Reviewed, UniProtKB/Swiss-Prot Q64430 (ATP7A_MOUSE)

Names and origin

Protein names

Recommended name:
    Copper-transporting ATPase 1
    EC=3.6.3.4
Alternative name(s):
    Copper pump 1
    Menkes disease-associated protein homolog

Gene names

Name:	Atp7a
Synonyms:	Mnk

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1491 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (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 + H(2)O + Cu(2+)(In) = ADP + phosphate + Cu(2+)(Out).
Subunit structure	Monomer.
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Multi-pass membrane proteinBy similarity. Cell membrane; Multi-pass membrane proteinBy 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.
Involvement in 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.
Sequence similarities	Belongs to the cation transport ATPase (P-type) family. Type IB subfamily. Contains 6 HMA domains.

Ontologies

Keywords
Biological process	Copper transport Ion transport Transport
Cellular component	Cell membrane Golgi apparatus Membrane
Disease	Disease mutation
Domain	Repeat Transmembrane
Ligand	ATP-binding Copper Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	ATP metabolic process Inferred from mutant phenotype. Source: MGI T-helper cell differentiation Inferred from mutant phenotype. Source: MGI alveolus development Inferred from mutant phenotype. Source: MGI blood vessel remodeling Inferred from mutant phenotype. Source: MGI cartilage development Inferred from mutant phenotype. Source: MGI cellular copper ion homeostasis Inferred from mutant phenotype. Source: MGI cerebellar Purkinje cell differentiation Inferred from mutant phenotype. Source: MGI collagen fibril organization Inferred from mutant phenotype. Source: MGI copper ion export Inferred from mutant phenotype. Source: MGI copper ion import Inferred from mutant phenotype. Source: MGI dendrite morphogenesis Inferred from mutant phenotype. Source: MGI detoxification of copper ion Inferred from mutant phenotype. Source: MGI dopamine metabolic process Inferred from mutant phenotype. Source: MGI elastic fiber assembly Inferred from mutant phenotype. Source: MGI elastin biosynthetic process Inferred from mutant phenotype. Source: MGI epinephrine metabolic process Inferred from mutant phenotype. Source: MGI hair follicle morphogenesis Inferred from mutant phenotype. Source: MGI locomotory behavior Inferred from mutant phenotype. Source: MGI negative regulation of metalloenzyme activity Inferred from mutant phenotype. Source: MGI neuroprotection Inferred from mutant phenotype. Source: MGI norepinephrine biosynthetic process Inferred from mutant phenotype. Source: MGI peptidyl-lysine modification Inferred from mutant phenotype. Source: MGI pigmentation Inferred from mutant phenotype. Source: MGI positive regulation of metalloenzyme activity Inferred from mutant phenotype. Source: MGI pyramidal neuron development Inferred from mutant phenotype. Source: MGI regulation of gene expression Inferred from mutant phenotype. Source: MGI regulation of oxidative phosphorylation Inferred from mutant phenotype. Source: MGI release of cytochrome c from mitochondria Inferred from mutant phenotype. Source: MGI removal of superoxide radicals Inferred from mutant phenotype. Source: MGI serotonin metabolic process Inferred from mutant phenotype. Source: MGI skin development Inferred from mutant phenotype. Source: MGI tryptophan metabolic process Inferred from mutant phenotype. Source: MGI tyrosine metabolic process Inferred from mutant phenotype. Source: MGI
Cellular component	cell soma Inferred from direct assay. Source: MGI integral to membrane Inferred from electronic annotation. Source: InterPro membrane fraction Ref.4 Inferred from direct assay. Source: MGI neuron projection Inferred from direct assay. Source: MGI plasma membrane Inferred from direct assay. Source: MGI trans-Golgi network Inferred from direct assay. Source: MGI trans-Golgi network transport vesicle Inferred from sequence or structural similarity. Source: HGNC
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro copper-exporting ATPase activity Inferred from direct assay. Source: MGI magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: MGI superoxide dismutase copper chaperone activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1491	1491	Copper-transporting ATPase 1		PRO_0000046312
Regions
	Topological domain	1 – 644	644	Cytoplasmic Potential
	Transmembrane	645 – 666	22	Potential
	Topological domain	667 – 705	39	Extracellular Potential
	Transmembrane	706 – 725	20	Potential
	Topological domain	726 – 732	7	Cytoplasmic Potential
	Transmembrane	733 – 753	21	Potential
	Topological domain	754 – 772	19	Extracellular Potential
	Transmembrane	773 – 793	21	Potential
	Topological domain	794 – 926	133	Cytoplasmic Potential
	Transmembrane	927 – 950	24	Potential
	Topological domain	951 – 980	30	Extracellular Potential
	Transmembrane	981 – 1002	22	Potential
	Topological domain	1003 – 1347	345	Cytoplasmic Potential
	Transmembrane	1348 – 1365	18	Potential
	Topological domain	1366 – 1376	11	Extracellular Potential
	Transmembrane	1377 – 1396	20	Potential
	Topological domain	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
	Compositional bias	356 – 362	7	Poly-Ser
Sites
	Active site	1035	1	4-aspartylphosphate intermediate Probable
	Metal binding	1292	1	Magnesium By similarity
	Metal binding	1296	1	Magnesium By similarity
Amino acid modifications
	Modified residue	353	1	Phosphoserine By similarity
	Modified residue	356	1	Phosphoserine By similarity
	Modified residue	357	1	Phosphoserine By similarity
	Glycosylation	677	1	N-linked (GlcNAc...) Potential
	Glycosylation	966	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	674	1	H → R in MD.
	Natural variant	1381	1	S → P in MD.
Experimental info
	Sequence conflict	44	1	D → E Ref.2 Ref.3
	Sequence conflict	103	1	V → I Ref.2 Ref.3
	Sequence conflict	172	1	R → M Ref.2 Ref.3
	Sequence conflict	245 – 246	2	LK → PI in AAB08487. Ref.2
	Sequence conflict	445	1	P → PA Ref.2 Ref.4
	Sequence conflict	470	1	P → L in AAA57445. Ref.1
	Sequence conflict	515	1	T → M Ref.2 Ref.3
	Sequence conflict	717	1	C → F in AAB08487. Ref.2
	Sequence conflict	770	1	T → A in AAB08487. Ref.2
	Sequence conflict	775	1	P → S in AAB08487. Ref.2
	Sequence conflict	885	1	I → T in AAB08487. Ref.2
	Sequence conflict	1169	1	Y → H in AAB08487. Ref.2
	Sequence conflict	1204	1	A → P Ref.2 Ref.4
	Sequence conflict	1217	1	I → M in AAA57445. Ref.1
	Sequence conflict	1253	1	R → Q in AAA57445. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q64430-1 [UniParc]. Last modified December 8, 2000. Version 2. Checksum: B916EF9E2565247C	FASTA	1,491	161,910
	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

