P00491 (PNPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence 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.11
Catalytic activity	Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate.
Pathway	Purine metabolism; purine nucleoside salvage.
Subunit structure	Homotrimer.
Subcellular location	Cytoplasm › cytoskeleton By similarity. Cytoplasm Ref.10.
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.10
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.12 Ref.13
Sequence similarities	Belongs to the PNP/MTAP phosphorylase family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	NAD 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 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 urate biosynthetic process Inferred from direct assay PubMed 16964310. Source: MGI
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome
Molecular_function	drug 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 289

289

Purine nucleoside phosphorylase

PRO_0000184536

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.8

Natural variations

Natural variant

51

1

G → S. Ref.1 Ref.2 Ref.3 Ref.4 Ref.12
Corresponds to variant rs1049564 [ dbSNP | Ensembl ].

VAR_002243

Natural variant

89

1

E → K in PNPD. Ref.2

VAR_002244

Natural variant

128

1

D → G in PNPD. Ref.12

VAR_002245

Natural variant

174

1

A → P in PNPD.

VAR_002246

Natural variant

192

1

Y → C in PNPD. Ref.13

VAR_010653

Natural variant

234

1

R → P in PNPD. Ref.12

VAR_002247

Secondary structure

1

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289

Helix Strand Turn

Details...

Helix

7 – 20

14

Beta strand

26 – 31

6

Helix

36 – 41

6

Beta strand

43 – 49

7

Helix

50 – 52

3

Beta strand

53 – 55

3

Helix

62 – 65

4

Beta strand

67 – 73

7

Beta strand

76 – 83

8

Helix

87 – 89

3

Helix

93 – 96

4

Helix

98 – 106

9

Beta strand

110 – 119

10

Beta strand

121 – 123

3

Beta strand

129 – 137

9

Helix

138 – 141

4

Turn

153 – 155

3

Turn

163 – 166

4

Helix

168 – 179

12

Turn

180 – 182

3

Beta strand

188 – 194

7

Beta strand

197 – 199

3

Helix

203 – 211

9

Beta strand

215 – 221

7

Helix

222 – 230

9

Beta strand

234 – 244

11

Beta strand

248 – 250

3

Helix

257 – 266

10

Helix

268 – 280

13

Turn

285 – 287

3

Sequences

	Sequence		Length	Mass (Da)
	P00491 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: 91622FB1D26479D3	FASTA	289	32,118
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. Tissue: Platelet.
[9]	"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].
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00737 mRNA. Translation: CAA25320.1.
M13953 , 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.

IPI

IPI00017672.

PIR

PHHUPN. A00578.

RefSeq

NP_000261.2. NM_000270.3.

UniGene

Hs.75514.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M73	X-ray	2.30	E	2-289	[»]
1PF7	X-ray	2.60	E	1-289	[»]
1PWY	X-ray	2.80	E	2-289	[»]
1RCT	X-ray	2.80	E	2-289	[»]
1RFG	X-ray	2.90	E	2-289	[»]
1RR6	X-ray	2.50	A	1-289	[»]
1RSZ	X-ray	2.20	A	1-289	[»]
1RT9	X-ray	2.30	A	1-289	[»]
1ULA	X-ray	2.75	A	1-289	[»]
1ULB	X-ray	2.75	A	1-289	[»]
1V2H	X-ray	2.70	E	2-289	[»]
1V3Q	X-ray	2.80	E	2-289	[»]
1V41	X-ray	2.85	E	2-289	[»]
1V45	X-ray	2.86	E	2-289	[»]
1YRY	X-ray	2.80	E	1-289	[»]
2A0W	X-ray	2.28	A	1-289	[»]
2A0X	X-ray	2.28	A	1-289	[»]
2A0Y	X-ray	2.28	A	1-289	[»]
2OC4	X-ray	2.59	A	1-289	[»]
2OC9	X-ray	2.59	A	1-289	[»]
2ON6	X-ray	2.50	A	1-289	[»]
2Q7O	X-ray	2.90	E	1-289	[»]
3BGS	X-ray	2.10	A	1-289	[»]
3D1V	X-ray	2.70	A	1-289	[»]
3GB9	X-ray	2.30	A/B/C	1-289	[»]
3GGS	X-ray	2.52	A/B/C	1-289	[»]
3INY	X-ray	2.75	A	1-289	[»]
3K8O	X-ray	2.40	E/Q/S/T/U/Y	1-289	[»]
3K8Q	X-ray	2.50	A	1-289	[»]
3PHB	X-ray	2.30	E/Q/S/T/U/Y	1-289	[»]
4EAR	X-ray	1.70	A/B/C	1-289	[»]
4EB8	X-ray	2.30	A/B/C	1-289	[»]
4ECE	X-ray	2.60	A/B/C/D/E/F	1-289	[»]
4GKA	X-ray	2.20	A/B/C/D/E/F	1-289	[»]

ProteinModelPortal

P00491.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-50406N.

IntAct

P00491. 7 interactions.

MINT

MINT-1375849.

STRING

9606.ENSP00000354532.

PTM databases

PhosphoSite

P00491.

Polymorphism databases

DMDM

108935929.

2D gel databases

OGP

P00491.

Proteomic databases

PaxDb

P00491.

PRIDE

P00491.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361505; ENSP00000354532; ENSG00000198805.

GeneID

4860.

KEGG

hsa:4860.

UCSC

uc001vxo.4. human.

Organism-specific databases

CTD

4860.

GeneCards

GC14P021021.

HGNC

HGNC:7892. PNP.

HPA

HPA001625.

MIM

164050. gene.
613179. phenotype.

neXtProt

NX_P00491.

Orphanet

760. Purine nucleoside phosphorylase deficiency.

PharmGKB

PA31694.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0005.

HOVERGEN

HBG002460.

KO

K03783.

OMA

MENGYTY.

OrthoDB

EOG4CZBGH.

PhylomeDB

P00491.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02151-MONOMER.

BRENDA

2.4.2.1. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P00491.

UniPathway

UPA00606.

Gene expression databases

ArrayExpress

P00491.

Bgee

P00491.

CleanEx

HS_NP.

Genevestigator

P00491.

GermOnline

ENSG00000198805. Homo sapiens.

Family and domain databases

InterPro

IPR000845. Nucleoside_phosphorylase_d.
IPR001369. PNP/MTAP.
IPR011270. Pur_Nuc_Pase_Ino/Guo-sp.
IPR011268. Purine_phosphorylase.
IPR018099. Purine_phosphorylase-2_CS.
[Graphical view]

PANTHER

PTHR11904. PTHR11904. 1 hit.
PTHR11904:SF9. PTHR11904:SF9. 1 hit.

Pfam

PF01048. PNP_UDP_1. 1 hit.
[Graphical view]

PIRSF

PIRSF000477. PurNPase. 1 hit.

TIGRFAMs

TIGR01700. PNPH. 1 hit.
TIGR01697. PNPH-PUNA-XAPA. 1 hit.

PROSITE

PS01240. PNP_MTAP_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00491.

ChEMBL

CHEMBL4338.

ChiTaRS

PNP. human.

DrugBank

DB00787. Aciclovir.
DB00242. Cladribine.
DB01033. Mercaptopurine.

EvolutionaryTrace

P00491.

GenomeRNAi

4860.

NextBio

18722.

SOURCE

Search...

Entry information

Entry name

PNPH_HUMAN

Accession

Primary (citable) accession number: P00491
Secondary accession number(s): B2R8S5 , D3DS00, Q15160, Q5PZ03

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	May 30, 2006
Last modified:	May 1, 2013
This is version 150 of the entry and version 2 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.