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

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	574 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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-anchor › GPI-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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Metal-binding Nucleotide-binding Zinc
Molecular function	Hydrolase
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA metabolic process Traceable author statement. Source: ProtInc purine base metabolic process Traceable author statement. Source: Reactome pyrimidine base metabolic process Traceable author statement. Source: Reactome pyrimidine nucleoside catabolic process Traceable author statement. Source: Reactome
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from direct assay. Source: HPA membrane fraction Traceable author statement. Source: ProtInc plasma membrane Inferred from direct assay. Source: HPA
Molecular function	5'-nucleotidase activity Inferred from experiment. Source: Reactome nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Ref.5
	Chain	27 – 549	523	5'-nucleotidase Ref.1		PRO_0000000015
	Propeptide	550 – 574	25	Removed in mature form		PRO_0000000016
Regions
	Region	500 – 506	7	Substrate binding By similarity
Sites
	Metal binding	36	1	Zinc 1 By similarity
	Metal binding	38	1	Zinc 1 By similarity
	Metal binding	85	1	Zinc 1 By similarity
	Metal binding	85	1	Zinc 2 By similarity
	Metal binding	117	1	Zinc 2 By similarity
	Metal binding	220	1	Zinc 2 By similarity
	Metal binding	243	1	Zinc 2 By similarity
	Binding site	417	1	Substrate By similarity
	Site	118	1	Transition state stabilizer By similarity
	Site	121	1	Transition state stabilizer By similarity
Amino acid modifications
	Lipidation	549	1	GPI-anchor amidated serine Ref.1
	Glycosylation	53	1	N-linked (GlcNAc...) Potential
	Glycosylation	311	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	333	1	N-linked (GlcNAc...) Ref.6 Ref.7
	Glycosylation	403	1	N-linked (GlcNAc...) Ref.6
Natural variations
	Natural variant	358	1	C → Y in CALJA.		VAR_065185
	Natural variant	376	1	T → A. Ref.4 Corresponds to variant rs2229523 [ dbSNP | Ensembl ].		VAR_022091
	Natural variant	379	1	M → T. Corresponds to variant rs2229524 [ dbSNP | Ensembl ].		VAR_048103

Sequences

	Sequence		Length	Mass (Da)
	P21589 [UniParc]. Last modified May 1, 1991. Version 1. Checksum: A99AF170AB7EAECE	FASTA	574	63,368
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00009456.
PIR	S11032.
RefSeq	NP_001191742.1. NM_001204813.1. NP_002517.1. NM_002526.3.
UniGene	Hs.153952.
3D structure databases
ProteinModelPortal	P21589.
SMR	P21589. Positions 27-550.
ModBase	Search...
Protein-protein interaction databases
STRING	P21589.
Polymorphism databases
DMDM	112825.
Proteomic databases
PRIDE	P21589.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257770; ENSP00000257770; ENSG00000135318.
GeneID	4907.
KEGG	hsa:4907.
UCSC	uc003pko.2. human.
Organism-specific databases
CTD	4907.
GeneCards	GC06P086216.
H-InvDB	HIX0032840.
HGNC	HGNC:8021. NT5E.
HPA	HPA017357.
MIM	129190. gene. 211800. phenotype.
neXtProt	NX_P21589.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17669.
HOGENOM	HBG534106.
HOVERGEN	HBG000026.
InParanoid	P21589.
OMA	TGSHCHG.
OrthoDB	EOG4TMR1Q.
PhylomeDB	P21589.
Enzyme and pathway databases
Pathway_Interaction_DB	hif1_tfpathway. HIF-1-alpha transcription factor network.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P21589.
Bgee	P21589.
CleanEx	HS_NT5E.
Genevestigator	P21589.
GermOnline	ENSG00000135318. Homo sapiens.
Family and domain databases
InterPro	IPR008334. 5'-Nucleotdase_C. IPR006146. 5'-Nucleotdase_CS. IPR006179. 5_nucleotidase/apyrase. IPR004843. Metallo_PEstase_dom. [Graphical view]
Gene3D	G3DSA:3.90.780.10. 5'-Nucleotdase_C. 1 hit.
KO	K01081.
PANTHER	PTHR11575. 5_nucleotidase. 1 hit.
Pfam	PF02872. 5_nucleotid_C. 1 hit. PF00149. Metallophos. 1 hit. [Graphical view]
PRINTS	PR01607. APYRASEFAMLY.
SUPFAM	SSF55816. 5'-Nucleotdase_C. 1 hit.
PROSITE	PS00785. 5_NUCLEOTIDASE_1. 1 hit. PS00786. 5_NUCLEOTIDASE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00806. Pentoxifylline.
NextBio	18883.
SOURCE	Search...

Entry information

Entry name

5NTD_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.