ID MINP1_HUMAN Reviewed; 487 AA.
AC Q9UNW1; F5H683; O95172; O95286; Q59EJ2; Q9UGA3;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 27-MAR-2024, entry version 186.
DE RecName: Full=Multiple inositol polyphosphate phosphatase 1 {ECO:0000305|PubMed:36589890, ECO:0000305|PubMed:9923613};
DE EC=3.1.3.62 {ECO:0000269|PubMed:36589890};
DE AltName: Full=2,3-bisphosphoglycerate 3-phosphatase {ECO:0000303|PubMed:18413611};
DE Short=2,3-BPG phosphatase {ECO:0000303|PubMed:18413611};
DE EC=3.1.3.80 {ECO:0000269|PubMed:18413611};
DE Flags: Precursor;
GN Name=MINPP1 {ECO:0000312|HGNC:HGNC:7102};
GN Synonyms=MIPP {ECO:0000303|PubMed:9923613}; ORFNames=UNQ900/PRO1917;
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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF HIS-370.
RX PubMed=9923613; DOI=10.1016/s0014-5793(98)01636-6;
RA Caffrey J.J., Hidaka K., Matsuda M., Hirata M., Shears S.B.;
RT "The human and rat forms of multiple inositol polyphosphate phosphatase:
RT functional homology with a histidine acid phosphatase up-regulated during
RT endochondral ossification.";
RL FEBS Lett. 442:99-104(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10087200; DOI=10.1006/geno.1998.5736;
RA Chi H., Tiller G.E., Dasouki M.J., Romano P.R., Wang J., O'keefe R.J.,
RA Puzas J.E., Rosier R.N., Reynolds P.R.;
RT "Multiple inositol polyphosphate phosphatase: evolution as a distinct group
RT within the histidine phosphatase family and chromosomal localization of the
RT human and mouse genes to chromosomes 10q23 and 19.";
RL Genomics 56:324-336(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Thalamus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-242.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [10]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16759730; DOI=10.1016/j.jbiotec.2006.04.028;
RA Cho J., Choi K., Darden T., Reynolds P.R., Petitte J.N., Shears S.B.;
RT "Avian multiple inositol polyphosphate phosphatase is an active phytase
RT that can be engineered to help ameliorate the planet's 'phosphate
RT crisis'.";
RL J. Biotechnol. 126:248-259(2006).
RN [11]
RP FUNCTION AS 2,3-BISPHOSPHOGLYCERATE 3-PHOSPHATASE, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-89.
RX PubMed=18413611; DOI=10.1073/pnas.0710980105;
RA Cho J., King J.S., Qian X., Harwood A.J., Shears S.B.;
RT "Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the
RT regulatory capacity of the Rapoport-Luebering glycolytic shunt.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:5998-6003(2008).
RN [12]
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=36589890; DOI=10.1021/acscentsci.2c01032;
RA Nguyen Trung M., Kieninger S., Fandi Z., Qiu D., Liu G., Mehendale N.K.,
RA Saiardi A., Jessen H., Keller B., Fiedler D.;
RT "Stable Isotopomers of myo-Inositol Uncover a Complex MINPP1-Dependent
RT Inositol Phosphate Network.";
RL ACS Cent. Sci. 8:1683-1694(2022).
RN [15]
RP INVOLVEMENT IN NMTC2, AND VARIANTS NMTC2 LEU-41 AND ARG-270.
RX PubMed=11297621; DOI=10.1210/jcem.86.4.7419;
RA Gimm O., Chi H., Dahia P.L., Perren A., Hinze R., Komminoth P., Dralle H.,
RA Reynolds P.R., Eng C.;
RT "Somatic mutation and germline variants of MINPP1, a phosphatase gene
RT located in proximity to PTEN on 10q23.3, in follicular thyroid
RT carcinomas.";
RL J. Clin. Endocrinol. Metab. 86:1801-1805(2001).
