NIT1_HUMAN
ID NIT1_HUMAN Reviewed; 327 AA.
AC Q86X76; B1AQP3; D3DVF4; O76091;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Deaminated glutathione amidase;
DE Short=dGSH amidase;
DE EC=3.5.1.128 {ECO:0000250|UniProtKB:Q8VDK1};
DE AltName: Full=Nitrilase homolog 1;
DE Flags: Precursor;
GN Name=NIT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 4 AND 5), AND
RP 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 2).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC TISSUE=Brain;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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. Plays
CC a role in cell growth and apoptosis: loss of expression promotes cell
CC growth, resistance to DNA damage stress and increased incidence to
CC NMBA-induced tumors. Has tumor suppressor properties that enhances the
CC apoptotic responsiveness in cancer cells; this effect is additive to
CC the tumor suppressor activity of FHIT. It is also a negative regulator
CC of primary T-cells. {ECO:0000250|UniProtKB:Q8VDK1}.
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:0000250|UniProtKB:Q8VDK1};
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion
CC {ECO:0000250|UniProtKB:Q8VDK1}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q8VDK1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=2;
CC IsoId=Q86X76-1; Sequence=Displayed;
CC Name=1; Synonyms=3;
CC IsoId=Q86X76-2; Sequence=VSP_011546;
CC Name=4;
CC IsoId=Q86X76-3; Sequence=VSP_011544, VSP_011547;
CC Name=5;
CC IsoId=Q86X76-4; Sequence=VSP_011545;
CC Name=6;
CC IsoId=Q86X76-5; Sequence=VSP_053711, VSP_053712;
CC -!- TISSUE SPECIFICITY: Detected in heart, brain, placenta, liver, skeletal
CC muscle, kidney and pancreas. {ECO:0000269|PubMed:9671749}.
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 -!- MISCELLANEOUS: [Isoform 2]: Major isoform.
CC -!- MISCELLANEOUS: [Isoform 6]: Based on a naturally occurring readthrough
CC transcript which produces a NIT1-DEDD fusion protein. The last 4 amino
CC acids of this isoform (PVSS) are encoded by the last DEDD exon.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the carbon-nitrogen hydrolase superfamily.
CC NIT1/NIT2 family. {ECO:0000305}.
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DR EMBL; AF069984; AAC39901.1; -; Genomic_DNA.
DR EMBL; AF069987; AAC39907.1; -; mRNA.
DR EMBL; CR541814; CAG46613.1; -; mRNA.
DR EMBL; CR541846; CAG46644.1; -; mRNA.
DR EMBL; AL591806; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52656.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52654.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW52657.1; -; Genomic_DNA.
DR EMBL; BC046149; AAH46149.1; -; mRNA.
DR CCDS; CCDS1218.1; -. [Q86X76-1]
DR CCDS; CCDS53401.1; -. [Q86X76-5]
DR CCDS; CCDS53402.1; -. [Q86X76-4]
DR CCDS; CCDS53403.1; -. [Q86X76-2]
DR RefSeq; NP_001172021.1; NM_001185092.1. [Q86X76-5]
DR RefSeq; NP_001172022.1; NM_001185093.1. [Q86X76-4]
DR RefSeq; NP_001172023.1; NM_001185094.1. [Q86X76-2]
DR RefSeq; NP_005591.1; NM_005600.2. [Q86X76-1]
DR RefSeq; XP_005245273.1; XM_005245216.3. [Q86X76-2]
DR AlphaFoldDB; Q86X76; -.
DR SMR; Q86X76; -.
DR BioGRID; 110882; 120.
DR IntAct; Q86X76; 54.
DR MINT; Q86X76; -.
DR STRING; 9606.ENSP00000356988; -.
DR ChEMBL; CHEMBL4295883; -.
DR GlyGen; Q86X76; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86X76; -.
DR PhosphoSitePlus; Q86X76; -.
DR BioMuta; NIT1; -.
DR DMDM; 51704324; -.
DR EPD; Q86X76; -.
DR jPOST; Q86X76; -.
DR MassIVE; Q86X76; -.
DR MaxQB; Q86X76; -.
DR PaxDb; Q86X76; -.
DR PeptideAtlas; Q86X76; -.
DR PRIDE; Q86X76; -.
DR ProteomicsDB; 70250; -. [Q86X76-1]
DR ProteomicsDB; 70251; -. [Q86X76-2]
DR ProteomicsDB; 70252; -. [Q86X76-3]
DR ProteomicsDB; 70253; -. [Q86X76-4]
DR Antibodypedia; 1672; 261 antibodies from 24 providers.
