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

Gene names

Name:	PNP
Synonyms:	NP

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.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Purine nucleoside + phosphate = purine + alpha-D-ribose 1-phosphate.
Subunit structure	Homotrimer.
Subcellular location	Cytoplasm › cytoskeleton By similarity.
Involvement in disease	Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children. Ref.2 Ref.13 Ref.14
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. Source: UniProtKB immune response Inferred from mutant phenotype. Source: UniProtKB inosine catabolic process Inferred from direct assay. Source: MGI interleukin-2 secretion Inferred from mutant phenotype. Source: UniProtKB 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 purine base 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. Source: UniProtKB urate biosynthetic process Inferred from direct assay. 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. Source: UniProtKB nucleoside binding Inferred from direct assay. Source: UniProtKB phosphate ion binding Inferred from direct assay. Source: UniProtKB purine base binding Inferred from direct assay. Source: UniProtKB purine-nucleoside phosphorylase activity Inferred from direct assay Ref.2. 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 Ref.9

Modified residue

95

1

N6-acetyllysine Ref.10

Natural variations

Natural variant

51

1

G → S. Ref.1 Ref.2 Ref.3 Ref.4 Ref.13
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.13

VAR_002245

Natural variant

174

1

A → P in PNPD.

VAR_002246

Natural variant

192

1

Y → C in PNPD. Ref.14

VAR_010653

Natural variant

234

1

R → P in PNPD. Ref.13

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 [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 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: 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]	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: 15489334] [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]	"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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-95, MASS SPECTROMETRY.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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).
[13]	"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 PNPD GLY-128 AND PRO-234.
[14]	"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 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	[»]

ProteinModelPortal

P00491.

SMR

P00491. Positions 2-289.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-50406N.

IntAct

P00491. 6 interactions.

MINT

MINT-1375849.

STRING

P00491.

PTM databases

PhosphoSite

P00491.

Polymorphism databases

DMDM

108935929.

2D gel databases

Aarhus/Ghent-2DPAGE

2108. IEF.

OGP

P00491.

Proteomic databases

PRIDE

P00491.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361505; ENSP00000354532; ENSG00000198805.

GeneID

4860.

KEGG

hsa:4860.

UCSC

uc001vxo.2. human.

Organism-specific databases

CTD

4860.

GeneCards

GC14P021021.

H-InvDB

HIX0011491.

HGNC

HGNC:7892. PNP.

HPA

HPA001625.

MIM

164050. gene.
613179. phenotype.

neXtProt

NX_P00491.

Orphanet

760. Purine nucleoside phosphorylase deficiency.

PharmGKB

PA165479257.
PA31694.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04330.

HOVERGEN

HBG002460.

OMA

LITNECI.

OrthoDB

EOG4CZBGH.

PhylomeDB

P00491.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02151-MONOMER.
MetaCyc:MONOMER-10501.

BRENDA

2.4.2.1. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P00491.

Bgee

P00491.

CleanEx

HS_NP.

Genevestigator

P00491.

GermOnline

ENSG00000198805. Homo sapiens.

Family and domain databases

InterPro

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

KO

K03783.

PANTHER

PTHR11904. Mtap_PNP. 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.

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 , D3DS00, Q15160, Q5PZ03

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	May 30, 2006
Last modified:	January 25, 2012
This is version 138 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.