RN [16]
RP INVOLVEMENT IN PCH16, VARIANTS PCH16 ASP-53; LEU-228; GLN-401 AND LYS-486,
RP CHARACTERIZATION OF VARIANTS PCH16 ASP-53 AND LYS-486, FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=33257696; DOI=10.1038/s41467-020-19919-y;
RA Ucuncu E., Rajamani K., Wilson M.S.C., Medina-Cano D., Altin N., David P.,
RA Barcia G., Lefort N., Banal C., Vasilache-Dangles M.T., Pitelet G.,
RA Lorino E., Rabasse N., Bieth E., Zaki M.S., Topcu M., Sonmez F.M.,
RA Musaev D., Stanley V., Bole-Feysot C., Nitschke P., Munnich A.,
RA Bahi-Buisson N., Fossoud C., Giuliano F., Colleaux L., Burglen L.,
RA Gleeson J.G., Boddaert N., Saiardi A., Cantagrel V.;
RT "MINPP1 prevents intracellular accumulation of the chelator inositol
RT hexakisphosphate and is mutated in Pontocerebellar Hypoplasia.";
RL Nat. Commun. 11:6087-6087(2020).
RN [17]
RP INVOLVEMENT IN PCH16, VARIANTS PCH16 ASP-284; SER-331 AND 404-ARG--LEU-487
RP DEL, AND TISSUE SPECIFICITY.
RX PubMed=33168985; DOI=10.1038/s41431-020-00749-x;
RA Appelhof B., Wagner M., Hoefele J., Heinze A., Roser T., Koch-Hogrebe M.,
RA Roosendaal S.D., Dehghani M., Mehrjardi M.Y.V., Torti E., Houlden H.,
RA Maroofian R., Rajabi F., Sticht H., Baas F., Wieczorek D., Jamra R.A.;
RT "Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1.";
RL Eur. J. Hum. Genet. 29:411-421(2021).
CC -!- FUNCTION: Multiple inositol polyphosphate phosphatase that hydrolyzes
CC 1D-myo-inositol 1,3,4,5,6-pentakisphosphate (InsP5[2OH]) and 1D-myo-
CC inositol hexakisphosphate (InsP6) to a range of less phosphorylated
CC inositol phosphates. This regulates the availability of these various
CC small molecule second messengers and metal chelators which control many
CC aspects of cell physiology (PubMed:36589890, PubMed:33257696). Has a
CC weak in vitro activity towards 1D-myo-inositol 1,4,5-trisphosphate
CC which is unlikely to be physiologically relevant (PubMed:36589890). By
CC regulating intracellular inositol polyphosphates pools, which act as
CC metal chelators, it may control the availability of intracellular
CC calcium and iron, which are important for proper neuronal development
CC and homeostasis (PubMed:33257696). May have a dual substrate
CC specificity, and function as a 2,3-bisphosphoglycerate 3-phosphatase
CC hydrolyzing 2,3-bisphosphoglycerate to 2-phosphoglycerate. 2,3-
CC bisphosphoglycerate (BPG) is formed as part of the Rapoport-Luebering
CC glycolytic bypass and is a regulator of systemic oxygen homeostasis as
CC the major allosteric effector of hemoglobin (PubMed:18413611).
CC {ECO:0000269|PubMed:18413611, ECO:0000269|PubMed:33257696,
CC ECO:0000269|PubMed:36589890}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol hexakisphosphate + H2O = 1D-myo-inositol
CC 1,2,4,5,6-pentakisphosphate + phosphate; Xref=Rhea:RHEA:16989,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57798,
CC ChEBI:CHEBI:58130; EC=3.1.3.62;
CC Evidence={ECO:0000269|PubMed:16759730, ECO:0000269|PubMed:33257696,
CC ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16990;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,2,4,5,6-pentakisphosphate + H2O = 1D-myo-
CC inositol 1,2,5,6-tetrakisphosphate + phosphate; Xref=Rhea:RHEA:77115,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57798,
CC ChEBI:CHEBI:195535; EC=3.1.3.62;
CC Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77116;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,2,5,6-tetrakisphosphate + H2O = 1D-myo-
CC inositol 1,2,6-trisphosphate + phosphate; Xref=Rhea:RHEA:77119,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:195535,
CC ChEBI:CHEBI:195537; EC=3.1.3.62;
CC Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77120;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,2,6-trisphosphate + H2O = 1D-myo-inositol
CC 1,2-bisphosphate + phosphate; Xref=Rhea:RHEA:77131,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:195537,
CC ChEBI:CHEBI:195539; EC=3.1.3.62;
CC Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77132;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,2-bisphosphate + H2O = 1D-myo-inositol 2-
CC phosphate + phosphate; Xref=Rhea:RHEA:77135, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:84142, ChEBI:CHEBI:195539;
CC EC=3.1.3.62; Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77136;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol hexakisphosphate + H2O = 1D-myo-inositol
CC 1,2,3,5,6-pentakisphosphate + phosphate; Xref=Rhea:RHEA:20960,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58130,
CC ChEBI:CHEBI:58747; Evidence={ECO:0000269|PubMed:16759730,
CC ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20961;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,2,3,5,6-pentakisphosphate + H2O = 1D-myo-