References

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

Web resources

Protein Spotlight

Heavy metal - Issue 79 of February 2007

Cross-references

Sequence databases
EMBLGenBankDDBJ	U03434 mRNA. Translation: AAA57445.1. U03736 mRNA. Translation: AAB08487.1. AB007134 mRNA. Translation: BAA22369.1. U71091 mRNA. Translation: AAB37301.1.
PIR	S43793.
UniGene	Mm.254297
3D structure databases
HSSP	HSSP built from PDB template 1AW0 based on UniProtKB Q04656.
SMR	Q64430. Positions 1-79, 164-246, 275-351, 375-446.
ModBase	Search...
PTM databases
PhosphoSite	Q64430.
Genome annotation databases
Ensembl	ENSMUSG00000033792. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:99400. Atp7a.
Phylogenomic databases
HOGENOM	Q64430.
HOVERGEN	Q64430.
Gene expression databases
ArrayExpress	Q64430.
CleanEx	MM_ATP7A.
GermOnline	ENSMUSG00000033792. Mus musculus.
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]
PANTHER	PTHR11939. ATPase_P. 1 hit.
Pfam	PF00122. E1-E2_ATPase. 1 hit. PF00403. HMA. 6 hits. PF00702. Hydrolase. 1 hit. [Graphical view]
PRINTS	PR00119. CATATPASE. PR00942. CUATPASEI.
TIGRFAMs	TIGR01511. ATPase-IB1_Cu. 1 hit. TIGR01525. ATPase-IB_hvy. 1 hit. TIGR01494. ATPase_P-type. 2 hits. TIGR00003. Cu_ion_bd. 4 hits.
PROSITE	PS00154. ATPASE_E1_E2. 1 hit. PS01047. HMA_1. 6 hits. PS50846. HMA_2. 6 hits. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name	ATP7A_MOUSE
Accession	Primary (citable) accession number: Q64430 Secondary accession number(s): O35101, P97422, Q64431
Entry history</