Full text data of MINPP1
MINPP1
(MIPP)
[Confidence: high (present in two of the MS resources)]
Multiple inositol polyphosphate phosphatase 1; 3.1.3.62 (2,3-bisphosphoglycerate 3-phosphatase; 2,3-BPG phosphatase; 3.1.3.80; Inositol (1,3,4,5)-tetrakisphosphate 3-phosphatase; Ins(1,3,4,5)P(4) 3-phosphatase; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Multiple inositol polyphosphate phosphatase 1; 3.1.3.62 (2,3-bisphosphoglycerate 3-phosphatase; 2,3-BPG phosphatase; 3.1.3.80; Inositol (1,3,4,5)-tetrakisphosphate 3-phosphatase; Ins(1,3,4,5)P(4) 3-phosphatase; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00028553
IPI00028553 Multiple inositol polyphosphate phosphatase-like protein Multiple inositol polyphosphate phosphatase-like protein membrane n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
IPI00028553 Multiple inositol polyphosphate phosphatase-like protein Multiple inositol polyphosphate phosphatase-like protein membrane n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a not mentioned n/a found at its expected molecular weight found at molecular weight
UniProt
Q9UNW1
ID MINP1_HUMAN Reviewed; 487 AA.
AC Q9UNW1; F5H683; O95172; O95286; Q59EJ2; Q9UGA3;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 115.
DE RecName: Full=Multiple inositol polyphosphate phosphatase 1;
DE EC=3.1.3.62;
DE AltName: Full=2,3-bisphosphoglycerate 3-phosphatase;
DE Short=2,3-BPG phosphatase;
DE EC=3.1.3.80;
DE AltName: Full=Inositol (1,3,4,5)-tetrakisphosphate 3-phosphatase;
DE Short=Ins(1,3,4,5)P(4) 3-phosphatase;
DE Flags: Precursor;
GN Name=MINPP1; Synonyms=MIPP; ORFNames=UNQ900/PRO1917;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (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
RT phosphatase: functional homology with a histidine acid phosphatase up-
RT regulated during 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
RT group within the histidine phosphatase family and chromosomal
RT localization of the human and mouse genes to chromosomes 10q23 and
RT 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.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-242, AND MASS
RP SPECTROMETRY.
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.,
RA Moore R.J., 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 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 [11]
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.,
RA Buerckstuemmer T., 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 [12]
RP VARIANT FOLLICULAR THYROID CARCINOMA LEU-41, AND VARIANT FOLLICULAR
RP THYROID ADENOMA ARG-270.
RX PubMed=11297621; DOI=10.1210/jc.86.4.1801;
RA Gimm O., Chi H., Dahia P.L., Perren A., Hinze R., Komminoth P.,
RA Dralle H., 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).
CC -!- FUNCTION: Acts as a phosphoinositide 5- and phosphoinositide 6-
CC phosphatase and regulates cellular levels of inositol
CC pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6).
CC Also acts as a 2,3-bisphosphoglycerate 3-phosphatase, by mediating
CC the dephosphorylation of 2,3-bisphosphoglycerate (2,3-BPG) to
CC produce phospho-D-glycerate without formation of 3-
CC phosphoglycerate. May play a role in bone development
CC (endochondral ossification).
CC -!- CATALYTIC ACTIVITY: Myo-inositol hexakisphosphate + H(2)O = myo-
CC inositol pentakisphosphate (mixed isomers) + phosphate.
CC -!- CATALYTIC ACTIVITY: 2,3-bisphospho-D-glycerate + H(2)O = 2-
CC phospho-D-glycerate + phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.61 mM for 2,3-bisphosphoglycerate;
CC Vmax=15.8 nmol/min/mg enzyme with 2,3-bisphospho-D-glycerate as
CC substrate;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen (By similarity).
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9UNW1-3; Sequence=VSP_014553, VSP_014554;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9UNW1-4; Sequence=VSP_044569;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in
CC kidney, liver and placenta.
CC -!- DISEASE: Note=Defects in MINPP1 may be involved in follicular
CC thyroid tumors development.
CC -!- SIMILARITY: Belongs to the histidine acid phosphatase family.
CC MINPP1 subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93056.1; Type=Erroneous initiation;
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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; AL355334; CAH73423.1; -; Genomic_DNA.
DR EMBL; AL138767; CAH73423.1; JOINED; Genomic_DNA.
DR EMBL; AL138767; CAI16030.1; -; Genomic_DNA.
DR EMBL; AL355334; CAI16030.1; JOINED; Genomic_DNA.
DR EMBL; AL355334; CAH73422.1; -; Genomic_DNA.
