NIT1_MOUSE
ID NIT1_MOUSE Reviewed; 323 AA.
AC Q8VDK1; O88526; Q9R1N4;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Deaminated glutathione amidase {ECO:0000303|PubMed:28373563};
DE Short=dGSH amidase {ECO:0000303|PubMed:28373563};
DE EC=3.5.1.128 {ECO:0000269|PubMed:28373563};
DE AltName: Full=Nitrilase homolog 1 {ECO:0000305};
DE Flags: Precursor;
GN Name=Nit1 {ECO:0000305};
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 [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=9671749; DOI=10.1073/pnas.95.15.8744;
RA Pekarsky Y., Campiglio M., Siprashvili Z., Druck T., Sedkov Y., Tillib S.,
RA Draganescu A., Wermuth P., Rothman J.H., Huebner K., Buchberg A.M.,
RA Mazo A., Brenner C., Croce C.M.;
RT "Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila
RT melanogaster and Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8744-8749(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
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 [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=16864578; DOI=10.1074/jbc.m603590200;
RA Semba S., Han S.-Y., Qin H.R., McCorkell K.A., Iliopoulos D., Pekarsky Y.,
RA Druck T., Trapasso F., Croce C.M., Huebner K.;
RT "Biological functions of mammalian Nit1, the counterpart of the
RT invertebrate NitFhit Rosetta stone protein, a possible tumor suppressor.";
RL J. Biol. Chem. 281:28244-28253(2006).
RN [4]
RP FUNCTION.
RX PubMed=19596042; DOI=10.1016/j.biochi.2009.07.002;
RA Jaisson S., Veiga-da-Cunha M., Van Schaftingen E.;
RT "Molecular identification of omega-amidase, the enzyme that is functionally
RT coupled with glutamine transaminases, as the putative tumor suppressor
RT Nit2.";
RL Biochimie 91:1066-1071(2009).
RN [5]
RP FUNCTION.
RX PubMed=19595734; DOI=10.1016/j.biochi.2009.07.003;
RA Krasnikov B.F., Chien C.-H., Nostramo R., Pinto J.T., Nieves E.,
RA Callaway M., Sun J., Huebner K., Cooper A.J.L.;
RT "Identification of the putative tumor suppressor Nit2 as omega-amidase, an
RT enzyme metabolically linked to glutamine and asparagine transamination.";
RL Biochimie 91:1072-1080(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19395373; DOI=10.1093/intimm/dxp038;
RA Zhang H., Hou Y.-J., Han S.-Y., Zhang E.C., Huebner K., Zhang J.;
RT "Mammalian nitrilase 1 homologue Nit1 is a negative regulator in T cells.";
RL Int. Immunol. 21:691-703(2009).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19479888; DOI=10.1002/jcb.22207;
RA Sun J., Okumura H., Yearsley M., Frankel W., Fong L.Y., Druck T.,
RA Huebner K.;
RT "Nit1 and Fhit tumor suppressor activities are additive.";
RL J. Cell. Biochem. 107:1097-1106(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
RX PubMed=28373563; DOI=10.1073/pnas.1613736114;
RA Peracchi A., Veiga-da-Cunha M., Kuhara T., Ellens K.W., Paczia N.,
RA Stroobant V., Seliga A.K., Marlaire S., Jaisson S., Bommer G.T., Sun J.,
RA Huebner K., Linster C.L., Cooper A.J.L., Van Schaftingen E.;
RT "Nit1 is a metabolite repair enzyme that hydrolyzes deaminated
RT glutathione.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E3233-E3242(2017).
CC -!- FUNCTION: Catalyzes the hydrolysis of the amide bond in N-(4-
CC oxoglutarate)-L-cysteinylglycine (deaminated glutathione), a metabolite
CC repair reaction to dispose of the harmful deaminated glutathione.
CC Possesses amidase activity toward deaminated ophthalmate in vitro
CC (PubMed:28373563). Plays a role in cell growth and apoptosis: loss of
CC expression promotes cell growth, resistance to DNA damage stress and
CC increased incidence to NMBA-induced tumors. Has tumor suppressor
CC properties that enhances the apoptotic responsiveness in cancer cells;
CC this effect is additive to the tumor suppressor activity of FHIT. It is
CC also a negative regulator of primary T-cells.
