ID PRUN1_HUMAN Reviewed; 453 AA. AC Q86TP1; B2RCH8; B4DFL7; Q5SZF9; Q659E5; Q6P4E0; Q8N654; Q96JU5; Q9C071; AC Q9C072; Q9UIV0; DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 02-SEP-2026, entry version 167. DE RecName: Full=Exopolyphosphatase PRUNE1; DE EC=3.6.1.14 {ECO:0000269|PubMed:18700747}; DE EC=3.6.1.25 {ECO:0000269|PubMed:18700747}; DE AltName: Full=Drosophila-related expressed sequence 17; DE Short=DRES-17; DE Short=DRES17; DE AltName: Full=HTcD37; DE AltName: Full=Protein prune homolog 1; DE Short=hPrune {ECO:0000303|PubMed:14998490}; GN Name=PRUNE1 {ECO:0000312|HGNC:HGNC:13420}; Synonyms=PRUNE; 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), TISSUE SPECIFICITY, INTERACTION RP WITH NME1, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=10602478; DOI=10.1038/sj.onc.1203140; RA Reymond A., Volorio S., Merla G., Al-Maghtheh M., Zuffardi O., Bulfone A., RA Ballabio A., Zollo M.; RT "Evidence for interaction between human PRUNE and nm23-H1 NDPKinase."; RL Oncogene 18:7244-7252(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4). RA Zollo M., Volorio S.; RT "Human Prune homolog."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 5 AND 7), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 211-453 (ISOFORMS 1/3). RC TISSUE=Brain cortex, Kidney, and Thyroid; 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=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). 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] (ISOFORMS 1; 3 AND 6). RC TISSUE=Blood, and Brain; 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 19-453 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10524757; DOI=10.3109/10425179809008469; RA Volorio S., Simon G., Repetto M., Cucciardi M., Banfi S., Borsani G., RA Ballabio A., Zollo M.; RT "Sequencing analysis of forty-eight human image cDNA clones similar to RT Drosophila mutant protein."; RL DNA Seq. 9:307-315(1998). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 368-453 (ISOFORMS 1/2/3/4/5/6/7). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=11687967; DOI=10.1038/sj.onc.1204874; RA Forus A., D'Angelo A., Henriksen J., Merla G., Maelandsmo G.M., RA Floerenes V.A., Olivieri S., Bjerkehagen B., Meza-Zepeda L.A., RA del Vecchio Blanco F., Mueller C., Sanvito F., Kononen J., Nesland J.M., RA Fodstad O., Reymond A., Kallioniemi O.-P., Arrigoni G., Ballabio A., RA Myklebost O., Zollo M.; RT "Amplification and overexpression of PRUNE in human sarcomas and breast RT carcinomas-a possible mechanism for altering the nm23-H1 activity."; RL Oncogene 20:6881-6890(2001). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION RP WITH NME1, ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-28; ASP-106; RP 126-ASP--PRO-129 AND ASP-179. RX PubMed=14998490; DOI=10.1016/s1535-6108(04)00021-2; RA D'Angelo A., Garzia L., Andre A., Carotenuto P., Aglio V., Guardiola O., RA Arrigoni G., Cossu A., Palmieri G., Aravind L., Zollo M.; RT "Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer RT metastasis."; RL Cancer Cell 5:137-149(2004). RN [11] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=15671547; DOI=10.1158/1078-0432.199.11.1; RA Zollo M., Andre A., Cossu A., Sini M.C., D'Angelo A., Marino N., RA Budroni M., Tanda F., Arrigoni G., Palmieri G.; RT "Overexpression of h-prune