DR EMBL; AL138767; CAH73422.1; JOINED; Genomic_DNA.
DR EMBL; AL138767; CAI16029.1; -; Genomic_DNA.
DR EMBL; AL355334; CAI16029.1; JOINED; Genomic_DNA.
DR EMBL; BC032504; AAH32504.1; -; mRNA.
DR RefSeq; NP_001171588.1; NM_001178117.1.
DR RefSeq; NP_001171589.1; NM_001178118.1.
DR RefSeq; NP_004888.2; NM_004897.4.
DR UniGene; Hs.121260; -.
DR ProteinModelPortal; Q9UNW1; -.
DR SMR; Q9UNW1; 71-445.
DR STRING; 9606.ENSP00000361064; -.
DR PhosphoSite; Q9UNW1; -.
DR DMDM; 68565617; -.
DR PaxDb; Q9UNW1; -.
DR PeptideAtlas; Q9UNW1; -.
DR PRIDE; Q9UNW1; -.
DR DNASU; 9562; -.
DR Ensembl; ENST00000371994; ENSP00000361062; ENSG00000107789.
DR Ensembl; ENST00000371996; ENSP00000361064; ENSG00000107789.
DR Ensembl; ENST00000536010; ENSP00000437823; ENSG00000107789.
DR GeneID; 9562; -.
DR KEGG; hsa:9562; -.
DR UCSC; uc021pvv.1; human.
DR CTD; 9562; -.
DR GeneCards; GC10P089264; -.
DR HGNC; HGNC:7102; MINPP1.
DR HPA; HPA026859; -.
DR MIM; 605391; gene.
DR neXtProt; NX_Q9UNW1; -.
DR PharmGKB; PA30820; -.
DR eggNOG; NOG260296; -.
DR HOGENOM; HOG000113591; -.
DR HOVERGEN; HBG052872; -.
DR InParanoid; Q9UNW1; -.
DR KO; K03103; -.
DR OMA; ADMECGP; -.
DR OrthoDB; EOG7992QC; -.
DR PhylomeDB; Q9UNW1; -.
DR BioCyc; MetaCyc:HS03025-MONOMER; -.
DR BRENDA; 3.1.3.62; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q9UNW1; -.
DR ChiTaRS; MINPP1; human.
DR GeneWiki; MINPP1; -.
DR GenomeRNAi; 9562; -.
DR NextBio; 35863; -.
DR PRO; PR:Q9UNW1; -.
DR ArrayExpress; Q9UNW1; -.
DR Bgee; Q9UNW1; -.
DR CleanEx; HS_MINPP1; -.
DR Genevestigator; Q9UNW1; -.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0003993; F:acid phosphatase activity; IEA:InterPro.
DR GO; GO:0034417; F:bisphosphoglycerate 3-phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0052826; F:inositol hexakisphosphate 2-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008969; F:phosphohistidine phosphatase activity; TAS:ProtInc.
DR GO; GO:0030282; P:bone mineralization; NAS:UniProtKB.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0006797; P:polyphosphate metabolic process; TAS:ProtInc.
DR InterPro; IPR000560; His_Pase_superF_clade-2.
DR InterPro; IPR016274; Histidine_acid_Pase_euk.
DR Pfam; PF00328; His_Phos_2; 1.
DR PIRSF; PIRSF000894; Acid_phosphatase; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disease mutation;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Polymorphism;
KW Reference proteome; Signal.
FT SIGNAL 1 30 By similarity.
FT CHAIN 31 487 Multiple inositol polyphosphate
FT phosphatase 1.
FT /FTId=PRO_0000019582.
FT MOTIF 484 487 Prevents secretion from ER (Potential).
FT ACT_SITE 89 89 Potential.
FT CARBOHYD 242 242 N-linked (GlcNAc...).
FT CARBOHYD 481 481 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 213 MLRAPGCLLRTSVAPAAALAAALLSSLARCSLLEPRDPVAS
FT SLSPYFGTKTRYEDVNPVLLSGPEAPWRDPELLEGTCTPVQ
FT LVALIRHGTRYPTVKQIRKLRQLHGLLQARGSRDGGASSTG
FT SRDLGAALADWPLWYADWMDGQLVEKGRQDMRQLALRLASL
FT FPALFSRENYGRLRLITSSKHRCMDSSAAFLQGLWQHYHPG
FT LPPPDVAD -> MCLFQLCGLVRY (in isoform 4).
FT /FTId=VSP_044569.
FT VAR_SEQ 279 312 DLIQVAFFTCSFDLAIKGVKSPWCDVFDIDDAKV -> GLS
FT QFLLQSSSSLVMQRLFFHCFLSWATSKTRNP (in
FT isoform 2).
