Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P21589 (5NTD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5'-nucleotidase

Short name=5'-NT
EC=3.1.3.5
Alternative name(s):
Ecto-5'-nucleotidase
CD_antigen=CD73
Gene names
Name:NT5E
Synonyms:NT5, NTE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length574 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities. Ref.9

Catalytic activity

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

Cofactor

Zinc.

Subunit structure

Homodimer. Ref.10

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor Ref.1.

Involvement in disease

Calcification of joints and arteries (CALJA) [MIM:211800]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

Belongs to the 5'-nucleotidase family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainSignal
   LigandMetal-binding
Nucleotide-binding
Zinc
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
GPI-anchor
Lipoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processAMP catabolic process

Inferred from electronic annotation. Source: Ensembl

DNA metabolic process

Traceable author statement Ref.1. Source: ProtInc

adenosine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

dephosphorylation

Inferred from experiment. Source: GOC

negative regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

purine nucleobase metabolic process

Traceable author statement. Source: Reactome

purine nucleotide catabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleobase metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleoside catabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentanchored component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay. Source: HPA

extracellular vesicular exosome

Inferred from direct assay PubMed 21362503. Source: UniProtKB

membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_function5'-nucleotidase activity

Inferred from experiment. Source: Reactome

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

nucleotide binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P21589-1)

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.
Isoform 2 (identifier: P21589-2)

The sequence of this isoform differs from the canonical sequence as follows:
     404-453: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.6
Chain27 – 5495235'-nucleotidase Ref.1
PRO_0000000015
Propeptide550 – 57425Removed in mature form
PRO_0000000016

Regions

Region500 – 5067Substrate binding

Sites

Metal binding361Zinc 1
Metal binding381Zinc 1
Metal binding851Zinc 1
Metal binding851Zinc 2
Metal binding1171Zinc 2
Metal binding2201Zinc 2
Metal binding2431Zinc 2
Binding site2451Substrate
Binding site3541Substrate
Binding site3901Substrate
Binding site3951Substrate
Binding site4171Substrate
Site1181Transition state stabilizer
Site1211Transition state stabilizer Probable

Amino acid modifications

Lipidation5491GPI-anchor amidated serine Ref.1
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Ref.7 Ref.10
Glycosylation3331N-linked (GlcNAc...) Ref.7 Ref.8
Glycosylation4031N-linked (GlcNAc...) Ref.7
Disulfide bond51 ↔ 57 Ref.10
Disulfide bond353 ↔ 358 Ref.10
Disulfide bond365 ↔ 387 Ref.10
Disulfide bond476 ↔ 479 Ref.10

Natural variations

Alternative sequence404 – 45350Missing in isoform 2.
VSP_043076
Natural variant3581C → Y in CALJA. Ref.11
VAR_065185
Natural variant3761T → A. Ref.5
Corresponds to variant rs2229523 [ dbSNP | Ensembl ].
VAR_022091
Natural variant3791M → T.
Corresponds to variant rs2229524 [ dbSNP | Ensembl ].
VAR_048103

Secondary structure

................................................................................................. 574
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1991. Version 1.
Checksum: A99AF170AB7EAECE

FASTA57463,368
        10         20         30         40         50         60 
MCPRAARAPA TLLLALGAVL WPAAGAWELT ILHTNDVHSR LEQTSEDSSK CVNASRCMGG 

        70         80         90        100        110        120 
VARLFTKVQQ IRRAEPNVLL LDAGDQYQGT IWFTVYKGAE VAHFMNALRY DAMALGNHEF 

       130        140        150        160        170        180 
DNGVEGLIEP LLKEAKFPIL SANIKAKGPL ASQISGLYLP YKVLPVGDEV VGIVGYTSKE 

       190        200        210        220        230        240 
TPFLSNPGTN LVFEDEITAL QPEVDKLKTL NVNKIIALGH SGFEMDKLIA QKVRGVDVVV 

       250        260        270        280        290        300 
GGHSNTFLYT GNPPSKEVPA GKYPFIVTSD DGRKVPVVQA YAFGKYLGYL KIEFDERGNV 

       310        320        330        340        350        360 
ISSHGNPILL NSSIPEDPSI KADINKWRIK LDNYSTQELG KTIVYLDGSS QSCRFRECNM 

       370        380        390        400        410        420 
GNLICDAMIN NNLRHTDEMF WNHVSMCILN GGGIRSPIDE RNNGTITWEN LAAVLPFGGT 

       430        440        450        460        470        480 
FDLVQLKGST LKKAFEHSVH RYGQSTGEFL QVGGIHVVYD LSRKPGDRVV KLDVLCTKCR 

       490        500        510        520        530        540 
VPSYDPLKMD EVYKVILPNF LANGGDGFQM IKDELLRHDS GDQDINVVST YISKMKVIYP 

       550        560        570 
AVEGRIKFST GSHCHGSFSL IFLSLWAVIF VLYQ 

« Hide

Isoform 2 [UniParc].

