ID   5NT1A_HUMAN             Reviewed;         368 AA.
AC   Q9BXI3; Q3SYB9; Q5TG98; Q9BWT8;
DT   10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 163.
DE   RecName: Full=Cytosolic 5'-nucleotidase 1A;
DE            Short=cN1A;
DE            EC=3.1.3.5 {ECO:0000269|PubMed:11133996, ECO:0000269|PubMed:34814800, ECO:0000269|PubMed:7599155, ECO:0000269|PubMed:8967393};
DE            EC=3.1.3.89 {ECO:0000269|PubMed:11133996};
DE            EC=3.1.3.99 {ECO:0000269|PubMed:11133996};
DE   AltName: Full=5'-deoxynucleotidase {ECO:0000303|PubMed:11133996};
DE   AltName: Full=Cytosolic 5'-nucleotidase IA;
DE            Short=cN-I;
DE            Short=cN-IA;
GN   Name=NT5C1A;
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 [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   TISSUE=Heart;
RX   PubMed=11133996; DOI=10.1074/jbc.m011218200;
RA   Hunsucker S.A., Spychala J., Mitchell B.S.;
RT   "Human cytosolic 5'-nucleotidase I: characterization and role in nucleoside
RT   analog resistance.";
RL   J. Biol. Chem. 276:10498-10504(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Heart;
RA   Lowenstein J.M., Huang J., Steiner A.;
RT   "5'-nucleotidase I from human heart.";
RL   Submitted (MAR-2001) 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 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, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=7599155; DOI=10.1016/0304-4165(95)98595-c;
RA   Tavenier M., Skladanowski A.C., De Abreu R.A., de Jong J.W.;
RT   "Kinetics of adenylate metabolism in human and rat myocardium.";
RL   Biochim. Biophys. Acta 1244:351-356(1995).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP   REGULATION, COFACTOR, AND TISSUE SPECIFICITY.
RX   PubMed=8967393; DOI=10.1152/ajpheart.1996.270.4.h1493;
RA   Skladanowski A.C., Smolenski R.T., Tavenier M., de Jong J.W., Yacoub M.H.,
RA   Seymour A.M.;
RT   "Soluble forms of 5'-nucleotidase in rat and human heart.";
RL   Am. J. Physiol. 270:H1493-H1500(1996).
RN   [7]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=34814800; DOI=10.1080/15257770.2021.2007396;
RA   Jedrzejewska A., Kutryb-Zajac B., Krol O., Harasim G., Franczak M.,
RA   Jablonska P., Slominska E., Smolenski R.T.;
RT   "The decreased serum activity of cytosolic 5'-nucleotidase IA as a
RT   potential marker of breast cancer-associated muscle inflammation.";
RL   Nucleosides Nucleotides Nucleic Acids 41:273-284(2022).
CC   -!- FUNCTION: Catalyzes the hydrolysis of ribonucleotide and
CC       deoxyribonucleotide monophosphates, releasing inorganic phosphate and
CC       the corresponding nucleoside (PubMed:11133996, PubMed:7599155,
CC       PubMed:8967393, PubMed:34814800). AMP is the major substrate but can
CC       also hydrolyze dCMP and IMP (PubMed:11133996, PubMed:7599155,
CC       PubMed:8967393, PubMed:34814800). {ECO:0000269|PubMed:11133996,
CC       ECO:0000269|PubMed:34814800, ECO:0000269|PubMed:7599155,
CC       ECO:0000269|PubMed:8967393}.
