair.
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TRIM72/MG53 is an ART1/ARH1 substrate pair, and ADP-ribosylated TRIM72 accumulates in Arh1-deficient mouse heart after ischaemia/reperfusion.
"The membrane repair protein TRIM72 was identified as a substrate for ART1 and ARH1; ADP-ribosylated TRIM72 levels were greater in ARH1-deficient mice following ischemia/reperfusion injury."
ADP-ribosylarginine hydrolase regulates cell proliferation and tumorigenesis.
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Arh1 heterozygous and null mice develop spontaneous lymphomas, adenocarcinomas and metastases, with loss of the remaining wild-type allele in tumours from heterozygotes.
"More significantly, ARH1(-/-) and ARH1(+/-) mice spontaneously developed lymphomas, adenocarcinomas, and metastases more frequently than wild-type ARH1(+/+) mice."
Hydrolysis of O-acetyl-ADP-ribose isomers by ADP-ribosylhydrolase 3.
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This ARH3-titled paper states in passing that ARH1 also hydrolyses O-acetyl-ADP-ribose and poly(ADP-ribose), which if measured for the human enzyme would widen its substrate scope beyond arginine.
"ARH1 also hydrolyzed OAADPr and poly(ADPr) as well as ADP-ribose-arginine, with arginine in α-anomeric linkage to C-1″ of ADP-ribose."
ARH Family of ADP-Ribose-Acceptor Hydrolases.
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Family review summarising ARH1's substrate range as alpha-ADP-ribose-arginine plus alpha-NAD+ and O-acetyl-ADP-ribose.
"ARH1 hydrolyzed α-ADP-ribose-arginine, in addition to α-NAD+ and O-acetyl-ADP-ribose."
Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase.
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ARH3 was identified as an ARH1-like protein with PARG activity that does NOT hydrolyse ADP-ribose-arginine - the reciprocal specificity boundary to ADPRH.
"We report here the identification of an ARH1-like protein, termed poly(ADP-ribose) hydrolase or ARH3, which exhibited PARG activity, generating ADP-ribose from poly-(ADP-ribose), but did not hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds."
Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1.
Side chain specificity of ADP-ribosylation by a sirtuin.
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ARH1 was used as the specificity reagent showing that arginine is the major ADP-ribose acceptor on unacetylated substrates - an in vitro demonstration of ADPRH acting on a protein substrate (histone H1.1) that is absent from GOA.
"Biochemical and MS data showed that arginine is the major ADP-ribose acceptor for unacetylated substrates, whereas arginine does not appear to be the major ADP-ribose acceptor in reactions with acetylated histone H1.1."
Affinage mechanistic annotation for ADPRH (human)
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The provider's one-line summary of the enzyme's reaction and direction, which agrees with UniProt and with PMID:30472116 and is used only as a corroborated restatement.
"ADPRH (ARH1) is a cytosolic, ubiquitously expressed enzyme that reverses arginine-specific mono-ADP-ribosylation"
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The provider asserts a cytosolic localisation for which no experimental evidence was found in UniProt or GOA; recorded as an unsupported provider claim, not as a basis for an annotation.
"ARH1 is a cytosolic protein ubiquitously expressed in mammalian tissues."
ADPRH catalytic-residue census across PANTHER PTHR16222
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Across the 31 reviewed Swiss-Prot members of PTHR16222 (0.104% of the family's 29,860 proteins), all five ADPRH-clade members retain every one of the five mutagenesis-validated catalytic residues and all five hold GO:0003875, whereas all seven ADPRHL1 orthologues have lost Asp56 and Ser305 and yet all seven hold GO:0003875 by IEA.
"| ADPRHL1 (ARH2) | 7 | 42.6-47.7 | 1-2 of 5 | 7/7 |"
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The residue argument is bounded by a positive control - Rhodospirillum rubrum DraG holds GO:0003875 by its own EXP evidence at only 27.5% identity and 3 of 5 residues, but both of its substitutions are hydroxyl-preserving Ser-to-Thr, i.e. zero disruptive changes.
"S305->T(conservative) | IEA(GO_REF:0000116), EXP(PMID:19706507) |"