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Protein

Copper-transporting ATPase 2

Gene

Atp7b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.By similarity

Catalytic activityi

ATP + H2O + Cu+(Side 1) = ADP + phosphate + Cu+(Side 2).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi68Copper 1PROSITE-ProRule annotation1
Metal bindingi71Copper 1PROSITE-ProRule annotation1
Metal bindingi153Copper 2PROSITE-ProRule annotation1
Metal bindingi156Copper 2PROSITE-ProRule annotation1
Metal bindingi267Copper 3PROSITE-ProRule annotation1
Metal bindingi270Copper 3PROSITE-ProRule annotation1
Metal bindingi492Copper 5PROSITE-ProRule annotation1
Metal bindingi495Copper 5PROSITE-ProRule annotation1
Metal bindingi568Copper 6PROSITE-ProRule annotation1
Metal bindingi571Copper 6PROSITE-ProRule annotation1
Active sitei10204-aspartylphosphate intermediateBy similarity1
Metal bindingi1255MagnesiumPROSITE-ProRule annotation1
Metal bindingi1259MagnesiumPROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • copper-exporting ATPase activity Source: RGD
  • copper ion binding Source: RGD
  • copper ion transmembrane transporter activity Source: RGD
  • copper-transporting ATPase activity Source: UniProtKB
  • zinc ion binding Source: RGD

GO - Biological processi

  • cellular copper ion homeostasis Source: GO_Central
  • cellular response to copper ion Source: RGD
  • cellular response to manganese ion Source: RGD
  • circadian rhythm Source: RGD
  • copper ion export Source: RGD
  • lactation Source: RGD
  • response to cAMP Source: RGD
  • response to copper ion Source: RGD
  • response to manganese ion Source: RGD
  • response to prolactin Source: RGD
  • response to zinc ion Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Biological rhythms, Copper transport, Ion transport, Transport

Keywords - Ligandi

ATP-binding, Copper, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.3.4. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Copper-transporting ATPase 2 (EC:3.6.3.54By similarity)
Alternative name(s):
Copper pump 2
Pineal night-specific ATPase
Wilson disease-associated protein homolog
Gene namesi
Name:Atp7b
Synonyms:Pina, Wnd
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2180. Atp7b.

Subcellular locationi

  • Golgi apparatustrans-Golgi network membrane By similarity; Multi-pass membrane protein Sequence analysis
  • Late endosome By similarity

  • Note: Predominantly found in the trans-Golgi network (TGN). Not redistributed to the plasma membrane in response to elevated copper levels.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 646CytoplasmicSequence analysisAdd BLAST646
Transmembranei647 – 668HelicalSequence analysisAdd BLAST22
Topological domaini669 – 690ExtracellularSequence analysisAdd BLAST22
Transmembranei691 – 710HelicalSequence analysisAdd BLAST20
Topological domaini711 – 717CytoplasmicSequence analysis7
Transmembranei718 – 738HelicalSequence analysisAdd BLAST21
Topological domaini739 – 757ExtracellularSequence analysisAdd BLAST19
Transmembranei758 – 778HelicalSequence analysisAdd BLAST21
Topological domaini779 – 912CytoplasmicSequence analysisAdd BLAST134
Transmembranei913 – 935HelicalSequence analysisAdd BLAST23
Topological domaini936 – 965ExtracellularSequence analysisAdd BLAST30
Transmembranei966 – 987HelicalSequence analysisAdd BLAST22
Topological domaini988 – 1310CytoplasmicSequence analysisAdd BLAST323
Transmembranei1311 – 1328HelicalSequence analysisAdd BLAST18
Topological domaini1329 – 1339ExtracellularSequence analysisAdd BLAST11
Transmembranei1340 – 1357HelicalSequence analysisAdd BLAST18
Topological domaini1358 – 1451CytoplasmicSequence analysisAdd BLAST94

GO - Cellular componenti

  • apical part of cell Source: RGD
  • basolateral plasma membrane Source: RGD
  • bicellular tight junction Source: RGD
  • endoplasmic reticulum Source: RGD
  • integral component of plasma membrane Source: GO_Central
  • late endosome Source: RGD
  • occluding junction Source: RGD
  • perinuclear region of cytoplasm Source: RGD
  • plasma membrane Source: RGD
  • trans-Golgi network Source: RGD
  • trans-Golgi network membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000025111 – 1451Copper-transporting ATPase 2Add BLAST1451

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei469PhosphoserineCombined sources1
Modified residuei471PhosphoserineCombined sources1
Modified residuei474PhosphoserineCombined sources1
Modified residuei1384PhosphoserineCombined sources1
Modified residuei1443PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ64535.
PRIDEiQ64535.

PTM databases

iPTMnetiQ64535.
PhosphoSitePlusiQ64535.

Expressioni

Tissue specificityi

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 stagei

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.

Interactioni

Subunit structurei

Monomer. Interacts with COMMD1/MURR1 (By similarity). Interacts with DCTN4, in a copper-dependent manner (By similarity). Interacts with ATOX1 (By similarity). Interacts (via C-terminus) with ZBTB16/PLZF (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000054880.

