PNPH_HUMAN
ID PNPH_HUMAN Reviewed; 289 AA.
AC P00491; B2R8S5; D3DS00; Q15160; Q5PZ03;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Purine nucleoside phosphorylase;
DE Short=PNP;
DE EC=2.4.2.1 {ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964};
DE AltName: Full=Inosine phosphorylase;
DE AltName: Full=Inosine-guanosine phosphorylase;
GN Name=PNP; Synonyms=NP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-51.
RX PubMed=6087295; DOI=10.1093/nar/12.14.5779;
RA Williams S.R., Goddard J.M., Martin D.W. Jr.;
RT "Human purine nucleoside phosphorylase cDNA sequence and genomic clone
RT characterization.";
RL Nucleic Acids Res. 12:5779-5787(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PNPD LYS-89, AND VARIANT SER-51.
RX PubMed=3029074; DOI=10.1016/s0021-9258(18)61658-8;
RA Williams S.R., Gekeler V., McIvor R.S., Martin D.W. Jr.;
RT "A human purine nucleoside phosphorylase deficiency caused by a single base
RT change.";
RL J. Biol. Chem. 262:2332-2338(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-51.
RX PubMed=12928150; DOI=10.1289/ehp.6420;
RA Yu L., Kalla K., Guthrie E., Vidrine A., Klimecki W.T.;
RT "Genetic variation in genes associated with arsenic metabolism: glutathione
RT S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms
RT in European and indigenous Americans.";
RL Environ. Health Perspect. 111:1421-1427(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-51.
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 1-22; 42-58; 68-76; 96-148; 212-229; 235-265 AND
RP 271-287, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (FEB-2006) to UniProtKB.
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP MUTAGENESIS OF GLU-201 AND ASN-243.
RX PubMed=9305964; DOI=10.1021/bi961971n;
RA Stoeckler J.D., Poirot A.F., Smith R.M., Parks R.E. Jr., Ealick S.E.,
RA Takabayashi K., Erion M.D.;
RT "Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by
RT site-directed mutagenesis.";
RL Biochemistry 36:11749-11756(1997).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [13]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=22509282; DOI=10.1371/journal.pone.0034237;
RA von Lohneysen K., Scott T.M., Soldau K., Xu X., Friedman J.S.;
RT "Assessment of the red cell proteome of young patients with unexplained
RT hemolytic anemia by two-dimensional differential in-gel electrophoresis
RT (DIGE).";
RL PLoS ONE 7:E34237-E34237(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-251, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
RX PubMed=2104852; DOI=10.2210/pdb2pnp/pdb;
RA Ealick S.E., Rule S.A., Carter D.C., Greenhough T.J., Babu Y.S., Cook W.J.,
RA Habash J., Helliwell J.R., Stoeckler J.D., Parks R.E. Jr., Chen S.-F.,
RA Bugg C.E.;
RT "Three-dimensional structure of human erythrocytic purine nucleoside
RT phosphorylase at 3.2-A resolution.";
RL J. Biol. Chem. 265:1812-1820(1990).
RN [18] {ECO:0007744|PDB:1ULA, ECO:0007744|PDB:1ULB}
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH GUANINE AND
RP PHOSPHATE ANALOG.
RX PubMed=1763067; DOI=10.1073/pnas.88.24.11540;
RA Ealick S.E., Babu Y.S., Bugg C.E., Erion M.D., Guida W.C., Montgomery J.A.,
RA Secrist J.A.;
RT "Application of crystallographic and modeling methods in the design of
RT purine nucleoside phosphorylase inhibitors.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:11540-11544(1991).
RN [19] {ECO:0007744|PDB:1RCT, ECO:0007744|PDB:1V3Q}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2-289 IN COMPLEX WITH INOSINE;
RP DIDEOXYINOSINE AND PHOSPHATE ANALOG.