FT /FTId=VSP_014552.
FT VAR_SEQ 279 284 DLIQVA -> GIRIFK (in isoform 3).
FT /FTId=VSP_014553.
FT VAR_SEQ 285 487 Missing (in isoform 3).
FT /FTId=VSP_014554.
FT VAR_SEQ 313 487 Missing (in isoform 2).
FT /FTId=VSP_014555.
FT VARIANT 41 41 S -> L (in a follicular thyroid
FT carcinoma; somatic mutation).
FT /FTId=VAR_022836.
FT VARIANT 270 270 Q -> R (in a follicular thyroid adenoma).
FT /FTId=VAR_022837.
FT MUTAGEN 89 89 H->A: Strong reduction of 2,3-
FT bisphosphoglycerate 3-phosphatase
FT activity.
FT MUTAGEN 370 370 H->A: Greatly diminishes phosphatase
FT activity.
FT CONFLICT 81 81 V -> A (in Ref. 3; CAB43673).
FT CONFLICT 111 111 A -> P (in Ref. 2; AAD02437).
FT CONFLICT 132 132 A -> R (in Ref. 2; AAD02437).
FT CONFLICT 156 157 QL -> HV (in Ref. 2; AAD02437).
FT CONFLICT 344 344 F -> S (in Ref. 3; CAB43673).
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
//
ID MINP1_HUMAN Reviewed; 487 AA.
AC Q9UNW1; F5H683; O95172; O95286; Q59EJ2; Q9UGA3;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 115.
DE RecName: Full=Multiple inositol polyphosphate phosphatase 1;
DE EC=3.1.3.62;
DE AltName: Full=2,3-bisphosphoglycerate 3-phosphatase;
DE Short=2,3-BPG phosphatase;
DE EC=3.1.3.80;
DE AltName: Full=Inositol (1,3,4,5)-tetrakisphosphate 3-phosphatase;
DE Short=Ins(1,3,4,5)P(4) 3-phosphatase;
DE Flags: Precursor;
GN Name=MINPP1; Synonyms=MIPP; ORFNames=UNQ900/PRO1917;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (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
RT phosphatase: functional homology with a histidine acid phosphatase up-
RT regulated during 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
RT group within the histidine phosphatase family and chromosomal
RT localization of the human and mouse genes to chromosomes 10q23 and
RT 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.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-242, AND MASS
RP SPECTROMETRY.
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.,
RA Moore R.J., 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 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 [11]
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.,
RA Buerckstuemmer T., 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 [12]
RP VARIANT FOLLICULAR THYROID CARCINOMA LEU-41, AND VARIANT FOLLICULAR
RP THYROID ADENOMA ARG-270.
RX PubMed=11297621; DOI=10.1210/jc.86.4.1801;
RA Gimm O., Chi H., Dahia P.L., Perren A., Hinze R., Komminoth P.,
RA Dralle H., 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).
CC -!- FUNCTION: Acts as a phosphoinositide 5- and phosphoinositide 6-
CC phosphatase and regulates cellular levels of inositol
CC pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6).
CC Also acts as a 2,3-bisphosphoglycerate 3-phosphatase, by mediating
CC the dephosphorylation of 2,3-bisphosphoglycerate (2,3-BPG) to
CC produce phospho-D-glycerate without formation of 3-
CC phosphoglycerate. May play a role in bone development
CC (endochondral ossification).
CC -!- CATALYTIC ACTIVITY: Myo-inositol hexakisphosphate + H(2)O = myo-
CC inositol pentakisphosphate (mixed isomers) + phosphate.
CC -!- CATALYTIC ACTIVITY: 2,3-bisphospho-D-glycerate + H(2)O = 2-
CC phospho-D-glycerate + phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.61 mM for 2,3-bisphosphoglycerate;
CC Vmax=15.8 nmol/min/mg enzyme with 2,3-bisphospho-D-glycerate as
CC substrate;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen (By similarity).
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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9UNW1-3; Sequence=VSP_014553, VSP_014554;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q9UNW1-4; Sequence=VSP_044569;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in
CC kidney, liver and placenta.
CC -!- DISEASE: Note=Defects in MINPP1 may be involved in follicular
CC thyroid tumors development.
CC -!- SIMILARITY: Belongs to the histidine acid phosphatase family.
CC MINPP1 subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93056.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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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; AL355334; CAH73423.1; -; Genomic_DNA.
DR EMBL; AL138767; CAH73423.1; JOINED; Genomic_DNA.
