ID PRPS1_HUMAN Reviewed; 318 AA. AC P60891; B1ALA8; B2R6T7; B4DNL6; D3DUX6; P09329; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 196. DE RecName: Full=Ribose-phosphate pyrophosphokinase 1 {ECO:0000305}; DE EC=2.7.6.1 {ECO:0000269|PubMed:16939420, ECO:0000269|PubMed:17701900, ECO:0000269|PubMed:7593598}; DE AltName: Full=PPRibP; DE AltName: Full=Phosphoribosyl pyrophosphate synthase I; DE Short=PRS-I; GN Name=PRPS1 {ECO:0000312|HGNC:HGNC:9462}; 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] (ISOFORM 1). RC TISSUE=Lymphoblast; RX PubMed=2155397; DOI=10.1093/nar/18.1.193; RA Roessler B.J., Bell G., Heidler S., Seino S., Becker M., Palella T.D.; RT "Cloning of two distinct copies of human phosphoribosylpyrophosphate RT synthetase cDNA."; RL Nucleic Acids Res. 18:193-193(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1650777; RA Sonoda T., Taira M., Ishijima S., Ishizuka T., Iizaka T., Tatibana M.; RT "Complete nucleotide sequence of human phosphoribosyl pyrophosphate RT synthetase subunit I (PRS I) cDNA and a comparison with human and rat PRPS RT gene families."; RL J. Biochem. 109:361-364(1991). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-41 (ISOFORM 1). RX PubMed=1314091; DOI=10.1016/0167-4781(92)90521-z; RA Ishizuka T., Iizasa T., Taira M., Ishijima S., Sonoda T., Shimada H., RA Nagatake N., Tatibana M.; RT "Promoter regions of the human X-linked housekeeping genes PRPS1 and PRPS2 RT encoding phosphoribosylpyrophosphate synthetase subunit I and II RT isoforms."; RL Biochim. Biophys. Acta 1130:139-148(1992). RN [8] RP PROTEIN SEQUENCE OF 2-33; 85-96; 164-176; 205-214; 236-260 AND 303-318, RP CLEAVAGE OF INITIATOR METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Zebisch A., Kolch W.; RL Submitted (JUL-2009) to UniProtKB. RN [9] RP PROTEIN SEQUENCE OF 244-260 AND 303-318, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Vishwanath V.; RL Submitted (MAR-2007) to UniProtKB. RN [10] 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 [11] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH AMP, SUBUNIT, RP MUTAGENESIS OF SER-132; ASN-144 AND TYR-146, FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=16939420; DOI=10.1042/bj20061066; RA Li S., Lu Y., Peng B., Ding J.; RT "Crystal structure of human phosphoribosylpyrophosphate synthetase 1 RT reveals a novel allosteric site."; RL Biochem. J. 401:39-47(2007). RN [12] RP VARIANTS PRPS1 SUPERACTIVITY SER-114 AND HIS-183. RA Roessler B.J., Palella T.D., Heidler S., Becker M.A.; RT "Identification of distinct PRPS1 mutations in two patients with X-linked RT phosphoribosylpyrophosphate synthetase superactivity."; RL Clin. Res. 39:267A-267A(1991). RN [13] RP VARIANTS PRPS1 SUPERACTIVITY HIS-52; SER-114; ILE-129; HIS-183; VAL-190 AND RP GLN-193, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, RP ACTIVITY REGULATION, AND CHARACTERIZATION OF VARIANTS PRPS1 SUPERACTIVITY RP HIS-52; SER-114; ILE-129; HIS-183; VAL-190 AND GLN-193. RX PubMed=7593598; DOI=10.1172/jci118267; RA Becker M.A., Smith P.R., Taylor W., Mustafi R., Switzer R.L.; RT "The genetic and functional basis of purine nucleotide feedback-resistant RT phosphoribosylpyrophosphate synthetase superactivity."; RL J. Clin. Invest. 96:2133-2141(1995). RN [14] RP VARIANTS [LARGE SCALE ANALYSIS] HIS-203; GLY-219 AND ASP-231. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [15] RP VARIANTS ARTS PRO-133 AND PRO-152. RX PubMed=17701896; DOI=10.1086/520706; RA de Brouwer A.P.M., Williams K.L., Duley J.A., van Kuilenburg A.B.P., RA Nabuurs S.B., Egmont-Petersen M., Lugtenberg D., Zoetekouw L., RA Banning M.J.G., Roeffen M., Hamel B.C.J., Weaving L., Ouvrier R.A., RA Donald J.A., Wevers R.A., Christodoulou J., van Bokhoven H.; RT "Arts syndrome is caused by loss-of-function mutations in PRPS1."; RL Am. J. Hum. Genet. 81:507-518(2007). RN [16] RP VARIANTS CMTX5 ASP-43 AND THR-115, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=17701900; DOI=10.1086/519529; RA Kim H.-J., Sohn K.-M., Shy M.E., Krajewski K.M., Hwang M., Park J.-H., RA Jang S.-Y., Won H.-H., Choi B.-O., Hong S.H., Kim B.-J., Suh Y.-L., RA Ki C.-S., Lee S.-Y., Kim S.-H., Kim J.