Structurei

3D structure databases

ProteinModelPortaliQ64535.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini58 – 124HMA 1PROSITE-ProRule annotationAdd BLAST67
Domaini143 – 209HMA 2PROSITE-ProRule annotationAdd BLAST67
Domaini257 – 323HMA 3PROSITE-ProRule annotationAdd BLAST67
Domaini356 – 422HMA 4PROSITE-ProRule annotationAdd BLAST67
Domaini482 – 548HMA 5PROSITE-ProRule annotationAdd BLAST67
Domaini558 – 624HMA 6PROSITE-ProRule annotationAdd BLAST67

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi921 – 924Poly-Ile4

Domaini

Each HMA domain can bind a copper ion, they are tightly packed and closely interact with each other. Wild-type ATP7B can usually be loaded with an average 5.5 copper atoms per molecule (By similarity).By similarity

Sequence similaritiesi

Contains 6 HMA domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0207. Eukaryota.
COG2217. LUCA.
HOVERGENiHBG050616.
InParanoidiQ64535.
PhylomeDBiQ64535.

Family and domain databases

CDDicd00371. HMA. 6 hits.
Gene3Di2.70.150.10. 1 hit.
3.40.1110.10. 1 hit.
3.40.50.1000. 2 hits.
InterProiIPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR017969. Heavy-metal-associated_CS.
IPR006122. HMA_Cu_ion-bd.
IPR006121. HMA_dom.
IPR027256. P-typ_ATPase_IB.
IPR001757. P_typ_ATPase.
[Graphical view]
PfamiPF00122. E1-E2_ATPase. 1 hit.
PF00403. HMA. 5 hits.
[Graphical view]
SUPFAMiSSF55008. SSF55008. 6 hits.
SSF56784. SSF56784. 2 hits.
TIGRFAMsiTIGR01525. ATPase-IB_hvy. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
TIGR00003. TIGR00003. 5 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
PS01047. HMA_1. 5 hits.
PS50846. HMA_2. 6 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform Long (identifier: Q64535-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPEQERKVTA KEASRKILSK LALPTRPWGQ SMKQSFAFDN VGYEGGLDST
60 70 80 90 100
CFILQLTTGV VSILGMTCHS CVKSIEDRIS SLKGIVSIKV SLEQGSATVK
110 120 130 140 150
YVPSVLNLQQ ICLQIEDMGF EASAAEGKAA SWPSRSSPAQ EAVVKLRVEG
160 170 180 190 200
MTCQSCVSSI EGKIRKLQGV VRVKVSLSNQ EAVITYQPYL IQPEDLRDHI
210 220 230 240 250
CDMGFEAAIK NRTAPLRLGP IDINKLESTN LKRAAVPPIQ NSNHLETPGH
260 270 280 290 300
QQNHLATLPL RIDGMHCKSC VLNIEGNIGQ LPGVQNIHVS LENKTAQVQY
310 320 330 340 350
DSSCITPLFL QTAIEALPPG YFKVSLPDGL EKESGSSSVP SLGSSQRQQE
360 370 380 390 400
PGPCRTAVLT ITGIPRDSSV QPMEDMLSQM KGVQQIDISL AEGTGAVLYD
410 420 430 440 450
PSVVSSDELR TAVEDMGFEV SVNPENITTN RVSSGNSVPQ AVGDSPGSVQ
460 470 480 490 500
NMASDTRGLL THQGPGYLSD SPPSPGGTAS QKCFVQIKGM TCASCVSNIE
510 520 530 540 550
RSLQRHAGIL SVLVALMSGK AEVKYDPEVI QSPRIAQLIE DLGFEAAIME
560 570 580 590 600
DNTVSEGDIE LIITGMTCAS CVHNIESKLT RTNGITYASV ALATSKAHVK
610 620 630 640 650
FDPEIIGPRD IIKVIEEIGF HASLAHRNPN AHHLDHKTEI KQWKKSFLCS
660 670 680 690 700
LVFGIPVMGL MIYMLIPSSK PHETMVLDHN IIPGLSVLNL IFFILCTFVQ
710 720 730 740 750
FLGGWYFYVQ AYKSLRHKSA NMDVLIVLAT TIAYAYSLVI LVVAIAEKAE
760 770 780 790 800
KSPVTFFDTP PMLFVFIALG RWLEHVAKSK TSEALAKLMS LQATEATVVT
810 820 830 840 850
LGEDNLILRE EQVPMELVQR GDIIKVVPGG KFPVDGKVLE GNTMADESLI
860 870 880 890 900
TGEAMPVTKK PGSIVIAGSI NAHGSVLIKA THVGNDTTLA QIVKLVEEAQ
910 920 930 940 950
MSKAPIQQLA DRFSGYFVPF IIIISTLTLV VWIIIGFVDF GIVQKYFPSP
960 970 980 990 1000
SKHISQTEVI IRFAFQTSIT VLCIACPCSL GLATPTAVMV GTGVAAQNGV
1010 1020 1030 1040 1050
LIKGGKPLEM AHKIKTVMFD KTGTITHGVP RVMRFLLLVD VATLSLRKVL
1060 1070 1080 1090 1100
AVVGTAEASS EHPLGVAVTK YCKEELGTET LGYSTDFQAV PGCGISCKVS
1110 1120 1130 1140 1150
NVESILAHRG PTAHPIGVGN PPIGEGTGPQ TFSVLIGNRE WMRRNGLTIS
1160 1170 1180 1190 1200
SDISDAMTDH EMKGQTAILV AIDGVLCGMI AIADAVKPEA ALASITLKSM
1210 1220 1230 1240 1250
GVDVALITGD NRKTARAIAT QVGINKVFAE VLPSHKVAKV QELQNKGKKV
1260 1270 1280 1290 1300
AMVGDGVNDS PALAQADVGI AIGTGTDVAI DAADVVLIRN DLLDVVASIH
1310 1320 1330 1340 1350
LSKRTVRRIR VNLVLALIYN MVGIPIAAGV FMPIGIVLQP WMGSAAASSV
1360 1370 1380 1390 1400
SVVLSSLQLK CYRKPDLERY EAQAHGRMKP LSASQVSVHV GMDDRRRDSP
1410 1420 1430 1440 1450
RATPWDQVSY VSQVSLSSLT SDRLSRHGGM AEDGGDKWSL LLSDRDEEQC

