NAR2A_MOUSE
ID NAR2A_MOUSE Reviewed; 287 AA.
AC P17981; O35278; Q0VB79; Q64173;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-2002, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=T-cell ecto-ADP-ribosyltransferase 1;
DE EC=2.4.2.31 {ECO:0000269|PubMed:11011142};
DE AltName: Full=ADP-ribosyltransferase 2a pseudogene;
DE AltName: Full=ADP-ribosyltransferase C2 and C3 toxin-like 2;
DE Short=ARTC2;
DE AltName: Full=Mono(ADP-ribosyl)transferase 2A;
DE AltName: Full=NAD(+) glycohydrolase;
DE EC=3.2.2.5 {ECO:0000269|PubMed:11011142};
DE AltName: Full=T-cell NAD(P)(+)--arginine ADP-ribosyltransferase 1;
DE AltName: Full=T-cell differentiation marker Rt6 homolog 1;
DE AltName: Full=T-cell mono(ADP-ribosyl)transferase 1;
DE Flags: Precursor;
GN Name=Art2a; Synonyms=Art2a-ps, Rt6-1, Rt6.1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RX PubMed=2362814; DOI=10.1093/nar/18.12.3636;
RA Koch F., Haag F., Thiele H.-G.;
RT "Nucleotide and deduced amino acid sequence for the mouse homologue of the
RT rat T-cell differentiation marker RT6.";
RL Nucleic Acids Res. 18:3636-3636(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP VARIANTS 22-THR--SER-24; THR-26 AND SER-40.
RC STRAIN=NZW/LacJ; TISSUE=Spleen;
RX PubMed=7547715; DOI=10.1093/intimm/7.5.883;
RA Koch-Nolte F., Klein J., Hollmann C., Kuehl M., Haag F., Gaskins H.R.,
RA Leiter E., Thiele H.-G.;
RT "Defects in the structure and expression of the genes for the T cell marker
RT Rt6 in NZW and (NZB x NZW)F1 mice.";
RL Int. Immunol. 7:883-890(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND VARIANTS
RP 22-THR--SER-24; THR-26; SER-40 AND ARG-161--PRO-287 DEL.
RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Spleen;
RX PubMed=9300695;
RA Kanaitsuka T., Bortell R., Stevens L.A., Moss J., Sardinha D., Rajan T.V.,
RA Zipris D., Mordes J.P., Greiner D.L., Rossini A.A.;
RT "Expression in BALB/c and C57BL/6 mice of Rt6-1 and Rt6-2 ADP-
RT ribosyltransferases that differ in enzymatic activity: C57BL/6 Rt6-1 is a
RT natural transferase knockout.";
RL J. Immunol. 159:2741-2749(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISULFIDE
RP BOND, AND MUTAGENESIS OF CYS-80 AND CYS-201.
RX PubMed=11011142; DOI=10.1093/oxfordjournals.jbchem.a022792;
RA Hara N., Terashima M., Shimoyama M., Tsuchiya M.;
RT "Mouse T-cell antigen rt6.1 has thiol-dependent NAD glycohydrolase
RT activity.";
RL J. Biochem. 128:601-607(2000).