-W.; RT "Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate RT synthetase enzyme critical for nucleotide biosynthesis, cause hereditary RT peripheral neuropathy with hearing loss and optic neuropathy (cmtx5)."; RL Am. J. Hum. Genet. 81:552-558(2007). RN [17] RP VARIANTS DFNX1 ASN-65; THR-87; THR-290 AND ARG-306. RX PubMed=20021999; DOI=10.1016/j.ajhg.2009.11.015; RA Liu X., Han D., Li J., Han B., Ouyang X., Cheng J., Li X., Jin Z., Wang Y., RA Bitner-Glindzicz M., Kong X., Xu H., Kantardzhieva A., Eavey R.D., RA Seidman C.E., Seidman J.G., Du L.L., Chen Z.Y., Dai P., Teng M., Yan D., RA Yuan H.; RT "Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic RT X-linked sensorineural deafness, DFN2."; RL Am. J. Hum. Genet. 86:65-71(2010). RN [18] RP INVOLVEMENT IN DISEASE, VARIANT LEU-142, AND CHARACTERIZATION OF VARIANT RP LEU-142. RX PubMed=22246954; DOI=10.1002/ajmg.a.34428; RA Moran R., Kuilenburg A.B., Duley J., Nabuurs S.B., Retno-Fitri A., RA Christodoulou J., Roelofsen J., Yntema H.G., Friedman N.R., RA van Bokhoven H., de Brouwer A.P.; RT "Phosphoribosylpyrophosphate synthetase superactivity and recurrent RT infections is caused by a p.Val142Leu mutation in PRS-I."; RL Am. J. Med. Genet. A 158A:455-460(2012). RN [19] RP VARIANT PRO-16. RX PubMed=25491489; DOI=10.1186/s13023-014-0190-9; RA Almoguera B., He S., Corton M., Fernandez-San Jose P., Blanco-Kelly F., RA Lopez-Molina M., Garcia-Sandoval B., Del Val J., Guo Y., Tian L., Liu X., RA Guan L., Torres R.J., Puig J.G., Hakonarson H., Xu X., Keating B., RA Ayuso C.; RT "Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing RT loss and retinopathy."; RL Orphanet J. Rare Dis. 9:190-190(2014). CC -!- FUNCTION: Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) CC that is essential for nucleotide synthesis. CC {ECO:0000269|PubMed:16939420, ECO:0000269|PubMed:17701900, CC ECO:0000269|PubMed:7593598}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + D-ribose 5-phosphate = 5-phospho-alpha-D-ribose 1- CC diphosphate + AMP + H(+); Xref=Rhea:RHEA:15609, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58017, ChEBI:CHEBI:78346, CC ChEBI:CHEBI:456215; EC=2.7.6.1; CC Evidence={ECO:0000269|PubMed:16939420, ECO:0000269|PubMed:17701900, CC ECO:0000269|PubMed:7593598}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15610; CC Evidence={ECO:0000305|PubMed:16939420, ECO:0000305|PubMed:17701900, CC ECO:0000305|PubMed:7593598}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- ACTIVITY REGULATION: Activated by magnesium and inorganic phosphate. CC Inhibited by ADP and GDP (PubMed:7593598). CC {ECO:0000269|PubMed:7593598}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=23 uM for ATP {ECO:0000269|PubMed:7593598}; CC KM=54 uM for D-ribose 5-phosphate {ECO:0000269|PubMed:7593598}; CC -!- PATHWAY: Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose CC 1-diphosphate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate from CC D-ribose 5-phosphate (route I): step 1/1. {ECO:0000269|PubMed:16939420, CC ECO:0000269|PubMed:17701900}. CC -!- SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3 CC homodimers. {ECO:0000269|PubMed:16939420}. CC -!- INTERACTION: CC P60891; P13928: ANXA8; NbExp=3; IntAct=EBI-749195, EBI-2556915; CC P60891; P05067: APP; NbExp=3; IntAct=EBI-749195, EBI-77613; CC P60891; O94778: AQP8; NbExp=3; IntAct=EBI-749195, EBI-19124986; CC P60891; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-749195, EBI-2875816; CC P60891; Q86TN1: ARNT2; NbExp=3; IntAct=EBI-749195, EBI-25844820; CC P60891; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-749195, EBI-14199987; CC P60891; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-749195, EBI-10254793; CC P60891; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-749195, EBI-9089489; CC P60891; Q16520: BATF; NbExp=3; IntAct=EBI-749195, EBI-749503; CC P60891; P23560-2: BDNF; NbExp=3; IntAct=EBI-749195, EBI-12275524; CC P60891; Q14457: BECN1; NbExp=3; IntAct=EBI-749195, EBI-949378; CC P60891; Q96LL4: C8orf48; NbExp=3; IntAct=EBI-749195, EBI-751596; CC P60891; Q8N5S9-2: CAMKK1; NbExp=3; IntAct=EBI-749195, EBI-25850646; CC P60891; Q6ZP82: CCDC141; NbExp=3; IntAct=EBI-749195, EBI-928795; CC P60891; Q96LX7-5: