Copper-transporting ATPase 2 - Rattus norvegicus (Rat)

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 homolog
    Pineal night-specific ATPase

Gene names

Name:	Atp7b
Synonyms:	Pina, Wnd

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

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Protein attributes

Sequence length	1451 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

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General annotation (Comments)

Function	Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile By similarity.
Catalytic activity	ATP + H(2)O + Cu(2+)(In) = ADP + phosphate + Cu(2+)(Out).
Subunit structure	Monomer. Interacts with COMMD1/MURR1 By similarity.
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 By similarity.
Tissue specificity	Expressed in brain, liver, kidney, spleen and stomach. In brain, detected in neuronal cells of the hippocampal formation, olfactory bulbs, cerebellum, cerebral cortex and nuclei in the brainstem. Isoform PINA is expressed during night in adult pineal gland (pinealocytes) and retina. Isoform PINA is not detected in other tissue.
Developmental stage	Isoform PINA is expressed during daytime in embryonic pineal (postnatal day 2 and 7) and embryonic retinal pigment epithelium (embryonic day 14.5 and postnatal day 16). Daytime expression disappears in pineal at postnatal day 16 and in adult retina.
Involvement in disease	Deficiency of Atp7b expression is the cause of the Long-Evans Cinnamon (LEC) phenotype, inherited in an autosomal recessive manner, characterized by excessive hepatic copper accumulation, defective holoceruloplasmin biosynthesis, impaired biliary copper excretion and the development of necrotizing hepatitis by 4 months of age.
Sequence similarities	Belongs to the cation transport ATPase (P-type) family. Type IB subfamily. Contains 6 HMA domains.

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Ontologies

Keywords
Biological process	Biological rhythms Copper transport Ion transport Transport
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative initiation Alternative splicing
Domain	Repeat Transmembrane
Ligand	ATP-binding Copper Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	metabolic process Inferred from electronic annotation. Source: InterPro rhythmic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: InterPro
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...

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Alternative products

This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Isoform Long (identifier: Q64535-1) 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 Short (identifier: Q64535-2) The sequence of this isoform differs from the canonical sequence as follows: 1-788: Missing.
Notes: Produced by alternative splicing. Does not show copper transport activity.

Isoform PINAM2 (identifier: Q64535-3) The sequence of this isoform differs from the canonical sequence as follows: 1-814: Missing.
Notes: Produced by alternative initiation at Met-815 of isoform Long. Shows copper transport activity.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1451

1451

Copper-transporting ATPase 2

PRO_0000002511

Regions

Topological domain

1 – 646

646

Cytoplasmic Potential

Transmembrane

647 – 668

22

Potential

Topological domain

669 – 690

22

Extracellular Potential

Transmembrane

691 – 710

20

Potential

Topological domain

711 – 717

7

Cytoplasmic Potential

Transmembrane

718 – 738

21

Potential

Topological domain

739 – 757

19

Extracellular Potential

Transmembrane

758 – 778

21

Potential

Topological domain

779 – 912

134

Cytoplasmic Potential

Transmembrane

913 – 935

23

Potential

Topological domain

936 – 965

30

Extracellular Potential

Transmembrane

966 – 987

22

Potential

Topological domain

988 – 1310

323

Cytoplasmic Potential

Transmembrane

1311 – 1328

18

Potential

Topological domain

1329 – 1339

11

Extracellular Potential

Transmembrane

1340 – 1357

18

Potential

Topological domain

1358 – 1451

94

Cytoplasmic Potential

Domain

58 – 124

67

HMA 1

Domain

143 – 209

67

HMA 2

Domain

257 – 323

67

HMA 3

Domain

356 – 422

67

HMA 4

Domain

482 – 548

67

HMA 5

Domain

558 – 624

67

HMA 6

Compositional bias

921 – 924

4

Poly-Ile

Sites

Active site

1020

1

4-aspartylphosphate intermediate By similarity

Metal binding

1255

1

Magnesium By similarity

Metal binding

1259

1

Magnesium By similarity

Natural variations

Alternative sequence

1 – 814

814

Missing in isoform PINAM2.

VSP_018666

Alternative sequence

1 – 788

788

Missing in isoform Short.

