ATP7B_MOUSE
ID ATP7B_MOUSE Reviewed; 1462 AA.
AC Q64446; B1AQ56;
DT 08-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Copper-transporting ATPase 2;
DE EC=7.2.2.8 {ECO:0000250|UniProtKB:P35670};
DE AltName: Full=Copper pump 2;
DE AltName: Full=Wilson disease-associated protein homolog;
GN Name=Atp7b; Synonyms=Wnd;
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 [MRNA], AND INVOLVEMENT IN TX PHENOTYPE.
RC STRAIN=DAT; TISSUE=Liver;
RX PubMed=8894697; DOI=10.1093/hmg/5.10.1619;
RA Theophilos M.B., Cox D.W., Mercer J.F.B.;
RT "The toxic milk mouse is a murine model of Wilson disease.";
RL Hum. Mol. Genet. 5:1619-1624(1996).
RN [2]
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 [3]
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
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: Copper ion transmembrane transporter involved in the export
CC of copper out of the cells, such as the efflux of hepatic copper into
CC the bile. {ECO:0000250|UniProtKB:P35670}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Cu(+)(in) + H2O = ADP + Cu(+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:25792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:49552,
CC ChEBI:CHEBI:456216; EC=7.2.2.8;
CC Evidence={ECO:0000250|UniProtKB:P35670};
CC -!- SUBUNIT: Monomer. Interacts with COMMD1/MURR1 (By similarity).
CC Interacts with DCTN4, in a copper-dependent manner (By similarity).
CC Interacts with ATOX1 (By similarity). Interacts (via C-terminus) with
CC ZBTB16/PLZF (By similarity). {ECO:0000250|UniProtKB:P35670}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:P35670}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome {ECO:0000250|UniProtKB:P35670}.
CC Note=Predominantly found in the trans-Golgi network (TGN). Not
CC redistributed to the plasma membrane in response to elevated copper
CC levels. {ECO:0000250|UniProtKB:P35670}.
CC -!- TISSUE SPECIFICITY: Detected in liver and kidney.
CC -!- DOMAIN: Each HMA domain can bind a copper ion, they are tightly packed
CC and closely interact with each other. Wild-type ATP7B can usually be
CC loaded with an average 5.5 copper atoms per molecule (By similarity).
CC {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Atp7b are the cause of the toxic milk mouse
CC mutant (tx) phenotype, characterized by accumulation of copper in the
CC liver in a manner similar to that observed in patients with Wilson
CC disease. {ECO:0000269|PubMed:8894697}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IB subfamily. {ECO:0000305}.
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DR EMBL; U38477; AAC52852.1; -; mRNA.
DR EMBL; AC163439; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590619; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466580; EDL32910.1; -; Genomic_DNA.
DR CCDS; CCDS22168.1; -.
DR RefSeq; NP_031537.2; NM_007511.2.
DR AlphaFoldDB; Q64446; -.
DR SMR; Q64446; -.
DR BioGRID; 198269; 4.
DR STRING; 10090.ENSMUSP00000006742; -.
DR iPTMnet; Q64446; -.
DR PhosphoSitePlus; Q64446; -.
DR MaxQB; Q64446; -.
DR PaxDb; Q64446; -.
DR PRIDE; Q64446; -.
DR ProteomicsDB; 277215; -.
DR Antibodypedia; 2396; 531 antibodies from 37 providers.
DR DNASU; 11979; -.
DR Ensembl; ENSMUST00000006742; ENSMUSP00000006742; ENSMUSG00000006567.
DR GeneID; 11979; -.
DR KEGG; mmu:11979; -.
DR UCSC; uc009lck.1; mouse.
DR CTD; 540; -.
DR MGI; MGI:103297; Atp7b.
DR VEuPathDB; HostDB:ENSMUSG00000006567; -.
DR eggNOG; KOG0207; Eukaryota.
DR GeneTree; ENSGT00940000155749; -.
DR InParanoid; Q64446; -.
DR OMA; NSWISGT; -.
DR OrthoDB; 649559at2759; -.
DR PhylomeDB; Q64446; -.
DR TreeFam; TF300460; -.
DR BRENDA; 7.2.2.8; 3474.
DR BRENDA; 7.2.2.9; 3474.
DR Reactome; R-MMU-936837; Ion transport by P-type ATPases.
DR BioGRID-ORCS; 11979; 3 hits in 71 CRISPR screens.
DR PRO; PR:Q64446; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q64446; protein.
DR Bgee; ENSMUSG00000006567; Expressed in yolk sac and 96 other tissues.
DR ExpressionAtlas; Q64446; baseline and differential.
DR Genevisible; Q64446; MM.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005923; C:bicellular tight junction; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; ISS:HGNC.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0070160; C:tight junction; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; IDA:MGI.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISS:HGNC-UCL.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005507; F:copper ion binding; ISS:HGNC-UCL.
DR GO; GO:0005375; F:copper ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0043682; F:P-type divalent copper transporter activity; IDA:MGI.
DR GO; GO:0140581; F:P-type monovalent copper transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:MGI.
DR GO; GO:0071280; P:cellular response to copper ion; ISO:MGI.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IMP:MGI.
DR GO; GO:0060003; P:copper ion export; ISO:MGI.
DR GO; GO:0055070; P:copper ion homeostasis; IBA:GO_Central.
DR GO; GO:0015677; P:copper ion import; ISO:MGI.
DR GO; GO:0006825; P:copper ion transport; IDA:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0007595; P:lactation; IMP:MGI.
DR GO; GO:0015680; P:protein maturation by copper ion transfer; IMP:MGI.