DR EMBL; AL138767; CAI16030.1; -; Genomic_DNA.
DR EMBL; AL355334; CAI16030.1; JOINED; Genomic_DNA.
DR EMBL; AL355334; CAH73422.1; -; Genomic_DNA.
DR EMBL; AL138767; CAH73422.1; JOINED; Genomic_DNA.
DR EMBL; AL138767; CAI16029.1; -; Genomic_DNA.
DR EMBL; AL355334; CAI16029.1; JOINED; Genomic_DNA.
DR EMBL; BC032504; AAH32504.1; -; mRNA.
DR RefSeq; NP_001171588.1; NM_001178117.1.
DR RefSeq; NP_001171589.1; NM_001178118.1.
DR RefSeq; NP_004888.2; NM_004897.4.
DR UniGene; Hs.121260; -.
DR ProteinModelPortal; Q9UNW1; -.
DR SMR; Q9UNW1; 71-445.
DR STRING; 9606.ENSP00000361064; -.
DR PhosphoSite; Q9UNW1; -.
DR DMDM; 68565617; -.
DR PaxDb; Q9UNW1; -.
DR PeptideAtlas; Q9UNW1; -.
DR PRIDE; Q9UNW1; -.
DR DNASU; 9562; -.
DR Ensembl; ENST00000371994; ENSP00000361062; ENSG00000107789.
DR Ensembl; ENST00000371996; ENSP00000361064; ENSG00000107789.
DR Ensembl; ENST00000536010; ENSP00000437823; ENSG00000107789.
DR GeneID; 9562; -.
DR KEGG; hsa:9562; -.
DR UCSC; uc021pvv.1; human.
DR CTD; 9562; -.
DR GeneCards; GC10P089264; -.
DR HGNC; HGNC:7102; MINPP1.
DR HPA; HPA026859; -.
DR MIM; 605391; gene.
DR neXtProt; NX_Q9UNW1; -.
DR PharmGKB; PA30820; -.
DR eggNOG; NOG260296; -.
DR HOGENOM; HOG000113591; -.
DR HOVERGEN; HBG052872; -.
DR InParanoid; Q9UNW1; -.
DR KO; K03103; -.
DR OMA; ADMECGP; -.
DR OrthoDB; EOG7992QC; -.
DR PhylomeDB; Q9UNW1; -.
DR BioCyc; MetaCyc:HS03025-MONOMER; -.
DR BRENDA; 3.1.3.62; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q9UNW1; -.
DR ChiTaRS; MINPP1; human.
DR GeneWiki; MINPP1; -.
DR GenomeRNAi; 9562; -.
DR NextBio; 35863; -.
DR PRO; PR:Q9UNW1; -.
DR ArrayExpress; Q9UNW1; -.
DR Bgee; Q9UNW1; -.
DR CleanEx; HS_MINPP1; -.
DR Genevestigator; Q9UNW1; -.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0003993; F:acid phosphatase activity; IEA:InterPro.
DR GO; GO:0034417; F:bisphosphoglycerate 3-phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0052826; F:inositol hexakisphosphate 2-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0008969; F:phosphohistidine phosphatase activity; TAS:ProtInc.
DR GO; GO:0030282; P:bone mineralization; NAS:UniProtKB.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0006797; P:polyphosphate metabolic process; TAS:ProtInc.
DR InterPro; IPR000560; His_Pase_superF_clade-2.
DR InterPro; IPR016274; Histidine_acid_Pase_euk.
DR Pfam; PF00328; His_Phos_2; 1.
DR PIRSF; PIRSF000894; Acid_phosphatase; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disease mutation;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Polymorphism;
KW Reference proteome; Signal.
FT SIGNAL 1 30 By similarity.
FT CHAIN 31 487 Multiple inositol polyphosphate
FT phosphatase 1.
FT /FTId=PRO_0000019582.
FT MOTIF 484 487 Prevents secretion from ER (Potential).
FT ACT_SITE 89 89 Potential.
FT CARBOHYD 242 242 N-linked (GlcNAc...).
FT CARBOHYD 481 481 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 1 213 MLRAPGCLLRTSVAPAAALAAALLSSLARCSLLEPRDPVAS
FT SLSPYFGTKTRYEDVNPVLLSGPEAPWRDPELLEGTCTPVQ
FT LVALIRHGTRYPTVKQIRKLRQLHGLLQARGSRDGGASSTG
FT SRDLGAALADWPLWYADWMDGQLVEKGRQDMRQLALRLASL
FT FPALFSRENYGRLRLITSSKHRCMDSSAAFLQGLWQHYHPG
FT LPPPDVAD -> MCLFQLCGLVRY (in isoform 4).