CC -!- FUNCTION: Has both ADP-ribosyltransferase activity and thiol-dependent
CC NAD(+) glycohydrolase activity. {ECO:0000269|PubMed:11011142,
CC ECO:0000269|PubMed:9300695}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + NAD(+) = H(+) + N(omega)-(ADP-D-
CC ribosyl)-L-arginyl-[protein] + nicotinamide; Xref=Rhea:RHEA:19149,
CC Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:142554; EC=2.4.2.31;
CC Evidence={ECO:0000269|PubMed:11011142};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.5;
CC Evidence={ECO:0000269|PubMed:11011142};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.12 mM for NAD for the NADase activity (in the presence of 0.03
CC mM DTT) {ECO:0000269|PubMed:11011142};
CC KM=0.41 mM for NAD for the NADase activity (in the presence of 2 mM
CC DTT) {ECO:0000269|PubMed:11011142};
CC KM=0.5 mM for NAD for the ADP-ribosyltransferase activity (in the
CC presence of 0.02 mM DTT) {ECO:0000269|PubMed:11011142};
CC KM=0.41 mM for NAD for the ADP-ribosyltransferase activity (in the
CC presence of 2 mM DTT) {ECO:0000269|PubMed:11011142};
CC KM=1.2 mM for L-arginine for the ADP-ribosyltransferase activity (in
CC the presence of 0.02 mM DTT) {ECO:0000269|PubMed:11011142};
CC KM=0.59 mM for L-arginine for the ADP-ribosyltransferase activity (in
CC the presence of 2 mM DTT) {ECO:0000269|PubMed:11011142};
CC Vmax=1.3 nmol/h/ug enzyme toward NAD for the NADase activity (in the
CC presence of 0.03 mM DTT) {ECO:0000269|PubMed:11011142};
CC Vmax=9.7 nmol/h/ug enzyme toward NAD for the NADase activity (in the
CC presence of 2 mM DTT) {ECO:0000269|PubMed:11011142};
CC Vmax=12.3 nmol/h/ug enzyme toward NAD for the ADP-ribosyltransferase
CC activity (in the presence of 0.02 mM DTT)
CC {ECO:0000269|PubMed:11011142};
CC Vmax=159 nmol/h/ug enzyme toward NAD for the ADP-ribosyltransferase
CC activity (in the presence of 2 mM DTT) {ECO:0000269|PubMed:11011142};
CC Vmax=6.8 nmol/h/ug enzyme toward L-arginine for the ADP-
CC ribosyltransferase activity (in the presence of 0.02 mM DTT)
CC {ECO:0000269|PubMed:11011142};
CC Vmax=77 nmol/h/ug enzyme toward L-arginine for the ADP-
CC ribosyltransferase activity (in the presence of 2 mM DTT)
CC {ECO:0000269|PubMed:11011142};
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
CC -!- TISSUE SPECIFICITY: Expressed in spleen, intestine and thymus.
CC {ECO:0000269|PubMed:7547715, ECO:0000269|PubMed:9300695}.
CC -!- DEVELOPMENTAL STAGE: In intestine, the expression levels are highest
CC during neonatal stages and decrease towards adulthood. In spleen, the
CC expression is lowest in neonatals and increases during further
CC developmental stages. {ECO:0000269|PubMed:7547715}.
CC -!- PTM: It is proposed that in the absence of reducing agents, a disulfide
CC bond is formed between Cys-80 and Cys-201, leading to a conformational
CC change that reduces the catalytic rate of NAD glycohydrolysis.
CC -!- DISEASE: Note=A subset of Rt6+ regulatory T-cells may confer protection
CC to autoimmune disease, and failure to develop this subset may result in
CC enhanced susceptibility for autoimmune disease.
CC -!- SIMILARITY: Belongs to the Arg-specific ADP-ribosyltransferase family.
CC {ECO:0000305}.
CC -!- CAUTION: Defined as a polymorphic pseudogene by MGI. In strain C57BL/6,
CC a polymorphism creates a premature stop codon at position 161.
CC PubMed:9300695 shows that the truncated protein is not functional.
CC {ECO:0000305}.
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DR EMBL; X52991; CAA37181.1; -; mRNA.
DR EMBL; S79913; AAB35402.1; -; mRNA.
DR EMBL; AF016462; AAB71682.1; -; mRNA.
DR EMBL; BC120753; AAI20754.1; -; mRNA.
DR PIR; S12738; S12738.
DR RefSeq; NP_031516.1; NM_007490.1.
DR AlphaFoldDB; P17981; -.
DR SMR; P17981; -.
DR GlyGen; P17981; 2 sites.
DR iPTMnet; P17981; -.
DR PhosphoSitePlus; P17981; -.
DR PRIDE; P17981; -.
DR DNASU; 11871; -.
DR GeneID; 11871; -.
DR KEGG; mmu:11871; -.
DR CTD; 11871; -.
DR MGI; MGI:107546; Art2a.
DR InParanoid; P17981; -.
DR SABIO-RK; P17981; -.