DR GO; GO:0046688; P:response to copper ion; ISO:MGI.
DR GO; GO:0051208; P:sequestering of calcium ion; ISO:MGI.
DR CDD; cd00371; HMA; 6.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR017969; Heavy-metal-associated_CS.
DR InterPro; IPR006122; HMA_Cu_ion-bd.
DR InterPro; IPR006121; HMA_dom.
DR InterPro; IPR036163; HMA_dom_sf.
DR InterPro; IPR027256; P-typ_ATPase_IB.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF00403; HMA; 6.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF55008; SSF55008; 6.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01525; ATPase-IB_hvy; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR TIGRFAMs; TIGR00003; TIGR00003; 5.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
DR PROSITE; PS01047; HMA_1; 5.
DR PROSITE; PS50846; HMA_2; 6.
PE 1: Evidence at protein level;
KW ATP-binding; Copper; Copper transport; Disease variant; Endosome;
KW Golgi apparatus; Ion transport; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1462
FT /note="Copper-transporting ATPase 2"
FT /id="PRO_0000046315"
FT TOPO_DOM 1..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 656..677
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 678..699
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 700..719
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 720..726
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 727..747
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 748..766
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 767..787
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 788..921
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 922..944
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 945..974
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 975..996
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 997..1319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1320..1337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1338..1348
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1349..1368
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1369..1462
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 68..134
FT /note="HMA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 153..219
FT /note="HMA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 267..333
FT /note="HMA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 361..427
FT /note="HMA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 490..556
FT /note="HMA 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 566..632
FT /note="HMA 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..361
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 471..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1029
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 82
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 164
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 167
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 278
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 281
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 372
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000305"
FT BINDING 501
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 504
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 577
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 580
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 1264
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 1268
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64535"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64535"
FT MOD_RES 1395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64535"
FT MOD_RES 1454
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64535"
FT VARIANT 1356
FT /note="M -> V (in tx mice)"
FT CONFLICT 107..108
FT /note="SA -> KH (in Ref. 1; AAC52852)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1462 AA; 157190 MW; BEC219F80EB74214 CRC64;
MDPRKNLASV GTMPEQERQV TAKEASRKIL SKLALPGRPW EQSMKQSFAF DNVGYEGGLD
STSSSPAATD VVNILGMTCH SCVKSIEDRI SSLKGIVNIK VSLEQGSATV RYVPSVMNLQ
QICLQIEDMG FEASAAEGKA ASWPSRSSPA QEAVVKLRVE GMTCQSCVSS IEGKIRKLQG
VVRIKVSLSN QEAVITYQPY LIQPEDLRDH ICDMGFEAAI KNRTAPLRLG PIDVNKLEST
NLKKETVSPV QISNHFETLG HQGSYLATLP LRIDGMHCKS CVLNIEGNIG QLPGVQNIHV
SLENKTAQIQ YDPSCVTPMF LQTAIEALPP GHFKVSLPDG VEENEPQSGS SQRHQEQGPG
RTAVLTISGI TCASSVQPIE DMLSQRKGVQ QTSISLAEGT GAVLYDPSIV SLDELRTAVE
DMGFEVSVNS ETFTINPVRN FKSGNSVPQT MGDIAGSVQK MAPDTRGLPT HQGPGHSSET
PSSPGATASQ KCFVQIKGMT CASCVSNIER SLQRHAGILS VLVALMSGKA EVKYDPEIIQ
SPRIAQLIQD LGFEASVMED NTVSEGDIEL IITGMTCASC VHNIESKLTR TNGITYASVA
LATSKAHVKF DPEIVGPRDI IKIIEEIGFH ASLAQRNPNA HHLDHKTEIK QWKKSFLCSL
VFGIPVMGLM VYMLIPSSTP QETMVLDHNI IPGLSVLNLI FFILCTFVQF LGGWYFYVQA
YKSLRHRSAN MDVLIVLATT IAYAYSLVIL VVAVAEKAEK SPVTFFDTPP MLFVFIALGR
WLEHVAKSKT SEALAKLMSL QATEATVVTL GEDNLILREE QVPMELVQRG DVIKVVPGGK
FPVDGKVLEG NTMADESLIT GEAMPVTKKP GSIVIAGSIN AHGSVLLKAT HVGNDTTLAQ
IVKLVEEAQM SKAPIQQLAD RFSGYFVPFI IIISTLTLVV WIVIGFVDFG VVQKYFPSPS
KHISQTEVII RFAFQTSITV LCIACPCSLG LATPTAVMVG TGVAAQNGVL IKGGKPLEMA
HKIKTVMFDK TGTITHGVPR VMRFLLLADV ATLPLRKVLA VVGTAEASSE HPLGVAVTKY
CKEELGTETL GYSTDFQAVP GCGISCKVSN VEGILARSDL TAHPVGVGNP PTGEGAGPQT
FSVLIGNREW MRRNGLTISS DISDAMTDHE MKGQTAILVA IDGVLCGMIA IADAVKPEAA
LAIYTLKSMG VDVALITGDN RKTARAIATQ VGINKVFAEV LPSHKVAKVQ ELQNEGKKVA
MVGDGVNDSP ALAQADVGIA IGTGTDVAIE AADVVLIRND LLDVVASIHL SKRTVRRIRV
NLVLALIYNM VGIPIAAGVF MPIGIVLQPW MGSAAMAASS VSVVLSSLQL KCYRKPDLER
YEAQAHGRMK PLSASQVSVH IGMDDRRRDS PRATAWDQVS YVSQVSLSSL TSDRLSRHGG
AAEDGGDKWS LLLSDRDEEQ CI