CC inositol 1,2,3,6-tetrakisphosphate + phosphate; Xref=Rhea:RHEA:77111,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58747,
CC ChEBI:CHEBI:195534; Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77112;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,2,3,6-tetrakisphosphate + H2O = 1D-myo-
CC inositol 1,2,3-trisphosphate + phosphate; Xref=Rhea:RHEA:77123,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:195534,
CC ChEBI:CHEBI:195536; Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77124;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,2,3-trisphosphate + H2O = 1D-myo-inositol
CC 2,3-bisphosphate + phosphate; Xref=Rhea:RHEA:77127,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:195536,
CC ChEBI:CHEBI:195538; Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77128;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 2,3-bisphosphate + H2O = 1D-myo-inositol 2-
CC phosphate + phosphate; Xref=Rhea:RHEA:77139, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:84142, ChEBI:CHEBI:195538;
CC Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77140;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H2O = 1D-myo-
CC inositol 1,4,5,6-tetrakisphosphate + phosphate; Xref=Rhea:RHEA:77143,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57627,
CC ChEBI:CHEBI:57733; Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77144;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,4,5,6-tetrakisphosphate + H2O = 1D-myo-
CC inositol 1,4,5-trisphosphate + phosphate; Xref=Rhea:RHEA:77147,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57627,
CC ChEBI:CHEBI:203600; Evidence={ECO:0000269|PubMed:36589890};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:77148;
CC Evidence={ECO:0000269|PubMed:36589890};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2,3-bisphosphoglycerate + H2O = (2R)-2-phosphoglycerate +
CC phosphate; Xref=Rhea:RHEA:27381, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58248, ChEBI:CHEBI:58289; EC=3.1.3.80;
CC Evidence={ECO:0000269|PubMed:18413611};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27382;
CC Evidence={ECO:0000269|PubMed:18413611};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.61 mM for 2,3-bisphosphoglycerate {ECO:0000269|PubMed:18413611};
CC KM=90 uM for 1D-myo-inositol hexakisphosphate
CC {ECO:0000269|PubMed:16759730};
CC Vmax=15.8 nmol/min/mg enzyme with 2,3-bisphospho-D-glycerate as
CC substrate {ECO:0000269|PubMed:18413611};
CC Vmax=6.2 nmol/min/mg enzyme with 1D-myo-inositol hexakisphosphate as
CC substrate {ECO:0000269|PubMed:16759730};
CC -!- INTERACTION:
CC Q9UNW1; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-4290963, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:O35217}. Secreted {ECO:0000269|PubMed:33257696}.
CC Cell membrane {ECO:0000250|UniProtKB:Q9Z2L6}. Note=Also associated with
CC the plasma membrane in erythrocytes. {ECO:0000250|UniProtKB:Q9Z2L6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UNW1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UNW1-2; Sequence=VSP_014552, VSP_014555;
CC Name=3;
CC IsoId=Q9UNW1-3; Sequence=VSP_014553, VSP_014554;
CC Name=4;
CC IsoId=Q9UNW1-4; Sequence=VSP_044569;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in kidney,
CC liver, cerebellum and placenta. {ECO:0000269|PubMed:33168985,
CC ECO:0000269|PubMed:33257696, ECO:0000269|PubMed:9923613}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:33257696}.
CC -!- DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form
CC of non-medullary thyroid cancer (NMTC), a cancer characterized by
CC tumors originating from the thyroid follicular cells. NMTCs represent
CC approximately 95% of all cases of thyroid cancer and are classified
CC into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
CC {ECO:0000269|PubMed:11297621}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Pontocerebellar hypoplasia 16 (PCH16) [MIM:619527]: A form of
CC pontocerebellar hypoplasia, a disorder characterized by structural
CC defects of the pons and cerebellum, evident upon brain imaging. PCH16
CC is an autosomal recessive, severe form characterized by hypotonia and
CC severe global developmental delay apparent from early infancy. Other
CC features may include stereotypic movements, spasticity, and progressive
CC microcephaly. {ECO:0000269|PubMed:33168985,
CC ECO:0000269|PubMed:33257696}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the histidine acid phosphatase family. MINPP1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93056.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF084943; AAD09751.1; -; mRNA.