Checksum: 98A11D22CFC7C610
Show »

FASTA52457,949

References

« Hide 'large scale' references
[1]"Primary structure of human placental 5'-nucleotidase and identification of the glycolipid anchor in the mature form."
Misumi Y., Ogata S., Ohkubo K., Hirose S., Ikehara Y.
Eur. J. Biochem. 191:563-569(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, GPI-ANCHOR AT SER-549.
Tissue: Placenta.
[2]"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. expand/collapse author list , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Isolation and characterization of the promoter of the human 5'-nucleotidase (CD73)-encoding gene."
Hansen K.R., Resta R., Webb C.F., Thompson L.F.
Gene 167:307-312(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-113.
Tissue: Placenta.
[5]Zanoni L., Rosi F., Pagani R., Marinello E.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 359-489, VARIANT ALA-376.
Tissue: Leukocyte.
[6]"Characterization of soluble vs membrane-bound human placental 5'-nucleotidase."
Klemens M.R., Sherman W.R., Holmberg N.J., Ruedi J.M., Low M.G., Thompson L.F.
Biochem. Biophys. Res. Commun. 172:1371-1377(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-40.
Tissue: Placenta.
[7]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-311; ASN-333 AND ASN-403.
Tissue: Liver.
[8]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-333.
Tissue: Leukemic T-cell.
[9]"The high-resolution crystal structure of periplasmic Haemophilus influenzae NAD nucleotidase reveals a novel enzymatic function of human CD73 related to NAD metabolism."
Garavaglia S., Bruzzone S., Cassani C., Canella L., Allegrone G., Sturla L., Mannino E., Millo E., De Flora A., Rizzi M.
Biochem. J. 441:131-141(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBSTRATE SPECIFICITY.
[10]"Crystal structure of the human ecto-5'-nucleotidase (CD73): insights into the regulation of purinergic signaling."
Knapp K., Zebisch M., Pippel J., El-Tayeb A., Muller C.E., Strater N.
Structure 20:2161-2173(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 27-549 IN COMPLEXES WITH ATP ANALOG AND ZINC IONS, SUBUNIT, GLYCOSYLATION AT ASN-311, DISULFIDE BONDS.
[11]"NT5E mutations and arterial calcifications."
St Hilaire C., Ziegler S.G., Markello T.C., Brusco A., Groden C., Gill F., Carlson-Donohoe H., Lederman R.J., Chen M.Y., Yang D., Siegenthaler M.P., Arduino C., Mancini C., Freudenthal B., Stanescu H.C., Zdebik A.A., Chaganti R.K., Nussbaum R.L. expand/collapse author list , Kleta R., Gahl W.A., Boehm M.
N. Engl. J. Med. 364:432-442(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CALJA TYR-358.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS5002.1. [P21589-1]
CCDS56439.1. [P21589-2]
PIRS11032.
RefSeqNP_001191742.1. NM_001204813.1. [P21589-2]
NP_002517.1. NM_002526.3. [P21589-1]
UniGeneHs.153952.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP21589.
SMRP21589. Positions 27-549.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110962. 8 interactions.
DIPDIP-59992N.
MINTMINT-5002487.
STRING9606.ENSP00000257770.

Chemistry

ChEMBLCHEMBL5957.
DrugBankDB00806. Pentoxifylline.
GuidetoPHARMACOLOGY1232.

PTM databases

PhosphoSiteP21589.

Polymorphism databases

DMDM112825.

Proteomic databases

MaxQBP21589.
PaxDbP21589.
PRIDEP21589.

Protocols and materials databases

DNASU4907.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257770; ENSP00000257770; ENSG00000135318. [P21589-1]
ENST00000369651; ENSP00000358665; ENSG00000135318. [P21589-2]
GeneID4907.
KEGGhsa:4907.
UCSCuc003pko.4. human. [P21589-1]
uc010kbr.3. human. [P21589-2]

Organism-specific databases

CTD4907.
GeneCardsGC06P086216.
HGNCHGNC:8021. NT5E.
HPAHPA017357.
MIM129190. gene.
211800. phenotype.
neXtProtNX_P21589.
Orphanet289601. Hereditary arterial and articular multiple calcification syndrome.
PharmGKBPA31804.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0737.
HOGENOMHOG000247215.
HOVERGENHBG000026.
InParanoidP21589.
KOK01081.
OMADKVQFPV.
OrthoDBEOG7TF78T.
PhylomeDBP21589.
TreeFamTF323589.

Enzyme and pathway databases

BioCycMetaCyc:HS05981-MONOMER.
RETL1328306-WGS:GSTH-3623-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP21589.
BgeeP21589.
CleanExHS_NT5E.
GenevestigatorP21589.

Family and domain databases

Gene3D3.60.21.10. 1 hit.
3.90.780.10. 1 hit.
InterProIPR008334. 5'-Nucleotdase_C.
IPR006146. 5'-Nucleotdase_CS.
IPR006179. 5_nucleotidase/apyrase.
IPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
[Graphical view]
PANTHERPTHR11575. PTHR11575. 1 hit.
PfamPF02872. 5_nucleotid_C. 1 hit.
PF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSPR01607. APYRASEFAMLY.
SUPFAMSSF55816. SSF55816. 1 hit.
SSF56300. SSF56300. 1 hit.
PROSITEPS00785. 5_NUCLEOTIDASE_1. 1 hit.
PS00786. 5_NUCLEOTIDASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNT5E. human.
GeneWikiNT5E.
GenomeRNAi4907.
NextBio18883.
PROP21589.
SOURCESearch...

Entry information

Entry name5NTD_HUMAN
AccessionPrimary (citable) accession number: P21589
Secondary accession number(s): B3KQI8, O75520, Q5W116
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: July 9, 2014
This is version 157 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries