ATP7B_SHEEP
ID ATP7B_SHEEP Reviewed; 1505 AA.
AC Q9XT50; O46518;
DT 08-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 144.
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 Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RX PubMed=10760584; DOI=10.1016/s0167-4781(00)00054-3;
RA Lockhart P.J., Wilcox S.A., Dahl H.-H.M., Mercer J.F.B.;
RT "Cloning, mapping and expression analysis of the sheep wilson disease gene
RT homologue.";
RL Biochim. Biophys. Acta 1491:229-239(2000).
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; Named isoforms=2;
CC Name=Long;
CC IsoId=Q9XT50-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q9XT50-2; Sequence=VSP_000429, VSP_000430;
CC -!- TISSUE SPECIFICITY: The short isoform is expressed primarily in the
CC liver with lower levels present in the intestine, hypothalamus and
CC ovary. The long isoform is expressed in the liver.
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 -!- 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; AF118225; AAD39371.1; -; mRNA.
DR EMBL; AF032881; AAB94620.1; -; mRNA.
DR RefSeq; NP_001009732.1; NM_001009732.1. [Q9XT50-1]
DR AlphaFoldDB; Q9XT50; -.
DR SMR; Q9XT50; -.
DR STRING; 9940.ENSOARP00000009727; -.
DR GeneID; 443046; -.
DR KEGG; oas:443046; -.
DR CTD; 540; -.
DR eggNOG; KOG0207; Eukaryota.
DR OrthoDB; 649559at2759; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
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:0006825; P:copper ion transport; ISS:UniProtKB.
DR GO; GO:0065008; P:regulation of biological quality; IEA:UniProt.
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; 6.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
DR PROSITE; PS01047; HMA_1; 6.
DR PROSITE; PS50846; HMA_2; 6.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Copper; Copper transport; 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..1505
FT /note="Copper-transporting ATPase 2"
FT /id="PRO_0000046316"
FT TOPO_DOM 1..694
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 695..716
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 717..737
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 738..757
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 758..764
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 765..785
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 786..804
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 805..825
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 826..959
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 960..982
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 983..1012
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1013..1034
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1035..1362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1363..1380
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1381..1391
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1392..1411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1412..1505
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 113..179
FT /note="HMA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 198..264
FT /note="HMA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 309..375
FT /note="HMA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 400..466
FT /note="HMA 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 529..595
FT /note="HMA 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT DOMAIN 605..671
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 36..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1158..1179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1475..1505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 289..306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1161..1179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1479..1505
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1067
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 124
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 127
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 209
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 212
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 320
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 323
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 411
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 414
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 540
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 543
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 616
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 619
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 1307
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 1311
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35670"
FT MOD_RES 1438
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64535"
FT VAR_SEQ 1..61
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10760584"
FT /id="VSP_000429"
FT VAR_SEQ 62..79
FT /note="GEFSQKVLNGSEEISSKQ -> MKPEEERPIIDREKASRR (in isoform
FT Short)"
FT /evidence="ECO:0000303|PubMed:10760584"
FT /id="VSP_000430"
SQ SEQUENCE 1505 AA; 161019 MW; 63202B55EB2CA8B5 CRC64;
MERAGDQAPG NPEPSSLATL GDPQVTLLTV HKRWSFKRSP GTGGSSRPVI SEEECPPPSE
EGEFSQKVLN GSEEISSKQI LSKLFQPAMK QSFAFDNNGY EDDLDGVCPS QTAAGTISIV
GMTCQSCVKS IEGRVSSLKG IVSIKVSLEQ SSAEVRYVPS VVSLMQICHQ IEDMGFQASV
AEGKATSWAS RVSPTSEAVV KLRVEGMTCQ SCVSSIEGKI GKLQGVMRVR VSLSNQEAVI
TYQPYLIQPQ DLRDHITDMG FEAVIKNKVA PVSLGPIDVR RLQSTLSVAP PAPVNQNDNN
SETPGGQGVP LHLRVDGMHC KSCVLNIEDN IGQLPGVQSI HVSLESRTAR VQYNPSLVSP
GALRRAIEAL PPGNFKVSFP NGAEGSGPDS RTPPAPSAPC TMMLAIAGMT CKSCVQSIEG
LISQRVGVHQ ISVFLAEGTA VVLYDPSRTH PEELRAAVED MGFEASILAE NCSSNQVGNH
SAGSAVGPEA AGAPVPMQGE APQPGGLHTN HIPHQSPKSL LASTTVAPKK CFLQISGMTC
ASCVSNIERN LQKEPGILSV LVALMAGKAE VKYNPEAIQP LEIAKLVQDL GFEAAVMEDY
TGSDGDLELM ITGMTCASCV HNIESKLRRT EGITYASVAL ATSKAHVKFD PEIIGPRDIV
KLIEEIGFRA SLAQRIPNAH HLDHKVEIKQ WKNSFLCSLV FGIPVMGLMI YMLIPSHEPQ
SSVLDHNVIP GLSILNLIFF ILCTFVQFLG GWYFYVQAYK SLRHGMANMD VLIVLATSIA
YVYSLVILVV AVAEKAERSP VTFFDTPPML FVFIALGRWL EHVVKSKTSE ALARLMSLQA
TEATVVTLGE DNVIIREEQV PMELVQRGDI IKVVPGGKFP VDGKVLEGNT MADESLITGE
AMPVTKKPGS MVIAGSMNAH GSVLITATHV GNDTTLAQIV KLVEEAQMSK APIQQLADRF
SGYFVPFIII ISTVTLVVWI VIGFIDFGVV QKYFPAPSKG ISQAEVVLRF AFQTSITVLC
IACPCSLGLA TPTAVMVGTG VAAQNGILIK GGKPLEMAHK IKTVMFDKTG TITHGVPKVS
RVLLLVDLAT LPLRKVLAVV GTAEASSEHP LGVAVTRYCK EELGTETLGC CMDFQAVPGC
GISCKVSSVE SILAQGERLQ GPPTAHQNRV GSEPSETDAA TQTFSVLIGN REWMRRNGLT
VTSDVRDAMT DHETKGQTAI LVAIDGVLCG MIAVADSVKQ EAALAVHTLK SMGVDVVLIT
GDNRKTARAI ATQVGINKVF AEVLPSHKVA KVQELQNQGK RVAMVGDGVN DSPALAQADV
GIAIGTGTDV AIEAADVVLI RNDLLDVVAS IHLSRRTVWR IRLNLVLALI YNLIGIPVAA
GVFIPIGVVL QPWMGSAAMA ASSVSVVLSS LQLKCYRKPD LARYEAQAHG HMKPLSASQV
SVRVGMDDRR RDSPRASAWD QVSYVSQVSL SPLKSDKLSR HSGAADDRGD KWSLLLNDRD
EEQGI