in breast cancer is correlated with advanced RT disease status."; RL Clin. Cancer Res. 11:199-205(2005). RN [12] RP INTERACTION WITH GSK3B, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=16428445; DOI=10.1128/mcb.26.3.898-911.2006; RA Kobayashi T., Hino S., Oue N., Asahara T., Zollo M., Yasui W., Kikuchi A.; RT "Glycogen synthase kinase 3 and h-prune regulate cell migration by RT modulating focal adhesions."; RL Mol. Cell. Biol. 26:898-911(2006). RN [13] RP FUNCTION, INTERACTION WITH NME1, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, AND SUBUNIT. RX PubMed=17655525; DOI=10.1042/bj20070408; RA Middelhaufe S., Garzia L., Ohndorf U.M., Kachholz B., Zollo M., RA Steegborn C.; RT "Domain mapping on the human metastasis regulator protein h-Prune reveals a RT C-terminal dimerization domain."; RL Biochem. J. 407:199-205(2007). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF ASN-24; ASP-28; ASP-106; HIS-107; HIS-108; ARG-128; ASP-179 RP AND ARG-348. RX PubMed=18700747; DOI=10.1021/bi8010847; RA Tammenkoski M., Koivula K., Cusanelli E., Zollo M., Steegborn C., RA Baykov A.A., Lahti R.; RT "Human metastasis regulator protein H-prune is a short-chain RT exopolyphosphatase."; RL Biochemistry 47:9707-9713(2008). RN [15] RP INTERACTION WITH NME1, AND FUNCTION. RX PubMed=17906697; DOI=10.1038/sj.onc.1210822; RA Garzia L., D'Angelo A., Amoresano A., Knauer S.K., Cirulli C., RA Campanella C., Stauber R.H., Steegborn C., Iolascon A., Zollo M.; RT "Phosphorylation of nm23-H1 by CKI induces its complex formation with h- RT prune and promotes cell motility."; RL Oncogene 27:1853-1864(2008). RN [16] 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 [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [18] RP ACETYLATION AT MET-1. RX PubMed=37316325; DOI=10.26508/lsa.202301972; RA Bogaert A., Fijalkowska D., Staes A., Van de Steene T., Vuylsteke M., RA Stadler C., Eyckerman S., Spirohn K., Hao T., Calderwood M.A., Gevaert K.; RT "N-terminal proteoforms may engage in different protein complexes."; RL Life. Sci Alliance 6:0-0(2023). RN [19] RP INVOLVEMENT IN NMIHBA. RX PubMed=28211990; DOI=10.1002/ajmg.a.38066; RA Costain G., Shugar A., Krishnan P., Mahmutoglu S., Laughlin S., Kannu P.; RT "Homozygous mutation in PRUNE1 in an Oji-Cree male with a complex RT neurological phenotype."; RL Am. J. Med. Genet. A 173:740-743(2017). RN [20] RP FUNCTION, INTERACTION WITH TUBULIN, INVOLVEMENT IN NMIHBA, VARIANTS NMIHBA RP ASN-30; THR-54; ASN-106 AND TRP-297, AND CHARACTERIZATION OF VARIANTS RP NMIHBA ASN-30 AND TRP-297. RX PubMed=28334956; DOI=10.1093/brain/awx014; RA Zollo M., Ahmed M., Ferrucci V., Salpietro V., Asadzadeh F., Carotenuto M., RA Maroofian R., Al-Amri A., Singh R., Scognamiglio I., Mojarrad M., RA Musella L., Duilio A., Di Somma A., Karaca E., Rajab A., Al-Khayat A., RA Mohan Mohapatra T., Eslahi A., Ashrafzadeh F., Rawlins L.E., Prasad R., RA Gupta R., Kumari P., Srivastava M., Cozzolino F., Kumar Rai S., Monti M., RA Harlalka G.V., Simpson M.A., Rich P., Al-Salmi F., Patton M.A., RA Chioza B.A., Efthymiou S., Granata F., Di Rosa G., Wiethoff S., RA Borgione E., Scuderi C., Mankad K., Hanna M.G., Pucci P., Houlden H., RA Lupski J.R., Crosby A.H., Baple E.L.; RT "PRUNE is crucial for normal brain development and mutated in microcephaly