RX PubMed=14706628; DOI=10.1016/j.bbrc.2003.11.179;
RA Canduri F., dos Santos D.M., Silva R.G., Mendes M.A., Basso L.A.,
RA Palma M.S., de Azevedo W.F., Santos D.S.;
RT "Structures of human purine nucleoside phosphorylase complexed with inosine
RT and ddI.";
RL Biochem. Biophys. Res. Commun. 313:907-914(2004).
RN [20] {ECO:0007744|PDB:4EAR, ECO:0007744|PDB:4EB8, ECO:0007744|PDB:4ECE, ECO:0007744|PDB:4GKA}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF MUTANT TRP-257 IN COMPLEX WITH
RP GUANINE; PHOSPHATE AND INHIBITOR DADME-IMMG, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP MUTAGENESIS OF HIS-64 AND HIS-257.
RX PubMed=23438750; DOI=10.1016/j.chembiol.2013.01.009;
RA Suarez J., Haapalainen A.M., Cahill S.M., Ho M.C., Yan F., Almo S.C.,
RA Schramm V.L.;
RT "Catalytic site conformations in human PNP by 19F-NMR and
RT crystallography.";
RL Chem. Biol. 20:212-222(2013).
RN [21]
RP VARIANT SER-51, AND VARIANTS PNPD GLY-128 AND PRO-234.
RX PubMed=1384322;
RA Aust M.R., Andrews L.G., Barrett M.J., Norby-Slycord C.J., Markert M.L.;
RT "Molecular analysis of mutations in a patient with purine nucleoside
RT phosphorylase deficiency.";
RL Am. J. Hum. Genet. 51:763-772(1992).
RN [22]
RP VARIANT PNPD CYS-192.
RX PubMed=8931706; DOI=10.1007/s004390050290;
RA Pannicke U., Tuchschmid P., Friedrich W., Bartram C.R., Schwarz K.;
RT "Two novel missense and frameshift mutations in exons 5 and 6 of the purine
RT nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency
RT (SCID) patient.";
RL Hum. Genet. 98:706-709(1996).
CC -!- FUNCTION: Catalyzes the phosphorolytic breakdown of the N-glycosidic
CC bond in the beta-(deoxy)ribonucleoside molecules, with the formation of
CC the corresponding free purine bases and pentose-1-phosphate
CC (PubMed:9305964, PubMed:23438750). Preferentially acts on 6-oxopurine
CC nucleosides including inosine and guanosine (PubMed:9305964).
CC {ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=inosine + phosphate = alpha-D-ribose 1-phosphate +
CC hypoxanthine; Xref=Rhea:RHEA:27646, ChEBI:CHEBI:17368,
CC ChEBI:CHEBI:17596, ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC Evidence={ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine + phosphate = alpha-D-ribose 1-phosphate + guanine;
CC Xref=Rhea:RHEA:13233, ChEBI:CHEBI:16235, ChEBI:CHEBI:16750,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.1;
CC Evidence={ECO:0000269|PubMed:9305964};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyguanosine + phosphate = 2-deoxy-alpha-D-ribose 1-
CC phosphate + guanine; Xref=Rhea:RHEA:27738, ChEBI:CHEBI:16235,
CC ChEBI:CHEBI:17172, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1;
CC Evidence={ECO:0000250|UniProtKB:P23492};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyinosine + phosphate = 2-deoxy-alpha-D-ribose 1-
CC phosphate + hypoxanthine; Xref=Rhea:RHEA:27750, ChEBI:CHEBI:17368,
CC ChEBI:CHEBI:28997, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259; EC=2.4.2.1;
CC Evidence={ECO:0000250|UniProtKB:P23492};
CC -!- ACTIVITY REGULATION: Inhibited by 5'-deaza-1'-aza-2c-deoxy-1'-(9-
CC methylene)-Immucilin-G (DADMe-ImmG). {ECO:0000269|PubMed:23438750}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=45 uM for inosine (at 30 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9305964};
CC KM=68 uM for inosine (at 25 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:23438750};
CC KM=10 uM for hypoxanthine (at 30 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9305964};
CC KM=6 uM for guanosine (at 30 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9305964};
CC KM=12 uM for guanine (at 30 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9305964};
CC KM=650 uM for adenosine (at 30 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9305964};
CC KM=440 uM for adenine (at 30 degrees Celsius and pH 7)
CC {ECO:0000269|PubMed:9305964};
CC Note=kcat is 57 sec(-1) with inosine as substrate (PubMed:9305964).