CC {ECO:0000269|PubMed:16864578, ECO:0000269|PubMed:19395373,
CC ECO:0000269|PubMed:19479888, ECO:0000269|PubMed:19595734,
CC ECO:0000269|PubMed:19596042, ECO:0000269|PubMed:28373563}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(4-oxoglutaryl)-L-cysteinylglycine = 2-oxoglutarate +
CC L-cysteinylglycine; Xref=Rhea:RHEA:54532, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:61694, ChEBI:CHEBI:138256;
CC EC=3.5.1.128; Evidence={ECO:0000269|PubMed:28373563};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54533;
CC Evidence={ECO:0000269|PubMed:28373563};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(4-carboxy-4-oxobutanoyl)-L-ethylglycylglycine = 2-
CC oxoglutarate + N-(2-aminobutanoyl)glycine; Xref=Rhea:RHEA:17125,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16810, ChEBI:CHEBI:144697,
CC ChEBI:CHEBI:144699; Evidence={ECO:0000269|PubMed:28373563};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17127;
CC Evidence={ECO:0000269|PubMed:28373563};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.17 mM for N-(4-oxoglutarate)-L-cysteinylglycine (at pH 8.5)
CC {ECO:0000269|PubMed:28373563};
CC Vmax=2.6 umol/min/mg enzyme with N-(4-oxoglutarate)-L-
CC cysteinylglycine as substrate (at pH 8.5)
CC {ECO:0000269|PubMed:28373563};
CC Note=kcat is 1.6 sec(-1) with N-(4-oxoglutarate)-L-cysteinylglycine
CC as substrate. {ECO:0000269|PubMed:28373563};
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion
CC {ECO:0000269|PubMed:19479888, ECO:0000269|PubMed:28373563}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:19479888, ECO:0000269|PubMed:28373563}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VDK1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VDK1-2; Sequence=VSP_011548;
CC -!- TISSUE SPECIFICITY: Expressed in most tissues with higher expression in
CC adult liver and kidney as well as in fetal adrenal gland and skeletal
CC muscle. {ECO:0000269|PubMed:16864578, ECO:0000269|PubMed:9671749}.
CC -!- DISRUPTION PHENOTYPE: Mice are normal at birth as well as during
CC growth. Mammary glands exhibit an increase in ductal and alveolar
CC structures as well as more cyclin-D1 positive cells in mid-pregnancy.
CC In the basal layer of epidermis, the number of cyclin-D1 positive cells
CC is also higher. No lymphoid malignancy is observed. Kidney cells
CC lacking Nit1 exhibit round and compact shapes, loss of lobular
CC structure, higher cell density with increased S and G2/M cell
CC populations. Cyclin D1 expression is increased, whereas differences in
CC the other cell cycle-associated proteins appeared minimal. T-cells
CC lacking NIT-1 display enhanced proliferation, elevated activation
CC marker expression, accelerated cell cycle progression and aberrant
CC expression of some cell cycle proteins. {ECO:0000269|PubMed:16864578,
CC ECO:0000269|PubMed:19395373}.
CC -!- MISCELLANEOUS: According to Rosetta Stone theory, the existence of a
CC fusion protein in one genome predicts that the separate polypeptides
CC expressed in other organisms function in the same cellular or
CC biochemical pathway. In Drosophila melanogaster and Caenorhabditis
CC elegans, NitFhit is a fusion protein composed of a C-terminal Fhit
CC domain and a domain related to plant and bacterial nitrilase.
CC -!- SIMILARITY: Belongs to the carbon-nitrogen hydrolase superfamily.
CC NIT1/NIT2 family. {ECO:0000305}.
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DR EMBL; AF069985; AAC40184.1; -; Genomic_DNA.
DR EMBL; AF069988; AAC40185.1; -; mRNA.
DR EMBL; BC021634; AAH21634.1; -; mRNA.
DR CCDS; CCDS35775.1; -. [Q8VDK1-1]
DR CCDS; CCDS56656.1; -. [Q8VDK1-2]
DR RefSeq; NP_001229509.1; NM_001242580.1. [Q8VDK1-2]
DR RefSeq; NP_036179.1; NM_012049.2. [Q8VDK1-1]
DR RefSeq; XP_006496929.1; XM_006496866.3. [Q8VDK1-2]
DR AlphaFoldDB; Q8VDK1; -.
DR SMR; Q8VDK1; -.
DR STRING; 10090.ENSMUSP00000106926; -.