RT with neurodevelopmental impairment."; RL Brain 140:940-952(2017). RN [21] RP VARIANTS NMIHBA ASN-30; ASN-106; GLN-128 AND 174-GLY--LYS-453 DEL. RX PubMed=26539891; DOI=10.1016/j.neuron.2015.09.048; RA Karaca E., Harel T., Pehlivan D., Jhangiani S.N., Gambin T., RA Coban Akdemir Z., Gonzaga-Jauregui C., Erdin S., Bayram Y., Campbell I.M., RA Hunter J.V., Atik M.M., Van Esch H., Yuan B., Wiszniewski W., Isikay S., RA Yesil G., Yuregir O.O., Tug Bozdogan S., Aslan H., Aydin H., Tos T., RA Aksoy A., De Vivo D.C., Jain P., Geckinli B.B., Sezer O., Gul D., RA Durmaz B., Cogulu O., Ozkinay F., Topcu V., Candan S., Cebi A.H., Ikbal M., RA Yilmaz Gulec E., Gezdirici A., Koparir E., Ekici F., Coskun S., Cicek S., RA Karaer K., Koparir A., Duz M.B., Kirat E., Fenercioglu E., Ulucan H., RA Seven M., Guran T., Elcioglu N., Yildirim M.S., Aktas D., Alikasifoglu M., RA Ture M., Yakut T., Overton J.D., Yuksel A., Ozen M., Muzny D.M., RA Adams D.R., Boerwinkle E., Chung W.K., Gibbs R.A., Lupski J.R.; RT "Genes that affect brain structure and function identified by rare variant RT analyses of mendelian neurologic disease."; RL Neuron 88:499-513(2015). CC -!- FUNCTION: Exopolyphosphatase that catalyzes the hydrolysis of inorganic CC polyphosphates, with preference for short-chain substrates, as well as CC nucleoside 5'-tetraphosphates, releasing terminal phosphate residues CC (PubMed:18700747). Also exhibits phosphodiesterase activity toward CC cyclic nucleotides, hydrolyzing cAMP and cGMP to their corresponding CC 5'-monophosphates (PubMed:14998490, PubMed:17655525). Requires divalent CC metal ions for activity (PubMed:14998490, PubMed:18700747). Plays a CC role in cell proliferation, migration and differentiation, and acts as CC a negative regulator of NME1 (PubMed:10602478, PubMed:11687967, CC PubMed:14998490, PubMed:16428445, PubMed:17906697). Plays a role in the CC regulation of neurogenesis. Involved in the regulation of microtubule CC polymerization (PubMed:28334956). {ECO:0000269|PubMed:10602478, CC ECO:0000269|PubMed:11687967, ECO:0000269|PubMed:14998490, CC ECO:0000269|PubMed:16428445, ECO:0000269|PubMed:17655525, CC ECO:0000269|PubMed:17906697, ECO:0000269|PubMed:18700747, CC ECO:0000269|PubMed:28334956}. CC -!- CATALYTIC ACTIVITY: CC Reaction=triphosphate + H2O = phosphate + diphosphate; CC Xref=Rhea:RHEA:14157, ChEBI:CHEBI:15377, ChEBI:CHEBI:18036, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:43474; EC=3.6.1.25; CC Evidence={ECO:0000269|PubMed:18700747}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14158; CC Evidence={ECO:0000305|PubMed:18700747}; CC -!- CATALYTIC ACTIVITY: CC Reaction=adenosine 5'-tetraphosphate + H2O = phosphate + ATP + H(+); CC Xref=Rhea:RHEA:24500, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:58450; EC=3.6.1.14; CC Evidence={ECO:0000269|PubMed:18700747}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24501; CC Evidence={ECO:0000305|PubMed:18700747}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165, CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:14998490, CC ECO:0000269|PubMed:17655525}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278; CC Evidence={ECO:0000305|PubMed:14998490, ECO:0000305|PubMed:17655525}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3',5'-cyclic GMP + H2O = GMP + H(+); Xref=Rhea:RHEA:16957, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57746, CC ChEBI:CHEBI:58115; Evidence={ECO:0000269|PubMed:14998490}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16958; CC Evidence={ECO:0000305|PubMed:14998490}; CC -!