FT /FTId=VSP_044569.
FT VAR_SEQ 279 312 DLIQVAFFTCSFDLAIKGVKSPWCDVFDIDDAKV -> GLS
FT QFLLQSSSSLVMQRLFFHCFLSWATSKTRNP (in
FT isoform 2).
FT /FTId=VSP_014552.
FT VAR_SEQ 279 284 DLIQVA -> GIRIFK (in isoform 3).
FT /FTId=VSP_014553.
FT VAR_SEQ 285 487 Missing (in isoform 3).
FT /FTId=VSP_014554.
FT VAR_SEQ 313 487 Missing (in isoform 2).
FT /FTId=VSP_014555.
FT VARIANT 41 41 S -> L (in a follicular thyroid
FT carcinoma; somatic mutation).
FT /FTId=VAR_022836.
FT VARIANT 270 270 Q -> R (in a follicular thyroid adenoma).
FT /FTId=VAR_022837.
FT MUTAGEN 89 89 H->A: Strong reduction of 2,3-
FT bisphosphoglycerate 3-phosphatase
FT activity.
FT MUTAGEN 370 370 H->A: Greatly diminishes phosphatase
FT activity.
FT CONFLICT 81 81 V -> A (in Ref. 3; CAB43673).
FT CONFLICT 111 111 A -> P (in Ref. 2; AAD02437).
FT CONFLICT 132 132 A -> R (in Ref. 2; AAD02437).
FT CONFLICT 156 157 QL -> HV (in Ref. 2; AAD02437).
FT CONFLICT 344 344 F -> S (in Ref. 3; CAB43673).
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
//
MIM
605391
*RECORD*
*FIELD* NO
605391
*FIELD* TI
*605391 MULTIPLE INOSITOL POLYPHOSPHATE PHOSPHATASE 1; MINPP1
;;MIPP, RAT, HOMOLOG OF;;
read moreHIPER1, CHICKEN, HOMOLOG OF
*FIELD* TX
DESCRIPTION
MINPP1 hydrolyzes the abundant metabolites inositol pentakisphosphate
and inositol hexakisphosphate and, like PTEN (601728), has the ability
to remove 3-phosphate from inositol phosphate substrates.
CLONING
In addition to inositol triphosphate, an important second messenger in
eukaryotic cells, there are a number of inositol polyphosphates, as well
as enzymes that affect their metabolism, that play a role in signaling
activity. The rat enzyme Mipp removes polyphosphate groups from a number
of inositol polyphosphates that contain at least 4 phosphates. The chick
gene HiPER1 (histidine phosphatase of the endoplasmic reticulum), a
homolog of Mipp, is expressed strongly in growth plate chondrocytes
transiting from proliferation to hypertrophy. By searching an EST
database with rat Mipp as the probe, Caffrey et al. (1999) identified a
cDNA encoding human MINPP1, which they called MIPP. Sequence analysis
predicted that the 487-amino acid MINPP1 protein is 84% identical to rat
Mipp and about 53% identical to chick HiPER1. The N terminus of MINPP1
contains an ER-targeting domain consisting of a relatively long
net-positive-charge (n) region, a hydrophobic core region, and a
recognition site for signal peptidases. Because of the
13-amino-acid-long n region, Caffrey et al. (1999) suggested that
translocation of MINPP1 to the ER may not require TRAM (605190), which
is needed for proteins with short (5 residues or less) n regions. MINPP1
catalytic activity appears to require sequences in the C terminus.
Western blot analysis demonstrated that MINPP1 is expressed as an
approximately 51-kD protein. Northern blot analysis detected a 2.5-kb
MINPP1 transcript in all tissues tested except for peripheral blood
leukocytes; highest expression was detected in kidney, liver, and
placenta. In situ hybridization analysis showed that Minpp1 is expressed
much more intensely in hypertrophic than in proliferating or resting rat
chondrocytes.
By RT-PCR, RACE, and library screening, Chi et al. (1999) identified a
cDNA encoding MINPP1. Northern blot analysis detected a 2.6-kb MINPP1
transcript in HeLa cells and human chondrocytes. The authors noted that
the C-terminal ER-retention signal is conserved between chick, rat, and
human MINPP1 sequences. Functional analysis showed that mouse Minpp1
converts inositol tetrakisphosphate to inositol triphosphate.
MAPPING
Using FISH, radiation hybrid analysis, and YAC screening, Chi et al.
(1999) mapped the MINPP1 gene to 10q23, proximal to the tumor suppressor
PTEN (601728), in a region that is frequently mutated in cancer. By
radiation hybrid analysis, Chi et al. (1999) mapped the mouse Minpp1
gene to chromosome 19, also in proximity to Pten.