CCDC17; NbExp=3; IntAct=EBI-749195, EBI-12165781; CC P60891; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-749195, EBI-396137; CC P60891; Q9Y3D0: CIAO2B; NbExp=3; IntAct=EBI-749195, EBI-744045; CC P60891; Q99967: CITED2; NbExp=3; IntAct=EBI-749195, EBI-937732; CC P60891; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-749195, EBI-2872414; CC P60891; P02489: CRYAA; NbExp=3; IntAct=EBI-749195, EBI-6875961; CC P60891; P02511: CRYAB; NbExp=3; IntAct=EBI-749195, EBI-739060; CC P60891; Q9Y4B6-3: DCAF1; NbExp=3; IntAct=EBI-749195, EBI-9915372; CC P60891; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-749195, EBI-742054; CC P60891; A0A024RCP2: DOM3Z; NbExp=3; IntAct=EBI-749195, EBI-25847826; CC P60891; Q92997: DVL3; NbExp=3; IntAct=EBI-749195, EBI-739789; CC P60891; O00303: EIF3F; NbExp=3; IntAct=EBI-749195, EBI-711990; CC P60891; Q13216-2: ERCC8; NbExp=3; IntAct=EBI-749195, EBI-16466949; CC P60891; Q6P587-2: FAHD1; NbExp=3; IntAct=EBI-749195, EBI-12902289; CC P60891; Q6P1L5: FAM117B; NbExp=3; IntAct=EBI-749195, EBI-3893327; CC P60891; O15287: FANCG; NbExp=3; IntAct=EBI-749195, EBI-81610; CC P60891; O00757: FBP2; NbExp=3; IntAct=EBI-749195, EBI-719781; CC P60891; Q9UHY8: FEZ2; NbExp=3; IntAct=EBI-749195, EBI-396453; CC P60891; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-749195, EBI-10226858; CC P60891; P15976-2: GATA1; NbExp=3; IntAct=EBI-749195, EBI-9090198; CC P60891; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-749195, EBI-8799578; CC P60891; Q9H8Y8: GORASP2; NbExp=6; IntAct=EBI-749195, EBI-739467; CC P60891; P52790: HK3; NbExp=3; IntAct=EBI-749195, EBI-2965780; CC P60891; Q14005-2: IL16; NbExp=3; IntAct=EBI-749195, EBI-17178971; CC P60891; Q8IXL9: IQCF2; NbExp=3; IntAct=EBI-749195, EBI-10238842; CC P60891; Q8WZ19: KCTD13; NbExp=3; IntAct=EBI-749195, EBI-742916; CC P60891; Q96SI1-2: KCTD15; NbExp=3; IntAct=EBI-749195, EBI-12382297; CC P60891; Q6ZU52: KIAA0408; NbExp=3; IntAct=EBI-749195, EBI-739493; CC P60891; O60333-2: KIF1B; NbExp=3; IntAct=EBI-749195, EBI-10975473; CC P60891; P57682: KLF3; NbExp=3; IntAct=EBI-749195, EBI-8472267; CC P60891; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-749195, EBI-714379; CC P60891; Q14525: KRT33B; NbExp=3; IntAct=EBI-749195, EBI-1049638; CC P60891; Q96PV6: LENG8; NbExp=3; IntAct=EBI-749195, EBI-739546; CC P60891; A2RU56: LOC401296; NbExp=3; IntAct=EBI-749195, EBI-9088215; CC P60891; Q9UDY8-2: MALT1; NbExp=3; IntAct=EBI-749195, EBI-12056869; CC P60891; Q99683: MAP3K5; NbExp=3; IntAct=EBI-749195, EBI-476263; CC P60891; P61244-4: MAX; NbExp=3; IntAct=EBI-749195, EBI-25848049; CC P60891; P51608: MECP2; NbExp=3; IntAct=EBI-749195, EBI-1189067; CC P60891; Q15528-2: MED22; NbExp=3; IntAct=EBI-749195, EBI-12954271; CC P60891; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-749195, EBI-8487781; CC P60891; Q9NYP9: MIS18A; NbExp=3; IntAct=EBI-749195, EBI-1104552; CC P60891; Q15049: MLC1; NbExp=3; IntAct=EBI-749195, EBI-8475277; CC P60891; Q8N594: MPND; NbExp=3; IntAct=EBI-749195, EBI-2512452; CC P60891; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-749195, EBI-995714; CC P60891; Q96HT8: MRFAP1L1; NbExp=3; IntAct=EBI-749195, EBI-748896; CC P60891; I6L9F6: NEFL; NbExp=3; IntAct=EBI-749195, EBI-10178578; CC P60891; O15381-5: NVL; NbExp=3; IntAct=EBI-749195, EBI-18577082; CC P60891; O43482: OIP5; NbExp=3; IntAct=EBI-749195, EBI-536879; CC P60891; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-749195, EBI-1058491; CC P60891; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-749195, EBI-25830200; CC P60891; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-749195, EBI-11022007; CC P60891; P22061-2: PCMT1; NbExp=3; IntAct=EBI-749195, EBI-12386584; CC P60891; Q9BRX2: PELO; NbExp=3; IntAct=EBI-749195, EBI-1043580; CC P60891; O15534: PER1; NbExp=3; IntAct=EBI-749195, EBI-2557276; CC P60891; Q96LB9: PGLYRP3; NbExp=3; IntAct=EBI-749195, EBI-12339509; CC P60891; Q7RTV0: PHF5A; NbExp=3; IntAct=EBI-749195, EBI-2555365; CC P60891; Q58EX7-2: PLEKHG4; NbExp=3; IntAct=EBI-749195, EBI-21503705; CC P60891; Q8TBJ4: PLPPR1; NbExp=3; IntAct=EBI-749195, EBI-18063495; CC P60891; Q9H1D9: POLR3F; NbExp=3; IntAct=EBI-749195, EBI-710067; CC P60891; P60891: PRPS1; NbExp=12; IntAct=EBI-749195, EBI-749195; CC