- COFACTOR: CC Name=Co(2+); Xref=ChEBI:CHEBI:48828; CC Evidence={ECO:0000269|PubMed:18700747}; CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:14998490, ECO:0000269|PubMed:18700747}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC Note=Binds 2 manganese ions per subunit. {ECO:0000250}; CC -!- ACTIVITY REGULATION: Phosphodiesterase activity is activated by CC magnesium ions and inhibited by manganese ions. Phosphodiesterase CC activity is inhibited by dipyridamole, moderately sensitive to IBMX and CC inhibited by vinpocetine. {ECO:0000269|PubMed:14998490}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.91 uM for cAMP {ECO:0000269|PubMed:14998490}; CC KM=1.4 uM for cAMP {ECO:0000269|PubMed:17655525}; CC KM=2.3 uM for cGMP {ECO:0000269|PubMed:14998490}; CC KM=2.2 uM for triphosphate with Mg(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=6.6 uM for triphosphate with Co(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=19 uM for tetraphosphate with Mg(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=41 uM for tetraphosphate with Co(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=28 uM for adenosine 5'-tetraphosphate with Mg(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=37 uM for adenosine 5'-tetraphosphate with Co(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=41 uM for guanosine 5'-tetraphosphate with Mg(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=99 uM for guanosine 5'-tetraphosphate with Co(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=6.9 uM for P25 polyphosphate with Mg(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=2.2 uM for P45 polyphosphate with Mg(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC KM=0.7 uM for P65 polyphosphate with Mg(2+) as cofactor CC {ECO:0000269|PubMed:18700747}; CC Vmax=12.8 pmol/min/ug enzyme with cAMP as substrate CC {ECO:0000269|PubMed:14998490}; CC Vmax=19 pmol/min/ug enzyme with cAMP as substrate CC {ECO:0000269|PubMed:17655525}; CC Vmax=0.8 pmol/min/ug enzyme with cGMP as substrate CC {ECO:0000269|PubMed:14998490}; CC Note=kcat is 13 sec(-1) with triphosphate as substrate and Mg(2+) as CC cofactor. kcat is 35 sec(-1) with triphosphate as substrate and CC Co(2+) as cofactor. kcat is 3.4 sec(-1) with tetraphosphate as CC substrate and Mg(2+) as cofactor. kcat is 7.1 sec(-1) with CC tetraphosphate as substrate and Co(2+) as cofactor. kcat is 39 CC sec(-1) with adenosine 5'-tetraphosphate as substrate and Mg(2+) as CC cofactor. kcat is 31 sec(-1) with adenosine 5'-tetraphosphate as CC substrate and Co(2+) as cofactor. kcat is 27 sec(-1) with guanosine CC 5'-tetraphosphate as substrate and Mg(2+) as cofactor. kcat is 24 CC sec(-1) with guanosine 5'-tetraphosphate as substrate and Co(2+) as CC cofactor. kcat is 0.16 sec(-1) with P25 polyphosphate as substrate CC and Mg(2+) as cofactor. kcat is 0.22 sec(-1) with P45 polyphosphate CC as substrate and Mg(2+) as cofactor. kcat is 0.03 sec(-1) with P65 CC polyphosphate as substrate and Mg(2+) as cofactor. CC {ECO:0000269|PubMed:18700747}; CC -!