PRPS1_HUMAN
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 03-AUG-2022, entry version 187.
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; Q8N865: C7orf31; NbExp=3; IntAct=EBI-749195, EBI-10174456;
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; 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}.
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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 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 AlphaFoldDB; P60891; -.
DR SMR; P60891; -.
DR BioGRID; 111615; 170.
DR DIP; DIP-61999N; -.
DR IntAct; P60891; 188.
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 UCD-2DPAGE; P60891; -.
DR EPD; P60891; -.
DR jPOST; P60891; -.
DR MassIVE; P60891; -.
DR MaxQB; P60891; -.
DR PaxDb; P60891; -.
DR PeptideAtlas; P60891; -.
DR PRIDE; P60891; -.
DR ProteomicsDB; 4706; -.
DR ProteomicsDB; 57233; -. [P60891-1]
DR Antibodypedia; 29313; 186 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 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; 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 Orphanet; 90625; X-linked non-syndromic sensorineural deafness type DFN.
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; 1043963at2759; -.
DR PhylomeDB; P60891; -.
DR TreeFam; TF106366; -.
DR BioCyc; MetaCyc:HS07410-MON; -.
DR BRENDA; 2.7.6.1; 2681.
DR PathwayCommons; P60891; -.
DR Reactome; R-HSA-73843; 5-Phosphoribose 1-diphosphate biosynthesis.
DR SignaLink; P60891; -.
DR SIGNOR; P60891; -.
DR UniPathway; UPA00087; UER00172.
DR BioGRID-ORCS; 5631; 18 hits in 703 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 205 other tissues.
DR ExpressionAtlas; P60891; baseline and differential.
DR Genevisible; P60891; HS.
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 PANTHER; PTHR10210; PTHR10210; 1.
DR Pfam; PF14572; Pribosyl_synth; 1.
DR Pfam; PF13793; Pribosyltran_N; 1.
DR SUPFAM; SSF53271; SSF53271; 1.
DR TIGRFAMs; TIGR01251; ribP_PPkin; 1.
DR PROSITE; PS00114; PRPP_SYNTHASE; 1.
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 (probable disease-associated variant found in
FT patients with phosphoribosyl pyrophosphate synthetase I
FT deficiency; 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 (probable disease-associated variant found in
FT a patient with an intermediate phenotype between ARTS and
FT PRPS1 superactivity; normal PRPP synthetase activity in
FT fibroblasts; loss of activity in erythrocytes;
FT 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:3S5J"
FT HELIX 14..22
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:2H06"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 63..79
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 83..91
FT /evidence="ECO:0007829|PDB:3S5J"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:2H06"
FT HELIX 108..119
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 132..137
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 148..158
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 166..171
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 175..185
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 214..225
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 227..238
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 242..251
FT /evidence="ECO:0007829|PDB:3S5J"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:4LYG"
FT HELIX 257..263
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 278..282
FT /evidence="ECO:0007829|PDB:3S5J"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 293..305
FT /evidence="ECO:0007829|PDB:3S5J"
FT HELIX 310..313
FT /evidence="ECO:0007829|PDB:3S5J"
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
