[1]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=BALB/c; TISSUE=Brain; DOI=10.1038/ng0494-369; PubMed=8054976 [NCBI, ExPASy, EBI, Israel, Japan] Levinson B., Vulpe C., Elder B., Martin C., Verley F., Packman S., Gitschier J.; "The mottled gene is the mouse homologue of the Menkes disease gene."; Nat. Genet. 6:369-373(1994).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=BALB/c, DL, and ICR X Swiss Webster; TISSUE=Embryo, and Kidney; DOI=10.1038/ng0494-374; PubMed=8054977 [NCBI, ExPASy, EBI, Israel, Japan] Mercer J.F.B., Grimes A., Ambrosini L., Lockhart P., Paynter J.A., Dierick H., Glover T.W.; "Mutations in the murine homologue of the Menkes gene in dappled and blotchy mice."; Nat. Genet. 6:374-378(1994).
[3]	NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-674 AND PRO-1381. STRAIN=C3H; TISSUE=Placenta; PubMed=9385451 [NCBI, ExPASy, EBI, Israel, Japan] Ohta Y., Shiraishi N., Nishikimi M.; "Occurrence of two missense mutations in Cu-ATPase of the macular mouse, a Menkes disease model."; Biochem. Mol. Biol. Int. 43:913-918(1997).
[4]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=CBA X C3H; DOI=10.1093/hmg/6.7.1037; PubMed=9215672 [NCBI, ExPASy, EBI, Israel, Japan] Grimes A., Hearn C.J., Lockhart P., Newgreen D.F., Mercer J.F.B.; "Molecular basis of the brindled mouse mutant (Mo(br)): a murine model of Menkes disease."; Hum. Mol. Genet. 6:1037-1042(1997).

Comments

FUNCTION: May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells (By similarity).
CATALYTIC ACTIVITY: ATP + H₂O + Cu²⁺(In) = ADP + phosphate + Cu²⁺(Out).
SUBUNIT: Monomer.
SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane; Multi-pass membrane protein (By similarity). Cell membrane; Multi-pass membrane protein (By similarity). Note=Constitutively cycles between the trans-Golgi network (TGN) and the plasma membrane. Predominantly found in the TGN and relocalized to the plasma membrane in response to elevated copper levels (By similarity).
TISSUE SPECIFICITY: Found in most tissues except liver. In the kidney, it is detected in the proximal and distal tubules.
DEVELOPMENTAL STAGE: Widespread expressed throughout development.
DOMAIN: The C-terminal di-leucine, 1478-Leu-Leu-1479, is an endocytic targeting signal which functions in retrieving recycling from the plasma membrane to the TGN. Mutation of the di-leucine signal results in the accumulation of the protein in the plasma membrane (By similarity).
DISEASE: Defects in Atp7a are associated with mottled, an X-linked recessive condition characterized by mottled pigmentation of the coat, defects in connective tissue and neonatal or fetal death. It is due to a defect in absorption and transport of copper. The mottled mutants exhibit a diversity of phenotypes. Two of these mutants are called brindled and blotchy and their phenotypes resemble classical Menkes disease (MD) and occipital horn syndrome (OHS) in humans, respectively. Other mutants are called dappled, mosaic, tortoiseshell, pewter, etc.
SIMILARITY: Belongs to the cation transport ATPase (P-type) family. Type IB subfamily.
SIMILARITY: Contains 6 HMA domains.
WEB RESOURCE: Name=Protein Spotlight; Note=Heavy metal - Issue 79 of February 2007; URL="http://www.expasy.org/spotlight/back_issues/sptlt079.shtml";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U03434; AAA57445.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U03736; AAB08487.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB007134; BAA22369.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U71091; AAB37301.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S43793; S43793.

UniGene

Mm.254297

3D structure databases

HSSP

Q04656; 1AW0. [HSSP ENTRY / PDB]

SMR

Q64430; 1-79, 164-246, 275-351, 375-446.

ModBase

Q64430.

PTM databases

PhosphoSite

Q64430; -.

Organism-specific databases

MGI

MGI:99400; Atp7a.

Gene expression databases

ArrayExpress

Q64430; -.

CleanEx

MM_ATP7A; -.

GermOnline

ENSMUSG00000033792; Mus musculus.