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:11133996, ECO:0000269|PubMed:34814800,
CC         ECO:0000269|PubMed:7599155, ECO:0000269|PubMed:8967393};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 2'-deoxyribonucleoside 5'-phosphate + H2O = a 2'-
CC         deoxyribonucleoside + phosphate; Xref=Rhea:RHEA:36167,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:18274, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:65317; EC=3.1.3.89;
CC         Evidence={ECO:0000269|PubMed:11133996};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + IMP = inosine + phosphate; Xref=Rhea:RHEA:27718,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:17596, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:58053; EC=3.1.3.99;
CC         Evidence={ECO:0000269|PubMed:11133996};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=AMP + H2O = adenosine + phosphate; Xref=Rhea:RHEA:29375,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:16335, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:11133996,
CC         ECO:0000269|PubMed:34814800, ECO:0000269|PubMed:7599155,
CC         ECO:0000269|PubMed:8967393};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dCMP + H2O = 2'-deoxycytidine + phosphate;
CC         Xref=Rhea:RHEA:29363, ChEBI:CHEBI:15377, ChEBI:CHEBI:15698,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:57566;
CC         Evidence={ECO:0000269|PubMed:11133996};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:8967393};
CC   -!- ACTIVITY REGULATION: Activated by ADP. {ECO:0000269|PubMed:11133996,
CC       ECO:0000269|PubMed:8967393}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2.96 mM for AMP {ECO:0000269|PubMed:11133996};
CC         KM=5320 uM for AMP {ECO:0000269|PubMed:7599155};
CC         KM=1.46 mM for AMP {ECO:0000269|PubMed:8967393};
CC         KM=0.193 mM for dCMP {ECO:0000269|PubMed:11133996};
CC         KM=12.11 mM for IMP {ECO:0000269|PubMed:11133996};
CC         Vmax=7.7 umol/min/mg enzyme for AMP {ECO:0000269|PubMed:11133996};
CC         Vmax=18.1 umol/min/mg enzyme for dCMP {ECO:0000269|PubMed:11133996};
CC         Vmax=33.2 umol/min/mg enzyme for IMP {ECO:0000269|PubMed:11133996};
CC       pH dependence:
CC         Optimum pH is 7.0. {ECO:0000269|PubMed:8967393};
CC   -!- INTERACTION:
CC       Q9BXI3; Q16543: CDC37; NbExp=3; IntAct=EBI-10441581, EBI-295634;
CC       Q9BXI3; Q96HA8: NTAQ1; NbExp=6; IntAct=EBI-10441581, EBI-741158;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:7599155}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle. Detected at
CC       intermediate levels in heart, brain, kidney and pancreas.
CC       {ECO:0000269|PubMed:11133996, ECO:0000269|PubMed:8967393}.
CC   -!- SIMILARITY: Belongs to the 5'-nucleotidase type 3 family.
CC       {ECO:0000305}.
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DR   EMBL; AF331801; AAK01294.1; -; mRNA.
DR   EMBL; AY028778; AAK30000.1; -; mRNA.
DR   EMBL; AL035404; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC103879; AAI03880.1; -; mRNA.
DR   EMBL; BC103880; AAI03881.1; -; mRNA.
DR   CCDS; CCDS440.1; -.
DR   RefSeq; NP_115915.1; NM_032526.2.
DR   AlphaFoldDB; Q9BXI3; -.
DR   BioGRID; 124149; 31.
DR   IntAct; Q9BXI3; 5.
DR   STRING; 9606.ENSP00000235628; -.
DR   DEPOD; NT5C1A; -.
DR   iPTMnet; Q9BXI3; -.
DR   PhosphoSitePlus; Q9BXI3; -.
DR   BioMuta; NT5C1A; -.
DR   DMDM; 47116736; -.
DR   MassIVE; Q9BXI3; -.
DR   PaxDb; 9606-ENSP00000235628; -.
DR   PeptideAtlas; Q9BXI3; -.
DR   ProteomicsDB; 79426; -.
DR   Antibodypedia; 54865; 231 antibodies from 25 providers.
DR   DNASU; 84618; -.
DR   Ensembl; ENST00000235628.2; ENSP00000235628.1; ENSG00000116981.4.
DR   GeneID; 84618; -.
DR   KEGG; hsa:84618; -.
DR   MANE-Select; ENST00000235628.2; ENSP00000235628.1; NM_032526.3; NP_115915.1.
DR   UCSC; uc001cdq.1; human.
DR   AGR; HGNC:17819; -.
DR   CTD; 84618; -.
DR   DisGeNET; 84618; -.
DR   GeneCards; NT5C1A; -.
DR   HGNC; HGNC:17819; NT5C1A.
DR   HPA; ENSG00000116981; Group enriched (skeletal muscle, tongue).
DR   MIM; 610525; gene.
