IMPA3_MOUSE
ID IMPA3_MOUSE Reviewed; 356 AA.
AC Q80V26; A6H6P6;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase {ECO:0000305|PubMed:18695242};
DE Short=Golgi-resident PAP phosphatase {ECO:0000303|PubMed:18695242};
DE Short=gPAPP {ECO:0000303|PubMed:18695242};
DE EC=3.1.3.7 {ECO:0000269|PubMed:18695242};
DE AltName: Full=3'(2'), 5'-bisphosphate nucleotidase 2;
DE AltName: Full=Inositol monophosphatase domain-containing protein 1 {ECO:0000303|PubMed:18695242};
DE AltName: Full=Myo-inositol monophosphatase A3 {ECO:0000250|UniProtKB:Q9NX62};
DE AltName: Full=Phosphoadenosine phosphate 3'-nucleotidase {ECO:0000303|PubMed:18695242};
GN Name=Bpnt2 {ECO:0000312|MGI:MGI:1915720};
GN Synonyms=Impa3 {ECO:0000312|MGI:MGI:1915720},
GN Impad1 {ECO:0000312|MGI:MGI:1915720};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TOPOLOGY, DISRUPTION
RP PHENOTYPE, AND PATHWAY.
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].
RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (PubMed:18695242). May
CC play a role in the formation of skeletal elements derived through
CC endochondral ossification, possibly by clearing adenosine 3',5'-
CC bisphosphate produced by Golgi sulfotransferases during
CC glycosaminoglycan sulfation (PubMed:18695242). Has no activity toward
CC 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or inositol phosphate (IP)
CC substrates including I(1)P, I(1,4)P2, I(1,3,4)P3, I(1,4,5)P3 and
CC I(1,3,4,5)P4. {ECO:0000269|PubMed:18695242}.
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:0000269|PubMed:18695242};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Strongly inhibited by lithium.
CC {ECO:0000269|PubMed:18695242}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21 uM for 3'-phosphoadenosine 5'- phosphate (PAP)
CC {ECO:0000269|PubMed:18695242};
CC Vmax=9.5 umol/min/mg enzyme {ECO:0000269|PubMed:18695242};
CC -!- PATHWAY: Sulfur metabolism. {ECO:0000305|PubMed:18695242}.
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:0000250|UniProtKB:Q9NX62}. Note=The catalytic core is predicted to
CC reside within the Golgi lumen. {ECO:0000250|UniProtKB:Q9NX62}.
CC -!- DEVELOPMENTAL STAGE: At 18.5 dpc, widely expressed with enhanced levels
CC in brain, spinal cord, lung and kidney, including medulla and cortex.
CC In the developing brain, strongly expressed in the neopallial cortex
CC and throughout the cerebellum with intense expression within the
CC developing Purkinje cells and adjacent choroid plexus. Strong
CC expression also observed within the pons and throughout the medulla
CC oblongata. In the lung, expressed in individual pneumocytes and
CC particularly in cells surrounding developing bronchi/bronchioles.
CC Moderate expression in chondrocytes of costal cartilage and in the
CC surrounding perichondrium. {ECO:0000269|PubMed:18695242}.
CC -!- PTM: N-glycosylated (By similarity). Contains N-linked glycan resistant
CC to endoglycosydase H (By similarity). {ECO:0000250|UniProtKB:Q9NX62}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals experience severe respiratory
CC distress and died within minutes after birth. At 18.5 dpc, lungs
CC exhibit small alveolar spaces and thickened septa. The rib cage
CC cartilage is hypocellular with abnormal, fibrous-appearing
CC extracellular matrix. Animals show severe skeletal abnormalities, most
CC notably in the longitudinal growth of bones formed by endochondral
CC ossification. The length of the axial skeleton is reduced. The
CC appendicular bones of the upper limbs, as well as the ilium, femur,
CC tibia and fibula of the lower limbs are markedly shorter than in wild-
CC type littermates. The rib cages display malformation characterized by
CC reduced sternal length and correspondingly diminished rib spacing. The
CC process of intramembranous ossification is normal. Mutant animals
CC exhibit a deficiency in glycosaminoglycan sulfation. Mutant cartilage
CC and lung exhibit a substantial decrease in chondroitin 4-sulfate and an
CC increase in nonsulfated chondroitin compared with wild type tissue.
