Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cytosolic 5'-nucleotidase 3A

Gene

NT5C3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m7GMP) (PubMed:24603684). CMP seems to be the preferred substrate (PubMed:15968458).2 Publications

Catalytic activityi

N7-methyl-GMP + H2O = N7-methyl-guanosine + phosphate.1 Publication
CMP + H2O = cytidine + phosphate.1 Publication
A 5'-ribonucleotide + H2O = a ribonucleoside + phosphate.1 Publication

Kineticsi

  1. KM=15 µM for m7GMP (at 37 degrees Celsius)1 Publication
  2. KM=66 µM for CMP1 Publication
  3. KM=80 µM for CMP (at 37 degrees Celsius)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei88Nucleophile1 Publication1
    Metal bindingi88Magnesium1 Publication1
    Active sitei90Proton donor1 Publication1
    Metal bindingi90Magnesium; via carbonyl oxygen1 Publication1
    Binding sitei135CMPBy similarity1
    Binding sitei135N(7)-methyl-GMPBy similarity1
    Binding sitei156N(7)-methyl-GMPBy similarity1
    Binding sitei252SubstrateBy similarity1
    Metal bindingi277Magnesium1 Publication1

    GO - Molecular functioni

    • 5'-nucleotidase activity Source: UniProtKB
    • magnesium ion binding Source: UniProtKB
    • nucleotide binding Source: UniProtKB-KW
    • tRNA 2'-phosphotransferase activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase, Transferase
    Biological processNucleotide metabolism
    LigandMagnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi3.1.3.91 2681
    ReactomeiR-HSA-73621 Pyrimidine catabolism
    SABIO-RKiQ9H0P0

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytosolic 5'-nucleotidase 3A2 Publications (EC:3.1.3.52 Publications)
    Alternative name(s):
    7-methylguanosine phosphate-specific 5'-nucleotidase1 Publication (EC:3.1.3.911 Publication)
    Short name:
    7-methylguanosine nucleotidase
    Cytosolic 5'-nucleotidase 3
    Cytosolic 5'-nucleotidase III
    Short name:
    cN-III
    Pyrimidine 5'-nucleotidase 1
    Short name:
    P5'N-1
    Short name:
    P5N-1
    Short name:
    PN-I
    Uridine 5'-monophosphate hydrolase 1
    p36
    Gene namesi
    Name:NT5C3A
    Synonyms:NT5C3, P5N1, UMPH1
    ORF Names:HSPC233
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 7

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000122643.18
    HGNCiHGNC:17820 NT5C3A
    MIMi606224 gene
    neXtProtiNX_Q9H0P0

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum

    Pathology & Biotechi

    Involvement in diseasei

    P5N deficiency (P5ND)8 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAutosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties.
    See also OMIM:266120
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07316095R → G in P5ND. 1 Publication1
    Natural variantiVAR_073161113C → R in P5ND; reduced catalytic activity especially towards UMP. 1 Publication1
    Natural variantiVAR_023511137D → V in P5ND; reduced catalytic activity. 2 PublicationsCorresponds to variant dbSNP:rs104894025EnsemblClinVar.1
    Natural variantiVAR_023512181L → P in P5ND; reduced catalytic activity in vitro; reduced protein stability in vivo, probably through increased proteasomal degradation. 3 Publications1
    Natural variantiVAR_073162207G → R in P5ND; reduced catalytic activity especially towards UMP. 2 Publications1
    Natural variantiVAR_023513229N → S in P5ND; almost complete loss of catalytic activity. 3 PublicationsCorresponds to variant dbSNP:rs104894028EnsemblClinVar.1
    Natural variantiVAR_023514280G → R in P5ND; greatly reduced catalytic activity. 3 PublicationsCorresponds to variant dbSNP:rs104894029EnsemblClinVar.1
    Natural variantiVAR_073163297I → T in P5ND. 2 Publications1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi88D → N: Loss of nucleotidase and phosphotransferase activity. 1 Publication1
    Mutagenesisi89F → A: Almost complete loss of nucleotidase and phosphotransferase activity. 1 Publication1
    Mutagenesisi90D → N: Loss of nucleotidase and phosphotransferase activity. 1 Publication1
    Mutagenesisi135E → D: No effect on nucleotidase activity. Almost complete loss of phosphotransferase activity. 1 Publication1
    Mutagenesisi232D → N: No effect on nucleotidase and phosphotransferase activity. 1 Publication1
    Mutagenesisi233F → A: Almost complete loss of nucleotidase and phosphotransferase activity. 1 Publication1
    Mutagenesisi234D → N: No effect on nucleotidase and phosphotransferase activity. 1 Publication1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi51251
    MalaCardsiNT5C3A
    MIMi266120 phenotype
    OpenTargetsiENSG00000122643
    Orphaneti35120 Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency
    PharmGKBiPA31802

