ID ATP7A_RAT Reviewed; 1492 AA. AC P70705; DT 08-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 197. DE RecName: Full=Copper-transporting ATPase 1; DE EC=7.2.2.8 {ECO:0000250|UniProtKB:Q04656}; DE AltName: Full=Copper pump 1; DE AltName: Full=Menkes disease-associated protein homolog; GN Name=Atp7a {ECO:0000312|RGD:2179}; Synonyms=Mnk; 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]. RC TISSUE=Astrocyte; RX PubMed=9562241; DOI=10.1023/a:1006896612272; RA Qian Y., Tiffany-Castiglioni E., Harris E.D.; RT "Sequence of a Menkes-type Cu-transporting ATPase from rat C6 glioma cells: RT comparison of the rat protein with other mammalian Cu-transporting RT ATPases."; RL Mol. Cell. Biochem. 181:49-61(1998). RN [2] RP TISSUE SPECIFICITY. RX PubMed=12488345; DOI=10.1210/en.2002-220716; RA Steveson T.C., Ciccotosto G.D., Ma X.M., Mueller G.P., Mains R.E., RA Eipper B.A.; RT "Menkes protein contributes to the function of peptidylglycine alpha- RT amidating monooxygenase."; RL Endocrinology 144:188-200(2003). RN [3] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=15634787; DOI=10.1523/jneurosci.3699-04.2005; RA Schlief M.L., Craig A.M., Gitlin J.D.; RT "NMDA receptor activation mediates copper homeostasis in hippocampal RT neurons."; RL J. Neurosci. 25:239-246(2005). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1204, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=16641100; DOI=10.1073/pnas.0600895103; RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.; RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: RT regulation of aquaporin-2 phosphorylation at two sites."; RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-353 AND SER-1465, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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: ATP-driven copper (Cu(+)) ion pump that plays an important CC role in intracellular copper ion homeostasis (By similarity). Within a CC catalytic cycle, acquires Cu(+) ion from donor protein on the CC cytoplasmic side of the membrane and delivers it to acceptor protein on CC the lumenal side. The transfer of Cu(+) ion across the membrane is CC coupled to ATP hydrolysis and is associated with a transient CC phosphorylation that shifts the pump conformation from inward-facing to CC outward-facing state (By similarity). Under physiological conditions, CC at low cytosolic copper concentration, it is localized at the trans- CC Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of CC the secretory pathway (By similarity). Upon elevated cytosolic copper CC concentrations, it relocalizes to the plasma membrane where it is CC responsible for the export of excess Cu(+) ions (By similarity). May CC play a dual role in neuron function and survival by regulating cooper CC efflux and neuronal transmission at the synapse as well as by supplying CC Cu(+) ions to enzymes such as PAM, TYR and SOD3 (By similarity). In the CC melanosomes of pigmented cells, provides copper cofactor to TYR to form CC an active TYR holoenzyme for melanin biosynthesis (By similarity). CC {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430}. 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:Q04656}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25793; CC Evidence={ECO:0000250|UniProtKB:Q04656}; CC -!- SUBUNIT: Monomer. Interacts with PDZD11. Interacts with ATOX1 and CC COMMD1 (By similarity). Interacts with TYRP1 (By similarity). Directly CC interacts with SOD3; this interaction is copper-dependent and is CC required for SOD3 activity (By similarity). CC {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430}. CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane CC {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430}; Multi- CC pass membrane protein {ECO:0000255}. Cell membrane CC {ECO:0000250|UniProtKB:Q04656, ECO:0000250|UniProtKB:Q64430}; Multi- CC pass membrane protein {ECO:0000255}. Melanosome membrane CC {ECO:0000250|UniProtKB:Q64430}; Multi-pass membrane protein CC {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q64430}; CC Multi-pass membrane protein {ECO:0000255}. Cell projection, axon CC {ECO:0000269|PubMed:15634787}. Cell projection, dendrite CC {ECO:0000269|PubMed:15634787}. Postsynaptic density CC {ECO:0000269|PubMed:15634787}. Note=Cycles constitutively between the CC trans-Golgi network (TGN) and the plasma membrane. Predominantly found CC in the TGN and relocalized to the plasma membrane in response to CC elevated copper levels. Targeting into melanosomes is regulated by CC BLOC-1 complex (By similarity). In response to glutamate translocates CC to neuron processes with a minor fraction at extrasynaptic sites CC (PubMed:15634787). {ECO:0000250|UniProtKB:Q04656, CC ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:15634787}. CC -!