5NT3B_HUMAN
ID 5NT3B_HUMAN Reviewed; 300 AA.
AC Q969T7; A8MWB9; C9JKC4; Q7L3B7;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 4.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=7-methylguanosine phosphate-specific 5'-nucleotidase {ECO:0000305|PubMed:23223233};
DE Short=7-methylguanosine nucleotidase;
DE EC=3.1.3.91 {ECO:0000269|PubMed:23223233};
DE AltName: Full=Cytosolic 5'-nucleotidase 3B;
DE AltName: Full=Cytosolic 5'-nucleotidase III-like protein {ECO:0000305|PubMed:23223233};
DE Short=cN-III-like protein;
DE EC=3.1.3.5 {ECO:0000269|PubMed:23223233};
DE AltName: Full=N(7)-methylguanylate 5'-phosphatase;
GN Name=NT5C3B; Synonyms=NT5C3L;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS VAL-209 AND
RP CYS-213.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS VAL-209
RP AND CYS-213.
RC TISSUE=Liver, Lung, and Testis;
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 [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-256, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=23223233; DOI=10.1074/jbc.m112.426700;
RA Buschmann J., Moritz B., Jeske M., Lilie H., Schierhorn A., Wahle E.;
RT "Identification of Drosophila and Human 7-Methyl GMP-specific
RT Nucleotidases.";
RL J. Biol. Chem. 288:2441-2451(2013).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24603684; DOI=10.1371/journal.pone.0090915;
RA Monecke T., Buschmann J., Neumann P., Wahle E., Ficner R.;
RT "Crystal structures of the novel cytosolic 5'-nucleotidase IIIB explain its
RT preference for m7GMP.";
RL PLoS ONE 9:90915-90915(2014).
CC -!- FUNCTION: Specifically hydrolyzes 7-methylguanosine monophosphate
CC (m(7)GMP) to 7-methylguanosine and inorganic phosphate
CC (PubMed:23223233, PubMed:24603684). The specific activity for m(7)GMP
CC may protect cells against undesired salvage of m(7)GMP and its
CC incorporation into nucleic acids (PubMed:23223233). Also has weak
CC activity for CMP (PubMed:23223233, PubMed:24603684). UMP and purine
CC nucleotides are poor substrates (PubMed:23223233).
CC {ECO:0000269|PubMed:23223233, ECO:0000269|PubMed:24603684}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(7)-methyl-GMP = N(7)-methylguanosine + phosphate;
CC Xref=Rhea:RHEA:37107, ChEBI:CHEBI:15377, ChEBI:CHEBI:20794,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58285; EC=3.1.3.91;
CC Evidence={ECO:0000269|PubMed:23223233};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP + H2O = cytidine + phosphate; Xref=Rhea:RHEA:29367,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17562, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:60377; EC=3.1.3.91;
CC Evidence={ECO:0000269|PubMed:23223233};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-phosphate + H2O = a ribonucleoside +
CC phosphate; Xref=Rhea:RHEA:12484, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:18254, ChEBI:CHEBI:43474, ChEBI:CHEBI:58043; EC=3.1.3.5;
CC Evidence={ECO:0000269|PubMed:23223233};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.8 uM for m(7)GMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:23223233};
CC KM=8 uM for m(7)GMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:24603684};
CC KM=79 uM for CMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:23223233, ECO:0000269|PubMed:24603684};
CC KM=355 uM for GMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:23223233};
CC KM=456 uM for AMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:23223233};
CC KM=439 uM for UMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:23223233};
CC Vmax=0.41 umol/min/mg enzyme with m(7)GMP as substrate
CC {ECO:0000269|PubMed:23223233};
CC Vmax=12 umol/min/mg enzyme with CMP as substrate
CC {ECO:0000269|PubMed:23223233};
CC Vmax=0.13 umol/min/mg enzyme with GMP as substrate
CC {ECO:0000269|PubMed:23223233};
CC Vmax=0.07 umol/min/mg enzyme with AMP as substrate
CC {ECO:0000269|PubMed:23223233};
CC Vmax=10.7 umol/min/mg enzyme with UMP as substrate
CC {ECO:0000269|PubMed:23223233};
CC Note=kcat is 0.24 sec(-1) with m(7)GMP. kcat is 7 sec(-1) with CMP.
CC kcat is 0.07 sec(-1) with GMP. kcat is 0.04 sec(-1) with AMP. kcat is
CC 6.2 sec(-1) with UMP.;
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23223233}.
CC -!- INTERACTION:
CC Q969T7; P40692: MLH1; NbExp=3; IntAct=EBI-2932564, EBI-744248;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969T7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969T7-2; Sequence=VSP_046297;
CC -!- SIMILARITY: Belongs to the pyrimidine 5'-nucleotidase family.
CC {ECO:0000305}.
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DR EMBL; AC091172; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471152; EAW60771.1; -; Genomic_DNA.
DR EMBL; BC013742; AAH13742.2; -; mRNA.
DR EMBL; BC014132; AAH14132.2; -; mRNA.
DR EMBL; BC016971; AAH16971.2; -; mRNA.
DR EMBL; BC067788; AAH67788.1; -; mRNA.
