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3.A.3.5.3
Cu+-, Ag+-ATPase (efflux from the cytosol into the secretory pathway) (Barnes et al., 2005); ATP7B (Wilson's disease protein, α-chain) (continuously expressed in Purkinje neurons). It delivers Cu+ to the ferroxidase, ceruloplasmin, in liver. May also transport Fe2+ (Takeda et al., 2005). Critical roles for the COOH terminus of ATP7B in protein stability, trans-Golgi network retention, copper sensing, and retrograde trafficking have been reported (Braiterman et al. 2011).  Modeling suggests that Cu+-binding sites HMBDs 5 and 6 are most important for function (Gourdon et al. 2012).  ATP7B loads Cu+ into newly synthesized cupro-enzymes in the trans-Golgi network and exports excess copper out of cells by trafficking from the Golgi to the plasma membrane.  Mutations causing disease can affect activity, stability or trafficking (Braiterman et al. 2014).  Cisplatin is a poor substrate relative to Cu+with a Km of 1 mμM, and copper and cisplatin compete with each other (Safaei et al. 2008).

Accession Number:P35670
Protein Name:AT7B aka ATP7B aka WND aka PWD aka WC1
Length:1465
Molecular Weight:157263.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:11
Location1 / Topology2 / Orientation3: Mitochondrion1
Substrate Fe2+, Cu+, Ag+

Cross database links:

Genevestigator: P35670
eggNOG: prNOG17026
HEGENOM: HBG507745
RefSeq: NP_000044.2    NP_001005918.1   
Entrez Gene ID: 540   
Pfam: PF00122    PF00403    PF00702   
OMIM: 277900  phenotype
606882  gene
KEGG: hsa:540   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005770 C:late endosome
GO:0005739 C:mitochondrion
GO:0005524 F:ATP binding
GO:0005507 F:copper ion binding
GO:0004008 F:copper-exporting ATPase activity
GO:0005515 F:protein binding
GO:0006754 P:ATP biosynthetic process
GO:0006878 P:cellular copper ion homeostasis
GO:0015677 P:copper ion import
GO:0046688 P:response to copper ion
GO:0051208 P:sequestering of calcium ion

References (58)