DR   neXtProt; NX_Q9BXI3; -.
DR   OpenTargets; ENSG00000116981; -.
DR   PharmGKB; PA31799; -.
DR   VEuPathDB; HostDB:ENSG00000116981; -.
DR   eggNOG; ENOG502QRJF; Eukaryota.
DR   GeneTree; ENSGT00390000017767; -.
DR   HOGENOM; CLU_060123_0_0_1; -.
DR   InParanoid; Q9BXI3; -.
DR   OMA; YQIEHED; -.
DR   OrthoDB; 2912584at2759; -.
DR   PhylomeDB; Q9BXI3; -.
DR   TreeFam; TF329831; -.
DR   BioCyc; MetaCyc:HS04074-MONOMER; -.
DR   BRENDA; 3.1.3.5; 2681.
DR   PathwayCommons; Q9BXI3; -.
DR   Reactome; R-HSA-73621; Pyrimidine catabolism.
DR   Reactome; R-HSA-74259; Purine catabolism.
DR   SABIO-RK; Q9BXI3; -.
DR   SignaLink; Q9BXI3; -.
DR   BioGRID-ORCS; 84618; 19 hits in 1161 CRISPR screens.
DR   GenomeRNAi; 84618; -.
DR   Pharos; Q9BXI3; Tbio.
DR   PRO; PR:Q9BXI3; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q9BXI3; Protein.
DR   Bgee; ENSG00000116981; Expressed in gastrocnemius and 85 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0008253; F:5'-nucleotidase activity; IDA:UniProtKB.
DR   GO; GO:0050483; F:IMP 5'-nucleotidase activity; IDA:MGI.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   GO; GO:0106411; F:XMP 5'-nucleosidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046085; P:adenosine metabolic process; IBA:GO_Central.
DR   GO; GO:0000255; P:allantoin metabolic process; IDA:MGI.
DR   GO; GO:0006196; P:AMP catabolic process; IDA:MGI.
DR   GO; GO:0046059; P:dAMP catabolic process; IDA:MGI.
DR   GO; GO:0046055; P:dGMP catabolic process; IDA:MGI.
DR   GO; GO:0006204; P:IMP catabolic process; IDA:MGI.
DR   GO; GO:0009116; P:nucleoside metabolic process; NAS:UniProtKB.
DR   InterPro; IPR010394; 5-nucleotidase.
DR   PANTHER; PTHR31367; CYTOSOLIC 5'-NUCLEOTIDASE 1 FAMILY MEMBER; 1.
DR   PANTHER; PTHR31367:SF2; CYTOSOLIC 5'-NUCLEOTIDASE 1A; 1.
DR   Pfam; PF06189; 5-nucleotidase; 1.
DR   Genevisible; Q9BXI3; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; Hydrolase; Magnesium; Nucleotide metabolism; Nucleotide-binding;
KW   Reference proteome.
FT   CHAIN           1..368
FT                   /note="Cytosolic 5'-nucleotidase 1A"
FT                   /id="PRO_0000144795"
FT   REGION          1..22
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        211
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        9..11
FT                   /note="Missing (in Ref. 2; AAK30000)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   368 AA;  41021 MW;  7FB3CCEED50BA50D CRC64;
     MEPGQPREPQ EPREPGPGAE TAAAPVWEEA KIFYDNLAPK KKPKSPKPQN AVTIAVSSRA
     LFRMDEEQQI YTEQGVEEYV RYQLEHENEP FSPGPAFPFV KALEAVNRRL RELYPDSEDV
     FDIVLMTNNH AQVGVRLINS INHYDLFIER FCMTGGNSPI CYLKAYHTNL YLSADAEKVR
     EAIDEGIAAA TIFSPSRDVV VSQSQLRVAF DGDAVLFSDE SERIVKAHGL DRFFEHEKAH
     ENKPLAQGPL KGFLEALGRL QKKFYSKGLR LECPIRTYLV TARSAASSGA RALKTLRSWG
     LETDEALFLA GAPKGPLLEK IRPHIFFDDQ MFHVAGAQEM GTVAAHVPYG VAQTPRRTAP
     AKQAPSAQ
//