- SUBUNIT: Homooligomer. Able to homodimerize via its C-terminal domain. CC Interacts with NME1. Interacts with GSK3; at focal adhesion complexes CC where paxillin and vinculin are colocalized. Interacts with alpha and CC beta tubulin (PubMed:28334956). {ECO:0000269|PubMed:10602478, CC ECO:0000269|PubMed:14998490, ECO:0000269|PubMed:16428445, CC ECO:0000269|PubMed:17655525, ECO:0000269|PubMed:17906697, CC ECO:0000269|PubMed:28334956}. CC -!- INTERACTION: CC Q86TP1; Q5JRM2: CXorf66; NbExp=2; IntAct=EBI-2127112, EBI-12823659; CC Q86TP1; P15531: NME1; NbExp=2; IntAct=EBI-2127112, EBI-741141; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell junction, focal CC adhesion. Note=In some transfected cells a nuclear staining is also CC observed. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; CC IsoId=Q86TP1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86TP1-2; Sequence=VSP_034016; CC Name=3; CC IsoId=Q86TP1-3; Sequence=VSP_034014; CC Name=4; CC IsoId=Q86TP1-4; Sequence=VSP_034015, VSP_034017; CC Name=5; CC IsoId=Q86TP1-5; Sequence=VSP_034014, VSP_034017; CC Name=6; CC IsoId=Q86TP1-6; Sequence=VSP_034013, VSP_034017; CC Name=7; CC IsoId=Q86TP1-7; Sequence=VSP_034013; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Seems to be overexpressed CC in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant CC fibrous histiocytomas (MFH) as well as in the less malignant CC liposarcomas. {ECO:0000269|PubMed:10602478, CC ECO:0000269|PubMed:11687967, ECO:0000269|PubMed:15671547}. CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, hypotonia, and CC variable brain anomalies (NMIHBA) [MIM:617481]: An autosomal recessive CC neurodevelopmental and degenerative disorder characterized by primary CC microcephaly, profound global developmental delay, and severe CC intellectual disability. Additional clinical features include CC dysmorphic features, truncal hypotonia, peripheral spasticity, and lack CC of independent ambulation or speech acquisition. Brain imaging shows CC cortical atrophy, thin corpus callosum, cerebellar hypoplasia, and CC delayed myelination. {ECO:0000269|PubMed:26539891, CC ECO:0000269|PubMed:28211990, ECO:0000269|PubMed:28334956}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the PPase class C family. Prune subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB55423.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAG60534.1; Type=Erroneous initiation; Evidence={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; AF051907; AAC95290.1; -; mRNA. DR EMBL; AF123538; AAK00592.1; -; mRNA. DR EMBL; AF123539; AAK00593.1; -; mRNA. DR EMBL; AK027875; BAB55423.1; ALT_INIT; mRNA. DR EMBL; AK294154; BAG57478.1; -; mRNA. DR EMBL; AK298273; BAG60534.1; ALT_INIT; mRNA. DR EMBL; AK315120; BAG37575.1; -; mRNA. DR EMBL; AL590133; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW53486.1; -; Genomic_DNA. DR EMBL; CH471121; EAW53488.1; -; Genomic_DNA. DR EMBL; CH471121; EAW53489.1; -; Genomic_DNA. DR EMBL; BC014886; AAH14886.1; -; mRNA. DR EMBL; BC025304; AAH25304.1; -; mRNA. DR EMBL; BC063481; AAH63481.1; -; mRNA. DR EMBL; U67085; AAF04914.1; -; mRNA. DR EMBL; AL122054; CAH56396.1; -; mRNA. DR CCDS; CCDS76211.1; -. [Q86TP1-3] DR CCDS; CCDS977.1; -. [Q86TP1-1] DR RefSeq; NP_001290158.1; NM_001303229.2. [Q86TP1-3] DR