Reviewed, UniProtKB/Swiss-Prot P70705 (ATP7A_RAT)

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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1492 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 By similarity.
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.
Domain	The C-terminal di-leucine, 1479-Leu-Leu-1480, 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.
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
Domain	Repeat Transmembrane
Ligand	ATP-binding Copper Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	copper ion transport Inferred from electronic annotation. Source: InterPro metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: InterPro integral to membrane of membrane fraction Inferred from direct assay. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW trans-Golgi network Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro copper ion binding Inferred from electronic annotation. Source: InterPro copper-exporting ATPase activity Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1492	1492	Copper-transporting ATPase 1		PRO_0000046313
Regions
	Topological domain	1 – 645	645	Cytoplasmic Potential
	Transmembrane	646 – 667	22	Potential
	Topological domain	668 – 706	39	Extracellular Potential
	Transmembrane	707 – 726	20	Potential
	Topological domain	727 – 733	7	Cytoplasmic Potential
	Transmembrane	734 – 754	21	Potential
	Topological domain	755 – 773	19	Extracellular Potential
	Transmembrane	774 – 794	21	Potential
	Topological domain	795 – 927	133	Cytoplasmic Potential
	Transmembrane	928 – 951	24	Potential
	Topological domain	952 – 981	30	Extracellular Potential
	Transmembrane	982 – 1003	22	Potential
	Topological domain	1004 – 1348	345	Cytoplasmic Potential
	Transmembrane	1349 – 1366	18	Potential
	Topological domain	1367 – 1377	11	Extracellular Potential
	Transmembrane	1378 – 1397	20	Potential
	Topological domain	1398 – 1492	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	481 – 547	67	HMA 5
	Domain	557 – 623	67	HMA 6
	Motif	1479 – 1480	2	Endocytosis signal By similarity
	Compositional bias	356 – 362	7	Poly-Ser
Sites
	Active site	1036	1	4-aspartylphosphate intermediate By similarity
	Metal binding	1293	1	Magnesium By similarity
	Metal binding	1297	1	Magnesium By similarity
Amino acid modifications
	Modified residue	353	1	Phosphoserine
	Modified residue	356	1	Phosphoserine
	Modified residue	357	1	Phosphoserine
	Glycosylation	678	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	P70705-1 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 34F75152B105AE9F	FASTA	1,492	162,093
	10 20 30 40 50 60 MEPNMDANSI TITVEGMTCI SCVRTIEQQI GKVNGVHHIK VSLEEKSATV IYNPKLQTPK 70 80 90 100 110 120 TLQEAIDDMG FDALLHNANP LPVLTNTVFL TVTAPLALPW DHIQSTLLKT KGVTGVKISP 130 140 150 160 170 180 QQRSAVVTII PSVVSANQIV ELVPDLSLDM GTQEKKSGTS EEHSTPQAGE VLLKMRVEGM 190 200 210 220 230 240 TCHSCTSTIE GKVGKLQGVQ RIKVSLDNQE ATIVYQPHLI TAEEIKKQIE AVGFPAFIKK 250 260 270 280 290 300 QPKYLKLGAI DVERLKSTPV KSSEGSQQKS PAYPSDSAIT FTIDGMHCKS CVSNIESALS 310 320 330 340 350 360 TLQYVSSIVV SLENRSAIVK YNASLVTPEI LRKAIEAVSP GQYRVSISSE VESPTSSPSS 370 380 390 400 410 420 SSLQKMPLNL VSQPLTQEVV ININGMTCNS CVQSIEGVIS KKPGVKSIHV SLTNSTGTIE 430 440 450 460 470 480 YDPLLTSPEP LREAIEDMGF DAVLPADMKE PLVVIAQPSL