P60891; P11908: PRPS2; NbExp=10; IntAct=EBI-749195, EBI-4290895; CC P60891; P11908-2: PRPS2; NbExp=4; IntAct=EBI-749195, EBI-12063547; CC P60891; Q14558: PRPSAP1; NbExp=11; IntAct=EBI-749195, EBI-724449; CC P60891; O60256: PRPSAP2; NbExp=8; IntAct=EBI-749195, EBI-724960; CC P60891; Q9Y5P3: RAI2; NbExp=3; IntAct=EBI-749195, EBI-746228; CC P60891; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-749195, EBI-1504830; CC P60891; Q96D59: RNF183; NbExp=3; IntAct=EBI-749195, EBI-743938; CC P60891; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-749195, EBI-11528848; CC P60891; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-749195, EBI-9089805; CC P60891; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-749195, EBI-11959123; CC P60891; Q9NZD8: SPG21; NbExp=8; IntAct=EBI-749195, EBI-742688; CC P60891; Q8N865: SPMIP4; NbExp=3; IntAct=EBI-749195, EBI-10174456; CC P60891; Q8TCT7-2: SPPL2B; NbExp=3; IntAct=EBI-749195, EBI-8345366; CC P60891; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-749195, EBI-7082156; CC P60891; Q9C004: SPRY4; NbExp=3; IntAct=EBI-749195, EBI-354861; CC P60891; Q8IXS7: SRGAP3; NbExp=3; IntAct=EBI-749195, EBI-18616594; CC P60891; O75886: STAM2; NbExp=3; IntAct=EBI-749195, EBI-373258; CC P60891; A1L190: SYCE3; NbExp=3; IntAct=EBI-749195, EBI-10283466; CC P60891; Q13148: TARDBP; NbExp=6; IntAct=EBI-749195, EBI-372899; CC P60891; Q5VWN6: TASOR2; NbExp=3; IntAct=EBI-749195, EBI-745958; CC P60891; Q13569: TDG; NbExp=3; IntAct=EBI-749195, EBI-348333; CC P60891; Q86WV5: TEN1; NbExp=3; IntAct=EBI-749195, EBI-2562799; CC P60891; Q96A09: TENT5B; NbExp=3; IntAct=EBI-749195, EBI-752030; CC P60891; P21980-2: TGM2; NbExp=3; IntAct=EBI-749195, EBI-25842075; CC P60891; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-749195, EBI-9089156; CC P60891; Q86WV8: TSC1; NbExp=3; IntAct=EBI-749195, EBI-12806590; CC P60891; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-749195, EBI-9090990; CC P60891; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-749195, EBI-9088812; CC P60891; Q9BSL1: UBAC1; NbExp=3; IntAct=EBI-749195, EBI-749370; CC P60891; Q969T4: UBE2E3; NbExp=3; IntAct=EBI-749195, EBI-348496; CC P60891; O75604-3: USP2; NbExp=3; IntAct=EBI-749195, EBI-10696113; CC P60891; P45880: VDAC2; NbExp=3; IntAct=EBI-749195, EBI-354022; CC P60891; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-749195, EBI-2850578; CC P60891; P58304: VSX2; NbExp=3; IntAct=EBI-749195, EBI-6427899; CC P60891; Q9BRX9: WDR83; NbExp=3; IntAct=EBI-749195, EBI-7705033; CC P60891; O76024: WFS1; NbExp=3; IntAct=EBI-749195, EBI-720609; CC P60891; Q15007-2: WTAP; NbExp=3; IntAct=EBI-749195, EBI-25840023; CC P60891; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-749195, EBI-12040603; CC P60891; O00308: WWP2; NbExp=3; IntAct=EBI-749195, EBI-743923; CC P60891; Q15776: ZKSCAN8; NbExp=3; IntAct=EBI-749195, EBI-2602314; CC P60891; Q9UJW8-4: ZNF180; NbExp=3; IntAct=EBI-749195, EBI-12055755; CC P60891; Q8WUU4: ZNF296; NbExp=3; IntAct=EBI-749195, EBI-8834821; CC P60891; Q8N895: ZNF366; NbExp=3; IntAct=EBI-749195, EBI-2813661; CC P60891; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-749195, EBI-12010736; CC P60891; Q96MN9-2: ZNF488; NbExp=3; IntAct=EBI-749195, EBI-25831733; CC P60891; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-749195, EBI-10486136; CC P60891; Q68EA5: ZNF57; NbExp=3; IntAct=EBI-749195, EBI-8490788; CC P60891; Q3KNS6-3: ZNF829; NbExp=3; IntAct=EBI-749195, EBI-18036029; CC P60891; O15535: ZSCAN9; NbExp=3; IntAct=EBI-749195, EBI-751531; CC P60891; Q2QGD7: ZXDC; NbExp=3; IntAct=EBI-749195, EBI-1538838; CC P60891; B7Z3E8; NbExp=3; IntAct=EBI-749195, EBI-25831617; CC P60891; Q86V28; NbExp=3; IntAct=EBI-749195, EBI-10259496; CC P60891-1; P50053-2: KHK; NbExp=4; IntAct=EBI-16205225, EBI-12204387; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P60891-1; Sequence=Displayed; CC Name=2; CC IsoId=P60891-2; Sequence=VSP_056028; CC -!- DISEASE: Note=Phosphoribosyl pyrophosphate synthetase I deficiency is a CC rare condition caused by mutations in PRPS1 that lead to variable CC disease phenotypes including optic atrophy, retinitis pigmentosa, CC ataxia, peripheral neuropathy and hearing loss. CC {ECO:0000269|PubMed:25491489}. CC -!