CC kcat is 47 sec(-1) with inosine as substrate (PubMed:23438750). kcat
CC is 70 sec(-1) with hypoxanthine as substrate (PubMed:9305964). kcat
CC is 28 sec(-1) with guanosine as substrate (PubMed:9305964). kcat is
CC 48 sec(-1) with guanine as substrate (PubMed:9305964). kcat is 0.0024
CC sec(-1) with adenosine as substrate (PubMed:9305964). kcat is 0.31
CC sec(-1) with adenine as substrate (PubMed:9305964).
CC {ECO:0000269|PubMed:23438750, ECO:0000269|PubMed:9305964};
CC -!- PATHWAY: Purine metabolism; purine nucleoside salvage.
CC {ECO:0000269|PubMed:9305964}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000305|PubMed:23438750}.
CC -!- INTERACTION:
CC P00491; P05067: APP; NbExp=9; IntAct=EBI-712238, EBI-77613;
CC P00491; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-712238, EBI-1383687;
CC P00491; O14576-2: DYNC1I1; NbExp=3; IntAct=EBI-712238, EBI-25840445;
CC P00491; P06241: FYN; NbExp=3; IntAct=EBI-712238, EBI-515315;
CC P00491; P14136: GFAP; NbExp=3; IntAct=EBI-712238, EBI-744302;
CC P00491; Q92993-2: KAT5; NbExp=3; IntAct=EBI-712238, EBI-20795332;
CC P00491; Q9BXM7: PINK1; NbExp=3; IntAct=EBI-712238, EBI-2846068;
CC P00491; P00491: PNP; NbExp=6; IntAct=EBI-712238, EBI-712238;
CC P00491; P17612: PRKACA; NbExp=3; IntAct=EBI-712238, EBI-476586;
CC P00491; P63000: RAC1; NbExp=3; IntAct=EBI-712238, EBI-413628;
CC P00491; Q92673: SORL1; NbExp=3; IntAct=EBI-712238, EBI-1171329;
CC P00491; Q15583: TGIF1; NbExp=3; IntAct=EBI-712238, EBI-714215;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22509282}.
CC -!- TISSUE SPECIFICITY: Expressed in red blood cells; overexpressed in red
CC blood cells (cytoplasm) of patients with hereditary non-spherocytic
CC hemolytic anemia of unknown etiology. {ECO:0000269|PubMed:22509282}.
CC -!- DISEASE: Purine nucleoside phosphorylase deficiency (PNPD)
CC [MIM:613179]: A disorder that interrupts both the catabolism of inosine
CC into hypoxanthine and guanosine into guanine, and leads to the
CC accumulation of guanosine, inosine, and their deoxified by-products.
CC The main clinical presentation is recurrent infections due to severe T-
CC cell immunodeficiency. Some patients also have neurologic impairment.
CC {ECO:0000269|PubMed:1384322, ECO:0000269|PubMed:3029074,
CC ECO:0000269|PubMed:8931706}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PNP/MTAP phosphorylase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NPbase; Note=NP mutation db;
CC URL="http://structure.bmc.lu.se/idbase/NPbase/";
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DR EMBL; X00737; CAA25320.1; -; mRNA.
DR EMBL; M13953; AAA36460.1; -; Genomic_DNA.
DR EMBL; J02672; AAA36460.1; JOINED; Genomic_DNA.
DR EMBL; M13951; AAA36460.1; JOINED; Genomic_DNA.
DR EMBL; M13952; AAA36460.1; JOINED; Genomic_DNA.
DR EMBL; AY817667; AAV68044.1; -; Genomic_DNA.
DR EMBL; AK313490; BAG36272.1; -; mRNA.
DR EMBL; CR407607; CAG28535.1; -; mRNA.