Ontologies

GO:0043025;	Cellular component: cell soma (inferred from direct assay from MGI).
GO:0005624;	Cellular component: membrane fraction (inferred from direct assay from MGI).
GO:0043005;	Cellular component: neuron projection (inferred from direct assay from MGI).
GO:0005886;	Cellular component: plasma membrane (inferred from direct assay from MGI).
GO:0005802;	Cellular component: trans-Golgi network (inferred from direct assay from MGI).
GO:0030140;	Cellular component: trans-Golgi network transport vesicle (inferred from sequence or structural similarity from HGNC).
GO:0004008;	Molecular function: copper-exporting ATPase activity (inferred from direct assay from MGI).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from MGI).
GO:0016532;	Molecular function: superoxide dismutase copper chaperone activity (inferred from direct assay from MGI).
GO:0048286;	Biological process: alveolus development (inferred from mutant phenotype from MGI).
GO:0046034;	Biological process: ATP metabolic process (inferred from mutant phenotype from MGI).
GO:0001974;	Biological process: blood vessel remodeling (inferred from mutant phenotype from MGI).
GO:0051216;	Biological process: cartilage development (inferred from mutant phenotype from MGI).
GO:0006878;	Biological process: cellular copper ion homeostasis (inferred from mutant phenotype from MGI).
GO:0021702;	Biological process: cerebellar Purkinje cell differentiation (inferred from mutant phenotype from MGI).
GO:0030199;	Biological process: collagen fibril organization (inferred from mutant phenotype from MGI).
GO:0060003;	Biological process: copper ion export (inferred from mutant phenotype from MGI).
GO:0015677;	Biological process: copper ion import (inferred from mutant phenotype from MGI).
GO:0048813;	Biological process: dendrite morphogenesis (inferred from mutant phenotype from MGI).
GO:0010273;	Biological process: detoxification of copper ion (inferred from mutant phenotype from MGI).
GO:0042417;	Biological process: dopamine metabolic process (inferred from mutant phenotype from MGI).
GO:0048251;	Biological process: elastic fiber assembly (inferred from mutant phenotype from MGI).
GO:0051542;	Biological process: elastin biosynthetic process (inferred from mutant phenotype from MGI).
GO:0042414;	Biological process: epinephrine metabolic process (inferred from mutant phenotype from MGI).
GO:0031069;	Biological process: hair follicle morphogenesis (inferred from mutant phenotype from MGI).
GO:0007626;	Biological process: locomotory behavior (inferred from mutant phenotype from MGI).
GO:0048553;	Biological process: negative regulation of metalloenzyme activity (inferred from mutant phenotype from MGI).
GO:0043526;	Biological process: neuroprotection (inferred from mutant phenotype from MGI).
GO:0042421;	Biological process: norepinephrine biosynthetic process (inferred from mutant phenotype from MGI).
GO:0018205;	Biological process: peptidyl-lysine modification (inferred from mutant phenotype from MGI).
GO:0043473;	Biological process: pigmentation (inferred from mutant phenotype from MGI).
GO:0048554;	Biological process: positive regulation of metalloenzyme activity (inferred from mutant phenotype from MGI).
GO:0021860;	Biological process: pyramidal neuron development (inferred from mutant phenotype from MGI).
GO:0010468;	Biological process: regulation of gene expression (inferred from mutant phenotype from MGI).
GO:0002082;	Biological process: regulation of oxidative phosphorylation (inferred from mutant phenotype from MGI).
GO:0001836;	Biological process: release of cytochrome c from mitochondria (inferred from mutant phenotype from MGI).
GO:0019430;	Biological process: removal of superoxide radicals (inferred from mutant phenotype from MGI).
GO:0042428;	Biological process: serotonin metabolic process (inferred from mutant phenotype from MGI).
GO:0043588;	Biological process: skin development (inferred from mutant phenotype from MGI).
GO:0042093;	Biological process: T-helper cell differentiation (inferred from mutant phenotype from MGI).
GO:0006568;	Biological process: tryptophan metabolic process (inferred from mutant phenotype from MGI).
GO:0006570;	Biological process: tyrosine metabolic process (inferred from mutant phenotype from MGI).
QuickGo view.

Family and domain databases

InterPro

IPR006416; ATPase-IB_hvy.
IPR001757; ATPase_P.
IPR006403; ATPase_P_cat/Cu.
IPR001877; Cu_ATPase1.
IPR006122; Cu_ion_bd.
IPR005834; Dehalogen-like_hydro.
IPR008250; E1-E2_ATPase_reg.
IPR006121; HeavyMe_transpt.
Graphical view of domain structure.

PANTHER

PTHR11939; ATPase_P; 1.

Pfam

PF00122; E1-E2_ATPase; 1.
PF00403; HMA; 6.
PF00702; Hydrolase; 1.
Pfam graphical view of domain structure.

PRINTS

PR00119; CATATPASE.
PR00942; CUATPASEI.

TIGRFAMs

TIGR01511; ATPase-IB1_Cu; 1.
TIGR01525; ATPase-IB_hvy; 1.
TIGR01494; ATPase_P-type; 2.
TIGR00003; Cu_ion_bd; 4.

PROSITE

PS00154; ATPASE_E1_E2; 1.
PS01047; HMA_1; 6.
PS50846; HMA_2; 6.
PROSITE graphical view of domain structure (profiles).