- DISEASE: Phosphoribosylpyrophosphate synthetase superactivity (PRPS1 CC superactivity) [MIM:300661]: Familial disorder characterized by CC excessive purine production, gout and uric acid urolithiasis. CC {ECO:0000269|PubMed:7593598, ECO:0000269|Ref.12}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Charcot-Marie-Tooth disease, X-linked recessive, 5 (CMTX5) CC [MIM:311070]: A form of Charcot-Marie-Tooth disease, a disorder of the CC peripheral nervous system, characterized by progressive weakness and CC atrophy, initially of the peroneal muscles and later of the distal CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two CC main groups on the basis of electrophysiologic properties and CC histopathology: primary peripheral demyelinating neuropathies CC characterized by severely reduced motor nerve conduction velocities CC (NCVs) (less than 38m/s) and segmental demyelination and remyelination, CC and primary peripheral axonal neuropathies characterized by normal or CC mildly reduced NCVs and chronic axonal degeneration and regeneration on CC nerve biopsy. {ECO:0000269|PubMed:17701900}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: ARTS syndrome (ARTS) [MIM:301835]: A disorder characterized by CC intellectual disability, early-onset hypotonia, ataxia, delayed motor CC development, hearing impairment, and optic atrophy. Susceptibility to CC infections, especially of the upper respiratory tract, can result in CC early death. {ECO:0000269|PubMed:17701896}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Deafness, X-linked, 1 (DFNX1) [MIM:304500]: A form of deafness CC characterized by progressive, severe-to-profound sensorineural hearing CC loss in males. Females manifest mild to moderate hearing loss. CC {ECO:0000269|PubMed:20021999}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=A mutation in PRPS1 has been found in a patient with a CC phenotype that bridges that of PRSPS1 superactivity and ARTS syndrome CC with uric acid overproduction without gout but with recurrent CC infections, sensorineural hearing loss and motor neuropathy. The CC intermediate phenotype may be because Leu-142 variant affects both CC allosteric sites that are involved in inhibition of PRPS1 and the ATP- CC binding site, which suggests that this substitution can result both in CC a gain-of-function and loss-of-function of PRPP synthetase. CC {ECO:0000269|PubMed:22246954}. CC -!- SIMILARITY: Belongs to the ribose-phosphate pyrophosphokinase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X15331; CAA33386.1; -; mRNA. DR EMBL; D00860; BAA00733.1; -; mRNA. DR EMBL; AK297968; BAG60278.1; -; mRNA. DR EMBL; AK312706; BAG35584.1; -; mRNA. DR EMBL; AL137787; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL772400; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471120; EAX02709.1; -; Genomic_DNA. DR EMBL; CH471120; EAX02710.1; -; Genomic_DNA. DR EMBL; CH471120; EAX02711.1; -; Genomic_DNA. DR EMBL; BC001605; AAH01605.1; -; mRNA. DR CCDS; CCDS14529.1; -. [P60891-1] DR PIR; JX0159; KIHUR1. DR RefSeq; NP_001191331.1; NM_001204402.1. DR RefSeq; NP_002755.1; NM_002764.3. [P60891-1] DR PDB; 2H06; X-ray; 2.20 A; A/B=1-318. DR PDB; 2H07; X-ray; 2.20 A; A/B=1-318. DR PDB; 2H08; X-ray; 2.50 A; A/B=1-318. DR PDB; 2HCR; X-ray; 2.20 A; A/B=1-318. DR PDB; 3EFH; X-ray; 2.60 A; A/B=1-318. DR PDB; 3S5J; X-ray; 2.02 A; A/B=1-318. DR PDB; 4F8E; X-ray; 2.27 A; A/B=1-318. DR PDB; 4LYG; X-ray; 3.00 A; A/B=1-318. DR PDB; 4LZN; X-ray; 2.14 A; A/B=1-318. DR PDB; 4LZO; X-ray; 3.31 A; A/B=1-318. DR PDB; 4M0P; X-ray; 2.11 A; A/B=1-318. DR PDB; 4M0U; X-ray; 2.74 A; A/B=1-318. DR PDB; 8DBC; EM; 3.20 A; A/B/C/D/E/F=1-318. DR PDB; 8DBD; EM; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=1-318. DR PDB; 8DBE; EM; 2.10 A; A/B/C/D/E/F=1-318. DR PDB; 8DBF; EM; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L=2-318. DR PDB; 8DBG; EM; 2.20 A; A/B/C/D/E/F=2-318. DR PDB; 8DBH; EM; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L=2-318. DR PDB; 8DBI; EM; 2.00 A; A/B/C/D/E/F=2-318. DR PDB; 8DBJ; EM; 2.00 A; A/B/C/D/E/F/G/H/I/J/K/L=2-318. DR PDB; 8DBK; EM; 2.10 A; A/B/C/D/E/F=2-318. DR PDB; 8DBL; EM; 2.40 