VSP_000428

Experimental info

Sequence conflict

1194 – 1195

2

SI → IY in AAD16009. Ref.2

Sequence conflict

1281

1

D → E in AAD16009. Ref.2

Sequence conflict

1346

1

A → AMA Ref.2

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Sequences

Sequence		Length	Mass (Da)
Isoform Long [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 2029940643318401 Show »	FASTA	1,451	155,990
10 20 30 40 50 60 MPEQERKVTA KEASRKILSK LALPTRPWGQ SMKQSFAFDN VGYEGGLDST CFILQLTTGV 70 80 90 100 110 120 VSILGMTCHS CVKSIEDRIS SLKGIVSIKV SLEQGSATVK YVPSVLNLQQ ICLQIEDMGF 130 140 150 160 170 180 EASAAEGKAA SWPSRSSPAQ EAVVKLRVEG MTCQSCVSSI EGKIRKLQGV VRVKVSLSNQ 190 200 210 220 230 240 EAVITYQPYL IQPEDLRDHI CDMGFEAAIK NRTAPLRLGP IDINKLESTN LKRAAVPPIQ 250 260 270 280 290 300 NSNHLETPGH QQNHLATLPL RIDGMHCKSC VLNIEGNIGQ LPGVQNIHVS LENKTAQVQY 310 320 330 340 350 360 DSSCITPLFL QTAIEALPPG YFKVSLPDGL EKESGSSSVP SLGSSQRQQE PGPCRTAVLT 370 380 390 400 410 420 ITGIPRDSSV QPMEDMLSQM KGVQQIDISL AEGTGAVLYD PSVVSSDELR TAVEDMGFEV 430 440 450 460 470 480 SVNPENITTN RVSSGNSVPQ AVGDSPGSVQ NMASDTRGLL THQGPGYLSD SPPSPGGTAS 490 500 510 520 530 540 QKCFVQIKGM TCASCVSNIE RSLQRHAGIL SVLVALMSGK AEVKYDPEVI QSPRIAQLIE 550 560 570 580 590 600 DLGFEAAIME DNTVSEGDIE LIITGMTCAS CVHNIESKLT RTNGITYASV ALATSKAHVK 610 620 630 640 650 660 FDPEIIGPRD IIKVIEEIGF HASLAHRNPN AHHLDHKTEI KQWKKSFLCS LVFGIPVMGL 670 680 690 700 710 720 MIYMLIPSSK PHETMVLDHN IIPGLSVLNL IFFILCTFVQ FLGGWYFYVQ AYKSLRHKSA 730 740 750 760 770 780 NMDVLIVLAT TIAYAYSLVI LVVAIAEKAE KSPVTFFDTP PMLFVFIALG RWLEHVAKSK 790 800 810 820 830 840 TSEALAKLMS LQATEATVVT LGEDNLILRE EQVPMELVQR GDIIKVVPGG KFPVDGKVLE 850 860 870 880 890 900 GNTMADESLI TGEAMPVTKK PGSIVIAGSI NAHGSVLIKA THVGNDTTLA QIVKLVEEAQ 910 920 930 940 950 960 MSKAPIQQLA DRFSGYFVPF IIIISTLTLV VWIIIGFVDF GIVQKYFPSP SKHISQTEVI 970 980 990 1000 1010 1020 IRFAFQTSIT VLCIACPCSL GLATPTAVMV GTGVAAQNGV LIKGGKPLEM AHKIKTVMFD 1030 1040 1050 1060 1070 1080 KTGTITHGVP RVMRFLLLVD VATLSLRKVL AVVGTAEASS EHPLGVAVTK YCKEELGTET 1090 1100 1110 1120 1130 1140 LGYSTDFQAV PGCGISCKVS NVESILAHRG PTAHPIGVGN PPIGEGTGPQ TFSVLIGNRE 1150 1160 1170 1180 1190 1200 WMRRNGLTIS SDISDAMTDH EMKGQTAILV AIDGVLCGMI AIADAVKPEA ALASITLKSM 1210 1220 1230 1240 1250 1260 GVDVALITGD NRKTARAIAT QVGINKVFAE VLPSHKVAKV QELQNKGKKV AMVGDGVNDS 1270 1280 1290 1300 1310 1320 PALAQADVGI AIGTGTDVAI DAADVVLIRN DLLDVVASIH LSKRTVRRIR VNLVLALIYN 1330 1340 1350 1360 1370 1380 MVGIPIAAGV FMPIGIVLQP WMGSAAASSV SVVLSSLQLK CYRKPDLERY EAQAHGRMKP 1390 1400 1410 1420 1430 1440 LSASQVSVHV GMDDRRRDSP RATPWDQVSY VSQVSLSSLT SDRLSRHGGM AEDGGDKWSL 1450 LLSDRDEEQC I « Hide
Isoform Short [UniParc]. Checksum: 9893B14F24813497 Show »		663	70,453
10 20 30 40 50 60 MSLQATEATV VTLGEDNLIL REEQVPMELV QRGDIIKVVP GGKFPVDGKV LEGNTMADES 70 80 90 100 110 120 LITGEAMPVT KKPGSIVIAG SINAHGSVLI KATHVGNDTT LAQIVKLVEE AQMSKAPIQQ 130 140 150 160 170 180 LADRFSGYFV PFIIIISTLT LVVWIIIGFV DFGIVQKYFP SPSKHISQTE VIIRFAFQTS 190 200 210 220 230 240 ITVLCIACPC SLGLATPTAV MVGTGVAAQN GVLIKGGKPL EMAHKIKTVM FDKTGTITHG 250 260 270 280 290 300 VPRVMRFLLL VDVATLSLRK VLAVVGTAEA SSEHPLGVAV TKYCKEELGT ETLGYSTDFQ 310 320 330 340 350 360 AVPGCGISCK VSNVESILAH RGPTAHPIGV GNPPIGEGTG PQTFSVLIGN REWMRRNGLT 370 380 390 400 410 420 ISSDISDAMT DHEMKGQTAI LVAIDGVLCG MIAIADAVKP EAALASITLK SMGVDVALIT 430 440 450 460 470 480 GDNRKTARAI ATQVGINKVF AEVLPSHKVA KVQELQNKGK KVAMVGDGVN DSPALAQADV 490 500 510 520 530 540 GIAIGTGTDV AIDAADVVLI RNDLLDVVAS IHLSKRTVRR IRVNLVLALI YNMVGIPIAA 550 560 570 580 590 600 GVFMPIGIVL QPWMGSAAAS SVSVVLSSLQ LKCYRKPDLE RYEAQAHGRM KPLSASQVSV 610 620 630 640 650 660 HVGMDDRRRD SPRATPWDQV SYVSQVSLSS LTSDRLSRHG GMAEDGGDKW SLLLSDRDEE QCI « Hide
Isoform PINAM2 [UniParc]. Checksum: DFCF672DFCD8F44F Show »		637	67,614
10 20 30 40 50 60 MELVQRGDII KVVPGGKFPV DGKVLEGNTM ADESLITGEA MPVTKKPGSI VIAGSINAHG 70 80 90 100 110 120 SVLIKATHVG NDTTLAQIVK LVEEAQMSKA PIQQLADRFS GYFVPFIIII STLTLVVWII 130 140 150 160 170 180 IGFVDFGIVQ KYFPSPSKHI SQTEVIIRFA FQTSITVLCI ACPCSLGLAT PTAVMVGTGV 190 200 210 220 230 240 AAQNGVLIKG GKPLEMAHKI KTVMFDKTGT ITHGVPRVMR FLLLVDVATL SLRKVLAVVG 250 260 270 280 290 300 TAEASSEHPL GVAVTKYCKE ELGTETLGYS TDFQAVPGCG ISCKVSNVES ILAHRGPTAH 310 320 330 340 350 360 PIGVGNPPIG EGTGPQTFSV LIGNREWMRR NGLTISSDIS DAMTDHEMKG QTAILVAIDG 370 380 390 400 410 420 VLCGMIAIAD AVKPEAALAS ITLKSMGVDV ALITGDNRKT ARAIATQVGI NKVFAEVLPS 430 440 450 460 470 480 HKVAKVQELQ NKGKKVAMVG DGVNDSPALA QADVGIAIGT GTDVAIDAAD VVLIRNDLLD 490 500 510 520 530 540 VVASIHLSKR TVRRIRVNLV LALIYNMVGI PIAAGVFMPI GIVLQPWMGS AAASSVSVVL 550 560 570 580 590 600 SSLQLKCYRK PDLERYEAQA HGRMKPLSAS QVSVHVGMDD RRRDSPRATP WDQVSYVSQV 610 620 630 SLSSLTSDRL SRHGGMAEDG GDKWSLLLSD RDEEQCI « Hide

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References

[1]	"The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene." Wu J., Forbes J.R., Chen H.S., Cox D.W. Nat. Genet. 7:541-545(1994) [PubMed: 7951327] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Liver.
[2]	"A novel pineal night-specific ATPase encoded by the Wilson disease gene." Borjigin J., Payne A.S., Deng J., Li X., Wang M.M., Ovodenko B., Gitlin J.D., Snyder S.H. J. Neurosci. 19:1018-1026(1999) [PubMed: 9920665] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Strain: Sprague-Dawley. Tissue: Pineal gland.
[3]	"Expression of the Wilson disease gene is deficient in the Long-Evans Cinnamon rat." Yamaguchi Y., Heiny M.E., Shimizu N., Aoki T., Gitlin J.D. Biochem. J. 301:1-4(1994) [PubMed: 8037655] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 530-616. Strain: Sprague-Dawley. Tissue: Liver.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	U08344 mRNA. Translation: AAA62157.1. AF120492 mRNA. Translation: AAD16009.1. L28173 mRNA. Translation: AAA21810.1.
PIR	I58124.
UniGene	Rn.10025
3D structure databases
HSSP	HSSP built from PDB template 1AW0 based on UniProtKB Q04656.
SMR	Q64535. Positions 478-550, 479-626, 1027-1184.
ModBase	Search...
Genome annotation databases
Ensembl	ENSRNOG00000012878. Rattus norvegicus. [Contig view]
Organism-specific databases
RGD	2180. Atp7b.
Phylogenomic databases
HOVERGEN	Q64535.
Gene expression databases
ArrayExpress	Q64535.
GermOnline	ENSRNOG00000012878. Rattus norvegicus.
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. 2 hits.
PROSITE	PS00154. ATPASE_E1_E2. 1 hit. PS01047. HMA_1. 5 hits. PS50846. HMA_2. 6 hits. [Graphical view]
ProtoNet	Search...

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Entry information

Entry name

ATP7B_RAT

Accession

Primary (citable) accession number: Q64535
Secondary accession number(s): Q63676, Q9JLY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Entry information

Relevant documents