ANIMAL MODEL
Chi et al. (2000) used homologous recombination to generate
Minpp1-deficient mice. They observed that these mice were fertile,
lacked obvious defects, and had normal chondrocyte differentiation. An
increase in levels of cytosolic inositol polyphosphates was reversible
by the introduction of Minpp1 to the ER, showing that ER-based Minpp1
plays a role in the maintenance of steady-state levels of these
polyphosphates. In contrast, introduction into the cytosol of truncated
Minpp1 lacking the ER-targeting domain reduced the polyphosphates to
below their natural levels and was accompanied by slowed cellular
proliferation.
MOLECULAR GENETICS
Germline mutations in the tumor suppressor gene PTEN, which encodes a
dual-specificity phosphatase, have been found in up to 80% of patients
with Cowden syndrome, suggesting a role of PTEN in the pathogenesis of
follicular thyroid tumors. Although somatic intragenic mutations in
PTEN, which maps to 10q23.3, are rarely found in follicular tumors, loss
of heterozygosity (LOH) of markers within 10q22-q24 occurs in about 25%.
MINPP1, another phosphatase gene, had also been mapped to 10q23.3.
MINPP1 has the ability to remove 3-phosphate from inositol phosphate
substrates, a function that overlaps that of PTEN. Because of this
overlapping function with PTEN and the physical location of MINPP1 to a
region with frequent LOH in follicular thyroid tumors, Gimm et al.
(2001) considered it to be an excellent candidate gene that could
contribute to the pathogenesis of follicular thyroid tumors. They
analyzed DNA from tumor and corresponding normal tissue from 23 patients
with follicular thyroid adenoma (FA) and 15 patients with follicular
thyroid carcinoma (FTC; 188470) for LOH or mutations at the MINPP1
locus. LOH was identified in 4 malignant and 3 benign tumors. One of
these FTCs with LOH was found to harbor a somatic ser41-to-leu mutation
(S41L; 605391.0001). They also found 2 germline sequence variants,
gln270 to arg (Q270R; 605391.0002) and IVS3+34T-A (605391.0003). Q270R
was found in only 1 patient with FA but not in patients with FTC or
normal controls. Interestingly, IVS3+34T-A was found in about 15% of FA
cases and normal controls but not in patients with FTC. The authors
concluded that these results suggest a role for MINPP1 in the
pathogenesis of at least a subset of malignant follicular thyroid
tumors, and that MINPP1 might act as a low penetrance predisposition
allele for FTC.
*FIELD* AV
.0001
THYROID CARCINOMA, FOLLICULAR
MINPP1, SER41LEU
In tumor DNA from 1 patient with FTC (188470), Gimm et al. (2001)
detected a somatic C-to-T transition at nucleotide 122 of the MINPP1
gene, resulting in a ser41-to-leu mutation (S41L).
.0002
THYROID CARCINOMA, FOLLICULAR
MINPP1, GLN270ARG
In a patient with follicular thyroid adenoma, Gimm et al. (2001)
detected a germline A-to-G transition at nucleotide 809 of the MINPP1
gene, resulting in a gln270-to-arg mutation (Q270R).
.0003
THYROID ADENOMA, FOLLICULAR
MINPP1, IVS3, T-A, +34
Gimm et al. (2001) found a germline sequence variant (IVS+34T-A) in a
patient with follicular thyroid adenoma.
*FIELD* RF
1. Caffrey, J. J.; Hidaka, K.; Matsuda, M.; Hirata, M.; Shears, S.
B.: The human and rat forms of multiple inositol polyphosphate phosphatase:
functional homology with a histidine acid phosphatase up-regulated
during endochondral ossification. FEBS Lett. 442: 99-104, 1999.
2. Chi, H.; Tiller, G. E.; Dasouki, M. J.; Romano, P. R.; Wang, J.;
O'Keefe, R. J.; Puzas, J. E.; Rosier, R. N.; Reynolds, P. R.: Multiple
inositol polyphosphate phosphatase: evolution as a distinct group
within the histidine phosphatase family and chromosomal localization
of the human and mouse genes to chromosomes 10q23 and 19. Genomics 56:
324-336, 1999.
3. Chi, H.; Yang, X.; Kingsley, P. D.; O'Keefe, R. J.; Puzas, J. E.;
Rosier, R. N.; Shears, S. B.; Reynolds, P. R.: Targeted deletion
of Minpp1 provides new insight into the activity of multiple inositol
polyphosphate phosphatase in vivo. Molec. Cell. Biol. 20: 6496-6507,
2000.