DR EMBL; CH471078; EAW66458.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66459.1; -; Genomic_DNA.
DR EMBL; BC104206; AAI04207.1; -; mRNA.
DR EMBL; BC104207; AAI04208.1; -; mRNA.
DR EMBL; BC106074; AAI06075.1; -; mRNA.
DR CCDS; CCDS9552.1; -.
DR PIR; A00578; PHHUPN.
DR RefSeq; NP_000261.2; NM_000270.3.
DR PDB; 1M73; X-ray; 2.30 A; E=2-289.
DR PDB; 1PF7; X-ray; 2.60 A; E=1-289.
DR PDB; 1PWY; X-ray; 2.80 A; E=2-289.
DR PDB; 1RCT; X-ray; 2.80 A; E=2-289.
DR PDB; 1RFG; X-ray; 2.90 A; E=2-289.
DR PDB; 1RR6; X-ray; 2.50 A; A=1-289.
DR PDB; 1RSZ; X-ray; 2.20 A; A=1-289.
DR PDB; 1RT9; X-ray; 2.30 A; A=1-289.
DR PDB; 1ULA; X-ray; 2.75 A; A=1-289.
DR PDB; 1ULB; X-ray; 2.75 A; A=1-289.
DR PDB; 1V2H; X-ray; 2.70 A; E=2-289.
DR PDB; 1V3Q; X-ray; 2.80 A; E=2-289.
DR PDB; 1V41; X-ray; 2.85 A; E=2-289.
DR PDB; 1V45; X-ray; 2.86 A; E=2-289.
DR PDB; 1YRY; X-ray; 2.80 A; E=1-289.
DR PDB; 2A0W; X-ray; 2.28 A; A=1-289.
DR PDB; 2A0X; X-ray; 2.28 A; A=1-289.
DR PDB; 2A0Y; X-ray; 2.28 A; A=1-289.
DR PDB; 2OC4; X-ray; 2.59 A; A=1-289.
DR PDB; 2OC9; X-ray; 2.59 A; A=1-289.
DR PDB; 2ON6; X-ray; 2.50 A; A=1-289.
DR PDB; 2Q7O; X-ray; 2.90 A; E=1-289.
DR PDB; 3BGS; X-ray; 2.10 A; A=1-289.
DR PDB; 3D1V; X-ray; 2.70 A; A=1-289.
DR PDB; 3GB9; X-ray; 2.30 A; A/B/C=1-289.
DR PDB; 3GGS; X-ray; 2.52 A; A/B/C=1-289.
DR PDB; 3INY; X-ray; 2.75 A; A=1-289.
DR PDB; 3K8O; X-ray; 2.40 A; E/Q/S/T/U/Y=1-289.
DR PDB; 3K8Q; X-ray; 2.50 A; A=1-289.
DR PDB; 3PHB; X-ray; 2.30 A; E/Q/S/T/U/Y=1-289.
DR PDB; 4EAR; X-ray; 1.70 A; A/B/C=1-289.
DR PDB; 4EB8; X-ray; 2.30 A; A/B/C=1-289.
DR PDB; 4ECE; X-ray; 2.60 A; A/B/C/D/E/F=1-289.
DR PDB; 4GKA; X-ray; 2.20 A; A/B/C/D/E/F=1-289.
DR PDB; 5ETJ; X-ray; 2.30 A; A/B/C/D/E/F=1-289.
DR PDB; 5UGF; X-ray; 2.20 A; A/B/C/D/E/F=1-289.
DR PDBsum; 1M73; -.
DR PDBsum; 1PF7; -.
DR PDBsum; 1PWY; -.
DR PDBsum; 1RCT; -.
DR PDBsum; 1RFG; -.
DR PDBsum; 1RR6; -.
DR PDBsum; 1RSZ; -.
DR PDBsum; 1RT9; -.
DR PDBsum; 1ULA; -.
DR PDBsum; 1ULB; -.
DR PDBsum; 1V2H; -.
DR PDBsum; 1V3Q; -.