DR DNASU; 4817; -.
DR Ensembl; ENST00000368007.8; ENSP00000356986.4; ENSG00000158793.14. [Q86X76-4]
DR Ensembl; ENST00000368008.5; ENSP00000356987.1; ENSG00000158793.14. [Q86X76-5]
DR Ensembl; ENST00000368009.7; ENSP00000356988.2; ENSG00000158793.14. [Q86X76-1]
DR Ensembl; ENST00000392190.9; ENSP00000376028.5; ENSG00000158793.14. [Q86X76-2]
DR GeneID; 4817; -.
DR KEGG; hsa:4817; -.
DR MANE-Select; ENST00000368009.7; ENSP00000356988.2; NM_005600.3; NP_005591.1.
DR UCSC; uc001fxv.3; human. [Q86X76-1]
DR CTD; 4817; -.
DR DisGeNET; 4817; -.
DR GeneCards; NIT1; -.
DR HGNC; HGNC:7828; NIT1.
DR HPA; ENSG00000158793; Low tissue specificity.
DR MIM; 604618; gene.
DR neXtProt; NX_Q86X76; -.
DR OpenTargets; ENSG00000158793; -.
DR PharmGKB; PA31636; -.
DR VEuPathDB; HostDB:ENSG00000158793; -.
DR eggNOG; KOG0807; Eukaryota.
DR GeneTree; ENSGT00550000075099; -.
DR HOGENOM; CLU_030130_1_1_1; -.
DR InParanoid; Q86X76; -.
DR OMA; MTCYDVR; -.
DR OrthoDB; 1154369at2759; -.
DR PhylomeDB; Q86X76; -.
DR TreeFam; TF313080; -.
DR PathwayCommons; Q86X76; -.
DR SignaLink; Q86X76; -.
DR BioGRID-ORCS; 4817; 13 hits in 1079 CRISPR screens.
DR ChiTaRS; NIT1; human.
DR GenomeRNAi; 4817; -.
DR Pharos; Q86X76; Tbio.
DR PRO; PR:Q86X76; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q86X76; protein.
DR Bgee; ENSG00000158793; Expressed in right adrenal gland cortex and 200 other tissues.
DR Genevisible; Q86X76; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0110050; F:deaminated glutathione amidase activity; ISS:UniProtKB.
DR GO; GO:0043605; P:cellular amide catabolic process; ISS:ARUK-UCL.
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..13
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 14..327
FT /note="Deaminated glutathione amidase"
FT /evidence="ECO:0000255"
FT /id="PRO_0000213251"
FT DOMAIN 46..298
FT /note="CN hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 86
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 161
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT ACT_SITE 203
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00054"
FT VAR_SEQ 1..36
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:9671749"
FT /id="VSP_011546"
FT VAR_SEQ 1..33
FT /note="MLGFITRPPHRFLSLLCPGLRIPQLSVLCAQPR -> MTFGLRKRLSEERGF
FT SLM (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:9671749"
FT /id="VSP_011545"
FT VAR_SEQ 1..31
FT /note="MLGFITRPPHRFLSLLCPGLRIPQLSVLCAQ -> MVLAISSCWASSPGLLT
FT DSCPFCVLDSGYLNSQYFVLSPGRTYSLSRR (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9671749"
FT /id="VSP_011544"
FT VAR_SEQ 240..243
FT /note="VLLR -> PVSS (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_053711"
FT VAR_SEQ 244..327
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_053712"
FT VAR_SEQ 327
FT /note="S -> SDLTSVSLDLPLPPPPCHYELVLM (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9671749"
FT /id="VSP_011547"
FT CONFLICT 79
FT /note="A -> P (in Ref. 5; AAH46149)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 35896 MW; 90F7FB9D4BA627B1 CRC64;
MLGFITRPPH RFLSLLCPGL RIPQLSVLCA QPRPRAMAIS SSSCELPLVA VCQVTSTPDK
QQNFKTCAEL VREAARLGAC LAFLPEAFDF IARDPAETLH LSEPLGGKLL EEYTQLAREC
GLWLSLGGFH ERGQDWEQTQ KIYNCHVLLN SKGAVVATYR KTHLCDVEIP GQGPMCESNS
TMPGPSLESP VSTPAGKIGL AVCYDMRFPE LSLALAQAGA EILTYPSAFG SITGPAHWEV
LLRARAIETQ CYVVAAAQCG RHHEKRASYG HSMVVDPWGT VVARCSEGPG LCLARIDLNY
LRQLRRHLPV FQHRRPDLYG NLGHPLS