4. Gimm, O.; Chi, H.; Dahia, P. L. M.; Perren, A.; Hinze, R.; Komminoth,
P.; Dralle, H.; Reynolds, P. R.; Eng, C.: Somatic mutation and germline
variants of MINPP1, a phosphatase gene located in proximity to PTEN
on 10q23.3, in follicular thyroid carcinomas. J. Clin. Endocr. Metab. 86:
1801-1805, 2001.
*FIELD* CN
John A. Phillips, III - updated: 9/24/2001
*FIELD* CD
Paul J. Converse: 11/7/2000
*FIELD* ED
alopez: 01/08/2003
cwells: 9/26/2001
cwells: 9/24/2001
mgross: 3/15/2001
mgross: 11/9/2000
mgross: 11/7/2000
*RECORD*
*FIELD* NO
605391
*FIELD* TI
*605391 MULTIPLE INOSITOL POLYPHOSPHATE PHOSPHATASE 1; MINPP1
;;MIPP, RAT, HOMOLOG OF;;
read moreHIPER1, CHICKEN, HOMOLOG OF
*FIELD* TX
DESCRIPTION
MINPP1 hydrolyzes the abundant metabolites inositol pentakisphosphate
and inositol hexakisphosphate and, like PTEN (601728), has the ability
to remove 3-phosphate from inositol phosphate substrates.
CLONING
In addition to inositol triphosphate, an important second messenger in
eukaryotic cells, there are a number of inositol polyphosphates, as well
as enzymes that affect their metabolism, that play a role in signaling
activity. The rat enzyme Mipp removes polyphosphate groups from a number
of inositol polyphosphates that contain at least 4 phosphates. The chick
gene HiPER1 (histidine phosphatase of the endoplasmic reticulum), a
homolog of Mipp, is expressed strongly in growth plate chondrocytes
transiting from proliferation to hypertrophy. By searching an EST
database with rat Mipp as the probe, Caffrey et al. (1999) identified a
cDNA encoding human MINPP1, which they called MIPP. Sequence analysis
predicted that the 487-amino acid MINPP1 protein is 84% identical to rat
Mipp and about 53% identical to chick HiPER1. The N terminus of MINPP1
contains an ER-targeting domain consisting of a relatively long
net-positive-charge (n) region, a hydrophobic core region, and a
recognition site for signal peptidases. Because of the
13-amino-acid-long n region, Caffrey et al. (1999) suggested that
translocation of MINPP1 to the ER may not require TRAM (605190), which
is needed for proteins with short (5 residues or less) n regions. MINPP1
catalytic activity appears to require sequences in the C terminus.
Western blot analysis demonstrated that MINPP1 is expressed as an
approximately 51-kD protein. Northern blot analysis detected a 2.5-kb
MINPP1 transcript in all tissues tested except for peripheral blood
leukocytes; highest expression was detected in kidney, liver, and
placenta. In situ hybridization analysis showed that Minpp1 is expressed
much more intensely in hypertrophic than in proliferating or resting rat
chondrocytes.
By RT-PCR, RACE, and library screening, Chi et al. (1999) identified a
cDNA encoding MINPP1. Northern blot analysis detected a 2.6-kb MINPP1
transcript in HeLa cells and human chondrocytes. The authors noted that
the C-terminal ER-retention signal is conserved between chick, rat, and
human MINPP1 sequences. Functional analysis showed that mouse Minpp1
converts inositol tetrakisphosphate to inositol triphosphate.
MAPPING
Using FISH, radiation hybrid analysis, and YAC screening, Chi et al.
(1999) mapped the MINPP1 gene to 10q23, proximal to the tumor suppressor
PTEN (601728), in a region that is frequently mutated in cancer. By
radiation hybrid analysis, Chi et al. (1999) mapped the mouse Minpp1
gene to chromosome 19, also in proximity to Pten.
ANIMAL MODEL
Chi et al. (2000) used homologous recombination to generate
Minpp1-deficient mice. They observed that these mice were fertile,
lacked obvious defects, and had normal chondrocyte differentiation. An
increase in levels of cytosolic inositol polyphosphates was reversible
by the introduction of Minpp1 to the ER, showing that ER-based Minpp1
plays a role in the maintenance of steady-state levels of these
polyphosphates. In contrast, introduction into the cytosol of truncated
Minpp1 lacking the ER-targeting domain reduced the polyphosphates to
below their natural levels and was accompanied by slowed cellular
proliferation.