[1] “Characterization of the Wilson disease gene encoding a P-type copper transporting ATPase: genomic organization, alternative splicing, and structure/function predictions.”  Petrukhin K.et.al.   7833924
[2] “The DNA sequence and analysis of human chromosome 13.”  Dunham A.et.al.   15057823
[3] “Cloning and characterization of the promoter region of the Wilson disease gene.”  Oh W.J.et.al.   10334941
[4] “The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.”  Bull P.C.et.al.   8298639
[5] “The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.”  Tanzi R.E.et.al.   8298641
[6] “Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease.”  Yamaguchi Y.et.al.   8250934
[7] “The Wilson disease gene: spectrum of mutations and their consequences.”  Thomas G.R.et.al.   7626145
[8] “Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.”  Yang X.-L.et.al.   9307043
[9] “Localization of the Wilson's disease protein product to mitochondria.”  Lutsenko S.et.al.   9600907
[10] “The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein.”  Tao T.Y.et.al.   12968035
[11] “Molecular pathology and haplotype analysis of Wilson disease in Mediterranean populations.”  Figus A.et.al.   8533760
[12] “Efficient detection of mutations in Wilson disease by manifold sequencing.”  Waldenstroem E.et.al.   8938442
[13] “Wilson disease mutations associated with uncommon haplotypes in Mediterranean patients.”  Loudianos G.et.al.   8931691
[14] “High frequency of two mutations in codon 778 in exon 8 of the ATP7B gene in Taiwanese families with Wilson disease.”  Chuang L.-M.et.al.   8782057
[15] “Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses.”  Shah A.B.et.al.   9311736
[16] “Identification of a novel missense mutation in Wilson's disease gene.”  Fan Y.et.al.   9772425
[17] “24 bp deletion and Ala1278 to Val mutation of the ATP7B gene in a Sardinian family with Wilson disease.”  Orru S.et.al.   9222767
[18] “A homozygous nonsense mutation and a combination of two mutations of the Wilson disease gene in patients with different lysyl oxidase activities in cultured fibroblasts.”  Kemppainen R.et.al.   8980283
[19] “His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype.”  Ha-Hao D.et.al.   9887381
[20] “Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups.”  Kalinsky H.et.al.   9482578
[21] “Identification of three novel mutations and a high frequency of the Arg778Leu mutation in Korean patients with Wilson disease.”  Kim E.K.et.al.   9554743
[22] “Mutations of ATP7B gene in Wilson disease in Japan: identification of nine mutations and lack of clear founder effect in a Japanese population.”  Yamaguchi A.et.al.   9452121
[23] “Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.”  Loudianos G.et.al.   9671269
[24] “Mutation analysis of Wilson disease in Taiwan and description of six new mutations.”  Tsai C.-H.et.al.   9829905
[25] “Missense mutations of exons 14 and 18 of Wilson's disease gene in Chinese patients.”  Wu Z.et.al.   10194254
[26] “Mutation analysis in patients with Wilson disease: identification of 4 novel mutations.”  Haas R.et.al.   10447265
[27] “Molecular characterization of Wilson disease in the Sardinian population -- evidence of a founder effect.”  Loudianos G.et.al.   10502776
[28] “A study of Wilson disease mutations in Britain.”  Curtis D.et.al.   10502777
[29] “The His1069Gln mutation in the ATP7B gene in Russian patients with Wilson disease.”  Ivanova-Smolenskaya I.A.et.al.   10051024
[30] “Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations.”  Loudianos G.et.al.   10544227
[31] “Molecular analysis and diagnosis in Japanese patients with Wilson's disease.”  Shimizu N.et.al.   10453196
[32] “Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations.”  Loudianos G.et.al.   11216666
[33] “High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.”  Garcia-Villarreal L.et.al.   11093740
[34] “Mutational analysis of ATP7B and genotype-phenotype correlation in Japanese with Wilson's disease.”  Okada T.et.al.   10790207
[35] “Novel mutations of the ATP7B gene in Japanese patients with Wilson disease.”  Kusuda Y.et.al.   10721669
[36] “Molecular analysis of Wilson disease in Taiwan: identification of one novel mutation and evidence of haplotype-mutation association.”  Lee C.C.et.al.   11043508
[37] “Three novel mutations (P760L, L1305P, Q1351Stop) causing Wilson disease.”  Genschel J.et.al.   11180609
[38] “High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis.”  Caca K.et.al.   11690702
[39] “Molecular diagnosis of Wilson disease.”  Butler P.et.al.   11243728
[40] “Presymptomatic diagnosis of Wilson disease associated with a novel mutation of the ATP7B gene.”  Ohya K.et.al.   11954751
[41] “Identification of novel mutations and the three most common mutations in the human ATP7B gene of Korean patients with Wilson disease.”  Yoo H.-W.et.al.   12544487
[42] “Abnormal mRNA splicing resulting from consensus sequence splicing mutations of ATP7B.”  Loudianos G.et.al.   12325021
[43] “Two families with Wilson disease in which siblings showed different phenotypes.”  Takeshita Y.et.al.   12376745
[44] “Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.”  Gu Y.-H.et.al.   14986826
[45] “A rare homozygous missense mutation in ATP7B exon 19 in a case of Wilson disease.”  Majumdar R.et.al.   14639035
[46] “Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients.”  Deguti M.M.et.al.   15024742
[47] “Strokelike presentation of Wilson disease with homozygosity for a novel T766R mutation.”  Pendlebury S.T.et.al.   15557537
[48] “Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson disease.”  Liu X.-Q.et.al.   14966923
[49] “Wilson disease: high prevalence in a mountainous area of Crete.”  Dedoussis G.V.Z.et.al.   15845031
[50] “Identification and molecular characterization of 18 novel mutations in the ATP7B gene from Indian Wilson disease patients: genotype.”  Kumar S.et.al.   15811015
[51] “Mutation analysis of Wilson disease in the Spanish population -identification of a prevalent substitution and eight novel mutations in the ATP7B gene.”  Margarit E.et.al.   15952988
[52] “Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population.”  Todorov T.et.al.   16207219
[53] “Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease.”  Gromadzka G.et.al.   16283883
[54] “Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry.”  Cox D.W.et.al.   16088907
[55] “Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease.”  Vrabelova S.et.al.   15967699
[56] “Early and severe liver disease associated with homozygosity for an exon 7 mutation, G691R, in Wilson's disease.”  Barada K.et.al.   17718866
[57] “New mutations in the Wilson disease gene, ATP7B: implications for molecular testing.”  Davies L.P.et.al.   18373411
[58] “Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system.”  Hsi G.et.al.   18203200
Structure:
2ARF   2EW9   2ROP   2KOY   2LQB     

