PRUN1_HUMAN
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 03-AUG-2022, entry version 148.
DE RecName: Full=Exopolyphosphatase PRUNE1;
DE EC=3.6.1.1;
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;
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, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH NME1, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF ASP-28; ASP-106; 126-ASP--PRO-129 AND
RP 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;
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 INTERACTION WITH NME1, BIOPHYSICOCHEMICAL 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 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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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: Phosphodiesterase (PDE) that has higher activity toward cAMP
CC than cGMP, as substrate. Plays a role in cell proliferation, migration
CC and differentiation, and acts as a negative regulator of NME1. Plays a
CC role in the regulation of neurogenesis (PubMed:28334956). Involved in
CC the regulation of microtubule polymerization (PubMed:28334956).
CC {ECO:0000269|PubMed:10602478, ECO:0000269|PubMed:11687967,
CC ECO:0000269|PubMed:14998490, ECO:0000269|PubMed:16428445,
CC ECO:0000269|PubMed:17906697, ECO:0000269|PubMed:28334956}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:43474; EC=3.6.1.1;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by magnesium ions and inhibited by
CC manganese ions. Inhibited by dipyridamole, moderately sensitive to IBMX
CC and 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 ECO:0000269|PubMed:17655525};
CC KM=2.3 uM for cGMP {ECO:0000269|PubMed:14998490,
CC ECO:0000269|PubMed:17655525};
CC Vmax=12.8 pmol/min/ug enzyme with cAMP as substrate
CC {ECO:0000269|PubMed:14998490, ECO:0000269|PubMed:17655525};
CC Vmax=0.8 pmol/min/ug enzyme with cGMP as substrate
CC {ECO:0000269|PubMed:14998490, ECO:0000269|PubMed:17655525};
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; 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};
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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_001303229.1. [Q86TP1-3]
DR RefSeq; NP_001290171.1; NM_001303242.1.
DR RefSeq; NP_001290172.1; NM_001303243.1.
DR RefSeq; NP_067045.1; NM_021222.2. [Q86TP1-1]
DR RefSeq; XP_011508134.1; XM_011509832.2. [Q86TP1-3]
DR RefSeq; XP_016857445.1; XM_017001956.1. [Q86TP1-3]
DR AlphaFoldDB; Q86TP1; -.
DR BMRB; Q86TP1; -.
DR SMR; Q86TP1; -.
DR BioGRID; 121827; 25.
DR CORUM; Q86TP1; -.
DR IntAct; Q86TP1; 10.
DR STRING; 9606.ENSP00000271620; -.
DR BindingDB; Q86TP1; -.
DR ChEMBL; CHEMBL2079850; -.
DR DrugCentral; Q86TP1; -.
DR GlyGen; Q86TP1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86TP1; -.
DR PhosphoSitePlus; Q86TP1; -.
DR BioMuta; PRUNE1; -.
DR DMDM; 229462737; -.
DR EPD; Q86TP1; -.
DR jPOST; Q86TP1; -.
DR MassIVE; Q86TP1; -.
DR MaxQB; Q86TP1; -.
DR PaxDb; Q86TP1; -.
DR PeptideAtlas; Q86TP1; -.
DR PRIDE; 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 Antibodypedia; 34044; 216 antibodies from 27 providers.
DR DNASU; 58497; -.
DR Ensembl; ENST00000271620.8; ENSP00000271620.3; ENSG00000143363.17. [Q86TP1-1]
DR Ensembl; ENST00000368934.1; ENSP00000357930.1; ENSG00000143363.17. [Q86TP1-5]
DR Ensembl; ENST00000368935.1; ENSP00000357931.1; ENSG00000143363.17. [Q86TP1-6]
DR Ensembl; ENST00000368936.5; ENSP00000357932.1; ENSG00000143363.17. [Q86TP1-3]
DR Ensembl; ENST00000368937.5; ENSP00000357933.1; ENSG00000143363.17. [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 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 neXtProt; NX_Q86TP1; -.
DR OpenTargets; ENSG00000143363; -.
DR Orphanet; 544469; PRUNE1-related neurological syndrome.
DR PharmGKB; PA134939749; -.
DR VEuPathDB; HostDB:ENSG00000143363; -.
DR eggNOG; KOG4129; Eukaryota.
DR GeneTree; ENSGT00450000040262; -.
DR HOGENOM; CLU_019358_2_0_1; -.
DR InParanoid; Q86TP1; -.
DR OMA; HSRKRVA; -.
DR OrthoDB; 1545660at2759; -.
DR PhylomeDB; Q86TP1; -.
DR TreeFam; TF323914; -.
DR PathwayCommons; Q86TP1; -.
DR SABIO-RK; Q86TP1; -.
DR SignaLink; Q86TP1; -.
DR BioGRID-ORCS; 58497; 77 hits in 1085 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 144 other tissues.
DR ExpressionAtlas; Q86TP1; baseline and differential.
DR Genevisible; Q86TP1; HS.
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:0004309; F:exopolyphosphatase activity; IBA:GO_Central.
DR GO; GO:0004427; F:inorganic diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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 Gene3D; 3.10.310.20; -; 1.
DR InterPro; IPR001667; DDH_dom.
DR InterPro; IPR038763; DHH_sf.
DR InterPro; IPR004097; DHHA2.
DR InterPro; IPR038222; DHHA2_dom_sf.
DR Pfam; PF01368; DHH; 1.
DR Pfam; PF02833; DHHA2; 1.
DR SMART; SM01131; DHHA2; 1.
DR SUPFAM; SSF64182; SSF64182; 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; 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: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; unknown pathological
FT significance; 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 28
FT /note="D->A: Partial loss of cAMP PDE activity. Partial
FT loss of cAMP PDE activity; when associated with D-106.
FT Partial loss of cAMP PDE activity; when associated with D-
FT 106 and D-179."
FT /evidence="ECO:0000269|PubMed:14998490"
FT MUTAGEN 106
FT /note="D->A: No change in cAMP PDE activity. Partial loss
FT of cAMP PDE activity; when associated with D-28. Partial
FT loss of cAMP PDE activity; when associated with D-28 and D-
FT 179."
FT /evidence="ECO:0000269|PubMed:14998490"
FT MUTAGEN 126..129
FT /note="DHRP->AAAA: Partial loss of cAMP PDE activity."
FT /evidence="ECO:0000269|PubMed:14998490"
FT MUTAGEN 179
FT /note="D->A: Partial loss of cAMP PDE activity. Partial
FT loss of cAMP PDE activity; when associated with D-28 and D-
FT 106."
FT /evidence="ECO:0000269|PubMed:14998490"
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
