ID   PRPS2_HUMAN             Reviewed;         318 AA.
AC   P11908; Q0VDH9; Q0VDI0; Q15245; Q2TAK7;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   27-MAR-2024, entry version 230.
DE   RecName: Full=Ribose-phosphate pyrophosphokinase 2;
DE            EC=2.7.6.1;
DE   AltName: Full=PPRibP;
DE   AltName: Full=Phosphoribosyl pyrophosphate synthase II;
DE            Short=PRS-II;
GN   Name=PRPS2;
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=Testis;
RX   PubMed=2538352; DOI=10.1016/0014-5793(89)81159-7;
RA   Iizasa T., Taira M., Shimada H., Ishijima S., Tatibana M.;
RT   "Molecular cloning and sequencing of human cDNA for phosphoribosyl
RT   pyrophosphate synthetase subunit II.";
RL   FEBS Lett. 244:47-50(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
RX   PubMed=2560337; DOI=10.1007/978-1-4684-5673-8_84;
RA   Iizasa T., Taira M., Shimada H., Tatibana M.;
RT   "Deduced amino acid sequence from human phosphoribosylpyrophosphate
RT   synthetase subunit II cDNA.";
RL   Adv. Exp. Med. Biol. 253A:519-523(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Testis, and Uterus;
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40.
RC   TISSUE=Leukocyte;
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   [5]
RP   PROTEIN SEQUENCE OF 2-29; 34-49; 85-96; 164-196; 205-214; 244-282 AND
RP   287-318, CLEAVAGE OF INITIATOR METHIONINE, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma, Mammary carcinoma, and Osteosarcoma;
RA   Bienvenut W.V., Calvo F., Bensaad K., Vousden K.H., Matallanas D.,
RA   Cooper W.N., Kolch W., Lourenco F., Olson M.F.;
RL   Submitted (DEC-2009) to UniProtKB.
RN   [6]
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).
CC   -!- FUNCTION: Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP)
CC       that is essential for nucleotide synthesis.
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   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- ACTIVITY REGULATION: Activated by magnesium and inorganic phosphate.
CC       Competitively or non-competitively inhibited by ADP, 2,3-
CC       bisphosphoglyceride or GDP.
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.
CC   -!- SUBUNIT: Homodimer. The active form is probably a hexamer composed of 3
CC       homodimers (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       P11908; P28799: GRN; NbExp=3; IntAct=EBI-4290895, EBI-747754;
CC       P11908; P04792: HSPB1; NbExp=3; IntAct=EBI-4290895, EBI-352682;
CC       P11908; O60333-2: KIF1B; NbExp=3; IntAct=EBI-4290895, EBI-10975473;
CC       P11908; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-4290895, EBI-945833;
CC       P11908; Q96HA8: NTAQ1; NbExp=4; IntAct=EBI-4290895, EBI-741158;
CC       P11908; P60891: PRPS1; NbExp=10; IntAct=EBI-4290895, EBI-749195;
CC       P11908; P11908: PRPS2; NbExp=4; IntAct=EBI-4290895, EBI-4290895;
CC       P11908; Q14558: PRPSAP1; NbExp=5; IntAct=EBI-4290895, EBI-724449;
CC       P11908; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-4290895, EBI-396669;
CC       P11908; P02766: TTR; NbExp=3; IntAct=EBI-4290895, EBI-711909;
CC       P11908; O76024: WFS1; NbExp=3; IntAct=EBI-4290895, EBI-720609;
CC       P11908-2; P60891: PRPS1; NbExp=4; IntAct=EBI-12063547, EBI-749195;
CC       P11908-2; Q14558: PRPSAP1; NbExp=3; IntAct=EBI-12063547, EBI-724449;
CC       P11908-2; O60256: PRPSAP2; NbExp=4; IntAct=EBI-12063547, EBI-724960;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P11908-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P11908-2; Sequence=VSP_027769;
CC   -!- SIMILARITY: Belongs to the ribose-phosphate pyrophosphokinase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH30019.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; Y00971; CAA68785.1; -; mRNA.
DR   EMBL; BC030019; AAH30019.2; ALT_INIT; mRNA.
DR   EMBL; BC040483; AAH40483.3; -; mRNA.
DR   EMBL; BC110875; AAI10876.2; -; mRNA.
DR   EMBL; BC119662; AAI19663.1; -; mRNA.
DR   EMBL; BC119663; AAI19664.1; -; mRNA.
DR   EMBL; D28134; BAA05676.1; -; Genomic_DNA.
DR   CCDS; CCDS14150.1; -. [P11908-1]
DR   CCDS; CCDS43918.1; -. [P11908-2]
DR   PIR; S02778; KIHUR2.
DR   RefSeq; NP_001034180.1; NM_001039091.2. [P11908-2]
DR   RefSeq; NP_002756.1; NM_002765.4. [P11908-1]
DR   PDB; 7YK1; EM; 3.08 A; A/B/C/D/E/F=1-318.
DR   PDBsum; 7YK1; -.
DR   AlphaFoldDB; P11908; -.
DR   EMDB; EMD-33883; -.
DR   SMR; P11908; -.
DR   BioGRID; 111617; 236.
DR   IntAct; P11908; 51.
DR   MINT; P11908; -.
DR   STRING; 9606.ENSP00000381504; -.
DR   GlyGen; P11908; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P11908; -.
DR   MetOSite; P11908; -.
DR   PhosphoSitePlus; P11908; -.
DR   SwissPalm; P11908; -.
DR   BioMuta; PRPS2; -.
DR   DMDM; 125583; -.
DR   REPRODUCTION-2DPAGE; IPI00219617; -.
DR   REPRODUCTION-2DPAGE; P11908; -.
DR   EPD; P11908; -.