DR EMBL; AF084944; AAD09752.1; -; mRNA.
DR EMBL; AF046914; AAD02437.1; -; mRNA.
DR EMBL; AL050356; CAB43673.1; -; mRNA.
DR EMBL; AY358938; AAQ89297.1; -; mRNA.
DR EMBL; AK309176; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AB209819; BAD93056.1; ALT_INIT; mRNA.
DR EMBL; AL138767; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355334; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032504; AAH32504.1; -; mRNA.
DR CCDS; CCDS53551.1; -. [Q9UNW1-2]
DR CCDS; CCDS53552.1; -. [Q9UNW1-4]
DR CCDS; CCDS7384.1; -. [Q9UNW1-1]
DR RefSeq; NP_001171588.1; NM_001178117.1. [Q9UNW1-2]
DR RefSeq; NP_001171589.1; NM_001178118.1. [Q9UNW1-4]
DR RefSeq; NP_004888.2; NM_004897.4. [Q9UNW1-1]
DR RefSeq; XP_011538681.1; XM_011540379.2. [Q9UNW1-4]
DR RefSeq; XP_016872455.1; XM_017016966.1.
DR AlphaFoldDB; Q9UNW1; -.
DR SMR; Q9UNW1; -.
DR BioGRID; 114932; 57.
DR IntAct; Q9UNW1; 12.
DR STRING; 9606.ENSP00000361064; -.
DR DEPOD; MINPP1; -.
DR GlyConnect; 1525; 2 N-Linked glycans (1 site).
DR GlyCosmos; Q9UNW1; 3 sites, 3 glycans.
DR GlyGen; Q9UNW1; 6 sites, 2 N-linked glycans (1 site), 3 O-linked glycans (4 sites).
DR iPTMnet; Q9UNW1; -.
DR PhosphoSitePlus; Q9UNW1; -.
DR BioMuta; MINPP1; -.
DR DMDM; 68565617; -.
DR CPTAC; CPTAC-1313; -.
DR EPD; Q9UNW1; -.
DR jPOST; Q9UNW1; -.
DR MassIVE; Q9UNW1; -.
DR MaxQB; Q9UNW1; -.
DR PaxDb; 9606-ENSP00000361064; -.
DR PeptideAtlas; Q9UNW1; -.
DR ProteomicsDB; 27109; -.
DR ProteomicsDB; 85333; -. [Q9UNW1-1]
DR ProteomicsDB; 85334; -. [Q9UNW1-2]
DR ProteomicsDB; 85335; -. [Q9UNW1-3]
DR Pumba; Q9UNW1; -.
DR Antibodypedia; 16040; 352 antibodies from 31 providers.
DR CPTC; Q9UNW1; 2 antibodies.
DR DNASU; 9562; -.
DR Ensembl; ENST00000371994.8; ENSP00000361062.4; ENSG00000107789.16. [Q9UNW1-2]
DR Ensembl; ENST00000371996.9; ENSP00000361064.4; ENSG00000107789.16. [Q9UNW1-1]
DR Ensembl; ENST00000536010.1; ENSP00000437823.1; ENSG00000107789.16. [Q9UNW1-4]
DR GeneID; 9562; -.
DR KEGG; hsa:9562; -.
DR MANE-Select; ENST00000371996.9; ENSP00000361064.4; NM_004897.5; NP_004888.2.
DR UCSC; uc001keu.4; human. [Q9UNW1-1]
DR AGR; HGNC:7102; -.
DR CTD; 9562; -.
DR DisGeNET; 9562; -.
DR GeneCards; MINPP1; -.
DR HGNC; HGNC:7102; MINPP1.
DR HPA; ENSG00000107789; Low tissue specificity.
DR MalaCards; MINPP1; -.
DR MIM; 188470; phenotype.
DR MIM; 605391; gene.
DR MIM; 619527; phenotype.
DR neXtProt; NX_Q9UNW1; -.
DR OpenTargets; ENSG00000107789; -.
DR Orphanet; 319487; Familial papillary or follicular thyroid carcinoma.