- TISSUE SPECIFICITY: Expressed in hippocampal neuron (at protein level) CC (PubMed:15634787). Expressed in anterior pituitary gland (at protein CC level) (PubMed:12488345). {ECO:0000269|PubMed:12488345, CC ECO:0000269|PubMed:15634787}. CC -!- DOMAIN: The nucleotide-binding domain consists of a twisted six- CC stranded antiparallel beta-sheet flanked by two pairs of alpha-helices, CC forming an hydrophobic pocket that interacts with the adenine ring of CC ATP. The ATP binding site comprises residues located in alpha-1 and CC alpha-2 helices and beta-2 and beta-3 strands, which are involved in CC van der Waal's interactions, and Glu-1073 which forms an hydrogen bond CC with the adenine ring. {ECO:0000250|UniProtKB:Q04656}. CC -!- DOMAIN: The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion CC via the cysteine residues within the CXXC motif. The transfer of Cu(+) CC ion from ATOX1 to ATP7A involves the formation of a three-coordinate CC Cu(+)-bridged heterodimer where the metal is shared between the two CC metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch CC between two coordination modes, forming two links with one protein and CC one with the other. Cisplatin, a chemotherapeutic drug, can bind the CC CXXC motif and hinder the release of Cu(+) ion. CC {ECO:0000250|UniProtKB:Q04656}. CC -!- DOMAIN: Contains three di-leucine motifs in the C-terminus which are CC required for recycling from the plasma membrane to the TGN. The di- CC leucine 1479-Leu-Leu-1480 motif mediates endocytosis at the plasma CC membrane, whereas the di-leucine 1459-Leu-Leu-1460 motif is a sorting CC signal for retrograde trafficking to TGN via early endosomes. CC {ECO:0000250|UniProtKB:Q64430}. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IB subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Heavy metal - Issue 79 of CC February 2007; CC URL="https://web.expasy.org/spotlight/back_issues/079"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U59245; AAB06393.1; -; mRNA. DR PIR; S46483; S46483. DR RefSeq; NP_434690.1; NM_052803.2. DR RefSeq; XP_006257057.1; XM_006256995.3. DR RefSeq; XP_008771556.1; XM_008773334.2. DR AlphaFoldDB; P70705; -. DR SMR; P70705; -. DR IntAct; P70705; 1. DR STRING; 10116.ENSRNOP00000073176; -. DR GlyCosmos; P70705; 1 site, No reported glycans. DR GlyGen; P70705; 1 site. DR iPTMnet; P70705; -. DR PhosphoSitePlus; P70705; -. DR jPOST; P70705; -. DR PaxDb; 10116-ENSRNOP00000063702; -. DR ABCD; P70705; 1 sequenced antibody. DR Ensembl; ENSRNOT00000080141.2; ENSRNOP00000071625.1; ENSRNOG00000061367.2. DR Ensembl; ENSRNOT00055044676; ENSRNOP00055036581; ENSRNOG00055025893. DR Ensembl; ENSRNOT00060039716; ENSRNOP00060032846; ENSRNOG00060022911. DR Ensembl; ENSRNOT00065042759; ENSRNOP00065035011; ENSRNOG00065024886. DR GeneID; 24941; -. DR KEGG; rno:24941; -. DR UCSC; RGD:2179; rat. DR AGR; RGD:2179; -. DR CTD; 538; -. DR RGD; 2179; Atp7a. DR eggNOG; KOG0207; Eukaryota. DR GeneTree; ENSGT00940000159568; -. DR HOGENOM; CLU_001771_0_1_1; -. DR InParanoid; P70705; -. DR OMA; EHPIANS; -. DR OrthoDB; 5480493at2759; -. DR PhylomeDB; P70705; -. DR BRENDA; 7.2.2.8; 5301. DR BRENDA; 7.2.2.9; 5301. DR Reactome; R-RNO-6803544; Ion influx/efflux at host-pathogen interface. DR Reactome; R-RNO-936837; Ion transport by P-type ATPases. DR PRO; PR:P70705; -. DR Proteomes; UP000002494; Chromosome X. DR Bgee; ENSRNOG00000061367; Expressed in duodenum and 18 other cell types or tissues. DR ExpressionAtlas; P70705; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD. DR GO; GO:0030424; C:axon; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD. DR GO; GO:0031526; C:brush border membrane; IDA:RGD. DR GO; GO:0031252; C:cell