BLOCKS

Q64430.

Genome annotation databases

Ensembl

ENSMUSG00000033792; Mus musculus. [Contig view]

Phylogenomic databases

HOGENOM

Q64430; -.

HOVERGEN

Q64430; -.

Other

Atp7a; Mus musculus.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

ATP-binding; Cell membrane; Copper; Copper transport; Disease mutation; Glycoprotein; Golgi apparatus; Hydrolase; Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Repeat; Transmembrane; Transport.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 1491`	`1491`	`Copper-transporting ATPase 1.`	`PRO_0000046312`
`TOPO_DOM`	`1 644`	`644`	`Cytoplasmic (Potential).`
`TRANSMEM`	`645 666`	`22`	`Potential.`
`TOPO_DOM`	`667 705`	`39`	`Extracellular (Potential).`
`TRANSMEM`	`706 725`	`20`	`Potential.`
`TOPO_DOM`	`726 732`	`7`	`Cytoplasmic (Potential).`
`TRANSMEM`	`733 753`	`21`	`Potential.`
`TOPO_DOM`	`754 772`	`19`	`Extracellular (Potential).`
`TRANSMEM`	`773 793`	`21`	`Potential.`
`TOPO_DOM`	`794 926`	`133`	`Cytoplasmic (Potential).`
`TRANSMEM`	`927 950`	`24`	`Potential.`
`TOPO_DOM`	`951 980`	`30`	`Extracellular (Potential).`
`TRANSMEM`	`981 1002`	`22`	`Potential.`
`TOPO_DOM`	`1003 1347`	`345`	`Cytoplasmic (Potential).`
`TRANSMEM`	`1348 1365`	`18`	`Potential.`
`TOPO_DOM`	`1366 1376`	`11`	`Extracellular (Potential).`
`TRANSMEM`	`1377 1396`	`20`	`Potential.`
`TOPO_DOM`	`1397 1491`	`95`	`Cytoplasmic (Potential).`
`DOMAIN`	`9 75`	`67`	`HMA 1.`
`DOMAIN`	`172 238`	`67`	`HMA 2.`
`DOMAIN`	`278 344`	`67`	`HMA 3.`
`DOMAIN`	`378 444`	`67`	`HMA 4.`
`DOMAIN`	`480 546`	`67`	`HMA 5.`
`DOMAIN`	`556 622`	`67`	`HMA 6.`
`MOTIF`	`1478 1479`	`2`	`Endocytosis signal (By similarity).`
`COMPBIAS`	`356 362`	`7`	`Poly-Ser.`
`ACT_SITE`	`1035 1035`		`4-aspartylphosphate intermediate (Probable).`
`METAL`	`1292 1292`		`Magnesium (By similarity).`
`METAL`	`1296 1296`		`Magnesium (By similarity).`
`MOD_RES`	`353 353`		`Phosphoserine (By similarity).`
`MOD_RES`	`356 356`		`Phosphoserine (By similarity).`
`MOD_RES`	`357 357`		`Phosphoserine (By similarity).`
`CARBOHYD`	`677 677`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`966 966`		`N-linked (GlcNAc...) (Potential).`
`VARIANT`	`674 674`	`1`	`H -> R (in MD).`
`VARIANT`	`1381 1381`	`1`	`S -> P (in MD).`
`CONFLICT`	`44 44`		`D -> E (in Ref. 2 and 3).`
`CONFLICT`	`103 103`		`V -> I (in Ref. 2 and 3).`
`CONFLICT`	`172 172`		`R -> M (in Ref. 2 and 3).`
`CONFLICT`	`245 246`		`LK -> PI (in Ref. 2; AAB08487).`
`CONFLICT`	`445 445`		`P -> PA (in Ref. 2 and 4).`
`CONFLICT`	`470 470`		`P -> L (in Ref. 1; AAA57445).`
`CONFLICT`	`515 515`		`T -> M (in Ref. 2 and 3).`
`CONFLICT`	`717 717`		`C -> F (in Ref. 2; AAB08487).`
`CONFLICT`	`770 770`		`T -> A (in Ref. 2; AAB08487).`
`CONFLICT`	`775 775`		`P -> S (in Ref. 2; AAB08487).`
`CONFLICT`	`885 885`		`I -> T (in Ref. 2; AAB08487).`
`CONFLICT`	`1169 1169`		`Y -> H (in Ref. 2; AAB08487).`
`CONFLICT`	`1204 1204`		`A -> P (in Ref. 2 and 4).`
`CONFLICT`	`1217 1217`		`I -> M (in Ref. 1; AAA57445).`
`CONFLICT`	`1253 1253`		`R -> Q (in Ref. 1; AAA57445).`

Sequence information

Length: 1491 AA [This is the length of the unprocessed precursor]

