IMPA3_HUMAN
ID IMPA3_HUMAN Reviewed; 359 AA.
AC Q9NX62; Q6NVY7;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase {ECO:0000250|UniProtKB:Q80V26};
DE Short=Golgi-resident PAP phosphatase {ECO:0000250|UniProtKB:Q80V26};
DE Short=gPAPP {ECO:0000250|UniProtKB:Q80V26};
DE EC=3.1.3.7 {ECO:0000250|UniProtKB:Q80V26};
DE AltName: Full=3'(2'), 5'-bisphosphate nucleotidase 2 {ECO:0000312|HGNC:HGNC:26019};
DE AltName: Full=Inositol monophosphatase domain-containing protein 1 {ECO:0000250|UniProtKB:Q80V26};
DE AltName: Full=Myo-inositol monophosphatase A3 {ECO:0000303|Ref.1};
DE AltName: Full=Phosphoadenosine phosphate 3'-nucleotidase {ECO:0000250|UniProtKB:Q80V26};
GN Name=BPNT2 {ECO:0000312|HGNC:HGNC:26019}; Synonyms=IMPA3, IMPAD1;
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].
RA Parthasarathy L., Parthasarathy R.;
RT "Molecular cloning and expression of human myo-inositol monophosphatase A3
RT cDNA (IMPA3).";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=18695242; DOI=10.1073/pnas.0801182105;
RA Frederick J.P., Tafari A.T., Wu S.M., Megosh L.C., Chiou S.T., Irving R.P.,
RA York J.D.;
RT "A role for a lithium-inhibited Golgi nucleotidase in skeletal development
RT and sulfation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11605-11612(2008).
RN [5]
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 [6]
RP IDENTIFICATION BY MASS 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 [7]
RP ACETYLATION AT MET-1.
RX PubMed=25732826; DOI=10.1016/j.celrep.2015.01.053;
RA Aksnes H., Van Damme P., Goris M., Starheim K.K., Marie M., Stoeve S.I.,
RA Hoel C., Kalvik T.V., Hole K., Glomnes N., Furnes C., Ljostveit S.,
RA Ziegler M., Niere M., Gevaert K., Arnesen T.;
RT "An organellar nalpha-acetyltransferase, naa60, acetylates cytosolic N
RT termini of transmembrane proteins and maintains Golgi integrity.";
RL Cell Rep. 10:1362-1374(2015).
RN [8]
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 [9]
RP VARIANTS CDP-GPAPP ASN-177 AND PRO-183.
RX PubMed=21549340; DOI=10.1016/j.ajhg.2011.04.002;
RA Vissers L.E., Lausch E., Unger S., Campos-Xavier A.B., Gilissen C.,
RA Rossi A., Del Rosario M., Venselaar H., Knoll U., Nampoothiri S., Nair M.,
RA Spranger J., Brunner H.G., Bonafe L., Veltman J.A., Zabel B.,
RA Superti-Furga A.;
RT "Chondrodysplasia and abnormal joint development associated with mutations
RT in IMPAD1, encoding the Golgi-resident nucleotide phosphatase, gPAPP.";
RL Am. J. Hum. Genet. 88:608-615(2011).
CC -!- FUNCTION: Exhibits 3'-nucleotidase activity toward adenosine 3',5'-
CC bisphosphate (PAP), namely hydrolyzes adenosine 3',5'-bisphosphate into
CC adenosine 5'-monophosphate (AMP) and a phosphate. May play a role in
CC the formation of skeletal elements derived through endochondral
CC ossification, possibly by clearing adenosine 3',5'-bisphosphate
CC produced by Golgi sulfotransferases during glycosaminoglycan sulfation.
CC Has no activity toward 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or
CC inositol phosphate (IP) substrates including I(1)P, I(1,4)P2,
CC I(1,3,4)P3, I(1,4,5)P3 and I(1,3,4,5)P4.
CC {ECO:0000250|UniProtKB:Q80V26}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine 3',5'-bisphosphate + H2O = AMP + phosphate;
CC Xref=Rhea:RHEA:10040, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:456215; EC=3.1.3.7;
CC Evidence={ECO:0000250|UniProtKB:Q80V26};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Strongly inhibited by lithium.
CC {ECO:0000250|UniProtKB:Q80V26}.
CC -!- PATHWAY: Sulfur metabolism. {ECO:0000250|UniProtKB:Q80V26}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000269|PubMed:18695242}.
CC Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:18695242}; Single-pass type II membrane protein
CC {ECO:0000255, ECO:0000269|PubMed:18695242}. Note=The catalytic core is
CC predicted to reside within the Golgi lumen.
CC {ECO:0000269|PubMed:18695242}.
CC -!- PTM: Contains N-linked glycan resistant to endoglycosydase H.
CC {ECO:0000269|PubMed:18695242}.
CC -!- DISEASE: Chondrodysplasia with joint dislocations, GPAPP type (CDP-
CC GPAPP) [MIM:614078]: A condition consisting of congenital joint
CC dislocations, chondrodysplasia with short stature, micrognathia and
CC cleft palate, and a distinctive face. {ECO:0000269|PubMed:21549340}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the inositol monophosphatase superfamily.
CC {ECO:0000305}.
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DR EMBL; AK000428; BAA91158.1; -; mRNA.
DR EMBL; AY032885; AAK52336.1; -; mRNA.
DR EMBL; BC017797; AAH17797.1; -; mRNA.
DR EMBL; BC067814; AAH67814.1; -; mRNA.
DR CCDS; CCDS6169.1; -.
DR RefSeq; NP_060283.3; NM_017813.4.
DR AlphaFoldDB; Q9NX62; -.
DR SMR; Q9NX62; -.
DR BioGRID; 120268; 46.
DR IntAct; Q9NX62; 21.
