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Protein

5'-nucleotidase

Gene

NT5E

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.1 Publication

Catalytic activityi

A 5'-ribonucleotide + H2O = a ribonucleoside + phosphate.

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi36Zinc 11
Metal bindingi38Zinc 11
Metal bindingi85Zinc 11
Metal bindingi85Zinc 21
Metal bindingi117Zinc 21
Sitei118Transition state stabilizer1
Sitei121Transition state stabilizerCurated1
Metal bindingi220Zinc 21
Metal bindingi243Zinc 21
Binding sitei245Substrate1
Binding sitei354Substrate1
Binding sitei390Substrate1
Binding sitei395Substrate1
Binding sitei417Substrate1

GO - Molecular functioni

  • 5'-nucleotidase activity Source: CACAO
  • metal ion binding Source: UniProtKB-KW
  • nucleotide binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS05981-MONOMER.
ZFISH:HS05981-MONOMER.
ReactomeiR-HSA-73621. Pyrimidine catabolism.
R-HSA-74259. Purine catabolism.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-nucleotidase (EC:3.1.3.5)
Short name:
5'-NT
Alternative name(s):
Ecto-5'-nucleotidase
CD_antigen: CD73
Gene namesi
Name:NT5E
Synonyms:NT5, NTE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:8021. NT5E.

Subcellular locationi

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • cell surface Source: UniProtKB
  • cytoplasm Source: HPA
  • extracellular exosome Source: UniProtKB
  • membrane Source: ProtInc
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Calcification of joints and arteries (CALJA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands.
See also OMIM:211800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065185358C → Y in CALJA; absence from the plasma-membrane; exhibits no catalytic AMPase activity. 2 PublicationsCorresponds to variant rs387906620dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4907.
MalaCardsiNT5E.
MIMi211800. phenotype.
OpenTargetsiENSG00000135318.
Orphaneti289601. Hereditary arterial and articular multiple calcification syndrome.
PharmGKBiPA31804.

Chemistry databases

ChEMBLiCHEMBL5957.
DrugBankiDB00987. Cytarabine.
DB00806. Pentoxifylline.
GuidetoPHARMACOLOGYi1232.

Polymorphism and mutation databases

BioMutaiNT5E.
DMDMi112825.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 261 PublicationAdd BLAST26
ChainiPRO_000000001527 – 5495'-nucleotidase1 PublicationAdd BLAST523
PropeptideiPRO_0000000016550 – 574Removed in mature formAdd BLAST25

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi51 ↔ 571 Publication
Glycosylationi53N-linked (GlcNAc...)Sequence analysis1
Glycosylationi311N-linked (GlcNAc...)2 Publications1
Glycosylationi333N-linked (GlcNAc...)2 Publications1
Disulfide bondi353 ↔ 3581 Publication
Disulfide bondi365 ↔ 3871 Publication
Glycosylationi403N-linked (GlcNAc...)1 Publication1
Disulfide bondi476 ↔ 4791 Publication
Lipidationi549GPI-anchor amidated serine1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

EPDiP21589.
MaxQBiP21589.
PaxDbiP21589.
PeptideAtlasiP21589.
PRIDEiP21589.

PTM databases

DEPODiP21589.
iPTMnetiP21589.
PhosphoSitePlusiP21589.
SwissPalmiP21589.

Expressioni

Gene expression databases

BgeeiENSG00000135318.
CleanExiHS_NT5E.
ExpressionAtlasiP21589. baseline and differential.
GenevisibleiP21589. HS.

Organism-specific databases

HPAiHPA017357.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

BioGridi110962. 48 interactors.
DIPiDIP-59992N.
MINTiMINT-5002487.
STRINGi9606.ENSP00000257770.

Chemistry databases

BindingDBiP21589.