DR PDBsum; 1V41; -.
DR PDBsum; 1V45; -.
DR PDBsum; 1YRY; -.
DR PDBsum; 2A0W; -.
DR PDBsum; 2A0X; -.
DR PDBsum; 2A0Y; -.
DR PDBsum; 2OC4; -.
DR PDBsum; 2OC9; -.
DR PDBsum; 2ON6; -.
DR PDBsum; 2Q7O; -.
DR PDBsum; 3BGS; -.
DR PDBsum; 3D1V; -.
DR PDBsum; 3GB9; -.
DR PDBsum; 3GGS; -.
DR PDBsum; 3INY; -.
DR PDBsum; 3K8O; -.
DR PDBsum; 3K8Q; -.
DR PDBsum; 3PHB; -.
DR PDBsum; 4EAR; -.
DR PDBsum; 4EB8; -.
DR PDBsum; 4ECE; -.
DR PDBsum; 4GKA; -.
DR PDBsum; 5ETJ; -.
DR PDBsum; 5UGF; -.
DR AlphaFoldDB; P00491; -.
DR SMR; P00491; -.
DR BioGRID; 110921; 61.
DR CORUM; P00491; -.
DR DIP; DIP-50406N; -.
DR IntAct; P00491; 30.
DR MINT; P00491; -.
DR STRING; 9606.ENSP00000354532; -.
DR BindingDB; P00491; -.
DR ChEMBL; CHEMBL4338; -.
DR DrugBank; DB03881; (2S,3R,4S,5S)-3,4-Dihydroxy-2-[(methylsulfanyl)methyl]-5-(4-oxo-4,5-dihydro-1H-pyrrolo[3,2-d]pyrimidin-7-yl)pyrrolidinium.
DR DrugBank; DB03551; (3R,4R)-3-Hydroxy-4-(hydroxymethyl)-1-[(4-oxo-4,4a,5,7a-tetrahydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]pyrrolidinium.
DR DrugBank; DB02222; 2,6-Diamino-(S)-9-[2-(Phosphonomethoxy)Propyl]Purine.
DR DrugBank; DB02391; 2-Amino-7-[2-(2-Hydroxy-1-Hydroxymethyl-Ethylamino)-Ethyl]-1,7-Dihydro-Purin-6-One.
DR DrugBank; DB03609; 3'-deoxyguanosine.
DR DrugBank; DB01667; 8-azaguanine.
DR DrugBank; DB04260; 9-(5,5-Difluoro-5-Phosphonopentyl)Guanine.
DR DrugBank; DB02796; 9-deazainosine.
DR DrugBank; DB04753; 9-DEAZAINOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE.
DR DrugBank; DB00640; Adenosine.
DR DrugBank; DB00242; Cladribine.
DR DrugBank; DB00900; Didanosine.
DR DrugBank; DB06185; Forodesine.
DR DrugBank; DB02377; Guanine.
DR DrugBank; DB02857; Guanosine.
DR DrugBank; DB04754; GUANOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE.
DR DrugBank; DB04757; GUANOSINE-2',3'-O-METHYLIDENEPHOSPHONATE.
DR DrugBank; DB04076; Hypoxanthine.
DR DrugBank; DB02230; Immucillin-G.
DR DrugBank; DB04335; Inosine.
DR DrugBank; DB02568; Peldesine.
DR DrugBank; DB03101; Ribose-1-Phosphate.
DR DrugCentral; P00491; -.
DR GuidetoPHARMACOLOGY; 2841; -.
DR GlyGen; P00491; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P00491; -.
DR MetOSite; P00491; -.
DR PhosphoSitePlus; P00491; -.
DR SwissPalm; P00491; -.
DR BioMuta; PNP; -.
DR DMDM; 108935929; -.
DR OGP; P00491; -.
DR CPTAC; CPTAC-570; -.
DR CPTAC; CPTAC-571; -.
DR EPD; P00491; -.
DR jPOST; P00491; -.
DR MassIVE; P00491; -.
DR PaxDb; P00491; -.