Molecular weight: 161910 Da [This is the MW of the unprocessed precursor]

CRC64: B916EF9E2565247C [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEPSVDANSI TITVEGMTCI SCVRTIEQQI GKVNGVHHIK VSLDEKSATI IYDPKLQTPK 

        70         80         90        100        110        120 
TLQEAIDDMG FDALLHNANP LPVLTNTVFL TVTAPLTLPW DHVQSTLLKT KGVTGVKISP 

       130        140        150        160        170        180 
QQRSAVVTII PSVVSASQIV ELVPDLSLDM GTQEKKSGAC EEHSTPQAGE VRLKMKVEGM 

       190        200        210        220        230        240 
TCHSCTSTIE GKVGKLQGVQ RIKVSLDNQE ATIVFQPHLI TAEEIKKQIE AVGFPAFIKK 

       250        260        270        280        290        300 
QPKYLKLGAI DVERLKNTPV KSSEGSQQKS PSYPSDSTTM FTIEGMHCKS CVSNIESALS 

       310        320        330        340        350        360 
TLQYVSSIVV SLENRSAIVK YNASLVTPEM LRKAIEAISP GQYRVSIASE VESTASSPSS 

       370        380        390        400        410        420 
SSLQKMPLNI VSQPLTQEAV ININGMTCNS CVQSIEGVIS KKPGVKSIHV SLANSTGTIE 

       430        440        450        460        470        480 
FDPLLTSPET LREAIEDMGF DAALPDMKEP LVVIAQPSLE TPLLPSSNEP ENVMTSVQNK 

       490        500        510        520        530        540 
CYIQVSGMTC ASCVANIERN LRREEGIYSV LVALTAGKAE VRYNPAVIQP RVIAEFIREL 

       550        560        570        580        590        600 
GFGAMVMENA GEGNGILELV VRGMTCASCV HKIESTLTKH KGIFYCSVAL ATNKAHIKYD 

       610        620        630        640        650        660 
PEIIGPRDII HTIGSLGFEA SLVKKDRSAN HLDHKREIKQ WRGSFLVSLF FCIPVMGLMV 

       670        680        690        700        710        720 
YMMVMDHHLA TLHHNQNMSN EEMINMHSAM FLERQILPGL SIMNLLSLLL CLPVQFCGGW 

       730        740        750        760        770        780 
YFYIQAYKAL KHKTANMDVL IVLATTIAFA YSLVILLVAM FERAKVNPIT FFDTPPMLFV 

       790        800        810        820        830        840 
FIALGRWLEH IAKGKTSEAL AKLISLQATE ATIVTLNSEN LLLSEEQVDV ELVQRGDIIK 

       850        860        870        880        890        900 
VVPGGKFPVD GRVIEGHSMV DESLITGEAM PVAKKPGSTV IAGSINQNGS LLIRATHVGA 

       910        920        930        940        950        960 
DTTLSQIVKL VEEAQTSKAP IQQFADKLSG YFVPFIVLVS IVTLLVWIII GFQNFEIVET 

       970        980        990       1000       1010       1020 
YFPGYNRSIS RTETIIRFAF QASITVLCIA CPCSLGLATP TAVMVGTGVG AQNGILIKGG 

      1030       1040       1050       1060       1070       1080 
EPLEMAHKVK VVVFDKTGTI THGTPVVNQV KVLVESNKIS RNKILAIVGT AESNSEHPLG 

      1090       1100       1110       1120       1130       1140 
AAVTKYCKKE LDTETLGTCT DFQVVPGCGI SCKVTNIEGL LHKSNLKIEE NNIKNASLVQ 

      1150       1160       1170       1180       1190       1200 
IDAINEQSST SSSMIIDAHL SNAVNTQQYK VLIGNREWMI RNGLVISNDV DESMIEHERR 

      1210       1220       1230       1240       1250       1260 
GRTAVLVTID DELCGLIAIA DTVKPEAELA VHILKSMGLE VVLMTGDNSK TARSIASQVG 

      1270       1280       1290       1300       1310       1320 
ITKVFAEVLP SHKVAKVKQL QEEGKRVAMV GDGINDSPAL AMANVGIAIG TGTDVAIEAA 

      1330       1340       1350       1360       1370       1380 
DVVLIRNDLL DVVASIDLSR KTVKRIRINF VFALIYNLVG IPIAAGVFLP IGLVLQPWMG 

      1390       1400       1410       1420       1430       1440 
SAAMAASSVS VVLSSLFLKL YRKPTYDNYE LHPRSHTGQR SPSEISVHVG IDDTSRNSPR 

      1450       1460       1470       1480       1490 
LGLLDRIVNY SRASINSLLS DKRSLNSVVT SEPDKHSLLV GDFREDDDTT L

Q64430 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools