ATP7B_RAT
ID ATP7B_RAT Reviewed; 1451 AA.
AC Q64535; Q63676; Q9JLY3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 171.
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=Pineal night-specific ATPase;
DE AltName: Full=Wilson disease-associated protein homolog;
GN Name=Atp7b; Synonyms=Pina, Wnd;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INVOLVEMENT IN LEC.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7951327; DOI=10.1038/ng0894-541;
RA Wu J., Forbes J.R., Chen H.S., Cox D.W.;
RT "The LEC rat has a deletion in the copper transporting ATPase gene
RT homologous to the Wilson disease gene.";
RL Nat. Genet. 7:541-545(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC STRAIN=Sprague-Dawley; TISSUE=Pineal gland;
RX PubMed=9920665; DOI=10.1523/jneurosci.19-03-01018.1999;
RA Borjigin J., Payne A.S., Deng J., Li X., Wang M.M., Ovodenko B.,
RA Gitlin J.D., Snyder S.H.;
RT "A novel pineal night-specific ATPase encoded by the Wilson disease gene.";
RL J. Neurosci. 19:1018-1026(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 530-616, AND INVOLVEMENT IN LEC.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8037655; DOI=10.1042/bj3010001;
RA Yamaguchi Y., Heiny M.E., Shimizu N., Aoki T., Gitlin J.D.;
RT "Expression of the Wilson disease gene is deficient in the Long-Evans
RT Cinnamon rat.";
RL Biochem. J. 301:1-4(1994).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469; SER-471; SER-474;
RP SER-1384 AND SER-1443, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Name=Long;
CC IsoId=Q64535-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q64535-2; Sequence=VSP_000428;
CC Name=PINAM2;
CC IsoId=Q64535-3; Sequence=VSP_018666;
CC -!- TISSUE SPECIFICITY: Expressed in brain, liver, kidney, spleen and
CC stomach. In brain, detected in neuronal cells of the hippocampal
CC formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in
CC the brainstem. Isoform PINA is expressed during night in adult pineal
CC gland (pinealocytes) and retina. Isoform PINA is not detected in other
CC tissue.
CC -!- DEVELOPMENTAL STAGE: Isoform PINA is expressed during daytime in
CC embryonic pineal (postnatal day 2 and 7) and embryonic retinal pigment
CC epithelium (embryonic day 14.5 and postnatal day 16). Daytime
CC expression disappears in pineal at postnatal day 16 and in adult
CC retina.
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=Deficiency of Atp7b expression is the cause of the Long-
CC Evans Cinnamon (LEC) phenotype, inherited in an autosomal recessive
CC manner, characterized by excessive hepatic copper accumulation,
CC defective holoceruloplasmin biosynthesis, impaired biliary copper
CC excretion and the development of necrotizing hepatitis by 4 months of
CC age. {ECO:0000269|PubMed:7951327, ECO:0000269|PubMed:8037655}.
CC -!- MISCELLANEOUS: [Isoform Short]: Produced by alternative splicing. Does
CC not show copper transport activity. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform PINAM2]: Produced by alternative initiation at
CC Met-815 of isoform Long. Shows copper transport activity.
CC {ECO:0000305}.
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; U08344; AAA62157.1; -; mRNA.
DR EMBL; AF120492; AAD16009.1; -; mRNA.
DR EMBL; L28173; AAA21810.1; -; mRNA.
DR PIR; I58124; I58124.
DR AlphaFoldDB; Q64535; -.
DR SMR; Q64535; -.
DR STRING; 10116.ENSRNOP00000054880; -.
DR iPTMnet; Q64535; -.
DR PhosphoSitePlus; Q64535; -.
DR PaxDb; Q64535; -.
DR PRIDE; Q64535; -.
DR UCSC; RGD:2180; rat. [Q64535-1]
DR RGD; 2180; Atp7b.
DR eggNOG; KOG0207; Eukaryota.
DR InParanoid; Q64535; -.
DR PhylomeDB; Q64535; -.
DR BRENDA; 7.2.2.9; 5301.
DR Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR PRO; PR:Q64535; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0005923; C:bicellular tight junction; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0070160; C:tight junction; IDA:RGD.
DR GO; GO:0005802; C:trans-Golgi network; IDA:RGD.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005507; F:copper ion binding; IDA:RGD.
DR GO; GO:0005375; F:copper ion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0043682; F:P-type divalent copper transporter activity; ISS:UniProtKB.
DR GO; GO:0140581; F:P-type monovalent copper transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0006878; P:cellular copper ion homeostasis; ISO:RGD.
DR GO; GO:0071280; P:cellular response to copper ion; IMP:RGD.
DR GO; GO:0071287; P:cellular response to manganese ion; IEP:RGD.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0060003; P:copper ion export; IMP:RGD.
DR GO; GO:0055070; P:copper ion homeostasis; IBA:GO_Central.
DR GO; GO:0015677; P:copper ion import; ISO:RGD.
DR GO; GO:0006825; P:copper ion transport; ISO:RGD.
DR GO; GO:0007595; P:lactation; IEP:RGD.
DR GO; GO:0015680; P:protein maturation by copper ion transfer; ISO:RGD.
DR GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR GO; GO:0046688; P:response to copper ion; IEP:RGD.
