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P00491 (PNPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Purine nucleoside phosphorylase

Short name=PNP
EC=2.4.2.1
Alternative name(s):
Inosine phosphorylase
Inosine-guanosine phosphorylase
Gene names
Name:PNP
Synonyms:NP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate. Ref.13

Catalytic activity

Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate.

Pathway

Purine metabolism; purine nucleoside salvage.

Subunit structure

Homotrimer.

Subcellular location

Cytoplasmcytoskeleton By similarity. Cytoplasm Ref.12.

Tissue specificity

Expressed in red blood cells; overexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology. Ref.12

Involvement in disease

Purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179]: A disorder that interrupts both the catabolism of inosine into hypoxanthine and guanosine into guanine, and leads to the accumulation of guanosine, inosine, and their deoxified by-products. The main clinical presentation is recurrent infections due to severe T-cell immunodeficiency. Some patients also have neurologic impairment.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.14 Ref.15

Sequence similarities

Belongs to the PNP/MTAP phosphorylase family.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoskeleton
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   Molecular functionGlycosyltransferase
Transferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processNAD biosynthesis via nicotinamide riboside salvage pathway

Inferred from genetic interaction PubMed 19001417. Source: UniProtKB

immune response

Inferred from mutant phenotype PubMed 16930574. Source: UniProtKB

inosine catabolic process

Inferred from direct assay PubMed 16964310. Source: MGI

interleukin-2 secretion

Inferred from mutant phenotype PubMed 16930574. Source: UniProtKB

nicotinamide riboside catabolic process

Inferred from direct assay PubMed 19001417. Source: UniProtKB

nucleobase-containing compound metabolic process

Inferred from direct assay Ref.2. Source: UniProtKB

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

positive regulation of T cell proliferation

Inferred from direct assay PubMed 16964310. Source: MGI

positive regulation of alpha-beta T cell differentiation

Inferred from direct assay PubMed 16964310. Source: MGI

purine nucleobase metabolic process

Traceable author statement. Source: Reactome

purine nucleotide catabolic process

Traceable author statement. Source: Reactome

purine-containing compound salvage

Traceable author statement. Source: Reactome

response to drug

Inferred from direct assay PubMed 18938130. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

urate biosynthetic process

Inferred from direct assay PubMed 16964310. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16930574Ref.2. Source: UniProtKB

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337PubMed 23376485. Source: UniProt

intracellular

Inferred from direct assay PubMed 15047506. Source: UniProtKB

   Molecular_functiondrug binding

Inferred from direct assay PubMed 18938130. Source: UniProtKB

nucleoside binding

Inferred from direct assay PubMed 9305962. Source: UniProtKB

phosphate ion binding

Inferred from direct assay PubMed 18938130. Source: UniProtKB

purine nucleobase binding

Inferred from direct assay PubMed 9305962. Source: UniProtKB

purine-nucleoside phosphorylase activity

Inferred from direct assay PubMed 16930574PubMed 18938130Ref.2PubMed 9305962. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 289289Purine nucleoside phosphorylase
PRO_0000184536

Amino acid modifications

Modified residue11N-acetylmethionine Ref.8 Ref.9

Natural variations

Natural variant511G → S. Ref.1 Ref.2 Ref.3 Ref.4 Ref.14
Corresponds to variant rs1049564 [ dbSNP | Ensembl ].
VAR_002243
Natural variant891E → K in PNPD. Ref.2
VAR_002244
Natural variant1281D → G in PNPD. Ref.14
VAR_002245
Natural variant1741A → P in PNPD.
VAR_002246
Natural variant1921Y → C in PNPD. Ref.15
VAR_010653
Natural variant2341R → P in PNPD. Ref.14
VAR_002247

Secondary structure

........................................................ 289
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00491 [UniParc].