leading edge; IDA:RGD. DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD. DR GO; GO:0030425; C:dendrite; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI. DR GO; GO:0005770; C:late endosome; IDA:RGD. DR GO; GO:0033162; C:melanosome membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0005902; C:microvillus; IDA:RGD. DR GO; GO:0043005; C:neuron projection; ISO:RGD. DR GO; GO:0043025; C:neuronal cell body; ISO:RGD. DR GO; GO:0043204; C:perikaryon; IDA:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0030141; C:secretory granule; IDA:RGD. DR GO; GO:0005802; C:trans-Golgi network; IDA:MGI. DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB. DR GO; GO:0030140; C:trans-Golgi network transport vesicle; ISO:RGD. DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0005507; F:copper ion binding; ISO:RGD. DR GO; GO:0005375; F:copper ion transmembrane transporter activity; ISO:RGD. DR GO; GO:0032767; F:copper-dependent protein binding; ISS:UniProtKB. DR GO; GO:1903136; F:cuprous ion binding; ISS:UniProtKB. DR GO; GO:0043682; F:P-type divalent copper transporter activity; ISO:RGD. DR GO; GO:0140581; F:P-type monovalent copper transporter activity; ISS:UniProtKB. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:RGD. DR GO; GO:0031267; F:small GTPase binding; IPI:RGD. DR GO; GO:0016532; F:superoxide dismutase copper chaperone activity; ISO:RGD. DR GO; GO:0046034; P:ATP metabolic process; ISO:RGD. DR GO; GO:0001568; P:blood vessel development; ISO:RGD. DR GO; GO:0001974; P:blood vessel remodeling; ISO:RGD. DR GO; GO:0051216; P:cartilage development; ISO:RGD. DR GO; GO:0006584; P:catecholamine metabolic process; ISO:RGD. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IMP:RGD. DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD. DR GO; GO:0071276; P:cellular response to cadmium ion; IEP:RGD. DR GO; GO:0071279; P:cellular response to cobalt ion; IEP:RGD. DR GO; GO:0071280; P:cellular response to copper ion; IDA:RGD. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD. DR GO; GO:0071281; P:cellular response to iron ion; IEP:RGD. DR GO; GO:0071284; P:cellular response to lead ion; IEP:RGD. DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IMP:RGD. DR GO; GO:0021954; P:central nervous system neuron development; ISO:RGD. DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; ISO:RGD. DR GO; GO:0030199; P:collagen fibril organization; ISO: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:0048813; P:dendrite morphogenesis; ISO:RGD. DR GO; GO:0010273; P:detoxification of copper ion; ISO:RGD. DR GO; GO:0042417; P:dopamine metabolic process; ISO:RGD. DR GO; GO:0048251; P:elastic fiber assembly; ISO:RGD. DR GO; GO:0051542; P:elastin biosynthetic process; ISO:RGD. DR GO; GO:0042414; P:epinephrine metabolic process; ISO:RGD. DR GO; GO:0051649; P:establishment of localization in cell; ISO:RGD. DR GO; GO:0030198; P:extracellular matrix organization; ISO:RGD. DR GO; GO:0007565; P:female pregnancy; IEP:RGD. DR GO; GO:0031069; P:hair follicle morphogenesis; ISO:RGD. DR GO; GO:0035137; P:hindlimb morphogenesis; ISO:RGD. DR GO; GO:0001701; P:in utero embryonic development; IEP:RGD. DR GO; GO:0006878; P:intracellular copper ion homeostasis; ISS:UniProtKB. DR GO; GO:0007595; P:lactation; IEP:RGD. DR GO; GO:0001889; P:liver development; IEP:RGD. DR GO; GO:0007626; P:locomotory behavior; ISO:RGD. DR GO; GO:0048286; P:lung alveolus development; ISO:RGD. DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD. DR GO; GO:0045914; P:negative regulation of catecholamine metabolic process; ISO:RGD. DR GO; GO:0034760; P:negative regulation of iron ion transmembrane transport; IMP:RGD. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD. DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD. DR GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD. DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD. DR GO; GO:0042421; P:norepinephrine biosynthetic process; ISO:RGD. DR GO; GO:0042415; P:norepinephrine metabolic process; ISO:RGD. DR GO; GO:0043473; P:pigmentation; ISO:RGD. DR GO; GO:0045793; P:positive regulation of cell size; IMP:RGD. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:RGD. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:RGD. DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; ISS:UniProtKB. DR GO; GO:1903036; P:positive regulation of response to wounding; IMP:RGD. DR GO; GO:0032773; P:positive regulation of tyrosinase activity; ISS:UniProtKB. DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IMP:RGD. DR GO; GO:0021860; P:pyramidal neuron development; ISO:RGD. DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD. DR GO; GO:0002082; P:regulation of oxidative phosphorylation; ISO:RGD. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISO:RGD. DR GO; GO:0019430; P:removal of superoxide radicals; ISO:RGD. DR GO; GO:0046688; P:response to copper ion; IDA:RGD. DR GO; GO:0010041; P:response to iron(III) ion; IEP:RGD. DR GO; GO:0010288; P:response to lead ion; IEP:RGD. DR GO; GO:0010042; P:response to manganese ion; IDA:RGD. DR GO; GO:0010043; P:response to zinc ion; IEP:RGD. DR GO; GO:0042428; P:serotonin metabolic process; ISO:RGD. DR GO; GO:0043588; P:skin development; ISO:RGD. DR GO; GO:0042093; P:T-helper cell differentiation; ISO:RGD. DR GO; GO:0006568; P:tryptophan metabolic process; ISO:RGD. DR GO; GO:0006570; P:tyrosine metabolic process; ISO:RGD. DR CDD; cd00371; HMA; 6. DR CDD; cd02094; P-type_ATPase_Cu-like; 1. DR Gene3D; 3.30.70.100; -; 6. DR Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1. DR Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 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 NCBIfam; TIGR01525; ATPase-IB_hvy; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 2. DR NCBIfam; TIGR00003; copper ion binding protein; 6. DR PANTHER; PTHR46594; P-TYPE CATION-TRANSPORTING ATPASE; 1. DR PANTHER; PTHR46594:SF4; P-TYPE CATION-TRANSPORTING ATPASE; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR Pfam; PF00403; HMA; 6. DR Pfam; PF00702; Hydrolase; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00942; CUATPASEI. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 1. DR SFLD; SFLDF00027; p-type_atpase; 1. DR SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1. DR SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR SUPFAM; SSF55008; HMA, heavy metal-associated domain; 6. DR PROSITE; PS00154; ATPASE_E1_E2; 1. DR PROSITE; PS01047; HMA_1; 6. DR PROSITE; PS50846; HMA_2; 7. DR Genevisible; P70705; RN. PE 1: Evidence at protein level; KW ATP-binding; Cell membrane; Cell projection; Copper; Copper transport; KW Endosome; Glycoprotein; Golgi apparatus; Ion transport; Magnesium; KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat; Synapse; Translocase; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..1492 FT /note="Copper-transporting ATPase 1" FT /id="PRO_0000046313" FT TOPO_DOM 1..645 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 646..667 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 668..706 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 707..726 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 727..733 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 734..754 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 755..773 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 774..794 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 795..927 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 928..951 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 952..981 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 982..1003 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1004..1348 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1349..1366 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1367..1377 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1378..1397 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1398..1492 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 8..74 FT /note="HMA 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT DOMAIN 85..151 FT /note="HMA 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT DOMAIN 171..237 FT /note="HMA 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT DOMAIN 277..343 FT /note="HMA 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT DOMAIN 377..443 FT /note="HMA 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT DOMAIN 480..546 FT /note="HMA 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT DOMAIN 556..622 FT /note="HMA 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT REGION 1478..1492 FT /note="PDZD11-binding" FT /evidence="ECO:0000250" FT MOTIF 1459..1460 FT /note="Endocytosis signal" FT /evidence="ECO:0000250|UniProtKB:Q64430" FT MOTIF 1479..1480 FT /note="Endocytosis signal" FT /evidence="ECO:0000250|UniProtKB:Q64430" FT ACT_SITE 1036 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250" FT BINDING 18 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT BINDING 19 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 22 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 182 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 185 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 288 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 291 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 388 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 391 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 491 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 494 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 567 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 570 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 1073 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT BINDING 1293 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 1297 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT MOD_RES 152 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 270 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 327 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 339 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 353 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 357 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 362 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64430" FT MOD_RES 1204 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:16641100" FT MOD_RES 1422 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 1424 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 1452 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 1455 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 1458 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 1461 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q04656" FT MOD_RES 1465 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 1468 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64430" FT MOD_RES 1478 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64430" FT CARBOHYD 678 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" SQ SEQUENCE 1492 AA; 162093 MW; 34F75152B105AE9F CRC64; MEPNMDANSI TITVEGMTCI SCVRTIEQQI GKVNGVHHIK VSLEEKSATV IYNPKLQTPK TLQEAIDDMG FDALLHNANP LPVLTNTVFL TVTAPLALPW DHIQSTLLKT KGVTGVKISP QQRSAVVTII PSVVSANQIV ELVPDLSLDM GTQEKKSGTS EEHSTPQAGE VLLKMRVEGM TCHSCTSTIE GKVGKLQGVQ RIKVSLDNQE ATIVYQPHLI TAEEIKKQIE AVGFPAFIKK QPKYLKLGAI DVERLKSTPV KSSEGSQQKS PAYPSDSAIT FTIDGMHCKS CVSNIESALS TLQYVSSIVV SLENRSAIVK YNASLVTPEI LRKAIEAVSP GQYRVSISSE VESPTSSPSS SSLQKMPLNL VSQPLTQEVV ININGMTCNS CVQSIEGVIS KKPGVKSIHV SLTNSTGTIE YDPLLTSPEP LREAIEDMGF DAVLPADMKE PLVVIAQPSL ETPLLPSTTE PENVMTPVQN KCYIQVSGMT CASCVANIER NLRREEGIYS VLVALMAGKA EVRYNPAVIQ PRVIAELIRE LGFGAVVMEN AGEGNGILEL VVRGMTCASC VHKIESTLTK HKGIFYCSVA LATNKAHIKY DPEIIGPRDI IHTIGNLGFE ASLVKKDRSA NHLDHKREIK QWRGSFLVSL FFCIPVMGLM IYMMVMDHHL ATLNHNQNMS NEEMINMHSS MFLERQILPG LSIMNLLSLL LCLPVQFCGG WYFYIQAYKA LRHKTANMDV LIVLATTIAF AYSLVILLVA MYERAKVNPI TFFDTPPMLF VFIALGRWLE HIAKGKTSEA LAKLISLQAT EATIVTLNSE NLLLSEEQVD VELVQRGDII KVVPGGKFPV DGRVIEGHSM VDESLITGEA MPVAKKPGST VIAGSINQNG SLLIRATHVG ADTTLSQIVK LVEEAQTSKA PIQQFADKLS GYFVPFIVLV SIVTLLVWII IGFQNFEIVE AYFPGYNRSI SRTETIIRFA FQASITVLCI ACPCSLGLAT PTAVMVGTGV GAQNGILIKG GEPLEMAHKV KVVVFDKTGT ITHGTPVVNQ VKVLVESNKI SRNKILAIVG TAESNSEHPL GAAVTKYCKQ ELDTETLGTC TDFQVVPGCG ISCKVTNIEG LLHKSNLKIE ENNIKNASLV QIDAINEQSS PSSSMIIDAH LSNAVNTQQY KVLIGNREWM IRNGLVISND VDESMIEHER RGRTAVLVTI DDELCGLIAI ADTVKPEAEL AVHILKSMGL EVVLMTGDNS KTARSIASQV GITKVFAEVL PSHKVAKVKQ LQEEGKRVAM VGDGINDSPA LAMASVGIAI GTGTDVAIEA ADVVLIRNDL LDVVASIDLS RKTVKRIRIN FVFALIYNLI GIPIAAGVFL PIGLVLQPWM GSAAMAASSV SVVLSSLFLK LYRKPTYDNY ELRPRSHTGQ RSPSEISVHV GIDDTSRNSP RLGLLDRIVN YSRASINSLL SDKRSLNSVV TSEPDKHSLL VGDFREDDDT TL //