DR Orphanet; 284339; Pontocerebellar hypoplasia type 7.
DR PharmGKB; PA30820; -.
DR VEuPathDB; HostDB:ENSG00000107789; -.
DR eggNOG; KOG1382; Eukaryota.
DR GeneTree; ENSGT00390000018409; -.
DR HOGENOM; CLU_029165_3_1_1; -.
DR InParanoid; Q9UNW1; -.
DR OMA; ANSPWFA; -.
DR OrthoDB; 1072311at2759; -.
DR PhylomeDB; Q9UNW1; -.
DR TreeFam; TF324072; -.
DR BioCyc; MetaCyc:HS03025-MONOMER; -.
DR BRENDA; 3.1.3.62; 2681.
DR PathwayCommons; Q9UNW1; -.
DR Reactome; R-HSA-1855231; Synthesis of IPs in the ER lumen.
DR SABIO-RK; Q9UNW1; -.
DR SignaLink; Q9UNW1; -.
DR BioGRID-ORCS; 9562; 14 hits in 1178 CRISPR screens.
DR ChiTaRS; MINPP1; human.
DR GeneWiki; MINPP1; -.
DR GenomeRNAi; 9562; -.
DR Pharos; Q9UNW1; Tbio.
DR PRO; PR:Q9UNW1; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9UNW1; Protein.
DR Bgee; ENSG00000107789; Expressed in trabecular bone tissue and 192 other cell types or tissues.
DR Genevisible; Q9UNW1; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0016158; F:3-phytase activity; IEA:RHEA.
DR GO; GO:0008707; F:4-phytase activity; IEA:RHEA.
DR GO; GO:0003993; F:acid phosphatase activity; IBA:GO_Central.
DR GO; GO:0034417; F:bisphosphoglycerate 3-phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0016312; F:inositol bisphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0052826; F:inositol hexakisphosphate 2-phosphatase activity; TAS:Reactome.
DR GO; GO:0052827; F:inositol pentakisphosphate phosphatase activity; IMP:UniProtKB.
DR GO; GO:0052745; F:inositol phosphate phosphatase activity; IBA:GO_Central.
DR GO; GO:0046030; F:inositol trisphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0030351; F:inositol-1,3,4,5,6-pentakisphosphate 3-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0051717; F:inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity; TAS:Reactome.
DR GO; GO:0030352; F:inositol-1,4,5,6-tetrakisphosphate 6-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004446; F:inositol-hexakisphosphate phosphatase activity; IDA:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; NAS:UniProtKB.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0030003; P:intracellular monoatomic cation homeostasis; IMP:UniProtKB.
DR GO; GO:0001503; P:ossification; NAS:UniProtKB.
DR CDD; cd07061; HP_HAP_like; 1.
DR Gene3D; 3.40.50.1240; Phosphoglycerate mutase-like; 1.
DR InterPro; IPR000560; His_Pase_clade-2.
DR InterPro; IPR029033; His_PPase_superfam.
DR InterPro; IPR016274; Histidine_acid_Pase_euk.
DR PANTHER; PTHR20963:SF57; MULTIPLE INOSITOL POLYPHOSPHATE PHOSPHATASE 1; 1.
DR PANTHER; PTHR20963; MULTIPLE INOSITOL POLYPHOSPHATE PHOSPHATASE-RELATED; 1.
DR Pfam; PF00328; His_Phos_2; 1.
DR PIRSF; PIRSF000894; Acid_phosphatase; 1.