Last modified May 30, 2006. Version 2.
Checksum: 91622FB1D26479D3

FASTA28932,118
        10         20         30         40         50         60 
MENGYTYEDY KNTAEWLLSH TKHRPQVAII CGSGLGGLTD KLTQAQIFDY GEIPNFPRST 

        70         80         90        100        110        120 
VPGHAGRLVF GFLNGRACVM MQGRFHMYEG YPLWKVTFPV RVFHLLGVDT LVVTNAAGGL 

       130        140        150        160        170        180 
NPKFEVGDIM LIRDHINLPG FSGQNPLRGP NDERFGDRFP AMSDAYDRTM RQRALSTWKQ 

       190        200        210        220        230        240 
MGEQRELQEG TYVMVAGPSF ETVAECRVLQ KLGADAVGMS TVPEVIVARH CGLRVFGFSL 

       250        260        270        280 
ITNKVIMDYE SLEKANHEEV LAAGKQAAQK LEQFVSILMA SIPLPDKAS 

« Hide

References

« Hide 'large scale' references
[1]"Human purine nucleoside phosphorylase cDNA sequence and genomic clone characterization."
Williams S.R., Goddard J.M., Martin D.W. Jr.
Nucleic Acids Res. 12:5779-5787(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-51.
[2]"A human purine nucleoside phosphorylase deficiency caused by a single base change."
Williams S.R., Gekeler V., McIvor R.S., Martin D.W. Jr.
J. Biol. Chem. 262:2332-2338(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PNPD LYS-89, VARIANT SER-51.
[3]"Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans."
Yu L., Kalla K., Guthrie E., Vidrine A., Klimecki W.T.
Environ. Health Perspect. 111:1421-1427(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-51.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-51.
Tissue: Tongue.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Ovary.
[8]Bienvenut W.V., Claeys D.
Submitted (FEB-2006) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-22; 42-58; 68-76; 96-148; 212-229; 235-265 AND 271-287, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Platelet.
[9]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Assessment of the red cell proteome of young patients with unexplained hemolytic anemia by two-dimensional differential in-gel electrophoresis (DIGE)."
von Lohneysen K., Scott T.M., Soldau K., Xu X., Friedman J.S.
PLoS ONE 7:E34237-E34237(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[13]"Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2-A resolution."
Ealick S.E., Rule S.A., Carter D.C., Greenhough T.J., Babu Y.S., Cook W.J., Habash J., Helliwell J.R., Stoeckler J.D., Parks R.E. Jr., Chen S.-F., Bugg C.E.
J. Biol. Chem. 265:1812-1820(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS), FUNCTION.
[14]"Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency."
Aust M.R., Andrews L.G., Barrett M.J., Norby-Slycord C.J., Markert M.L.
Am. J. Hum. Genet. 51:763-772(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-51, VARIANTS PNPD GLY-128 AND PRO-234.
[15]"Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient."
Pannicke U., Tuchschmid P., Friedrich W., Bartram C.R., Schwarz K.
Hum. Genet. 98:706-709(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PNPD CYS-192.
+Additional computationally mapped references.

Web resources

NPbase

NP mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X00737 mRNA. Translation: CAA25320.1.
M13953 expand/collapse EMBL AC list , J02672, M13951, M13952 Genomic DNA. Translation: AAA36460.1.
AY817667 Genomic DNA. Translation: AAV68044.1.
AK313490 mRNA. Translation: BAG36272.1.
CR407607 mRNA. Translation: CAG28535.1.
CH471078 Genomic DNA. Translation: EAW66458.1.
CH471078 Genomic DNA. Translation: EAW66459.1.
BC104206 mRNA. Translation: AAI04207.1.
BC104207 mRNA. Translation: AAI04208.1.
BC106074 mRNA. Translation: AAI06075.1.
CCDSCCDS9552.1.
PIRPHHUPN. A00578.
RefSeqNP_000261.2. NM_000270.3.
UniGeneHs.75514.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M73X-ray2.30E2-289[»]
1PF7X-ray2.60E1-289[»]
1PWYX-ray2.80E2-289[»]
1RCTX-ray2.80E2-289[»]
1RFGX-ray2.90E2-289[»]
1RR6X-ray2.50A1-289[»]
1RSZX-ray2.20A1-289[»]
1RT9X-ray2.30A1-289[»]
1ULAX-ray2.75A1-289[»]
1ULBX-ray2.75A1-289[»]
1V2HX-ray2.70E2-289[»]
1V3QX-ray2.80E2-289[»]
1V41X-ray2.85E2-289[»]
1V45X-ray2.86E2-289[»]
1YRYX-ray2.80E1-289[»]
2A0WX-ray2.28A1-289[»]
2A0XX-ray2.28A1-289[»]
2A0YX-ray2.28A1-289[»]
2OC4X-ray2.59A1-289[»]
2OC9X-ray2.59A1-289[»]
2ON6X-ray2.50A1-289[»]
2Q7OX-ray2.90E1-289[»]
3BGSX-ray2.10A1-289[»]
3D1VX-ray2.70A1-289[»]
3GB9X-ray2.30A/B/C1-289[»]
3GGSX-ray2.52A/B/C1-289[»]
3INYX-ray2.75A1-289[»]
3K8OX-ray2.40E/Q/S/T/U/Y1-289[»]
3K8QX-ray2.50A1-289[»]
3PHBX-ray2.30E/Q/S/T/U/Y1-289[»]
4EARX-ray1.70A/B/C1-289[»]
4EB8X-ray2.30A/B/C1-289[»]
4ECEX-ray2.60A/B/C/D/E/F1-289[»]
4GKAX-ray2.20A/B/C/D/E/F1-289[»]
ProteinModelPortalP00491.
SMRP00491. Positions 2-289.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110921. 26 interactions.
DIPDIP-50406N.
IntActP00491. 7 interactions.
MINTMINT-1375849.
STRING9606.ENSP00000354532.