    Polymorphism and mutation databases

    BioMutaiNT5C3A
    DMDMi117949804

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000643871 – 336Cytosolic 5'-nucleotidase 3AAdd BLAST336

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei278PhosphoserineBy similarity1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ9H0P0
    PaxDbiQ9H0P0
    PeptideAtlasiQ9H0P0
    PRIDEiQ9H0P0
    ProteomicsDBi80305
    80306 [Q9H0P0-1]
    80307 [Q9H0P0-2]
    80308 [Q9H0P0-3]

    PTM databases

    DEPODiQ9H0P0
    iPTMnetiQ9H0P0
    PhosphoSitePlusiQ9H0P0

    Expressioni

    Tissue specificityi

    Isoforms 1, 3 and 4 are expressed in reticulocytes. Isoform 4 is hardly detectable in bone marrow and fetal liver.2 Publications

    Inductioni

    Isoform 2 is induced by interferon alpha in Raji cells in association with lupus inclusions.1 Publication

    Gene expression databases

    BgeeiENSG00000122643 Expressed in 98 organ(s), highest expression level in quadriceps femoris
    ExpressionAtlasiQ9H0P0 baseline and differential
    GenevisibleiQ9H0P0 HS

    Organism-specific databases

    HPAiHPA010630
    HPA029058

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi119408, 24 interactors
    IntActiQ9H0P0, 11 interactors
    STRINGi9606.ENSP00000242210

    Structurei

    Secondary structure

    1336
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ9H0P0
    SMRiQ9H0P0
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9H0P0

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni203 – 204Substrate binding1 Publication2

    Sequence similaritiesi

    Belongs to the pyrimidine 5'-nucleotidase family.Curated

    Phylogenomic databases

    eggNOGiKOG3128 Eukaryota
    ENOG410ZQJ8 LUCA
    GeneTreeiENSGT00390000012959
    HOVERGENiHBG059750
    KOiK01081
    OMAiHNVIDNC
    OrthoDBiEOG091G0BCN
    PhylomeDBiQ9H0P0
    TreeFamiTF314663

    Family and domain databases

    CDDicd07504 HAD_5NT, 1 hit
    Gene3Di3.40.50.1000, 2 hits
    InterProiView protein in InterPro
    IPR036412 HAD-like_sf
    IPR023214 HAD_sf
    IPR006434 Pyrimidine_nucleotidase_eu
    PfamiView protein in Pfam
    PF05822 UMPH-1, 1 hit
    SFLDiSFLDG01128 C1.4:_5'-Nucleotidase_Like, 1 hit
    SUPFAMiSSF56784 SSF56784, 1 hit
    TIGRFAMsiTIGR01544 HAD-SF-IE, 1 hit

    Sequences (4+)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

    Isoform 2 (identifier: Q9H0P0-4) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MRAPSMDRAA VARVGAVASA SVCALVAGVV LAQYIFTLKR KTGRKTKIIE
    60 70 80 90 100
    MMPEFQKSSV RIKNPTRVEE IICGLIKGGA AKLQIITDFD MTLSRFSYKG
    110 120 130 140 150
    KRCPTCHNII DNCKLVTDEC RKKLLQLKEK YYAIEVDPVL TVEEKYPYMV
    160 170 180 190 200
    EWYTKSHGLL VQQALPKAKL KEIVAESDVM LKEGYENFFD KLQQHSIPVF
    210 220 230 240 250
    IFSAGIGDVL EEVIRQAGVY HPNVKVVSNF MDFDETGVLK GFKGELIHVF
    260 270 280 290 300
    NKHDGALRNT EYFNQLKDNS NIILLGDSQG DLRMADGVAN VEHILKIGYL
    310 320 330
    NDRVDELLEK YMDSYDIVLV QDESLEVANS ILQKIL
    Length:336
    Mass (Da):37,948
    Last modified:November 14, 2006 - v3
    Checksum:iC5D75CCF1BB61021
    GO
    Isoform 1 (identifier: Q9H0P0-1) [UniParc]FASTAAdd to basket
    Also known as: P5N-I

    The sequence of this isoform differs from the canonical sequence as follows:
         1-50: MRAPSMDRAAVARVGAVASASVCALVAGVVLAQYIFTLKRKTGRKTKIIE → MTNQESAVHVK

    Show »
    Length:297
    Mass (Da):33,915
    Checksum:iFB91A66DD2273598
    GO
    Isoform 3 (identifier: Q9H0P0-2) [UniParc]FASTAAdd to basket
    Also known as: p36

    The sequence of this isoform differs from the canonical sequence as follows:
         1-50: Missing.

    Show »
    Length:286
    Mass (Da):32,690
    Checksum:i29313E2790194ED9
    GO
    Isoform 4 (identifier: Q9H0P0-3) [UniParc]FASTAAdd to basket
    Also known as: P5N-R

    The sequence of this isoform differs from the canonical sequence as follows:
         1-51: Missing.