Structurei

Secondary structure

1574
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 34Combined sources8
Beta strandi48 – 50Combined sources3
Helixi54 – 56Combined sources3
Helixi61 – 74Combined sources14
Beta strandi76 – 82Combined sources7
Beta strandi87 – 90Combined sources4
Helixi91 – 96Combined sources6
Helixi99 – 108Combined sources10
Beta strandi111 – 114Combined sources4
Helixi117 – 120Combined sources4
Helixi123 – 128Combined sources6
Turni129 – 134Combined sources6
Beta strandi142 – 146Combined sources5
Helixi150 – 154Combined sources5
Turni155 – 157Combined sources3
Beta strandi158 – 166Combined sources9
Beta strandi169 – 177Combined sources9
Helixi181 – 184Combined sources4
Beta strandi189 – 193Combined sources5
Helixi196 – 209Combined sources14
Beta strandi215 – 221Combined sources7
Helixi223 – 232Combined sources10
Beta strandi238 – 240Combined sources3
Beta strandi250 – 252Combined sources3
Beta strandi254 – 256Combined sources3
Beta strandi263 – 268Combined sources6
Beta strandi274 – 278Combined sources5
Beta strandi285 – 294Combined sources10
Beta strandi300 – 305Combined sources6
Helixi318 – 335Combined sources18
Beta strandi337 – 344Combined sources8
Helixi350 – 353Combined sources4
Helixi359 – 371Combined sources13
Helixi379 – 381Combined sources3
Beta strandi386 – 390Combined sources5
Helixi391 – 393Combined sources3
Turni401 – 404Combined sources4
Beta strandi405 – 407Combined sources3
Helixi408 – 414Combined sources7
Beta strandi420 – 427Combined sources8
Helixi428 – 439Combined sources12
Turni440 – 443Combined sources4
Beta strandi450 – 459Combined sources10
Beta strandi469 – 475Combined sources7
Beta strandi477 – 481Combined sources5
Beta strandi484 – 486Combined sources3
Beta strandi492 – 498Combined sources7
Helixi499 – 502Combined sources4
Helixi505 – 507Combined sources3
Helixi509 – 514Combined sources6
Beta strandi516 – 523Combined sources8
Helixi524 – 535Combined sources12
Beta strandi536 – 538Combined sources3
Beta strandi544 – 548Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H1SX-ray2.20A/B27-549[»]
4H1YX-ray1.58P27-549[»]
4H2BX-ray1.70A27-549[»]
4H2FX-ray1.85A27-549[»]
4H2GX-ray1.55A27-549[»]
4H2IX-ray2.00A27-549[»]
ProteinModelPortaliP21589.
SMRiP21589.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni500 – 506Substrate binding7

Sequence similaritiesi

Belongs to the 5'-nucleotidase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4419. Eukaryota.
COG0737. LUCA.
GeneTreeiENSGT00530000063775.
HOGENOMiHOG000247215.
HOVERGENiHBG000026.
KOiK19970.
OMAiWAVIFVL.
OrthoDBiEOG091G08IK.
PhylomeDBiP21589.
TreeFamiTF323589.