DR PeptideAtlas; P00491; -.
DR PRIDE; P00491; -.
DR ProteomicsDB; 51256; -.
DR TopDownProteomics; P00491; -.
DR Antibodypedia; 766; 323 antibodies from 35 providers.
DR DNASU; 4860; -.
DR Ensembl; ENST00000361505.10; ENSP00000354532.6; ENSG00000198805.12.
DR GeneID; 4860; -.
DR KEGG; hsa:4860; -.
DR MANE-Select; ENST00000361505.10; ENSP00000354532.6; NM_000270.4; NP_000261.2.
DR CTD; 4860; -.
DR DisGeNET; 4860; -.
DR GeneCards; PNP; -.
DR HGNC; HGNC:7892; PNP.
DR HPA; ENSG00000198805; Tissue enhanced (bone marrow, epididymis).
DR MalaCards; PNP; -.
DR MIM; 164050; gene.
DR MIM; 613179; phenotype.
DR neXtProt; NX_P00491; -.
DR OpenTargets; ENSG00000198805; -.
DR Orphanet; 760; Purine nucleoside phosphorylase deficiency.
DR PharmGKB; PA31694; -.
DR VEuPathDB; HostDB:ENSG00000198805; -.
DR eggNOG; KOG3984; Eukaryota.
DR GeneTree; ENSGT00950000182991; -.
DR HOGENOM; CLU_054456_1_2_1; -.
DR InParanoid; P00491; -.
DR OMA; EGVYAQF; -.
DR OrthoDB; 1078969at2759; -.
DR PhylomeDB; P00491; -.
DR TreeFam; TF300049; -.
DR BioCyc; MetaCyc:HS02151-MON; -.
DR BRENDA; 2.4.2.1; 2681.
DR PathwayCommons; P00491; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-74217; Purine salvage.
DR Reactome; R-HSA-74259; Purine catabolism.
DR Reactome; R-HSA-9735763; Defective PNP disrupts phosphorolysis of (deoxy)guanosine and (deoxy)inosine.
DR SABIO-RK; P00491; -.
DR SignaLink; P00491; -.
DR UniPathway; UPA00606; -.
DR BioGRID-ORCS; 4860; 10 hits in 1082 CRISPR screens.
DR ChiTaRS; PNP; human.
DR EvolutionaryTrace; P00491; -.
DR GeneWiki; Purine_nucleoside_phosphorylase; -.
DR GenomeRNAi; 4860; -.
DR Pharos; P00491; Tclin.
DR PRO; PR:P00491; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P00491; protein.
DR Bgee; ENSG00000198805; Expressed in corpus epididymis and 169 other tissues.
DR ExpressionAtlas; P00491; baseline and differential.
DR Genevisible; P00491; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0047975; F:guanosine phosphorylase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0001882; F:nucleoside binding; IDA:UniProtKB.
DR GO; GO:0042301; F:phosphate ion binding; IDA:UniProtKB.
DR GO; GO:0002060; F:purine nucleobase binding; IDA:UniProtKB.
DR GO; GO:0004731; F:purine-nucleoside phosphorylase activity; IDA:UniProtKB.
DR GO; GO:0000255; P:allantoin metabolic process; IDA:MGI.
DR GO; GO:0046059; P:dAMP catabolic process; IDA:MGI.
DR GO; GO:0006157; P:deoxyadenosine catabolic process; IDA:MGI.
DR GO; GO:0006149; P:deoxyinosine catabolic process; IDA:MGI.
DR GO; GO:0006955; P:immune response; IMP:UniProtKB.
DR GO; GO:0006204; P:IMP catabolic process; IDA:MGI.
DR GO; GO:0006148; P:inosine catabolic process; IDA:UniProtKB.
DR GO; GO:0006738; P:nicotinamide riboside catabolic process; IDA:UniProtKB.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; IDA:UniProtKB.
DR GO; GO:0009165; P:nucleotide biosynthetic process; IGI:UniProtKB.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IDA:MGI.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:MGI.
