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

Last modified January 25, 2012. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
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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)
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.

Catalytic activity

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

Cofactor

Zinc.

Subunit structure

Homodimer; disulfide-linked.

Subcellular location

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

Involvement in disease

Defects in NT5E are the cause of 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. Ref.8

Sequence similarities

Belongs to the 5'-nucleotidase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.5
Chain27 – 5495235'-nucleotidase Ref.1
PRO_0000000015
Propeptide550 – 57425Removed in mature form
PRO_0000000016

Regions

Region500 – 5067Substrate binding By similarity

Sites

Metal binding361Zinc 1 By similarity
Metal binding381Zinc 1 By similarity
Metal binding851Zinc 1 By similarity
Metal binding851Zinc 2 By similarity
Metal binding1171Zinc 2 By similarity
Metal binding2201Zinc 2 By similarity
Metal binding2431Zinc 2 By similarity
Binding site4171Substrate By similarity
Site1181Transition state stabilizer By similarity
Site1211Transition state stabilizer By similarity

Amino acid modifications

Lipidation5491GPI-anchor amidated serine Ref.1
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Ref.6
Glycosylation3331N-linked (GlcNAc...) Ref.6 Ref.7
Glycosylation4031N-linked (GlcNAc...) Ref.6

Natural variations

Natural variant3581C → Y in CALJA.
VAR_065185
Natural variant3761T → A. Ref.4
Corresponds to variant rs2229523 [ dbSNP | Ensembl ].
VAR_022091
Natural variant3791M → T.
Corresponds to variant rs2229524 [ dbSNP | Ensembl ].
VAR_048103

Sequences

Sequence LengthMass (Da)Tools
P21589 [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

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: 2129526] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GPI-ANCHOR AT SER-549.
Tissue: Placenta.
[2]"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: 14574404] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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: 8566797] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-113.
Tissue: Placenta.
[4]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.
[5]"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: 2173922] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-40.
Tissue: Placenta.
[6]"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: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-311; ASN-333 AND ASN-403, MASS SPECTROMETRY.
Tissue: Liver.
[7]"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: 19349973] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-333, MASS SPECTROMETRY.
Tissue: Leukemic T-cell.
[8]"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: 21288095] [Abstract]
Cited for: VARIANT CALJA TYR-358.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X55740 mRNA. Translation: CAA39271.1.
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.
IPIIPI00009456.
PIRS11032.
RefSeqNP_001191742.1. NM_001204813.1.
NP_002517.1. NM_002526.3.
UniGeneHs.153952.

3D structure databases

ProteinModelPortalP21589.
SMRP21589. Positions 27-550.
ModBaseSearch...

Protein-protein interaction databases

STRINGP21589.

Polymorphism databases

DMDM112825.

Proteomic databases

PRIDEP21589.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257770; ENSP00000257770; ENSG00000135318.
GeneID4907.
KEGGhsa:4907.
UCSCuc003pko.2. human.

Organism-specific databases

CTD4907.
GeneCardsGC06P086216.
H-InvDBHIX0032840.
HGNCHGNC:8021. NT5E.
HPAHPA017357.
MIM129190. gene.
211800. phenotype.
neXtProtNX_P21589.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17669.
HOGENOMHBG534106.
HOVERGENHBG000026.
InParanoidP21589.
OMATGSHCHG.
OrthoDBEOG4TMR1Q.
PhylomeDBP21589.

Enzyme and pathway databases

Pathway_Interaction_DBhif1_tfpathway. HIF-1-alpha transcription factor network.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP21589.
BgeeP21589.
CleanExHS_NT5E.
GenevestigatorP21589.
GermOnlineENSG00000135318. Homo sapiens.

Family and domain databases

InterProIPR008334. 5'-Nucleotdase_C.
IPR006146. 5'-Nucleotdase_CS.
IPR006179. 5_nucleotidase/apyrase.
IPR004843. Metallo_PEstase_dom.
[Graphical view]
Gene3DG3DSA:3.90.780.10. 5'-Nucleotdase_C. 1 hit.
KOK01081.
PANTHERPTHR11575. 5_nucleotidase. 1 hit.
PfamPF02872. 5_nucleotid_C. 1 hit.
PF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSPR01607. APYRASEFAMLY.
SUPFAMSSF55816. 5'-Nucleotdase_C. 1 hit.
PROSITEPS00785. 5_NUCLEOTIDASE_1. 1 hit.
PS00786. 5_NUCLEOTIDASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00806. Pentoxifylline.
NextBio18883.
SOURCESearch...

Entry information

Entry name5NTD_HUMAN
AccessionPrimary (citable) accession number: P21589
Secondary accession number(s): O75520, Q5W116
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: January 25, 2012
This is version 129 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

Human cell differentiation molecules

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

Human chromosome 6

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families