Family and domain databases

Gene3Di3.60.21.10. 1 hit.
3.90.780.10. 1 hit.
InterProiIPR008334. 5'-Nucleotdase_C.
IPR006146. 5'-Nucleotdase_CS.
IPR006179. 5_nucleotidase/apyrase.
IPR004843. Calcineurin-like_PHP_ApaH.
IPR029052. Metallo-depent_PP-like.
[Graphical view]
PANTHERiPTHR11575. PTHR11575. 1 hit.
PfamiPF02872. 5_nucleotid_C. 1 hit.
PF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSiPR01607. APYRASEFAMLY.
SUPFAMiSSF55816. SSF55816. 1 hit.
SSF56300. SSF56300. 1 hit.
PROSITEiPS00785. 5_NUCLEOTIDASE_1. 1 hit.
PS00786. 5_NUCLEOTIDASE_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P21589-1) [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
MCPRAARAPA TLLLALGAVL WPAAGAWELT ILHTNDVHSR LEQTSEDSSK
60 70 80 90 100
CVNASRCMGG VARLFTKVQQ IRRAEPNVLL LDAGDQYQGT IWFTVYKGAE
110 120 130 140 150
VAHFMNALRY DAMALGNHEF DNGVEGLIEP LLKEAKFPIL SANIKAKGPL
160 170 180 190 200
ASQISGLYLP YKVLPVGDEV VGIVGYTSKE TPFLSNPGTN LVFEDEITAL
210 220 230 240 250
QPEVDKLKTL NVNKIIALGH SGFEMDKLIA QKVRGVDVVV GGHSNTFLYT
260 270 280 290 300
GNPPSKEVPA GKYPFIVTSD DGRKVPVVQA YAFGKYLGYL KIEFDERGNV
310 320 330 340 350
ISSHGNPILL NSSIPEDPSI KADINKWRIK LDNYSTQELG KTIVYLDGSS
360 370 380 390 400
QSCRFRECNM GNLICDAMIN NNLRHTDEMF WNHVSMCILN GGGIRSPIDE
410 420 430 440 450
RNNGTITWEN LAAVLPFGGT FDLVQLKGST LKKAFEHSVH RYGQSTGEFL
460 470 480 490 500
QVGGIHVVYD LSRKPGDRVV KLDVLCTKCR VPSYDPLKMD EVYKVILPNF
510 520 530 540 550
LANGGDGFQM IKDELLRHDS GDQDINVVST YISKMKVIYP AVEGRIKFST
560 570
GSHCHGSFSL IFLSLWAVIF VLYQ
Length:574
Mass (Da):63,368
Last modified:May 1, 1991 - v1
Checksum:iA99AF170AB7EAECE
GO
Isoform 2 (identifier: P21589-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     404-453: Missing.

Note: No experimental confirmation available.
Show »
Length:524
Mass (Da):57,949
Checksum:i98A11D22CFC7C610
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065185358C → Y in CALJA; absence from the plasma-membrane; exhibits no catalytic AMPase activity. 2 PublicationsCorresponds to variant rs387906620dbSNPEnsembl.1
Natural variantiVAR_022091376T → A.1 PublicationCorresponds to variant rs2229523dbSNPEnsembl.1
Natural variantiVAR_048103379M → T.Corresponds to variant rs2229524dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043076404 – 453Missing in isoform 2. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55740 mRNA. Translation: CAA39271.1.
AK075008 mRNA. Translation: BAG52050.1.
AL135903, AL589666 Genomic DNA. Translation: CAH72337.1.
AL589666, AL135903 Genomic DNA. Translation: CAI40168.1.
U21730 Genomic DNA. Translation: AAA96950.1.
AF069067 Genomic DNA. Translation: AAC98672.1.
CCDSiCCDS5002.1. [P21589-1]
CCDS56439.1. [P21589-2]
PIRiS11032.
RefSeqiNP_001191742.1. NM_001204813.1. [P21589-2]
NP_002517.1. NM_002526.3. [P21589-1]
UniGeneiHs.153952.

Genome annotation databases

EnsembliENST00000257770; ENSP00000257770; ENSG00000135318. [P21589-1]
ENST00000369651; ENSP00000358665; ENSG00000135318. [P21589-2]
GeneIDi4907.
KEGGihsa:4907.
UCSCiuc003pko.5. human. [P21589-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55740 mRNA. Translation: CAA39271.1.
AK075008 mRNA. Translation: BAG52050.1.
AL135903, AL589666 Genomic DNA. Translation: CAH72337.1.
AL589666, AL135903 Genomic DNA. Translation: CAI40168.1.
U21730 Genomic DNA. Translation: AAA96950.1.
AF069067 Genomic DNA. Translation: AAC98672.1.
CCDSiCCDS5002.1. [P21589-1]
CCDS56439.1. [P21589-2]
PIRiS11032.
RefSeqiNP_001191742.1. NM_001204813.1. [P21589-2]
NP_002517.1. NM_002526.3. [P21589-1]
UniGeneiHs.153952.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H1SX-ray2.20A/B27-549[»]
4H1YX-ray1.58P27-549[»]
4H2BX-ray1.70A27-549[»]
4H2FX-ray1.85A27-549[»]
4H2GX-ray1.55A27-549[»]
4H2IX-ray2.00A27-549[»]
ProteinModelPortaliP21589.
SMRiP21589.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110962. 48 interactors.
DIPiDIP-59992N.
MINTiMINT-5002487.
STRINGi9606.ENSP00000257770.

Chemistry databases

BindingDBiP21589.
ChEMBLiCHEMBL5957.
DrugBankiDB00987. Cytarabine.
DB00806. Pentoxifylline.
GuidetoPHARMACOLOGYi1232.

PTM databases

DEPODiP21589.
iPTMnetiP21589.
PhosphoSitePlusiP21589.
SwissPalmiP21589.

Polymorphism and mutation databases

BioMutaiNT5E.
DMDMi112825.

Proteomic databases

EPDiP21589.
MaxQBiP21589.
PaxDbiP21589.
PeptideAtlasiP21589.
PRIDEiP21589.

Protocols and materials databases

DNASUi4907.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257770; ENSP00000257770; ENSG00000135318. [P21589-1]
ENST00000369651; ENSP00000358665; ENSG00000135318. [P21589-2]
GeneIDi4907.
KEGGihsa:4907.
UCSCiuc003pko.5. human. [P21589-1]

Organism-specific databases

CTDi4907.
DisGeNETi4907.
GeneCardsiNT5E.
HGNCiHGNC:8021. NT5E.
HPAiHPA017357.
MalaCardsiNT5E.
MIMi129190. gene.
211800. phenotype.
neXtProtiNX_P21589.
OpenTargetsiENSG00000135318.
Orphaneti289601. Hereditary arterial and articular multiple calcification syndrome.
PharmGKBiPA31804.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4419. Eukaryota.
COG0737. LUCA.
GeneTreeiENSGT00530000063775.
HOGENOMiHOG000247215.
HOVERGENiHBG000026.
KOiK19970.
OMAiWAVIFVL.
OrthoDBiEOG091G08IK.
PhylomeDBiP21589.
TreeFamiTF323589.

Enzyme and pathway databases

BioCyciMetaCyc:HS05981-MONOMER.
ZFISH:HS05981-MONOMER.
ReactomeiR-HSA-73621. Pyrimidine catabolism.
R-HSA-74259. Purine catabolism.

Miscellaneous databases

ChiTaRSiNT5E. human.
GeneWikiiNT5E.
GenomeRNAii4907.
PROiP21589.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135318.
CleanExiHS_NT5E.
ExpressionAtlasiP21589. baseline and differential.
GenevisibleiP21589. HS.

Family and domain databases

Gene3Di3.60.21.10. 1 hit.
3.90.780.10. 1 hit.
InterProiIPR008334. 5'-Nucleotdase_C.
IPR006146. 5'-Nucleotdase_CS.
IPR006179. 5_nucleotidase/apyrase.
IPR004843. Calcineurin-like_PHP_ApaH.
IPR029052. Metallo-depent_PP-like.
[Graphical view]
PANTHERiPTHR11575. PTHR11575. 1 hit.
PfamiPF02872. 5_nucleotid_C. 1 hit.
PF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSiPR01607. APYRASEFAMLY.
SUPFAMiSSF55816. SSF55816. 1 hit.
SSF56300. SSF56300. 1 hit.
PROSITEiPS00785. 5_NUCLEOTIDASE_1. 1 hit.
PS00786. 5_NUCLEOTIDASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei5NTD_HUMAN
AccessioniPrimary (citable) accession number: P21589
Secondary accession number(s): B3KQI8, O75520, Q5W116
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: November 30, 2016
This is version 180 of the entry and version 1 of the sequence. [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

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.