Reviewed, UniProtKB/Swiss-Prot P00491 (PNPH_HUMAN)

Names and origin

Protein names

Recommended name:
    Purine nucleoside phosphorylase
      Short name=PNP
    EC=2.4.2.1
Alternative name(s):
    Inosine phosphorylase

Gene names

Name:	NP
Synonyms:	PNP

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	289 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate.
Subunit structure	Homotrimer.
Involvement in disease	Defects in NP are the cause of nucleoside phosphorylase deficiency (NP deficiency) [MIM:164050]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.
Sequence similarities	Belongs to the PNP/MTAP phosphorylase family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	NAD biosynthesis via nicotinamide riboside salvage pathway Inferred from genetic interaction. Source: UniProtKB immune response Inferred from mutant phenotype. Source: UniProtKB inosine catabolic process Inferred from direct assay. Source: MGI nicotinamide riboside catabolic process Inferred from direct assay. Source: UniProtKB positive regulation of T cell proliferation Inferred from direct assay. Source: MGI positive regulation of alpha-beta T cell differentiation Inferred from direct assay. Source: MGI response to drug Inferred from direct assay. Source: UniProtKB urate biosynthetic process Inferred from direct assay. Source: MGI
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	drug binding Inferred from direct assay. Source: UniProtKB nucleoside binding Inferred from direct assay. Source: UniProtKB phosphate binding Inferred from direct assay. Source: UniProtKB purine binding Inferred from direct assay. Source: UniProtKB purine-nucleoside phosphorylase activity Ref.2 Inferred from direct assay. 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.7

Natural variations

Natural variant

51

1

G → S: dbSNP rs1049564. Ref.1 Ref.2 Ref.3 Ref.4 Ref.10

VAR_002243

Natural variant

89

1

E → K in NP deficiency.

VAR_002244

Natural variant

128

1

D → G in NP deficiency.

VAR_002245

Natural variant

174

1

A → P in NP deficiency.

VAR_002246

Natural variant

192

1

Y → C in NP deficiency.

VAR_010653

Natural variant

234

1

R → P in NP deficiency.

VAR_002247

Secondary structure

1

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289

Helix Strand Turn

Details...

Helix

7 – 18

12

Beta strand

26 – 31

6

Helix

36 – 41

6

Beta strand

43 – 49

7

Helix

50 – 52

3

Beta strand

61 – 64

4

Beta strand

67 – 73

7

Beta strand

76 – 83

8

Helix

87 – 89

3

Helix

93 – 96

4

Helix

98 – 105

8

Beta strand

110 – 119

10

Beta strand

129 – 137

9

Helix

138 – 142

5

Turn

153 – 155

3

Helix

168 – 179

12

Turn

180 – 182

3

Beta strand

188 – 194

7

Helix

203 – 211

9

Beta strand

215 – 221

7

Helix

222 – 231

10

Beta strand

234 – 244

11

Helix

257 – 266

10

Helix

268 – 281

14

Sequences

	Sequence		Length	Mass (Da)
	P00491-1 [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: 6087295] [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: 3029074] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT NP DEFICIENCY 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: 12928150] [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: 14702039] [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]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[7]	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.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"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: 2104852] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
[10]	"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: 1384322] [Abstract] Cited for: VARIANT SER-51, VARIANTS NP DEFICIENCY GLY-128 AND PRO-234.
[11]	"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: 8931706] [Abstract] Cited for: VARIANT NP DEFICIENCY CYS-192.
+	Additional computationally mapped references.

Web resources

NPbase

NP mutation db

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
BC104206 mRNA. Translation: AAI04207.1.
BC104207 mRNA. Translation: AAI04208.1.
BC106074 mRNA. Translation: AAI06075.1.

IPI

IPI00871140.

PIR

PHHUPN. A00578.

RefSeq

NP_000261.2.

UniGene

Hs.75514

3D structure databases

PDBPDBe

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	[»]
3GB9	X-ray	2.30	A/B/C	1-289	[»]
3GGS	X-ray	2.52	A/B/C	1-289	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P00491. 10 interactions.

2-D gel databases

Aarhus/Ghent-2DPAGE

2108. IEF.

OGP

P00491.

Proteomic databases

PRIDE

P00491.

Genome annotation databases

Ensembl

ENSG00000198805. Homo sapiens. [Contig view]

GeneID

4860.

KEGG

hsa:4860.

Organism-specific databases

GeneCards

GC14P020007.

HGNC

HGNC:7892. NP.

HPA

HPA001625.

MIM

164050. gene+phenotype.

Orphanet

760. Purine nucleoside phosphorylase deficiency.

PharmGKB

PA24582.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P00491.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-10501.

BRENDA

2.4.2.1. 247.

Reactome

REACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpress

P00491.

Bgee

P00491.

CleanEx

HS_NP.

GermOnline

ENSG00000198805. Homo sapiens.

Family and domain databases

InterPro

IPR000845. Nucleoside_phosphorylase.
IPR011268. PNPHPUNA_XAPA.
IPR011270. Pur_Nuc_Pase_Ino/Guo-sp.
IPR001369. Purine_phosphorylase-2.
IPR018099. Purine_phosphorylase-2_CS.
[Graphical view]

PANTHER

PTHR11904. Mtap_PNP. 1 hit.
PTHR11904:SF9. PNPHPUNA_XAPA. 1 hit.

Pfam

PF01048. PNP_UDP_1. 1 hit.
[Graphical view]

TIGRFAMs

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

PROSITE

PS01240. PNP_MTAP_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P00491.

DrugBank

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

NextBio

18722.

SOURCE

Search...

Entry information

Entry name

PNPH_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	May 30, 2006
Last modified:	June 16, 2009
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)