CC {ECO:0000269|PubMed:18695242}.
CC -!- SIMILARITY: Belongs to the inositol monophosphatase superfamily.
CC {ECO:0000305}.
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DR EMBL; AL772346; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466538; EDL05698.1; -; Genomic_DNA.
DR EMBL; BC048776; AAH48776.1; -; mRNA.
DR EMBL; BC138209; AAI38210.1; -; mRNA.
DR EMBL; BC145952; AAI45953.1; -; mRNA.
DR CCDS; CCDS17947.1; -.
DR RefSeq; NP_808398.1; NM_177730.3.
DR AlphaFoldDB; Q80V26; -.
DR SMR; Q80V26; -.
DR BioGRID; 232391; 2.
DR STRING; 10090.ENSMUSP00000082013; -.
DR GlyGen; Q80V26; 1 site.
DR PhosphoSitePlus; Q80V26; -.
DR SwissPalm; Q80V26; -.
DR EPD; Q80V26; -.
DR jPOST; Q80V26; -.
DR MaxQB; Q80V26; -.
DR PaxDb; Q80V26; -.
DR PeptideAtlas; Q80V26; -.
DR PRIDE; Q80V26; -.
DR ProteomicsDB; 267333; -.
DR TopDownProteomics; Q80V26; -.
DR Antibodypedia; 2290; 106 antibodies from 23 providers.
DR DNASU; 242291; -.
DR Ensembl; ENSMUST00000084949; ENSMUSP00000082013; ENSMUSG00000066324.
DR GeneID; 242291; -.
DR KEGG; mmu:242291; -.
DR UCSC; uc008rxc.2; mouse.
DR CTD; 54928; -.
DR MGI; MGI:1915720; Bpnt2.
DR VEuPathDB; HostDB:ENSMUSG00000066324; -.
DR eggNOG; KOG3853; Eukaryota.
DR GeneTree; ENSGT00940000160216; -.
DR HOGENOM; CLU_034742_0_0_1; -.
DR InParanoid; Q80V26; -.
DR OMA; GNSMSEY; -.
DR OrthoDB; 1096950at2759; -.
DR PhylomeDB; Q80V26; -.
DR TreeFam; TF314300; -.
DR BRENDA; 3.1.3.7; 3474.
DR Reactome; R-MMU-156584; Cytosolic sulfonation of small molecules.
DR BioGRID-ORCS; 242291; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Impad1; mouse.
DR PRO; PR:Q80V26; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q80V26; protein.
DR Bgee; ENSMUSG00000066324; Expressed in rostral migratory stream and 259 other tissues.
DR Genevisible; Q80V26; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA: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; IDA:UniProtKB.
DR GO; GO:0008254; F:3'-nucleotidase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002063; P:chondrocyte development; IMP:MGI.
DR GO; GO:0030204; P:chondroitin sulfate metabolic process; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
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; Glycoprotein; Golgi apparatus; Hydrolase; Magnesium; Membrane;
KW Metal-binding; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..356
FT /note="Golgi-resident adenosine 3',5'-bisphosphate 3'-
FT phosphatase"
FT /id="PRO_0000289042"
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..356
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 84..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 131
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 172
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 172
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
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 175
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1N4"
FT BINDING 298
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:0000250|UniProtKB:Q9NX62"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 356 AA; 38616 MW; F01BF0082F5C7C82 CRC64;
MAPMGIRLSP LGVAVFFLLG LGVLYHLYSG FLAGRFSLFG LGSEPAAGEA EVASDGGTVD
LREMLAVAVL AAERGGDEVR RVRESNVLHE KSKGKTREGA DDKMTSGDVL SNRKMFYLLK
TAFPNVQINT EEHVDASDKE VIVWNRKIPE DILKEIAAPK EVPAESVTVW IDPLDATQEY
TEDLRKYVTT MVCVAVNGKP VLGVIHKPFS EYTAWAMVDG GSNVKARSSY NEKTPKIIVS
RSHAGMVKQV ALQTFGNQTS IIPAGGAGYK VLALLDVPDM TQEKADLYIH VTYIKKWDIC
AGNAILKALG GHMTTLNGEE ISYTGSDGIE GGLLASIRMN HQALVRKLPD LEKSGH