DR MINT; Q9NX62; -.
DR STRING; 9606.ENSP00000262644; -.
DR DEPOD; IMPAD1; -.
DR GlyConnect; 1400; 14 N-Linked glycans (1 site).
DR GlyGen; Q9NX62; 2 sites, 13 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q9NX62; -.
DR MetOSite; Q9NX62; -.
DR PhosphoSitePlus; Q9NX62; -.
DR BioMuta; IMPAD1; -.
DR DMDM; 74734687; -.
DR EPD; Q9NX62; -.
DR jPOST; Q9NX62; -.
DR MassIVE; Q9NX62; -.
DR MaxQB; Q9NX62; -.
DR PaxDb; Q9NX62; -.
DR PeptideAtlas; Q9NX62; -.
DR PRIDE; Q9NX62; -.
DR ProteomicsDB; 83047; -.
DR Antibodypedia; 2290; 106 antibodies from 23 providers.
DR DNASU; 54928; -.
DR Ensembl; ENST00000262644.9; ENSP00000262644.4; ENSG00000104331.9.
DR GeneID; 54928; -.
DR KEGG; hsa:54928; -.
DR MANE-Select; ENST00000262644.9; ENSP00000262644.4; NM_017813.5; NP_060283.3.
DR UCSC; uc003xte.5; human.
DR CTD; 54928; -.
DR DisGeNET; 54928; -.
DR GeneCards; BPNT2; -.
DR HGNC; HGNC:26019; BPNT2.
DR HPA; ENSG00000104331; Low tissue specificity.
DR MalaCards; BPNT2; -.
DR MIM; 614010; gene.
DR MIM; 614078; phenotype.
DR neXtProt; NX_Q9NX62; -.
DR OpenTargets; ENSG00000104331; -.
DR Orphanet; 280586; Chondrodysplasia with joint dislocations, gPAPP type.
DR VEuPathDB; HostDB:ENSG00000104331; -.
DR eggNOG; KOG3853; Eukaryota.
DR GeneTree; ENSGT00940000160216; -.
DR HOGENOM; CLU_034742_0_0_1; -.
DR InParanoid; Q9NX62; -.
DR OMA; GNSMSEY; -.
DR OrthoDB; 1096950at2759; -.
DR PhylomeDB; Q9NX62; -.
DR TreeFam; TF314300; -.
DR BioCyc; MetaCyc:HS02567-MON; -.
DR PathwayCommons; Q9NX62; -.
DR Reactome; R-HSA-156584; Cytosolic sulfonation of small molecules.
DR SignaLink; Q9NX62; -.
DR BioGRID-ORCS; 54928; 20 hits in 1076 CRISPR screens.
DR ChiTaRS; IMPAD1; human.
DR GenomeRNAi; 54928; -.
DR Pharos; Q9NX62; Tbio.
DR PRO; PR:Q9NX62; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9NX62; protein.
DR Bgee; ENSG00000104331; Expressed in medial globus pallidus and 202 other tissues.
DR ExpressionAtlas; Q9NX62; baseline and differential.
DR Genevisible; Q9NX62; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0008441; F:3'(2'),5'-bisphosphate nucleotidase activity; IEA:UniProtKB-EC.
DR GO; GO:0097657; F:3',5'-nucleotide bisphosphate phosphatase activity; ISS:UniProtKB.
DR GO; GO:0008254; F:3'-nucleotidase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002063; P:chondrocyte development; IEA:Ensembl.
DR GO; GO:0030204; P:chondroitin sulfate metabolic process; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IEA:InterPro.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IEA:InterPro.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IBA:GO_Central.
DR InterPro; IPR000760; Inositol_monophosphatase-like.
DR InterPro; IPR020550; Inositol_monophosphatase_CS.
DR Pfam; PF00459; Inositol_P; 1.
DR PROSITE; PS00630; IMP_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Disease variant; Glycoprotein; Golgi apparatus; Hydrolase;
KW Magnesium; Membrane; Metal-binding; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..359
FT /note="Golgi-resident adenosine 3',5'-bisphosphate 3'-
FT phosphatase"
FT /id="PRO_0000289041"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..359
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 86..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 133
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 174
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 174
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 176
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 177
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 300
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:25732826"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:18695242"
FT VARIANT 177
FT /note="D -> N (in CDP-GPAPP; dbSNP:rs387907101)"
FT /evidence="ECO:0000269|PubMed:21549340"
FT /id="VAR_065847"
FT VARIANT 183
FT /note="T -> P (in CDP-GPAPP; dbSNP:rs387907102)"
FT /evidence="ECO:0000269|PubMed:21549340"
FT /id="VAR_065848"
FT CONFLICT 51
FT /note="G -> E (in Ref. 3; AAH67814)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="T -> A (in Ref. 3; AAH67814)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="K -> E (in Ref. 3; AAH67814)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 38681 MW; 4818E989A9684847 CRC64;
MAPMGIRLSP LGVAVFCLLG LGVLYHLYSG FLAGRFSLFG LGGEPGGGAA GPAAAADGGT
VDLREMLAVS VLAAVRGGDE VRRVRESNVL HEKSKGKTRE GAEDKMTSGD VLSNRKMFYL
LKTAFPSVQI NTEEHVDAAD QEVILWDHKI PEDILKEVTT PKEVPAESVT VWIDPLDATQ
EYTEDLRKYV TTMVCVAVNG KPMLGVIHKP FSEYTAWAMV DGGSNVKARS SYNEKTPRIV
VSRSHSGMVK QVALQTFGNQ TTIIPAGGAG YKVLALLDVP DKSQEKADLY IHVTYIKKWD
ICAGNAILKA LGGHMTTLSG EEISYTGSDG IEGGLLASIR MNHQALVRKL PDLEKTGHK