DR GO; GO:0006166; P:purine ribonucleoside salvage; IEA:UniProtKB-KW.
DR GO; GO:0043101; P:purine-containing compound salvage; IDA:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:UniProtKB.
DR GO; GO:0034418; P:urate biosynthetic process; IDA:MGI.
DR CDD; cd09009; PNP-EcPNPII_like; 1.
DR Gene3D; 3.40.50.1580; -; 1.
DR InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR InterPro; IPR011270; Pur_Nuc_Pase_Ino/Guo-sp.
DR InterPro; IPR011268; Purine_phosphorylase.
DR InterPro; IPR018099; Purine_phosphorylase-2_CS.
DR PANTHER; PTHR11904; PTHR11904; 1.
DR Pfam; PF01048; PNP_UDP_1; 1.
DR PIRSF; PIRSF000477; PurNPase; 1.
DR SUPFAM; SSF53167; SSF53167; 1.
DR TIGRFAMs; TIGR01700; PNPH; 1.
DR TIGRFAMs; TIGR01697; PNPH-PUNA-XAPA; 1.
DR PROSITE; PS01240; PNP_MTAP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Disease variant; Glycosyltransferase; Phosphoprotein; Purine salvage;
KW Reference proteome; Transferase.
FT CHAIN 1..289
FT /note="Purine nucleoside phosphorylase"
FT /id="PRO_0000184536"
FT BINDING 33
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:23438750,
FT ECO:0000305|PubMed:14706628, ECO:0000305|PubMed:1763067,
FT ECO:0007744|PDB:1RCT, ECO:0007744|PDB:1ULA,
FT ECO:0007744|PDB:1ULB, ECO:0007744|PDB:4EAR,
FT ECO:0007744|PDB:4EB8, ECO:0007744|PDB:4GKA"
FT BINDING 64
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000250|UniProtKB:P55859"
FT BINDING 84..86
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:23438750,
FT ECO:0000305|PubMed:14706628, ECO:0000305|PubMed:1763067,
FT ECO:0007744|PDB:1RCT, ECO:0007744|PDB:1ULA,
FT ECO:0007744|PDB:1ULB, ECO:0007744|PDB:1V3Q,
FT ECO:0007744|PDB:4EAR, ECO:0007744|PDB:4EB8,
FT ECO:0007744|PDB:4GKA"
FT BINDING 88
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:14706628,
FT ECO:0000269|PubMed:23438750, ECO:0007744|PDB:1RCT,
FT ECO:0007744|PDB:4EAR, ECO:0007744|PDB:4EB8"
FT BINDING 116
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:14706628,
FT ECO:0000269|PubMed:23438750, ECO:0000305|PubMed:1763067,
FT ECO:0007744|PDB:1RCT, ECO:0007744|PDB:1ULB,
FT ECO:0007744|PDB:4EAR, ECO:0007744|PDB:4EB8,
FT ECO:0007744|PDB:4GKA"
FT BINDING 201
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:14706628,
FT ECO:0000269|PubMed:23438750, ECO:0000305|PubMed:1763067,
FT ECO:0007744|PDB:1RCT, ECO:0007744|PDB:1ULB,
FT ECO:0007744|PDB:4EAR, ECO:0007744|PDB:4EB8,
FT ECO:0007744|PDB:4GKA"
FT BINDING 219
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:14706628,
FT ECO:0007744|PDB:1RCT"
FT BINDING 220
FT /ligand="phosphate"
FT /ligand_id="ChEBI:CHEBI:43474"
FT /evidence="ECO:0000269|PubMed:14706628,
FT ECO:0000269|PubMed:23438750, ECO:0000305|PubMed:1763067,
FT ECO:0007744|PDB:1RCT, ECO:0007744|PDB:1ULB,
FT ECO:0007744|PDB:4EAR, ECO:0007744|PDB:4EB8,
FT ECO:0007744|PDB:4GKA"
FT BINDING 243
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:14706628,
FT ECO:0000269|PubMed:23438750, ECO:0000305|PubMed:1763067,
FT ECO:0007744|PDB:1RCT, ECO:0007744|PDB:1ULB,
FT ECO:0007744|PDB:4EAR, ECO:0007744|PDB:4EB8,
FT ECO:0007744|PDB:4GKA"
FT BINDING 257
FT /ligand="a purine D-ribonucleoside"
FT /ligand_id="ChEBI:CHEBI:142355"
FT /evidence="ECO:0000269|PubMed:14706628,