Chemistry

BindingDBP00491.
ChEMBLCHEMBL4338.
DrugBankDB00787. Aciclovir.
DB00242. Cladribine.
DB01033. Mercaptopurine.

PTM databases

PhosphoSiteP00491.

Polymorphism databases

DMDM108935929.

2D gel databases

OGPP00491.

Proteomic databases

MaxQBP00491.
PaxDbP00491.
PRIDEP00491.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361505; ENSP00000354532; ENSG00000198805.
GeneID4860.
KEGGhsa:4860.
UCSCuc001vxo.4. human.

Organism-specific databases

CTD4860.
GeneCardsGC14P021021.
HGNCHGNC:7892. PNP.
HPAHPA001625.
MIM164050. gene.
613179. phenotype.
neXtProtNX_P00491.
Orphanet760. Purine nucleoside phosphorylase deficiency.
PharmGKBPA31694.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0005.
HOVERGENHBG002460.
KOK03783.
OMAGDIMFIR.
PhylomeDBP00491.
TreeFamTF300049.

Enzyme and pathway databases

BioCycMetaCyc:HS02151-MONOMER.
BRENDA2.4.2.1. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP00491.
SignaLinkP00491.
UniPathwayUPA00606.

Gene expression databases

ArrayExpressP00491.
BgeeP00491.
CleanExHS_NP.
GenevestigatorP00491.

Family and domain databases

Gene3D3.40.50.1580. 1 hit.
InterProIPR000845. Nucleoside_phosphorylase_d.
IPR001369. PNP/MTAP.
IPR011270. Pur_Nuc_Pase_Ino/Guo-sp.
IPR011268. Purine_phosphorylase.
IPR018099. Purine_phosphorylase-2_CS.
[Graphical view]
PANTHERPTHR11904. PTHR11904. 1 hit.
PfamPF01048. PNP_UDP_1. 1 hit.
[Graphical view]
PIRSFPIRSF000477. PurNPase. 1 hit.
SUPFAMSSF53167. SSF53167. 1 hit.
TIGRFAMsTIGR01700. PNPH. 1 hit.
TIGR01697. PNPH-PUNA-XAPA. 1 hit.
PROSITEPS01240. PNP_MTAP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPNP. human.
EvolutionaryTraceP00491.
GeneWikiPurine_nucleoside_phosphorylase.
GenomeRNAi4860.
NextBio18722.
PROP00491.
SOURCESearch...

Entry information

Entry namePNPH_HUMAN
AccessionPrimary (citable) accession number: P00491
Secondary accession number(s): B2R8S5 expand/collapse secondary AC list , D3DS00, Q15160, Q5PZ03
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: May 30, 2006
Last modified: July 9, 2014
This is version 162 of the entry and version 2 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 14

Human chromosome 14: entries, gene names and cross-references to MIM