DR GO; GO:1990637; P:response to prolactin; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0051208; P:sequestering of calcium ion; ISO:RGD.
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; 5.
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 Alternative initiation; Alternative splicing; ATP-binding;
KW Biological rhythms; Copper; Copper transport; Endosome; Golgi apparatus;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1451
FT /note="Copper-transporting ATPase 2"
FT /id="PRO_0000002511"
FT TOPO_DOM 1..646
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 647..668
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 669..690
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 691..710
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 711..717
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 718..738
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 739..757
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 758..778
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 779..912
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 913..935
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 936..965
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 966..987
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 988..1310
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1311..1328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1329..1339
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1340..1357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1358..1451
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 57..123
FT /note="HMA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 142..208
FT /note="HMA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 256..322
FT /note="HMA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 355..421
FT /note="HMA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 481..547
FT /note="HMA 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 557..623
FT /note="HMA 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT REGION 328..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1020
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 68
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 71
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 153
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 156
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 267
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 270
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 492
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 495
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 568
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 571
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 1255
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 1259
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1384
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1443
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 1..814
FT /note="Missing (in isoform PINAM2)"
FT /evidence="ECO:0000305"
FT /id="VSP_018666"
FT VAR_SEQ 1..788
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:9920665"
FT /id="VSP_000428"
FT CONFLICT 1194..1195
FT /note="SI -> IY (in Ref. 2; AAD16009)"
FT /evidence="ECO:0000305"
FT CONFLICT 1281
FT /note="D -> E (in Ref. 2; AAD16009)"
FT /evidence="ECO:0000305"
FT CONFLICT 1346
FT /note="A -> AMA (in Ref. 2; AAD16009)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1451 AA; 155990 MW; 2029940643318401 CRC64;
MPEQERKVTA KEASRKILSK LALPTRPWGQ SMKQSFAFDN VGYEGGLDST CFILQLTTGV
VSILGMTCHS CVKSIEDRIS SLKGIVSIKV SLEQGSATVK YVPSVLNLQQ ICLQIEDMGF
EASAAEGKAA SWPSRSSPAQ EAVVKLRVEG MTCQSCVSSI EGKIRKLQGV VRVKVSLSNQ
EAVITYQPYL IQPEDLRDHI CDMGFEAAIK NRTAPLRLGP IDINKLESTN LKRAAVPPIQ
NSNHLETPGH QQNHLATLPL RIDGMHCKSC VLNIEGNIGQ LPGVQNIHVS LENKTAQVQY
DSSCITPLFL QTAIEALPPG YFKVSLPDGL EKESGSSSVP SLGSSQRQQE PGPCRTAVLT
ITGIPRDSSV QPMEDMLSQM KGVQQIDISL AEGTGAVLYD PSVVSSDELR TAVEDMGFEV
SVNPENITTN RVSSGNSVPQ AVGDSPGSVQ NMASDTRGLL THQGPGYLSD SPPSPGGTAS
QKCFVQIKGM TCASCVSNIE RSLQRHAGIL SVLVALMSGK AEVKYDPEVI QSPRIAQLIE
DLGFEAAIME DNTVSEGDIE LIITGMTCAS CVHNIESKLT RTNGITYASV ALATSKAHVK
FDPEIIGPRD IIKVIEEIGF HASLAHRNPN AHHLDHKTEI KQWKKSFLCS LVFGIPVMGL
MIYMLIPSSK PHETMVLDHN IIPGLSVLNL IFFILCTFVQ FLGGWYFYVQ AYKSLRHKSA
NMDVLIVLAT TIAYAYSLVI LVVAIAEKAE KSPVTFFDTP PMLFVFIALG RWLEHVAKSK
TSEALAKLMS LQATEATVVT LGEDNLILRE EQVPMELVQR GDIIKVVPGG KFPVDGKVLE
GNTMADESLI TGEAMPVTKK PGSIVIAGSI NAHGSVLIKA THVGNDTTLA QIVKLVEEAQ
MSKAPIQQLA DRFSGYFVPF IIIISTLTLV VWIIIGFVDF GIVQKYFPSP SKHISQTEVI
IRFAFQTSIT VLCIACPCSL GLATPTAVMV GTGVAAQNGV LIKGGKPLEM AHKIKTVMFD
KTGTITHGVP RVMRFLLLVD VATLSLRKVL AVVGTAEASS EHPLGVAVTK YCKEELGTET
LGYSTDFQAV PGCGISCKVS NVESILAHRG PTAHPIGVGN PPIGEGTGPQ TFSVLIGNRE
WMRRNGLTIS SDISDAMTDH EMKGQTAILV AIDGVLCGMI AIADAVKPEA ALASITLKSM
GVDVALITGD NRKTARAIAT QVGINKVFAE VLPSHKVAKV QELQNKGKKV AMVGDGVNDS
PALAQADVGI AIGTGTDVAI DAADVVLIRN DLLDVVASIH LSKRTVRRIR VNLVLALIYN
MVGIPIAAGV FMPIGIVLQP WMGSAAASSV SVVLSSLQLK CYRKPDLERY EAQAHGRMKP
LSASQVSVHV GMDDRRRDSP RATPWDQVSY VSQVSLSSLT SDRLSRHGGM AEDGGDKWSL
LLSDRDEEQC I
