Reviewed, UniProtKB/Swiss-Prot P35670 (ATP7B_HUMAN)

Names and origin

Protein names

Recommended name:
    Copper-transporting ATPase 2
    EC=3.6.3.4
Alternative name(s):
    Copper pump 2
    Wilson disease-associated protein
Cleaved into the following 1 chains:
    1- Recommended name:
            WND/140 kDa

Gene names

Name:	ATP7B
Synonyms:	PWD, WC1, WND

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.
Catalytic activity	ATP + H(2)O + Cu(2+)(In) = ADP + phosphate + Cu(2+)(Out).
Subunit structure	Monomer. Interacts with COMMD1/MURR1.
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Multi-pass membrane proteinBy similarity. Note= Predominantly found in the trans-Golgi network (TGN). Not redistributed to the plasma membrane in response to elevated copper levels. Isoform 2: Cytoplasm. WND/140 kDa: Mitochondrion.
Tissue specificity	Most abundant in liver and kidney and also found in brain. Isoform 2 is expressed in brain but not in liver. The cleaved form WND/140 kDa is found in liver cell lines and other tissues.
Post-translational modification	Isoform 1 may be proteolytically cleaved at the N-terminus to produce the WND/140 kDa form.
Involvement in disease	Defects in ATP7B are the cause of Wilson disease (WD) [MIM:277900]. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.
Sequence similarities	Belongs to the cation transport ATPase (P-type) family. Type IB subfamily. Contains 6 HMA domains.
Sequence caution	The sequence AAA16173.1 differs from that shown. Reason: Frameshift at position 830. The sequence AAA79211.1 differs from that shown. Reason: Frameshift at position 456. The sequence AAA79212.1 differs from that shown. Reason: Frameshift at position 456.

Ontologies

Keywords
Biological process	Copper transport Ion transport Transport
Cellular component	Cytoplasm Golgi apparatus Membrane Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane
Ligand	ATP-binding Copper Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cellular copper ion homeostasis Traceable author statement. Source: UniProtKB copper ion import Inferred from direct assay. Source: UniProtKB response to copper ion Inferred from direct assay. Source: UniProtKB sequestering of calcium ion Inferred from direct assay. Source: UniProtKB
Cellular component	integral to plasma membrane Ref.7 Traceable author statement. Source: UniProtKB late endosome Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from direct assay. Source: UniProtKB copper ion binding Inferred from direct assay. Source: UniProtKB copper-exporting ATPase activity Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35670-1)

Also known as: A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P35670-2)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     624-785: Missing.
     911-955: Missing.

Isoform 3 (identifier: P35670-3)

The sequence of this isoform differs from the canonical sequence as follows:
     269-379: Missing.

Isoform 4 (identifier: P35670-4)

The sequence of this isoform differs from the canonical sequence as follows:
     938-955: Missing.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 1465	1465	Copper-transporting ATPase 2
	Chain	? – 1465		WND/140 kDa
Regions
	Topological domain	1 – 653	653	Cytoplasmic Potential
	Transmembrane	654 – 675	22	Potential
	Topological domain	676 – 697	22	Extracellular Potential
	Transmembrane	698 – 717	20	Potential
	Topological domain	718 – 724	7	Cytoplasmic Potential
	Transmembrane	725 – 745	21	Potential
	Topological domain	746 – 764	19	Extracellular Potential
	Transmembrane	765 – 785	21	Potential
	Topological domain	786 – 919	134	Cytoplasmic Potential
	Transmembrane	920 – 942	23	Potential
	Topological domain	943 – 972	30	Extracellular Potential
	Transmembrane	973 – 994	22	Potential
	Topological domain	995 – 1322	328	Cytoplasmic Potential
	Transmembrane	1323 – 1340	18	Potential
	Topological domain	1341 – 1351	11	Extracellular Potential
	Transmembrane	1352 – 1371	20	Potential
	Topological domain	1372 – 1465	94	Cytoplasmic Potential
	Domain	59 – 125	67	HMA 1
	Domain	144 – 210	67	HMA 2
	Domain	258 – 327	70	HMA 3
	Domain	360 – 426	67	HMA 4
	Domain	489 – 555	67	HMA 5
	Domain	565 – 631	67	HMA 6
	Compositional bias	340 – 345	6	Poly-Ser
Sites
	Active site	1027	1	4-aspartylphosphate intermediate By similarity
	Metal binding	1267	1	Magnesium By similarity
	Metal binding	1271	1	Magnesium By similarity
Natural variations
	Alternative sequence	269 – 379	111	Missing in isoform 3.
	Alternative sequence	624 – 785	162	Missing in isoform 2.
	Alternative sequence	911 – 955	45	Missing in isoform 2.
	Alternative sequence	938 – 955	18	Missing in isoform 4.
	Natural variant	14	1	A → D
	Natural variant	41	1	N → S in WD.
	Natural variant	85	1	G → V in WD.
	Natural variant	96	1	G → D
	Natural variant	290	1	V → L
	Natural variant	390	1	I → V
	Natural variant	406	1	S → A: dbSNP rs1801243.
	Natural variant	446	1	V → L
	Natural variant	456	1	V → L: dbSNP rs1801244.
	Natural variant	466	1	L → V
	Natural variant	486	1	A → S in WD.
	Natural variant	492	1	L → S in WD.
	Natural variant	532	1	Y → H in WD.
	Natural variant	565	1	N → S
	Natural variant	591	1	G → D in WD.
	Natural variant	604	1	A → P in WD.
	Natural variant	608 – 609	2	FD → Y in WD.
	Natural variant	616	1	R → Q in WD.
	Natural variant	616	1	R → W in WD.
	Natural variant	626	1	G → A in WD.
	Natural variant	639	1	H → Y in WD.
	Natural variant	641	1	L → S in WD.
	Natural variant	642	1	D → H in WD.
	Natural variant	645	1	M → R in WD.
	Natural variant	653	1	S → Y in WD.
	Natural variant	665	1	M → I in WD.
	Natural variant	670 – 671	2	Missing in WD.
	Natural variant	690	1	P → L in WD.
	Natural variant	691	1	G → R in WD.
	Natural variant	693	1	S → C in WD.
	Natural variant	703	1	C → Y in WD.
	Natural variant	708	1	L → P in WD.
	Natural variant	710	1	G → A in WD.
	Natural variant	710	1	G → R in WD.
	Natural variant	710	1	G → S in WD.
	Natural variant	710	1	G → V in WD.
	Natural variant	711	1	G → E in WD.
	Natural variant	711	1	G → R in WD.
	Natural variant	711	1	G → W in WD.
	Natural variant	713	1	Y → C in WD.
	Natural variant	721	1	S → P in WD.
	Natural variant	723	1	R → G
	Natural variant	737	1	T → R in WD.
	Natural variant	741	1	Y → C in WD.
	Natural variant	744	1	S → P in WD.
	Natural variant	747	1	I → F in WD.
	Natural variant	756	1	A → G in WD.
	Natural variant	760	1	P → L in WD.
	Natural variant	765	1	D → G in WD.
	Natural variant	765	1	D → N in WD.
	Natural variant	766	1	T → M in WD.
	Natural variant	766	1	T → R in WD.
	Natural variant	768	1	P → H in WD.
	Natural variant	769	1	M → I in WD.
	Natural variant	769	1