ETPLLPSTTE PENVMTPVQN 490 500 510 520 530 540 KCYIQVSGMT CASCVANIER NLRREEGIYS VLVALMAGKA EVRYNPAVIQ PRVIAELIRE 550 560 570 580 590 600 LGFGAVVMEN AGEGNGILEL VVRGMTCASC VHKIESTLTK HKGIFYCSVA LATNKAHIKY 610 620 630 640 650 660 DPEIIGPRDI IHTIGNLGFE ASLVKKDRSA NHLDHKREIK QWRGSFLVSL FFCIPVMGLM 670 680 690 700 710 720 IYMMVMDHHL ATLNHNQNMS NEEMINMHSS MFLERQILPG LSIMNLLSLL LCLPVQFCGG 730 740 750 760 770 780 WYFYIQAYKA LRHKTANMDV LIVLATTIAF AYSLVILLVA MYERAKVNPI TFFDTPPMLF 790 800 810 820 830 840 VFIALGRWLE HIAKGKTSEA LAKLISLQAT EATIVTLNSE NLLLSEEQVD VELVQRGDII 850 860 870 880 890 900 KVVPGGKFPV DGRVIEGHSM VDESLITGEA MPVAKKPGST VIAGSINQNG SLLIRATHVG 910 920 930 940 950 960 ADTTLSQIVK LVEEAQTSKA PIQQFADKLS GYFVPFIVLV SIVTLLVWII IGFQNFEIVE 970 980 990 1000 1010 1020 AYFPGYNRSI SRTETIIRFA FQASITVLCI ACPCSLGLAT PTAVMVGTGV GAQNGILIKG 1030 1040 1050 1060 1070 1080 GEPLEMAHKV KVVVFDKTGT ITHGTPVVNQ VKVLVESNKI SRNKILAIVG TAESNSEHPL 1090 1100 1110 1120 1130 1140 GAAVTKYCKQ ELDTETLGTC TDFQVVPGCG ISCKVTNIEG LLHKSNLKIE ENNIKNASLV 1150 1160 1170 1180 1190 1200 QIDAINEQSS PSSSMIIDAH LSNAVNTQQY KVLIGNREWM IRNGLVISND VDESMIEHER 1210 1220 1230 1240 1250 1260 RGRTAVLVTI DDELCGLIAI ADTVKPEAEL AVHILKSMGL EVVLMTGDNS KTARSIASQV 1270 1280 1290 1300 1310 1320 GITKVFAEVL PSHKVAKVKQ LQEEGKRVAM VGDGINDSPA LAMASVGIAI GTGTDVAIEA 1330 1340 1350 1360 1370 1380 ADVVLIRNDL LDVVASIDLS RKTVKRIRIN FVFALIYNLI GIPIAAGVFL PIGLVLQPWM 1390 1400 1410 1420 1430 1440 GSAAMAASSV SVVLSSLFLK LYRKPTYDNY ELRPRSHTGQ RSPSEISVHV GIDDTSRNSP 1450 1460 1470 1480 1490 RLGLLDRIVN YSRASINSLL SDKRSLNSVV TSEPDKHSLL VGDFREDDDT TL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a Menkes-type Cu-transporting ATPase from rat C6 glioma cells: comparison of the rat protein with other mammalian Cu-transporting ATPases." Qian Y., Tiffany-Castiglioni E., Harris E.D. Mol. Cell. Biochem. 181:49-61(1998) [PubMed: 9562241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Astrocyte.
[2]	"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites." Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A. Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed: 16641100] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-353; SER-356 AND SER-357, MASS SPECTROMETRY. Tissue: Kidney.

Web resources

Protein Spotlight

Heavy metal - Issue 79 of February 2007

Cross-references

Sequence databases
EMBLGenBankDDBJ	U59245 mRNA. Translation: AAB06393.1.
PIR	S46483.
RefSeq	NP_434690.1.
UniGene	Rn.10554
3D structure databases
HSSP	HSSP built from PDB template 1AW0 based on UniProtKB Q04656.
SMR	P70705. Positions 1-79, 164-246, 275-351, 375-444.
ModBase	Search...
PTM databases
PhosphoSite	P70705.
Genome annotation databases
Ensembl	ENSRNOG00000002515. Rattus norvegicus. [Contig view]
GeneID	24941.
KEGG	rno:24941.
Organism-specific databases
RGD	2179. Atp7a.
Phylogenomic databases
HOVERGEN	P70705.
Gene expression databases
ArrayExpress	P70705.
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
NextBio	604931.

Entry information

Entry name

ATP7A_RAT

Accession

Primary (citable) accession number: P70705

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 8, 2000
Last sequence update:	February 1, 1997
Last modified:	November 25, 2008
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)