DR CCDS; CCDS11410.2; -. [Q969T7-1]
DR RefSeq; NP_443167.4; NM_052935.4. [Q969T7-1]
DR PDB; 7ZEE; X-ray; 1.36 A; A=1-300.
DR PDB; 7ZEG; X-ray; 1.56 A; A/B=1-300.
DR PDBsum; 7ZEE; -.
DR PDBsum; 7ZEG; -.
DR AlphaFoldDB; Q969T7; -.
DR SMR; Q969T7; -.
DR BioGRID; 125410; 6.
DR IntAct; Q969T7; 1.
DR STRING; 9606.ENSP00000389948; -.
DR BindingDB; Q969T7; -.
DR ChEMBL; CHEMBL4295921; -.
DR DEPOD; NT5C3B; -.
DR iPTMnet; Q969T7; -.
DR PhosphoSitePlus; Q969T7; -.
DR BioMuta; NT5C3B; -.
DR DMDM; 476007845; -.
DR EPD; Q969T7; -.
DR jPOST; Q969T7; -.
DR MassIVE; Q969T7; -.
DR MaxQB; Q969T7; -.
DR PaxDb; Q969T7; -.
DR PeptideAtlas; Q969T7; -.
DR PRIDE; Q969T7; -.
DR ProteomicsDB; 10565; -.
DR ProteomicsDB; 75844; -. [Q969T7-1]
DR Antibodypedia; 28986; 79 antibodies from 17 providers.
DR DNASU; 115024; -.
DR Ensembl; ENST00000435506.7; ENSP00000389948.2; ENSG00000141698.17. [Q969T7-1]
DR GeneID; 115024; -.
DR KEGG; hsa:115024; -.
DR MANE-Select; ENST00000435506.7; ENSP00000389948.2; NM_052935.5; NP_443167.4.
DR UCSC; uc021txo.2; human. [Q969T7-1]
DR CTD; 115024; -.
DR DisGeNET; 115024; -.
DR GeneCards; NT5C3B; -.
DR HGNC; HGNC:28300; NT5C3B.
DR HPA; ENSG00000141698; Low tissue specificity.
DR neXtProt; NX_Q969T7; -.
DR OpenTargets; ENSG00000141698; -.
DR VEuPathDB; HostDB:ENSG00000141698; -.
DR eggNOG; KOG3128; Eukaryota.
DR GeneTree; ENSGT00390000012959; -.
DR OMA; EIDPYRT; -.
DR OrthoDB; 1171042at2759; -.
DR TreeFam; TF314663; -.
DR PathwayCommons; Q969T7; -.
DR Reactome; R-HSA-429958; mRNA decay by 3' to 5' exoribonuclease.
DR SABIO-RK; Q969T7; -.
DR SignaLink; Q969T7; -.
DR BioGRID-ORCS; 115024; 15 hits in 1064 CRISPR screens.
DR ChiTaRS; NT5C3B; human.
DR GenomeRNAi; 115024; -.
DR Pharos; Q969T7; Tbio.
DR PRO; PR:Q969T7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q969T7; protein.
DR Bgee; ENSG00000141698; Expressed in nucleus accumbens and 184 other tissues.
DR ExpressionAtlas; Q969T7; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008253; F:5'-nucleotidase activity; TAS:Reactome.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0043928; P:exonucleolytic catabolism of deadenylated mRNA; TAS:Reactome.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR CDD; cd07504; HAD_5NT; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006434; Pyrimidine_nucleotidase_eu.
DR Pfam; PF05822; UMPH-1; 1.
DR SFLD; SFLDG01128; C1.4:_5'-Nucleotidase_Like; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01544; HAD-SF-IE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Hydrolase;
KW Magnesium; Metal-binding; Nucleotide metabolism; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..300
FT /note="7-methylguanosine phosphate-specific 5'-
FT nucleotidase"
FT /id="PRO_0000328948"
FT ACT_SITE 41
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT ACT_SITE 43
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 41
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 43
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 88
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 88
FT /ligand="N(7)-methyl-GMP"
FT /ligand_id="ChEBI:CHEBI:58285"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 156..157
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9H0P0"
FT BINDING 205
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9H0P0"
FT BINDING 230
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT MOD_RES 256
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..8
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046297"
FT VARIANT 209
FT /note="A -> V (in dbSNP:rs1046403)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_042582"
FT VARIANT 213
FT /note="S -> C (in dbSNP:rs1046404)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_042583"
SQ SEQUENCE 300 AA; 34389 MW; 3E221583153381F8 CRC64;
MAEEVSTLMK ATVLMRQPGR VQEIVGALRK GGGDRLQVIS DFDMTLSRFA YNGKRCPSSY
NILDNSKIIS EECRKELTAL LHHYYPIEID PHRTVKEKLP HMVEWWTKAH NLLCQQKIQK
FQIAQVVRES NAMLREGYKT FFNTLYHNNI PLFIFSAGIG DILEEIIRQM KVFHPNIHIV
SNYMDFNEDG FLQGFKGQLI HTYNKNSSAC ENSGYFQQLE GKTNVILLGD SIGDLTMADG
VPGVQNILKI GFLNDKVEER RERYMDSYDI VLEKDETLDV VNGLLQHILC QGVQLEMQGP