DR SUPFAM; SSF53254; Phosphoglycerate mutase-like; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Membrane;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000250"
FT CHAIN 31..487
FT /note="Multiple inositol polyphosphate phosphatase 1"
FT /id="PRO_0000019582"
FT MOTIF 484..487
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT ACT_SITE 89
FT /evidence="ECO:0000250|UniProtKB:Q9Z2L6"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..213
FT /note="MLRAPGCLLRTSVAPAAALAAALLSSLARCSLLEPRDPVASSLSPYFGTKTR
FT YEDVNPVLLSGPEAPWRDPELLEGTCTPVQLVALIRHGTRYPTVKQIRKLRQLHGLLQA
FT RGSRDGGASSTGSRDLGAALADWPLWYADWMDGQLVEKGRQDMRQLALRLASLFPALFS
FT RENYGRLRLITSSKHRCMDSSAAFLQGLWQHYHPGLPPPDVAD -> MCLFQLCGLVRY
FT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044569"
FT VAR_SEQ 279..312
FT /note="DLIQVAFFTCSFDLAIKGVKSPWCDVFDIDDAKV -> GLSQFLLQSSSSLV
FT MQRLFFHCFLSWATSKTRNP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9923613"
FT /id="VSP_014552"
FT VAR_SEQ 279..284
FT /note="DLIQVA -> GIRIFK (in isoform 3)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_014553"
FT VAR_SEQ 285..487
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_014554"
FT VAR_SEQ 313..487
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9923613"
FT /id="VSP_014555"
FT VARIANT 41
FT /note="S -> L (in NMTC2; somatic mutation;
FT dbSNP:rs119486096)"
FT /evidence="ECO:0000269|PubMed:11297621"
FT /id="VAR_022836"
FT VARIANT 53
FT /note="Y -> D (in PCH16; loss of enzymatic activity)"
FT /evidence="ECO:0000269|PubMed:33257696"
FT /id="VAR_086289"
FT VARIANT 228
FT /note="F -> L (in PCH16; uncertain significance;
FT dbSNP:rs1456945513)"
FT /evidence="ECO:0000269|PubMed:33257696"
FT /id="VAR_086290"
FT VARIANT 270
FT /note="Q -> R (in NMTC2; dbSNP:rs104894171)"
FT /evidence="ECO:0000269|PubMed:11297621"
FT /id="VAR_022837"
FT VARIANT 284
FT /note="A -> D (in PCH16; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:33168985"
FT /id="VAR_086291"
FT VARIANT 331
FT /note="I -> S (in PCH16; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:33168985"
FT /id="VAR_086292"
FT VARIANT 401
FT /note="R -> Q (in PCH16; uncertain significance;
FT dbSNP:rs1381093602)"
FT /evidence="ECO:0000269|PubMed:33257696"
FT /id="VAR_086293"
FT VARIANT 404..487
FT /note="Missing (in PCH16; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:33168985"
FT /id="VAR_086294"
FT VARIANT 486
FT /note="E -> K (in PCH16; uncertain significance; contary to
FT wild-type, does not rescue normal growth in a MINPP1
FT knockout cell line)"
FT /evidence="ECO:0000269|PubMed:33257696"
FT /id="VAR_086295"
FT MUTAGEN 89
FT /note="H->A: Strong reduction of 2,3-bisphosphoglycerate 3-
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:18413611"
FT MUTAGEN 370
FT /note="H->A: Greatly diminishes phosphatase activity."
FT /evidence="ECO:0000269|PubMed:9923613"
FT CONFLICT 81
FT /note="V -> A (in Ref. 3; CAB43673)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="A -> P (in Ref. 2; AAD02437)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="A -> R (in Ref. 2; AAD02437)"
FT /evidence="ECO:0000305"
FT CONFLICT 156..157
FT /note="QL -> HV (in Ref. 2; AAD02437)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="F -> S (in Ref. 3; CAB43673)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 487 AA; 55051 MW; 89B8F347885B320A CRC64;
MLRAPGCLLR TSVAPAAALA AALLSSLARC SLLEPRDPVA SSLSPYFGTK TRYEDVNPVL
LSGPEAPWRD PELLEGTCTP VQLVALIRHG TRYPTVKQIR KLRQLHGLLQ ARGSRDGGAS
STGSRDLGAA LADWPLWYAD WMDGQLVEKG RQDMRQLALR LASLFPALFS RENYGRLRLI
TSSKHRCMDS SAAFLQGLWQ HYHPGLPPPD VADMEFGPPT VNDKLMRFFD HCEKFLTEVE
KNATALYHVE AFKTGPEMQN ILKKVAATLQ VPVNDLNADL IQVAFFTCSF DLAIKGVKSP
WCDVFDIDDA KVLEYLNDLK QYWKRGYGYT INSRSSCTLF QDIFQHLDKA VEQKQRSQPI
SSPVILQFGH AETLLPLLSL MGYFKDKEPL TAYNYKKQMH RKFRSGLIVP YASNLIFVLY
HCENAKTPKE QFRVQMLLNE KVLPLAYSQE TVSFYEDLKN HYKDILQSCQ TSEECELARA
NSTSDEL
//