I
Length:1,451
Mass (Da):155,990
Last modified:November 1, 1996 - v1
Checksum:i2029940643318401
GO
Isoform Short (identifier: Q64535-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-788: Missing.

Note: Produced by alternative splicing. Does not show copper transport activity.
Show »
Length:663
Mass (Da):70,453
Checksum:i9893B14F24813497
GO
Isoform PINAM2 (identifier: Q64535-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-814: Missing.

Note: Produced by alternative initiation at Met-815 of isoform Long. Shows copper transport activity.
Show »
Length:637
Mass (Da):67,614
Checksum:iDFCF672DFCD8F44F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1194 – 1195SI → IY in AAD16009 (PubMed:9920665).Curated2
Sequence conflicti1281D → E in AAD16009 (PubMed:9920665).Curated1
Sequence conflicti1346A → AMA in AAD16009 (PubMed:9920665).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0186661 – 814Missing in isoform PINAM2. CuratedAdd BLAST814
Alternative sequenceiVSP_0004281 – 788Missing in isoform Short. 1 PublicationAdd BLAST788

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08344 mRNA. Translation: AAA62157.1.
AF120492 mRNA. Translation: AAD16009.1.
L28173 mRNA. Translation: AAA21810.1.
PIRiI58124.
UniGeneiRn.10025.

Genome annotation databases

UCSCiRGD:2180. rat. [Q64535-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08344 mRNA. Translation: AAA62157.1.
AF120492 mRNA. Translation: AAD16009.1.
L28173 mRNA. Translation: AAA21810.1.
PIRiI58124.
UniGeneiRn.10025.

3D structure databases

ProteinModelPortaliQ64535.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000054880.

PTM databases

iPTMnetiQ64535.
PhosphoSitePlusiQ64535.

Proteomic databases

PaxDbiQ64535.
PRIDEiQ64535.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2180. rat. [Q64535-1]

Organism-specific databases

RGDi2180. Atp7b.

Phylogenomic databases

eggNOGiKOG0207. Eukaryota.
COG2217. LUCA.
HOVERGENiHBG050616.
InParanoidiQ64535.
PhylomeDBiQ64535.

Enzyme and pathway databases

BRENDAi3.6.3.4. 5301.

Miscellaneous databases

PROiQ64535.

Family and domain databases

CDDicd00371. HMA. 6 hits.
Gene3Di2.70.150.10. 1 hit.
3.40.1110.10. 1 hit.
3.40.50.1000. 2 hits.
InterProiIPR023299. ATPase_P-typ_cyto_domN.
IPR018303. ATPase_P-typ_P_site.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR023214. HAD-like_dom.
IPR017969. Heavy-metal-associated_CS.
IPR006122. HMA_Cu_ion-bd.
IPR006121. HMA_dom.
IPR027256. P-typ_ATPase_IB.
IPR001757. P_typ_ATPase.
[Graphical view]
PfamiPF00122. E1-E2_ATPase. 1 hit.
PF00403. HMA. 5 hits.
[Graphical view]
SUPFAMiSSF55008. SSF55008. 6 hits.
SSF56784. SSF56784. 2 hits.
TIGRFAMsiTIGR01525. ATPase-IB_hvy. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
TIGR00003. TIGR00003. 5 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
PS01047. HMA_1. 5 hits.
PS50846. HMA_2. 6 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATP7B_RAT
AccessioniPrimary (citable) accession number: Q64535
Secondary accession number(s): Q63676, Q9JLY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.