    Show »
    Length:285
    Mass (Da):32,559
    Checksum:iCB3B6812C90A5578
    GO

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    X6RM59X6RM59_HUMAN
    5'-nucleotidase
    NT5C3A
    331Annotation score:
    B9A035B9A035_HUMAN
    Cytosolic 5'-nucleotidase 3A
    NT5C3A
    205Annotation score:
    C9K084C9K084_HUMAN
    Cytosolic 5'-nucleotidase 3A
    NT5C3A
    42Annotation score:
    F8WDR0F8WDR0_HUMAN
    Cytosolic 5'-nucleotidase 3A
    NT5C3A
    54Annotation score:

    Sequence cautioni

    The sequence AAF36153 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
    The sequence AAG33630 differs from that shown. Reason: Frameshift at several positions.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti95R → K AA sequence (PubMed:8557639).Curated1
    Sequence conflicti144E → Q AA sequence (PubMed:8557639).Curated1
    Sequence conflicti329N → R AA sequence (PubMed:8557639).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07316095R → G in P5ND. 1 Publication1
    Natural variantiVAR_073161113C → R in P5ND; reduced catalytic activity especially towards UMP. 1 Publication1
    Natural variantiVAR_023511137D → V in P5ND; reduced catalytic activity. 2 PublicationsCorresponds to variant dbSNP:rs104894025EnsemblClinVar.1
    Natural variantiVAR_023512181L → P in P5ND; reduced catalytic activity in vitro; reduced protein stability in vivo, probably through increased proteasomal degradation. 3 Publications1
    Natural variantiVAR_073162207G → R in P5ND; reduced catalytic activity especially towards UMP. 2 Publications1
    Natural variantiVAR_023513229N → S in P5ND; almost complete loss of catalytic activity. 3 PublicationsCorresponds to variant dbSNP:rs104894028EnsemblClinVar.1
    Natural variantiVAR_023514280G → R in P5ND; greatly reduced catalytic activity. 3 PublicationsCorresponds to variant dbSNP:rs104894029EnsemblClinVar.1
    Natural variantiVAR_073163297I → T in P5ND. 2 Publications1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0156241 – 51Missing in isoform 4. 1 PublicationAdd BLAST51
    Alternative sequenceiVSP_0215651 – 50MRAPS…TKIIE → MTNQESAVHVK in isoform 1. 2 PublicationsAdd BLAST50
    Alternative sequenceiVSP_0156231 – 50Missing in isoform 3. 2 PublicationsAdd BLAST50

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF312735 mRNA Translation: AAG33630.1 Sequence problems.
    AL136716 mRNA Translation: CAB66650.1
    AK290118 mRNA Translation: BAF82807.1
    AK314109 mRNA Translation: BAG36802.1
    CR533518 mRNA Translation: CAG38549.1
    AC074338 Genomic DNA No translation available.
    AC083863 Genomic DNA No translation available.
    CH471073 Genomic DNA Translation: EAW94007.1
    CH471073 Genomic DNA Translation: EAW94008.1
    BC013292 mRNA Translation: AAH13292.2
    BC015856 mRNA Translation: AAH15856.2
    BC066914 mRNA Translation: AAH66914.1
    BC071652 mRNA Translation: AAH71652.2
    AF151067 mRNA Translation: AAF36153.1 Different initiation.
    CCDSiCCDS34617.1 [Q9H0P0-1]
    CCDS55101.1 [Q9H0P0-3]
    RefSeqiNP_001002009.1, NM_001002009.2 [Q9H0P0-1]
    NP_001002010.1, NM_001002010.2
    NP_001159590.1, NM_001166118.2 [Q9H0P0-3]
    NP_057573.2, NM_016489.12 [Q9H0P0-1]
    XP_011513711.1, XM_011515409.2
    UniGeneiHs.487933

    Genome annotation databases

    EnsembliENST00000381626; ENSP00000371039; ENSG00000122643 [Q9H0P0-3]
    ENST00000396152; ENSP00000379456; ENSG00000122643 [Q9H0P0-1]
    ENST00000405342; ENSP00000385261; ENSG00000122643 [Q9H0P0-1]
    ENST00000409467; ENSP00000387166; ENSG00000122643 [Q9H0P0-3]
    ENST00000620705; ENSP00000484415; ENSG00000122643 [Q9H0P0-4]
    ENST00000643244; ENSP00000496364; ENSG00000122643 [Q9H0P0-1]
    GeneIDi51251
    KEGGihsa:51251
    UCSCiuc003tdi.5 human [Q9H0P0-4]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry namei5NT3A_HUMAN
    AccessioniPrimary (citable) accession number: Q9H0P0
    Secondary accession number(s): A8K253
    , B2RAA5, B8ZZC4, Q6IPZ1, Q6NXS6, Q7L3G6, Q9P0P5, Q9UC42, Q9UC43, Q9UC44, Q9UC45
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 13, 2005
    Last sequence update: November 14, 2006
    Last modified: September 12, 2018
    This is version 163 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again