MOLECULAR GENETICS
Germline mutations in the tumor suppressor gene PTEN, which encodes a
dual-specificity phosphatase, have been found in up to 80% of patients
with Cowden syndrome, suggesting a role of PTEN in the pathogenesis of
follicular thyroid tumors. Although somatic intragenic mutations in
PTEN, which maps to 10q23.3, are rarely found in follicular tumors, loss
of heterozygosity (LOH) of markers within 10q22-q24 occurs in about 25%.
MINPP1, another phosphatase gene, had also been mapped to 10q23.3.
MINPP1 has the ability to remove 3-phosphate from inositol phosphate
substrates, a function that overlaps that of PTEN. Because of this
overlapping function with PTEN and the physical location of MINPP1 to a
region with frequent LOH in follicular thyroid tumors, Gimm et al.
(2001) considered it to be an excellent candidate gene that could
contribute to the pathogenesis of follicular thyroid tumors. They
analyzed DNA from tumor and corresponding normal tissue from 23 patients
with follicular thyroid adenoma (FA) and 15 patients with follicular
thyroid carcinoma (FTC; 188470) for LOH or mutations at the MINPP1
locus. LOH was identified in 4 malignant and 3 benign tumors. One of
these FTCs with LOH was found to harbor a somatic ser41-to-leu mutation
(S41L; 605391.0001). They also found 2 germline sequence variants,
gln270 to arg (Q270R; 605391.0002) and IVS3+34T-A (605391.0003). Q270R
was found in only 1 patient with FA but not in patients with FTC or
normal controls. Interestingly, IVS3+34T-A was found in about 15% of FA
cases and normal controls but not in patients with FTC. The authors
concluded that these results suggest a role for MINPP1 in the
pathogenesis of at least a subset of malignant follicular thyroid
tumors, and that MINPP1 might act as a low penetrance predisposition
allele for FTC.
*FIELD* AV
.0001
THYROID CARCINOMA, FOLLICULAR
MINPP1, SER41LEU
In tumor DNA from 1 patient with FTC (188470), Gimm et al. (2001)
detected a somatic C-to-T transition at nucleotide 122 of the MINPP1
gene, resulting in a ser41-to-leu mutation (S41L).
.0002
THYROID CARCINOMA, FOLLICULAR
MINPP1, GLN270ARG
In a patient with follicular thyroid adenoma, Gimm et al. (2001)
detected a germline A-to-G transition at nucleotide 809 of the MINPP1
gene, resulting in a gln270-to-arg mutation (Q270R).
.0003
THYROID ADENOMA, FOLLICULAR
MINPP1, IVS3, T-A, +34
Gimm et al. (2001) found a germline sequence variant (IVS+34T-A) in a
patient with follicular thyroid adenoma.
*FIELD* RF
1. Caffrey, J. J.; Hidaka, K.; Matsuda, M.; Hirata, M.; Shears, S.
B.: The human and rat forms of multiple inositol polyphosphate phosphatase:
functional homology with a histidine acid phosphatase up-regulated
during endochondral ossification. FEBS Lett. 442: 99-104, 1999.
2. Chi, H.; Tiller, G. E.; Dasouki, M. J.; Romano, P. R.; Wang, J.;
O'Keefe, R. J.; Puzas, J. E.; Rosier, R. N.; Reynolds, P. R.: Multiple
inositol polyphosphate phosphatase: evolution as a distinct group
within the histidine phosphatase family and chromosomal localization
of the human and mouse genes to chromosomes 10q23 and 19. Genomics 56:
324-336, 1999.
3. Chi, H.; Yang, X.; Kingsley, P. D.; O'Keefe, R. J.; Puzas, J. E.;
Rosier, R. N.; Shears, S. B.; Reynolds, P. R.: Targeted deletion
of Minpp1 provides new insight into the activity of multiple inositol
polyphosphate phosphatase in vivo. Molec. Cell. Biol. 20: 6496-6507,
2000.
4. Gimm, O.; Chi, H.; Dahia, P. L. M.; Perren, A.; Hinze, R.; Komminoth,
P.; Dralle, H.; Reynolds, P. R.; Eng, C.: Somatic mutation and germline
variants of MINPP1, a phosphatase gene located in proximity to PTEN
on 10q23.3, in follicular thyroid carcinomas. J. Clin. Endocr. Metab. 86:
1801-1805, 2001.
*FIELD* CN
John A. Phillips, III - updated: 9/24/2001
*FIELD* CD
Paul J. Converse: 11/7/2000
*FIELD* ED
alopez: 01/08/2003
cwells: 9/26/2001
cwells: 9/24/2001
mgross: 3/15/2001
mgross: 11/9/2000
mgross: 11/7/2000