DR BioGRID-ORCS; 11871; 0 hits in 19 CRISPR screens.
DR ChiTaRS; Art2a; mouse.
DR PRO; PR:P17981; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P17981; protein.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IDA:UniProtKB.
DR GO; GO:0061810; F:NAD glycohydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IBA:GO_Central.
DR GO; GO:0106274; F:NAD+-protein-arginine ADP-ribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019677; P:NAD catabolic process; IDA:UniProtKB.
DR GO; GO:0018120; P:peptidyl-arginine ADP-ribosylation; IDA:UniProtKB.
DR InterPro; IPR000768; ART.
DR Pfam; PF01129; ART; 1.
DR PRINTS; PR00970; RIBTRNSFRASE.
DR PROSITE; PS01291; ART; 1.
DR PROSITE; PS51996; TR_MART; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Glycosyltransferase;
KW GPI-anchor; Hydrolase; Lipoprotein; Membrane; NAD; NADP;
KW Nucleotidyltransferase; Reference proteome; Signal; Transferase.
FT SIGNAL 1..20
FT CHAIN 21..258
FT /note="T-cell ecto-ADP-ribosyltransferase 1"
FT /id="PRO_0000019317"
FT PROPEP 259..287
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000019318"
FT DOMAIN 61..241
FT /note="TR mART core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT ACT_SITE 146
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT ACT_SITE 167
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT ACT_SITE 209
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT BINDING 98
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 146
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 202
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 80
FT /note="Required for the thiol-dependency of NADase
FT activity"
FT SITE 201
FT /note="Required for the thiol-dependency of NADase
FT activity"
FT LIPID 258
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..246
FT /evidence="ECO:0000250"
FT DISULFID 80..201
FT /note="Alternate; present in the absence of reducing
FT agents"
FT /evidence="ECO:0000305|PubMed:11011142"
FT DISULFID 141..193
FT /evidence="ECO:0000250"
FT VARIANT 22..24
FT /note="AVP -> TGS (in strain: NZW and C57BL/6)"
FT VARIANT 26
FT /note="M -> T (in strain: NZW and C57BL/6)"
FT /evidence="ECO:0000269|PubMed:7547715,
FT ECO:0000269|PubMed:9300695"
FT VARIANT 40
FT /note="G -> S (in strain: NZW and C57BL/6)"
FT /evidence="ECO:0000269|PubMed:7547715,
FT ECO:0000269|PubMed:9300695"
FT VARIANT 161..287
FT /note="Missing (in strain: C57BL/6)"
FT MUTAGEN 80
FT /note="C->S: Loss of thiol-dependency of NADase activity."
FT /evidence="ECO:0000269|PubMed:11011142"
FT MUTAGEN 201
FT /note="C->F: Loss of thiol-dependency of NADase activity."
FT /evidence="ECO:0000269|PubMed:11011142"
FT CONFLICT 2..4
FT /note="PSN -> TSK (in Ref. 4; AAI20754)"
FT /evidence="ECO:0000305"
FT CONFLICT 5
FT /note="N -> K (in Ref. 2; AAB35402)"
FT /evidence="ECO:0000305"
FT CONFLICT 11
FT /note="T -> A (in Ref. 2; AAB35402)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="S -> P (in Ref. 1; CAA37181)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="P -> L (in Ref. 4; AAI20754)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 287 AA; 32801 MW; 606A7F69943E2692 CRC64;
MPSNNFKFFL TWWLTQQVTG LAVPFMLDMA PNAFDDQYEG CVEDMEKKAP QLLQEDFNMN
EELKLEWEKA EIKWKEIKNC MSYPAGFHDF HGTALVAYTG NIHRSLNEAT REFKINPGNF
HYKAFHYYLT RALQLLSDQG CRSVYRGTNV RFRYTGKGSV RFGHFASSSL NRSVATSSPF
FNGQGTLFII KTCLGAHIKH CSYYTHEEEV LIPGYEVFHK VKTQSVERYI QISLDSPKRK
KSNFNCFYSG STQAANVSSL GSRESCVSLF LVVLLGLLVQ QLTLAEP