A; A/B/C/D/E/F=2-318. DR PDB; 8DBM; EM; 2.40 A; A/B/C/D/E/F/G/H/I/J/K/L=2-318. DR PDB; 8DBN; EM; 2.40 A; A/B/C/D/E/F=2-318. DR PDB; 8DBO; EM; 2.50 A; A/B/C/D/E/F=2-318. DR PDBsum; 2H06; -. DR PDBsum; 2H07; -. DR PDBsum; 2H08; -. DR PDBsum; 2HCR; -. DR PDBsum; 3EFH; -. DR PDBsum; 3S5J; -. DR PDBsum; 4F8E; -. DR PDBsum; 4LYG; -. DR PDBsum; 4LZN; -. DR PDBsum; 4LZO; -. DR PDBsum; 4M0P; -. DR PDBsum; 4M0U; -. DR PDBsum; 8DBC; -. DR PDBsum; 8DBD; -. DR PDBsum; 8DBE; -. DR PDBsum; 8DBF; -. DR PDBsum; 8DBG; -. DR PDBsum; 8DBH; -. DR PDBsum; 8DBI; -. DR PDBsum; 8DBJ; -. DR PDBsum; 8DBK; -. DR PDBsum; 8DBL; -. DR PDBsum; 8DBM; -. DR PDBsum; 8DBN; -. DR PDBsum; 8DBO; -. DR AlphaFoldDB; P60891; -. DR EMDB; EMD-27279; -. DR EMDB; EMD-27280; -. DR EMDB; EMD-27281; -. DR EMDB; EMD-27282; -. DR EMDB; EMD-27283; -. DR EMDB; EMD-27284; -. DR EMDB; EMD-27285; -. DR EMDB; EMD-27286; -. DR EMDB; EMD-27287; -. DR EMDB; EMD-27288; -. DR EMDB; EMD-27289; -. DR EMDB; EMD-27290; -. DR EMDB; EMD-27291; -. DR EMDB; EMD-27292; -. DR EMDB; EMD-27293; -. DR EMDB; EMD-27294; -. DR EMDB; EMD-27295; -. DR SMR; P60891; -. DR BioGRID; 111615; 205. DR DIP; DIP-61999N; -. DR IntAct; P60891; 193. DR MINT; P60891; -. DR STRING; 9606.ENSP00000361512; -. DR BindingDB; P60891; -. DR ChEMBL; CHEMBL2638; -. DR DrugCentral; P60891; -. DR GlyGen; P60891; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P60891; -. DR PhosphoSitePlus; P60891; -. DR SwissPalm; P60891; -. DR BioMuta; PRPS1; -. DR DMDM; 46397477; -. DR EPD; P60891; -. DR jPOST; P60891; -. DR MassIVE; P60891; -. DR MaxQB; P60891; -. DR PaxDb; 9606-ENSP00000361512; -. DR PeptideAtlas; P60891; -. DR ProteomicsDB; 4706; -. DR ProteomicsDB; 57233; -. [P60891-1] DR Pumba; P60891; -. DR Antibodypedia; 29313; 196 antibodies from 29 providers. DR DNASU; 5631; -. DR Ensembl; ENST00000372435.10; ENSP00000361512.4; ENSG00000147224.13. [P60891-1] DR GeneID; 5631; -. DR KEGG; hsa:5631; -. DR MANE-Select; ENST00000372435.10; ENSP00000361512.4; NM_002764.4; NP_002755.1. DR UCSC; uc004ene.5; human. [P60891-1] DR AGR; HGNC:9462; -. DR CTD; 5631; -. DR DisGeNET; 5631; -. DR GeneCards; PRPS1; -. DR GeneReviews; PRPS1; -. DR HGNC; HGNC:9462; PRPS1. DR HPA; ENSG00000147224; Low tissue specificity. DR MalaCards; PRPS1; -. DR MIM; 300661; phenotype. DR MIM; 301835; phenotype. DR MIM; 304500; phenotype. DR MIM; 311070; phenotype. DR MIM; 311850; gene. DR neXtProt; NX_P60891; -. DR OpenTargets; ENSG00000147224; -. DR Orphanet; 1187; Lethal ataxia with deafness and optic atrophy. DR Orphanet; 411536; Mild phosphoribosylpyrophosphate synthetase superactivity. DR Orphanet; 90625; Rare X-linked non-syndromic sensorineural deafness type DFN. DR Orphanet; 411543; Severe phosphoribosylpyrophosphate synthetase superactivity. DR Orphanet; 99014; X-linked Charcot-Marie-Tooth disease type 5. DR Orphanet; 423479; X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome. DR PharmGKB; PA33817; -. DR VEuPathDB; HostDB:ENSG00000147224; -. DR eggNOG; KOG1448; Eukaryota. DR GeneTree; ENSGT00950000182803; -. DR HOGENOM; CLU_033546_4_0_1; -. DR InParanoid; P60891; -. DR OMA; FGWARQD; -. DR OrthoDB; 276387at2759; -. DR PhylomeDB; P60891; -. DR TreeFam; TF106366; -. DR BioCyc; MetaCyc:HS07410-MONOMER; -. DR BRENDA; 2.7.6.1; 2681. DR PathwayCommons; P60891; -. DR Reactome; R-HSA-73843; 5-Phosphoribose 1-diphosphate biosynthesis. DR SABIO-RK; P60891; -. DR SignaLink; P60891; -. DR SIGNOR; P60891; -. DR UniPathway; UPA00087; UER00172. DR BioGRID-ORCS; 5631; 20 hits in 779 CRISPR screens. DR ChiTaRS; PRPS1; human. DR EvolutionaryTrace; P60891; -. DR GenomeRNAi; 5631; -. DR Pharos; P60891; Tbio. DR PRO; PR:P60891; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P60891; Protein. DR Bgee; ENSG00000147224; Expressed in islet of Langerhans and 207 other cell types or tissues. DR ExpressionAtlas; P60891; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0002189; C:ribose phosphate diphosphokinase complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0004749; F:ribose phosphate diphosphokinase activity; IDA:UniProtKB. DR GO; GO:0006015; P:5-phosphoribose 1-diphosphate biosynthetic process; IBA:GO_Central. DR GO; GO:0046101; P:hypoxanthine biosynthetic