FT ECO:0007744|PDB:1RCT"
FT SITE 243
FT /note="Important for substrate specificity"
FT /evidence="ECO:0000269|PubMed:9305964"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 51
FT /note="G -> S (in dbSNP:rs1049564)"
FT /evidence="ECO:0000269|PubMed:12928150,
FT ECO:0000269|PubMed:1384322, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:3029074, ECO:0000269|PubMed:6087295"
FT /id="VAR_002243"
FT VARIANT 89
FT /note="E -> K (in PNPD; dbSNP:rs104894453)"
FT /evidence="ECO:0000269|PubMed:3029074"
FT /id="VAR_002244"
FT VARIANT 128
FT /note="D -> G (in PNPD; dbSNP:rs104894450)"
FT /evidence="ECO:0000269|PubMed:1384322"
FT /id="VAR_002245"
FT VARIANT 174
FT /note="A -> P (in PNPD; dbSNP:rs104894454)"
FT /id="VAR_002246"
FT VARIANT 192
FT /note="Y -> C (in PNPD; dbSNP:rs104894452)"
FT /evidence="ECO:0000269|PubMed:8931706"
FT /id="VAR_010653"
FT VARIANT 234
FT /note="R -> P (in PNPD; dbSNP:rs104894451)"
FT /evidence="ECO:0000269|PubMed:1384322"
FT /id="VAR_002247"
FT MUTAGEN 64
FT /note="H->W: Reduces catalytic activity towards inosine."
FT /evidence="ECO:0000269|PubMed:23438750"
FT MUTAGEN 201
FT /note="E->A,Q: Severe loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:9305964"
FT MUTAGEN 243
FT /note="N->A: Reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:9305964"
FT MUTAGEN 243
FT /note="N->D: Reduces catalytic activity towards inosine,
FT hypoxanthine, guanosine and guanine. Increases catalytic
FT activity towards adenosine and adenine."
FT /evidence="ECO:0000269|PubMed:9305964"
FT MUTAGEN 257
FT /note="H->W: Reduces catalytic activity towards inosine."
FT /evidence="ECO:0000269|PubMed:23438750"
FT HELIX 7..20
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 36..41
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:1PWY"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:3BGS"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 98..106
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 110..119
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:1V2H"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 138..141
FT /evidence="ECO:0007829|PDB:4EAR"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:4EAR"
FT TURN 163..166
FT /evidence="ECO:0007829|PDB:1V41"
FT HELIX 168..179
FT /evidence="ECO:0007829|PDB:4EAR"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:1RSZ"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:1M73"
FT HELIX 203..211
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 222..230
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 234..244
FT /evidence="ECO:0007829|PDB:4EAR"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 257..266
FT /evidence="ECO:0007829|PDB:4EAR"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:4EAR"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:1M73"
SQ SEQUENCE 289 AA; 32118 MW; 91622FB1D26479D3 CRC64;
MENGYTYEDY KNTAEWLLSH TKHRPQVAII CGSGLGGLTD KLTQAQIFDY GEIPNFPRST
VPGHAGRLVF GFLNGRACVM MQGRFHMYEG YPLWKVTFPV RVFHLLGVDT LVVTNAAGGL
NPKFEVGDIM LIRDHINLPG FSGQNPLRGP NDERFGDRFP AMSDAYDRTM RQRALSTWKQ
MGEQRELQEG TYVMVAGPSF ETVAECRVLQ KLGADAVGMS TVPEVIVARH CGLRVFGFSL
ITNKVIMDYE SLEKANHEEV LAAGKQAAQK LEQFVSILMA SIPLPDKAS