DR iPTMnet; Q8VDK1; -.
DR PhosphoSitePlus; Q8VDK1; -.
DR SwissPalm; Q8VDK1; -.
DR CPTAC; non-CPTAC-3849; -.
DR EPD; Q8VDK1; -.
DR jPOST; Q8VDK1; -.
DR MaxQB; Q8VDK1; -.
DR PaxDb; Q8VDK1; -.
DR PeptideAtlas; Q8VDK1; -.
DR PRIDE; Q8VDK1; -.
DR ProteomicsDB; 293564; -. [Q8VDK1-1]
DR ProteomicsDB; 293565; -. [Q8VDK1-2]
DR Antibodypedia; 1672; 261 antibodies from 24 providers.
DR DNASU; 27045; -.
DR Ensembl; ENSMUST00000111289; ENSMUSP00000106920; ENSMUSG00000013997. [Q8VDK1-2]
DR Ensembl; ENSMUST00000111295; ENSMUSP00000106926; ENSMUSG00000013997. [Q8VDK1-1]
DR GeneID; 27045; -.
DR KEGG; mmu:27045; -.
DR UCSC; uc007doa.2; mouse. [Q8VDK1-1]
DR CTD; 4817; -.
DR MGI; MGI:1350916; Nit1.
DR VEuPathDB; HostDB:ENSMUSG00000013997; -.
DR eggNOG; KOG0807; Eukaryota.
DR GeneTree; ENSGT00550000075099; -.
DR HOGENOM; CLU_030130_1_2_1; -.
DR InParanoid; Q8VDK1; -.
DR OMA; MTCYDVR; -.
DR OrthoDB; 1154369at2759; -.
DR PhylomeDB; Q8VDK1; -.
DR TreeFam; TF313080; -.
DR BRENDA; 3.5.1.128; 3474.
DR BioGRID-ORCS; 27045; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Nit1; mouse.
DR PRO; PR:Q8VDK1; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8VDK1; protein.
DR Bgee; ENSMUSG00000013997; Expressed in right kidney and 261 other tissues.
DR ExpressionAtlas; Q8VDK1; baseline and differential.
DR Genevisible; Q8VDK1; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0050406; F:[acetyl-CoA carboxylase]-phosphatase activity; IEA:RHEA.
DR GO; GO:0110050; F:deaminated glutathione amidase activity; IDA:UniProtKB.
DR GO; GO:0043605; P:cellular amide catabolic process; IDA:UniProtKB.
DR CDD; cd07572; nit; 1.
DR Gene3D; 3.60.110.10; -; 1.
DR InterPro; IPR003010; C-N_Hydrolase.
DR InterPro; IPR036526; C-N_Hydrolase_sf.
DR InterPro; IPR045254; Nit1/2_C-N_Hydrolase.
DR InterPro; IPR001110; UPF0012_CS.
DR Pfam; PF00795; CN_hydrolase; 1.
DR SUPFAM; SSF56317; SSF56317; 1.
DR PROSITE; PS50263; CN_HYDROLASE; 1.
DR PROSITE; PS01227; UPF0012; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Hydrolase; Mitochondrion;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 34..323
FT /note="Deaminated glutathione amidase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000213252"
FT DOMAIN 42..294
FT /note="CN hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 82
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 157
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 199
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT VAR_SEQ 1..33
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_011548"
FT CONFLICT 22
FT /note="T -> I (in Ref. 1; AAC40184)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="P -> S (in Ref. 2; AAH21634)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 323 AA; 35705 MW; F8CD7730713665EF CRC64;
MLGFITRPPH QLLCTGYRLL RTPVLCTQPR PRTMSSSTSW ELPLVAVCQV TSTPNKQENF
KTCAELVQEA ARLGACLAFL PEAFDFIARN PAETLLLSEP LNGDLLGQYS QLARECGIWL
SLGGFHERGQ DWEQNQKIYN CHVLLNSKGS VVASYRKTHL CDVEIPGQGP MRESNYTKPG
GTLEPPVKTP AGKVGLAICY DMRFPELSLK LAQAGAEILT YPSAFGSVTG PAHWEVLLRA
RAIESQCYVI AAAQCGRHHE TRASYGHSMV VDPWGTVVAR CSEGPGLCLA RIDLHFLQQM
RQHLPVFQHR RPDLYGSLGH PLS