process; IMP:UniProtKB. DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0006144; P:purine nucleobase metabolic process; IMP:UniProtKB. DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IMP:UniProtKB. DR GO; GO:0006221; P:pyrimidine nucleotide biosynthetic process; NAS:UniProtKB. DR GO; GO:0009156; P:ribonucleoside monophosphate biosynthetic process; IEA:InterPro. DR GO; GO:0034418; P:urate biosynthetic process; IMP:UniProtKB. DR CDD; cd06223; PRTases_typeI; 1. DR Gene3D; 3.40.50.2020; -; 2. DR HAMAP; MF_00583_B; RibP_PPkinase_B; 1. DR InterPro; IPR000842; PRib_PP_synth_CS. DR InterPro; IPR029099; Pribosyltran_N. DR InterPro; IPR000836; PRibTrfase_dom. DR InterPro; IPR029057; PRTase-like. DR InterPro; IPR005946; Rib-P_diPkinase. DR InterPro; IPR037515; Rib-P_diPkinase_bac. DR NCBIfam; TIGR01251; ribP_PPkin; 1. DR PANTHER; PTHR10210:SF32; RIBOSE-PHOSPHATE DIPHOSPHOKINASE; 1. DR PANTHER; PTHR10210; RIBOSE-PHOSPHATE DIPHOSPHOKINASE FAMILY MEMBER; 1. DR Pfam; PF14572; Pribosyl_synth; 1. DR Pfam; PF13793; Pribosyltran_N; 1. DR SMART; SM01400; Pribosyltran_N; 1. DR SUPFAM; SSF53271; PRTase-like; 1. DR PROSITE; PS00114; PRPP_SYNTHASE; 1. DR UCD-2DPAGE; P60891; -. DR Genevisible; P60891; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; KW Charcot-Marie-Tooth disease; Deafness; Direct protein sequencing; KW Disease variant; Gout; Intellectual disability; Kinase; Magnesium; KW Metal-binding; Neurodegeneration; Neuropathy; Non-syndromic deafness; KW Nucleotide biosynthesis; Nucleotide-binding; Reference proteome; KW Retinitis pigmentosa; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8" FT CHAIN 2..318 FT /note="Ribose-phosphate pyrophosphokinase 1" FT /id="PRO_0000141071" FT REGION 212..227 FT /note="Binding of phosphoribosylpyrophosphate" FT /evidence="ECO:0000255" FT BINDING 96..101 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 128 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255" FT BINDING 130 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 130 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255" FT BINDING 139 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255" FT BINDING 143 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000255" FT VAR_SEQ 1..67 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056028" FT VARIANT 16 FT /note="S -> P (found in patients with phosphoribosyl FT pyrophosphate synthetase I deficiency; likely pathogenic; FT dbSNP:rs869025594)" FT /evidence="ECO:0000269|PubMed:25491489" FT /id="VAR_072719" FT VARIANT 43 FT /note="E -> D (in CMTX5; dbSNP:rs80338731)" FT /evidence="ECO:0000269|PubMed:17701900" FT /id="VAR_036941" FT VARIANT 52 FT /note="D -> H (in PRPS1 superactivity; no effect on Km; FT resistant to inhibition by ADP and GDP; dbSNP:rs137852542)" FT /evidence="ECO:0000269|PubMed:7593598" FT /id="VAR_016044" FT VARIANT 65 FT /note="D -> N (in DFNX1; dbSNP:rs180177151)" FT /evidence="ECO:0000269|PubMed:20021999" FT /id="VAR_063522" FT VARIANT 87 FT /note="A -> T (in DFNX1; dbSNP:rs180177152)" FT /evidence="ECO:0000269|PubMed:20021999" FT /id="VAR_063523" FT VARIANT 114 FT /note="N -> S (in PRPS1 superactivity; no effect on Km; FT resistant to inhibition by ADP and GDP; dbSNP:rs137852540)" FT /evidence="ECO:0000269|PubMed:7593598, ECO:0000269|Ref.12" FT /id="VAR_004163" FT VARIANT 115 FT /note="M -> T (in CMTX5; dbSNP:rs80338732)" FT /evidence="ECO:0000269|PubMed:17701900" FT /id="VAR_036942" FT VARIANT 129 FT /note="L -> I (in PRPS1 superactivity; no effect on Km; FT resistant to inhibition by ADP and GDP; dbSNP:rs137852543)" FT /evidence="ECO:0000269|PubMed:7593598" FT /id="VAR_016045" FT VARIANT 133 FT /note="Q -> P (in ARTS; dbSNP:rs80338675)" FT /evidence="ECO:0000269|PubMed:17701896" FT /id="VAR_036943" FT VARIANT 142 FT /note="V -> L (found in a patient with an intermediate FT phenotype between ARTS and PRPS1 superactivity; likely FT pathogenic; normal PRPP synthetase activity in fibroblasts; FT loss of activity in erythrocytes; dbSNP:rs398122855)" FT /evidence="ECO:0000269|PubMed:22246954" FT /id="VAR_078489" FT VARIANT 152 FT /note="L -> P (in ARTS; dbSNP:rs80338676)" FT /evidence="ECO:0000269|PubMed:17701896" FT /id="VAR_036944" FT