ID PRPS1_HUMAN Reviewed; 318 AA. AC P60891; P09329; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 23-OCT-2007, entry version 42. DE Ribose-phosphate pyrophosphokinase 1 (EC 2.7.6.1) (Phosphoribosyl DE pyrophosphate synthetase I) (PRS-I) (PPRibP). GN Name=PRPS1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Lymphoblast; RX MEDLINE=90174926; 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]. RX MEDLINE=91324322; 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 RT PRPS gene families."; RL J. Biochem. 109:361-364(1991). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-41. RX MEDLINE=92223087; 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 RT PRPS2 encoding phosphoribosylpyrophosphate synthetase subunit I and II RT isoforms."; RL Biochim. Biophys. Acta 1130:139-148(1992). RN [5] RP PROTEIN SEQUENCE OF 244-260 AND 303-318, AND MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Vishwanath V.; RL Submitted (MAR-2007) to UniProtKB. RN [6] RP VARIANTS PRPS-RELATED GOUT 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- RT linked phosphoribosylpyrophosphate synthetase superactivity."; RL Clin. Res. 39:267A-267A(1991). RN [7] RP VARIANTS PRPS-RELATED GOUT HIS-52; SER-114; ILE-129; HIS-183; VAL-190 RP AND GLN-193. RX MEDLINE=96066677; PubMed=7593598; RA Becker M.A., Smith P.R., Taylor W., Mustafi R., Switzer R.L.; RT "The genetic and functional basis of purine nucleotide feedback- RT resistant phosphoribosylpyrophosphate synthetase superactivity."; RL J. Clin. Invest. 96:2133-2141(1995). RN [8] 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., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- CATALYTIC ACTIVITY: ATP + D-ribose 5-phosphate = AMP + 5-phospho- CC alpha-D-ribose 1-diphosphate. CC -!- COFACTOR: Magnesium. CC -!- ENZYME REGULATION: Activated by magnesium and inorganic phosphate. CC -!- PATHWAY: Metabolic intermediate biosynthesis; 5-phospho-alpha-D- CC ribose 1-diphosphate biosynthesis; 5-phospho-alpha-D-ribose 1- CC diphosphate from D-ribose 5-phosphate (route I): step 1/1. CC -!- DISEASE: Defects in PRPS1 are the cause of PRPS-related gout CC [MIM:311850]; also known as gout due to PRPS1 superactivity. It is CC a familial disorder characterized by excessive purine production, CC gout and uric acid urolithiasis. CC -!- SIMILARITY: Belongs to the ribose-phosphate pyrophosphokinase CC family. 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; BC001605; AAH01605.1; -; mRNA. DR PIR; JX0159; KIHUR1. DR RefSeq; NP_002755.1; -. DR UniGene; Hs.56; -. DR PDB; 2H07; X-ray; A/B=1-318. DR PDB; 2H08; X-ray; A/B=1-318. DR SMR; P60891; 3-317. DR REPRODUCTION-2DPAGE; P60891; HUMAN. DR Ensembl; ENSG00000147224; Homo sapiens. DR KEGG; hsa:5631; -. DR H-InvDB; HIX0016976; -. DR HGNC; HGNC:9462; PRPS1. DR MIM; 311850; gene+phenotype. DR Orphanet; 3222; Phosphoribosylpyrophosphate synthetase superactivity. DR PharmGKB; PA33817; -. DR Reactome; REACT_1698; Nucleotide metabolism. DR LinkHub; P60891; -. DR ArrayExpress; P60891; -. DR GermOnline; ENSG00000147224; Homo sapiens. DR GO; GO:0004749; F:ribose phosphate diphosphokinase activity; TAS:ProtInc. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0006144; P:purine base metabolic process; TAS:ProtInc. DR InterPro; IPR000842; PRPP_synthetase. DR InterPro; IPR000836; PRtransferase. DR InterPro; IPR005946; RibP_Ppkin. DR Pfam; PF00156; Pribosyltran; 1. DR TIGRFAMs; TIGR01251; ribP_PPkin; 1. DR PROSITE; PS00114; PRPP_SYNTHETASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disease mutation; Gout; KW Kinase; Magnesium; Metal-binding; Nucleotide biosynthesis; KW Polymorphism; Transferase. FT INIT_MET 1 1 Removed (By similarity). FT CHAIN 2 318 Ribose-phosphate pyrophosphokinase 1. FT /FTId=PRO_0000141071. FT REGION 212 227 Binding of phosphoribosylpyrophosphate FT (Potential). FT METAL 128 128 Magnesium (Potential). FT METAL 130 130 Magnesium (Potential). FT METAL 139 139 Magnesium (Potential). FT METAL 143 143 Magnesium (Potential). FT VARIANT 52 52 D -> H (in PRPS-related gout). FT /FTId=VAR_016044. FT VARIANT 114 114 N -> S (in PRPS-related gout). FT /FTId=VAR_004163. FT VARIANT 129 129 L -> I (in PRPS-related gout). FT /FTId=VAR_016045. FT VARIANT 183 183 D -> H (in PRPS-related gout). FT /FTId=VAR_004164. FT VARIANT 190 190 A -> V (in PRPS-related gout). FT /FTId=VAR_016046. FT VARIANT 193 193 H -> Q (in PRPS-related gout). FT /FTId=VAR_016047. FT VARIANT 203 203 D -> H (in a breast cancer sample; FT somatic mutation). FT /FTId=VAR_036593. FT VARIANT 219 219 V -> G (in a breast cancer sample; FT somatic mutation). FT /FTId=VAR_036594. FT VARIANT 231 231 H -> D (in a breast cancer sample; FT somatic mutation). FT /FTId=VAR_036595. 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 //