DR   jPOST; P11908; -.
DR   MassIVE; P11908; -.
DR   MaxQB; P11908; -.
DR   PaxDb; 9606-ENSP00000381504; -.
DR   PeptideAtlas; P11908; -.
DR   ProteomicsDB; 52809; -. [P11908-1]
DR   ProteomicsDB; 52810; -. [P11908-2]
DR   Pumba; P11908; -.
DR   Antibodypedia; 8471; 265 antibodies from 29 providers.
DR   DNASU; 5634; -.
DR   Ensembl; ENST00000380668.10; ENSP00000370043.5; ENSG00000101911.13. [P11908-1]
DR   Ensembl; ENST00000398491.6; ENSP00000381504.2; ENSG00000101911.13. [P11908-2]
DR   GeneID; 5634; -.
DR   KEGG; hsa:5634; -.
DR   MANE-Select; ENST00000380668.10; ENSP00000370043.5; NM_002765.5; NP_002756.1.
DR   UCSC; uc004cva.4; human. [P11908-1]
DR   AGR; HGNC:9465; -.
DR   CTD; 5634; -.
DR   DisGeNET; 5634; -.
DR   GeneCards; PRPS2; -.
DR   HGNC; HGNC:9465; PRPS2.
DR   HPA; ENSG00000101911; Tissue enhanced (ovary, parathyroid gland).
DR   MIM; 311860; gene.
DR   neXtProt; NX_P11908; -.
DR   OpenTargets; ENSG00000101911; -.
DR   PharmGKB; PA33820; -.
DR   VEuPathDB; HostDB:ENSG00000101911; -.
DR   eggNOG; KOG1448; Eukaryota.
DR   GeneTree; ENSGT00950000182803; -.
DR   HOGENOM; CLU_033546_4_0_1; -.
DR   InParanoid; P11908; -.
DR   OMA; AHEFARY; -.
DR   OrthoDB; 276387at2759; -.
DR   PhylomeDB; P11908; -.
DR   TreeFam; TF106366; -.
DR   BioCyc; MetaCyc:HS02317-MONOMER; -.
DR   PathwayCommons; P11908; -.
DR   Reactome; R-HSA-73843; 5-Phosphoribose 1-diphosphate biosynthesis.
DR   SignaLink; P11908; -.
DR   SIGNOR; P11908; -.
DR   UniPathway; UPA00087; UER00172.
DR   BioGRID-ORCS; 5634; 22 hits in 779 CRISPR screens.
DR   ChiTaRS; PRPS2; human.
DR   GenomeRNAi; 5634; -.
DR   Pharos; P11908; Tbio.
DR   PRO; PR:P11908; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; P11908; Protein.
DR   Bgee; ENSG00000101911; Expressed in seminal vesicle and 201 other cell types or tissues.
DR   ExpressionAtlas; P11908; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0002189; C:ribose phosphate diphosphokinase complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; ISS: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; ISS:UniProtKB.
DR   GO; GO:0004749; F:ribose phosphate diphosphokinase activity; ISS:UniProtKB.
DR   GO; GO:0006015; P:5-phosphoribose 1-diphosphate biosynthetic process; IBA:GO_Central.
DR   GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR   GO; GO:0006098; P:pentose-phosphate shunt; IEA:Ensembl.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IBA:GO_Central.
DR   GO; GO:0009156; P:ribonucleoside monophosphate biosynthetic process; IEA:InterPro.
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; RIBOSE-PHOSPHATE DIPHOSPHOKINASE FAMILY MEMBER; 1.
DR   PANTHER; PTHR10210:SF110; RIBOSE-PHOSPHATE PYROPHOSPHOKINASE 2; 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   Genevisible; P11908; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Direct protein sequencing;
KW   Kinase; Magnesium; Metal-binding; Nucleotide biosynthesis;
KW   Nucleotide-binding; Reference proteome; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|Ref.5"
FT   CHAIN           2..318
FT                   /note="Ribose-phosphate pyrophosphokinase 2"
FT                   /id="PRO_0000141074"
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                   /evidence="ECO:0000250"
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                   /evidence="ECO:0000250"
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         102
FT                   /note="K -> KVGE (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_027769"
FT   STRAND          4..8
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           13..23
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          30..34
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          40..44
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          52..56
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           63..79
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          83..91
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   TURN            93..96
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          102..104
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           108..119
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          123..128
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           132..137
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          142..145
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           148..158
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           162..164
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          166..168
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          170..172
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           175..183
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          191..193
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          206..209
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          216..219
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          221..225
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           228..238
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          244..247
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          249..251
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   TURN            255..257
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           258..262
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          266..272
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   TURN            278..282
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   STRAND          287..290
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           293..305
FT                   /evidence="ECO:0007829|PDB:7YK1"
FT   HELIX           309..314
FT                   /evidence="ECO:0007829|PDB:7YK1"
SQ   SEQUENCE   318 AA;  34769 MW;  72A2873408250C31 CRC64;
     MPNIVLFSGS SHQDLSQRVA DRLGLELGKV VTKKFSNQET SVEIGESVRG EDVYIIQSGC
     GEINDNLMEL LIMINACKIA SSSRVTAVIP CFPYARQDKK DKSRAPISAK LVANMLSVAG
     ADHIITMDLH ASQIQGFFDI PVDNLYAEPA VLQWIRENIA EWKNCIIVSP DAGGAKRVTS
     IADRLNVEFA LIHKERKKAN EVDRMVLVGD VKDRVAILVD DMADTCGTIC HAADKLLSAG
     ATKVYAILTH GIFSGPAISR INNAAFEAVV VTNTIPQEDK MKHCTKIQVI DISMILAEAI
     RRTHNGESVS YLFSHVPL
//