VARIANT 183 FT /note="D -> H (in PRPS1 superactivity; no effect on Km; FT resistant to inhibition by ADP and GDP; dbSNP:rs137852541)" FT /evidence="ECO:0000269|PubMed:7593598, ECO:0000269|Ref.12" FT /id="VAR_004164" FT VARIANT 190 FT /note="A -> V (in PRPS1 superactivity; no effect on Km; FT resistant to inhibition by ADP and GDP; dbSNP:rs137852544)" FT /evidence="ECO:0000269|PubMed:7593598" FT /id="VAR_016046" FT VARIANT 193 FT /note="H -> Q (in PRPS1 superactivity; no effect on Km; FT resistant to inhibition by ADP and GDP; dbSNP:rs137852545)" FT /evidence="ECO:0000269|PubMed:7593598" FT /id="VAR_016047" FT VARIANT 203 FT /note="D -> H (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036593" FT VARIANT 219 FT /note="V -> G (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036594" FT VARIANT 231 FT /note="H -> D (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036595" FT VARIANT 290 FT /note="I -> T (in DFNX1; dbSNP:rs180177153)" FT /evidence="ECO:0000269|PubMed:20021999" FT /id="VAR_063524" FT VARIANT 306 FT /note="G -> R (in DFNX1; dbSNP:rs180177154)" FT /evidence="ECO:0000269|PubMed:20021999" FT /id="VAR_063525" FT MUTAGEN 132 FT /note="S->A: Reduces catalytic activity." FT /evidence="ECO:0000269|PubMed:16939420" FT MUTAGEN 132 FT /note="S->F: No effect on catalytic activity." FT /evidence="ECO:0000269|PubMed:16939420" FT MUTAGEN 144 FT /note="N->H: No effect on catalytic activity." FT /evidence="ECO:0000269|PubMed:16939420" FT MUTAGEN 146 FT /note="Y->F: No effect on catalytic activity." FT /evidence="ECO:0000269|PubMed:16939420" FT MUTAGEN 146 FT /note="Y->M: Reduces catalytic activity." FT /evidence="ECO:0000269|PubMed:16939420" FT CONFLICT 82 FT /note="A -> G (in Ref. 3; BAG35584)" FT /evidence="ECO:0000305" FT CONFLICT 122 FT /note="D -> G (in Ref. 3; BAG35584)" FT /evidence="ECO:0000305" FT CONFLICT 278 FT /note="E -> G (in Ref. 3; BAG35584)" FT /evidence="ECO:0000305" FT STRAND 4..8 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 13..22 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 30..34 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:2H06" FT STRAND 40..44 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 52..56 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 63..79 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 83..91 FT /evidence="ECO:0007829|PDB:8DBI" FT TURN 93..96 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 101..104 FT /evidence="ECO:0007829|PDB:8DBK" FT HELIX 108..119 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 122..128 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 132..137 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 142..145 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 148..158 FT /evidence="ECO:0007829|PDB:8DBI" FT TURN 160..164 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 166..171 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 172..174 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 175..185 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 191..194 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 199..201 FT /evidence="ECO:0007829|PDB:8DBE" FT STRAND 205..209 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 214..226 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 227..238 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 242..251 FT /evidence="ECO:0007829|PDB:8DBI" FT TURN 254..256 FT /evidence="ECO:0007829|PDB:4LYG" FT HELIX 257..263 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 267..272 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 278..283 FT /evidence="ECO:0007829|PDB:8DBI" FT STRAND 287..290 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 293..305 FT /evidence="ECO:0007829|PDB:8DBI" FT HELIX 310..313 FT /evidence="ECO:0007829|PDB:8DBI" SQ SEQUENCE 318 AA; 34834 MW; 46D017E969908BA0 CRC64; MPNIKIFSGS SHQDLSQKIA DRLGLELGKV VTKKFSNQET CVEIGESVRG EDVYIVQSGC GEINDNLMEL LIMINACKIA SASRVTAVIP CFPYARQDKK DKSRAPISAK LVANMLSVAG ADHIITMDLH ASQIQGFFDI PVDNLYAEPA VLKWIRENIS EWRNCTIVSP DAGGAKRVTS IADRLNVDFA LIHKERKKAN EVDRMVLVGD VKDRVAILVD DMADTCGTIC HAADKLLSAG ATRVYAILTH GIFSGPAISR INNACFEAVV VTNTIPQEDK MKHCSKIQVI DISMILAEAI RRTHNGESVS YLFSHVPL //