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FASTA formatted sequence
1:	MPEQERQITA REGASRKILS KLSLPTRAWE PAMKKSFAFD NVGYEGGLDG LGPSSQVATS 
61:	TVRILGMTCQ SCVKSIEDRI SNLKGIISMK VSLEQGSATV KYVPSVVCLQ QVCHQIGDMG 
121:	FEASIAEGKA ASWPSRSLPA QEAVVKLRVE GMTCQSCVSS IEGKVRKLQG VVRVKVSLSN 
181:	QEAVITYQPY LIQPEDLRDH VNDMGFEAAI KSKVAPLSLG PIDIERLQST NPKRPLSSAN 
241:	QNFNNSETLG HQGSHVVTLQ LRIDGMHCKS CVLNIEENIG QLLGVQSIQV SLENKTAQVK 
301:	YDPSCTSPVA LQRAIEALPP GNFKVSLPDG AEGSGTDHRS SSSHSPGSPP RNQVQGTCST 
361:	TLIAIAGMTC ASCVHSIEGM ISQLEGVQQI SVSLAEGTAT VLYNPSVISP EELRAAIEDM 
421:	GFEASVVSES CSTNPLGNHS AGNSMVQTTD GTPTSVQEVA PHTGRLPANH APDILAKSPQ 
481:	STRAVAPQKC FLQIKGMTCA SCVSNIERNL QKEAGVLSVL VALMAGKAEI KYDPEVIQPL 
541:	EIAQFIQDLG FEAAVMEDYA GSDGNIELTI TGMTCASCVH NIESKLTRTN GITYASVALA 
601:	TSKALVKFDP EIIGPRDIIK IIEEIGFHAS LAQRNPNAHH LDHKMEIKQW KKSFLCSLVF 
661:	GIPVMALMIY MLIPSNEPHQ SMVLDHNIIP GLSILNLIFF ILCTFVQLLG GWYFYVQAYK 
721:	SLRHRSANMD VLIVLATSIA YVYSLVILVV AVAEKAERSP VTFFDTPPML FVFIALGRWL 
781:	EHLAKSKTSE ALAKLMSLQA TEATVVTLGE DNLIIREEQV PMELVQRGDI VKVVPGGKFP 
841:	VDGKVLEGNT MADESLITGE AMPVTKKPGS TVIAGSINAH GSVLIKATHV GNDTTLAQIV 
901:	KLVEEAQMSK APIQQLADRF SGYFVPFIII MSTLTLVVWI VIGFIDFGVV QRYFPNPNKH 
961:	ISQTEVIIRF AFQTSITVLC IACPCSLGLA TPTAVMVGTG VAAQNGILIK GGKPLEMAHK 
1021:	IKTVMFDKTG TITHGVPRVM RVLLLGDVAT LPLRKVLAVV GTAEASSEHP LGVAVTKYCK 
1081:	EELGTETLGY CTDFQAVPGC GIGCKVSNVE GILAHSERPL SAPASHLNEA GSLPAEKDAV 
1141:	PQTFSVLIGN REWLRRNGLT ISSDVSDAMT DHEMKGQTAI LVAIDGVLCG MIAIADAVKQ 
1201:	EAALAVHTLQ SMGVDVVLIT GDNRKTARAI ATQVGINKVF AEVLPSHKVA KVQELQNKGK 
1261:	KVAMVGDGVN DSPALAQADM GVAIGTGTDV AIEAADVVLI RNDLLDVVAS IHLSKRTVRR 
1321:	IRINLVLALI YNLVGIPIAA GVFMPIGIVL QPWMGSAAMA ASSVSVVLSS LQLKCYKKPD 
1381:	LERYEAQAHG HMKPLTASQV SVHIGMDDRW RDSPRATPWD QVSYVSQVSL SSLTSDKPSR 
1441:	HSAAADDDGD KWSLLLNGRD EEQYI