RefSeq; NP_001290171.1; NM_001303242.2. DR RefSeq; NP_001290172.1; NM_001303243.2. DR RefSeq; NP_067045.1; NM_021222.3. [Q86TP1-1] DR RefSeq; XP_011508134.1; XM_011509832.3. [Q86TP1-3] DR RefSeq; XP_047282563.1; XM_047426607.1. [Q86TP1-3] DR RefSeq; XP_054193971.1; XM_054337996.1. [Q86TP1-3] DR RefSeq; XP_054193972.1; XM_054337997.1. [Q86TP1-3] DR AlphaFoldDB; Q86TP1; -. DR BMRB; Q86TP1; -. DR SMR; Q86TP1; -. DR BioGRID; 121827; 38. DR CORUM; Q86TP1; -. DR FunCoup; Q86TP1; 1272. DR IntAct; Q86TP1; 114. DR STRING; 9606.ENSP00000271620; -. DR BindingDB; Q86TP1; -. DR ChEMBL; CHEMBL2079850; -. DR DrugCentral; Q86TP1; -. DR GlyGen; Q86TP1; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q86TP1; -. DR PhosphoSitePlus; Q86TP1; -. DR BioMuta; PRUNE1; -. DR DMDM; 229462737; -. DR jPOST; Q86TP1; -. DR MassIVE; Q86TP1; -. DR PaxDb; 9606-ENSP00000271620; -. DR PeptideAtlas; Q86TP1; -. DR ProteomicsDB; 69719; -. [Q86TP1-1] DR ProteomicsDB; 69720; -. [Q86TP1-2] DR ProteomicsDB; 69721; -. [Q86TP1-3] DR ProteomicsDB; 69722; -. [Q86TP1-4] DR ProteomicsDB; 69723; -. [Q86TP1-5] DR ProteomicsDB; 69724; -. [Q86TP1-6] DR ProteomicsDB; 69725; -. [Q86TP1-7] DR Pumba; Q86TP1; -. DR Antibodypedia; 34044; 208 antibodies from 29 providers. DR DNASU; 58497; -. DR Ensembl; ENST00000271620.8; ENSP00000271620.3; ENSG00000143363.18. [Q86TP1-1] DR Ensembl; ENST00000368934.1; ENSP00000357930.1; ENSG00000143363.18. [Q86TP1-5] DR Ensembl; ENST00000368935.1; ENSP00000357931.1; ENSG00000143363.18. [Q86TP1-6] DR Ensembl; ENST00000368936.5; ENSP00000357932.1; ENSG00000143363.18. [Q86TP1-3] DR Ensembl; ENST00000368937.5; ENSP00000357933.1; ENSG00000143363.18. [Q86TP1-5] DR GeneID; 58497; -. DR KEGG; hsa:58497; -. DR MANE-Select; ENST00000271620.8; ENSP00000271620.3; NM_021222.3; NP_067045.1. DR UCSC; uc001ewh.2; human. [Q86TP1-1] DR AGR; HGNC:13420; -. DR ClinPGx; PA134939749; -. DR CTD; 58497; -. DR DisGeNET; 58497; -. DR GeneCards; PRUNE1; -. DR HGNC; HGNC:13420; PRUNE1. DR HPA; ENSG00000143363; Low tissue specificity. DR MalaCards; PRUNE1; -. DR MIM; 617413; gene. DR MIM; 617481; phenotype. DR OpenTargets; ENSG00000143363; -. DR Orphanet; 544469; PRUNE1-related neurological syndrome. DR VEuPathDB; HostDB:ENSG00000143363; -. DR eggNOG; KOG4129; Eukaryota. DR GeneTree; ENSGT00450000040262; -. DR HOGENOM; CLU_019358_2_0_1; -. DR InParanoid; Q86TP1; -. DR OMA; TMTIFFN; -. DR OrthoDB; 374045at2759; -. DR PAN-GO; Q86TP1; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q86TP1; -. DR BRENDA; 3.6.1.11; 2681. DR PathwayCommons; Q86TP1; -. DR SABIO-RK; Q86TP1; -. DR SignaLink; Q86TP1; -. DR Agora; ENSG00000143363; -. DR BioGRID-ORCS; 58497; 96 hits in 1165 CRISPR screens. DR ChiTaRS; PRUNE1; human. DR GenomeRNAi; 58497; -. DR Pharos; Q86TP1; Tchem. DR PRO; PR:Q86TP1; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q86TP1; protein. DR Bgee; ENSG00000143363; Expressed in islet of Langerhans and 146 other cell types or tissues. DR ExpressionAtlas; Q86TP1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IEA:RHEA. DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IEA:RHEA. DR GO; GO:0047624; F:adenosine-tetraphosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0004309; F:exopolyphosphatase activity; IBA:GO_Central. DR GO; GO:0050355; F:inorganic triphosphate phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB. DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB. DR GO; GO:0031113; P:regulation of microtubule polymerization; IMP:UniProtKB. DR GO; GO:0050767; P:regulation of neurogenesis; IMP:UniProtKB. DR FunFam; 3.10.310.20:FF:000003; Prune exopolyphosphatase 1; 1. DR FunFam; 3.90.1640.10:FF:000004; Prune exopolyphosphatase 1; 1. DR Gene3D; 3.10.310.20; DHHA2 domain; 1. DR Gene3D; 3.90.1640.10; inorganic pyrophosphatase (n-terminal core); 1. DR InterPro; IPR001667; DDH_dom. DR InterPro; IPR038763; DHH_sf. DR InterPro; IPR004097; DHHA2. DR InterPro; IPR038222; DHHA2_dom_sf. DR PANTHER; PTHR12112; BNIP - RELATED; 1. DR PANTHER; PTHR12112:SF47; EXOPOLYPHOSPHATASE PRUNE1; 1. DR Pfam; PF01368; DHH; 1. DR Pfam; PF02833; DHHA2; 1. DR SMART; SM01131; DHHA2; 1. DR SUPFAM; SSF64182; DHH phosphoesterases; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell junction; Cytoplasm; KW Disease variant; Hydrolase; Intellectual disability; Manganese; KW Metal-binding; Neurodegeneration; Nucleus; Phosphoprotein; KW Primary microcephaly; Proteomics identification; Reference proteome. FT CHAIN 1..453 FT /note="Exopolyphosphatase PRUNE1" FT /id="PRO_0000337987" FT REGION 393..420 FT /note="Essential for homodimerization" FT REGION 395..421 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 106..108 FT /note="DHH motif" FT BINDING 28 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 30 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 106 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 106 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 179 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000250" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:37316325, FT ECO:0007744|PubMed:22814378" FT MOD_RES 399 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BIW1" FT MOD_RES 410 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q8BIW1" FT MOD_RES 414 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BIW1" FT VAR_SEQ 1..232 FT /note="Missing (in isoform 6 and isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_034013" FT VAR_SEQ 1..182 FT /note="Missing (in isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_034014" FT VAR_SEQ 15..174 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_034015" FT VAR_SEQ 45..112 FT /note="TTEAEEVFVPVLNIKRSELPLRGDIVFFLQKVHIPESILIFRDEIDLHALYQ FT AGQLTLILVDHHILSK -> A (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_034016" FT VAR_SEQ 259..311 FT /note="Missing (in isoform 4, isoform 5 and isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2" FT /id="VSP_034017" FT VARIANT 30 FT /note="D -> N (in NMIHBA; loss of function in regulation of FT cell proliferation and migration; loss of function in FT neurogenesis; impaired regulation of microtubule FT polymerization; increased phosphatase activity; no effect FT on interaction with tubulin beta; dbSNP:rs1057521927)" FT /evidence="ECO:0000269|PubMed:26539891, FT ECO:0000269|PubMed:28334956" FT /id="VAR_078986" FT VARIANT 54 FT /note="P -> T (in NMIHBA; uncertain significance; FT dbSNP:rs1085308033)" FT /evidence="ECO:0000269|PubMed:28334956" FT /id="VAR_078987" FT VARIANT 106 FT /note="D -> N (in NMIHBA; dbSNP:rs773618224)" FT /evidence="ECO:0000269|PubMed:26539891, FT ECO:0000269|PubMed:28334956" FT /id="VAR_078988" FT VARIANT 128 FT /note="R -> Q (in NMIHBA; dbSNP:rs767769359)" FT /evidence="ECO:0000269|PubMed:26539891" FT /id="VAR_078989" FT VARIANT 174..453 FT /note="Missing (in NMIHBA)" FT /evidence="ECO:0000269|PubMed:26539891" FT /id="VAR_078990" FT VARIANT 297 FT /note="R -> W (in NMIHBA; loss of function in regulation of FT cell proliferation and migration; loss of function in FT neurogenesis; impaired regulation of microtubule FT polymerization; increased phosphatase activity; decreased FT interaction with tubulin beta; dbSNP:rs752599948)" FT /evidence="ECO:0000269|PubMed:28334956" FT /id="VAR_078991" FT VARIANT 397 FT /note="G -> R (in dbSNP:rs3738477)" FT /id="VAR_059559" FT VARIANT 397 FT /note="G -> S (in dbSNP:rs3738477)" FT /id="VAR_043728" FT MUTAGEN 24 FT /note="N->H: Loss of triphosphate exopolyphosphatase FT activity." FT /evidence="ECO:0000269|PubMed:18700747" FT MUTAGEN 28 FT /note="D->A: Partial loss of cAMPPDE activity. Partial loss FT of cAMPPDE activity; when associated with D-106. Partial FT loss of cAMPPDE activity; when associated with D-106 and FT D-179. Loss of triphosphate exopolyphosphatase activity." FT /evidence="ECO:0000269|PubMed:14998490, FT ECO:0000269|PubMed:18700747" FT MUTAGEN 106 FT /note="D->A: No change in cAMPPDE activity. Partial loss of FT cAMPPDE activity; when associated with D-28. Partial loss FT of cAMPPDE activity; when associated with D-28 and D-179. FT Reduced triphosphate exopolyphosphatase activity." FT /evidence="ECO:0000269|PubMed:14998490, FT ECO:0000269|PubMed:18700747" FT MUTAGEN 107 FT /note="H->N: Reduced triphosphate exopolyphosphatase FT activity." FT /evidence="ECO:0000269|PubMed:18700747" FT MUTAGEN 108 FT /note="H->N: Reduced triphosphate exopolyphosphatase FT activity." FT /evidence="ECO:0000269|PubMed:18700747" FT MUTAGEN 126..129 FT /note="DHRP->AAAA: Partial loss of cAMPPDE activity." FT /evidence="ECO:0000269|PubMed:14998490" FT MUTAGEN 128 FT /note="R->H: Impaired triphosphate exopolyphosphatase FT activity." FT /evidence="ECO:0000269|PubMed:18700747" FT MUTAGEN 179 FT /note="D->A: Partial loss of cAMPPDE activity. Partial loss FT of cAMPPDE activity; when associated with D-28 and D-106. FT Loss of triphosphate exopolyphosphatase activity." FT /evidence="ECO:0000269|PubMed:14998490, FT ECO:0000269|PubMed:18700747" FT MUTAGEN 348 FT /note="R->A: Loss of triphosphate exopolyphosphatase FT activity." FT /evidence="ECO:0000269|PubMed:18700747" FT CONFLICT 14 FT /note="E -> A (in Ref. 2; AAK00592)" FT /evidence="ECO:0000305" FT CONFLICT 19..22 FT /note="HVVL -> AWHE (in Ref. 7; AAF04914)" FT /evidence="ECO:0000305" FT CONFLICT 221 FT /note="A -> V (in Ref. 1; AAC95290 and 7; AAF04914)" FT /evidence="ECO:0000305" SQ SEQUENCE 453 AA; 50200 MW; 34BE1909AB89DBD5 CRC64; MEDYLQGCRA ALQESRPLHV VLGNEACDLD STVSALALAF YLAKTTEAEE VFVPVLNIKR SELPLRGDIV FFLQKVHIPE SILIFRDEID LHALYQAGQL TLILVDHHIL SKSDTALEEA VAEVLDHRPI EPKHCPPCHV SVELVGSCAT LVTERILQGA PEILDRQTAA LLHGTIILDC VNMDLKIGKA TPKDSKYVEK LEALFPDLPK RNDIFDSLQK AKFDVSGLTT EQMLRKDQKT IYRQGVKVAI SAIYMDLEAF LQRSNLLADL HAFCQAHSYD VLVAMTIFFN THNEPVRQLA IFCPHVALQT TICEVLERSH SPPLKLTPAS STHPNLHAYL QGNTQVSRKK LLPLLQEALS AYFDSMKIPS GQPETADVSR EQVDKELDRA SNSLISGLSQ DEEDPPLPPT PMNSLVDECP LDQGLPKLSA EAVFEKCSQI SLSQSTTASL SKK //