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Protein

Copper-transporting ATPase 1

Gene

ATP7A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei10444-aspartylphosphate intermediateBy similarity1
Metal bindingi1301MagnesiumPROSITE-ProRule annotation1
Metal bindingi1305MagnesiumPROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: HGNC
  • copper-dependent protein binding Source: UniProtKB
  • copper-exporting ATPase activity Source: UniProtKB
  • copper ion binding Source: UniProtKB
  • copper ion transmembrane transporter activity Source: UniProtKB
  • superoxide dismutase copper chaperone activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Copper transport, Ion transport, Transport

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:HS09205-MONOMER.
BRENDAi3.6.3.4. 2681.
ReactomeiR-HSA-3299685. Detoxification of Reactive Oxygen Species.
R-HSA-6803544. Ion influx/efflux at host-pathogen interface.
R-HSA-936837. Ion transport by P-type ATPases.
SABIO-RKQ04656.

Protein family/group databases

TCDBi3.A.3.5.6. the p-type atpase (p-atpase) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Copper-transporting ATPase 1 (EC:3.6.3.54)
Alternative name(s):
Copper pump 1
Menkes disease-associated protein
Gene namesi
Name:ATP7A
Synonyms:MC1, MNK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:869. ATP7A.

Subcellular locationi

Isoform 5 :
  • Endoplasmic reticulum 1 Publication

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 653CytoplasmicSequence analysisAdd BLAST653
Transmembranei654 – 675HelicalSequence analysisAdd BLAST22
Topological domaini676 – 714ExtracellularSequence analysisAdd BLAST39
Transmembranei715 – 734HelicalSequence analysisAdd BLAST20
Topological domaini735 – 741CytoplasmicSequence analysis7
Transmembranei742 – 762HelicalSequence analysisAdd BLAST21
Topological domaini763 – 781ExtracellularSequence analysisAdd BLAST19
Transmembranei782 – 802HelicalSequence analysisAdd BLAST21
Topological domaini803 – 936CytoplasmicSequence analysisAdd BLAST134
Transmembranei937 – 959HelicalSequence analysisAdd BLAST23
Topological domaini960 – 989ExtracellularSequence analysisAdd BLAST30
Transmembranei990 – 1011HelicalSequence analysisAdd BLAST22
Topological domaini1012 – 1356CytoplasmicSequence analysisAdd BLAST345
Transmembranei1357 – 1374HelicalSequence analysisAdd BLAST18
Topological domaini1375 – 1385ExtracellularSequence analysisAdd BLAST11
Transmembranei1386 – 1405HelicalSequence analysisAdd BLAST20
Topological domaini1406 – 1500CytoplasmicSequence analysisAdd BLAST95

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB
  • brush border membrane Source: Ensembl
  • cytosol Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • integral component of plasma membrane Source: GO_Central
  • late endosome Source: UniProtKB
  • membrane Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • secretory granule Source: Ensembl
  • trans-Golgi network Source: UniProtKB
  • trans-Golgi network transport vesicle Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Menkes disease (MNKD)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes. A mild form of the disease has been described, in which cerebellar ataxia and moderate developmental delay predominate.
See also OMIM:309400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000699629A → P in MNKD. 1 Publication1
Natural variantiVAR_023261706L → R in MNKD. 1 Publication1
Natural variantiVAR_000700727G → R in MNKD. 1 Publication1
Natural variantiVAR_023262844R → H in MNKD. 1 Publication1
Natural variantiVAR_023263853G → R in MNKD. 1 Publication1
Natural variantiVAR_023264860G → V in MNKD. 1 Publication1
Natural variantiVAR_010001873L → R in MNKD; increased protein abundance; does not affect interaction with ATOX1; does not affect interaction with COMMD1; increased localization at the plasma membrane; does not cycle back to TGN under conditions of copper depletion. 2 Publications1
Natural variantiVAR_010002876G → E in MNKD. 1 Publication1
Natural variantiVAR_023265876G → R in MNKD. 1 Publication1
Natural variantiVAR_023266924Q → R in MNKD. 1 Publication1
Natural variantiVAR_0100031000C → R in MNKD; decreased protein abundance; increased protein degradation; does not affect interaction with ATOX1; does not affect interaction with COMMD1; subcellular location restricted to TGN; does not localizes to the plasma membrane in response to elevated copper levels. 2 Publications1
Natural variantiVAR_0007011006L → P in MNKD. 1 Publication1
Natural variantiVAR_0232671007A → V in MNKD. 1 Publication1
Natural variantiVAR_0232681015G → D in MNKD. 1 Publication1
Natural variantiVAR_0007021019G → D in MNKD. 1 Publication1
Natural variantiVAR_0232691044D → G in MNKD. 1 Publication1
Natural variantiVAR_0688311048T → I in MNKD. 1 Publication1
Natural variantiVAR_0232701100L → P in MNKD. 1 Publication1
Natural variantiVAR_0232711118G → D in MNKD. 1 Publication1
Natural variantiVAR_0232721255G → R in MNKD. 1 Publication1
Natural variantiVAR_0232731282K → E in MNKD. 1 Publication1
Natural variantiVAR_0100041300G → E in MNKD. 1 Publication1
Natural variantiVAR_0100051302G → R in MNKD. 1 Publication1
Natural variantiVAR_0100061302G → V in MNKD. 1 Publication1
Natural variantiVAR_0232741304N → K in MNKD. 1 Publication1
Natural variantiVAR_0100071305D → A in MNKD. 1 Publication1
Natural variantiVAR_0232751315G → R in MNKD. 1 Publication1
Natural variantiVAR_0232761325A → V in MNKD. 1 Publication1
Natural variantiVAR_0232771344S → R in MNKD. 1 Publication1
Natural variantiVAR_0232781345I → F in MNKD. 1 Publication1
Natural variantiVAR_0100081362A → V in MNKD; decreased protein abundance; increased protein degradation; does not affect interaction with ATOX1; does not affect interaction with COMMD1; subcellular location restricted to TGN; does not localizes to the plasma membrane in response to elevated copper levels. 2 Publications1
Natural variantiVAR_0232791369G → R in MNKD. 1 Publication1
Natural variantiVAR_0232801397S → F in MNKD. 1 Publication1
Occipital horn syndrome (OHS)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities include occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga.
See also OMIM:304150
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_009999637S → L in OHS. 1 PublicationCorresponds to variant rs28936068dbSNPEnsembl.1
Natural variantiVAR_0638831304N → S in OHS; has approximately 33% residual copper transport; increased protein abundance; increased localization at the plasma membrane; does not cycle back to TGN under conditions of copper depletion; does not affect interaction with ATOX1; does not affect interaction with COMMD1. 2 Publications1
Distal spinal muscular atrophy, X-linked, 3 (DSMAX3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.
See also OMIM:300489
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063882994T → I in DSMAX3; demonstrates impaired intracellular trafficking compared to control with some of the mutant protein remaining in the Golgi apparatus after exposure to copper. 1 Publication1
Natural variantiVAR_0638841386P → S in DSMAX3; demonstrates impaired intracellular trafficking compared to control with some mutant protein remaining in the Golgi apparatus after exposure to copper. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1487 – 1488LL → AA: Loss of relocalization to the trans-Golgi. 1 Publication2

Keywords - Diseasei

Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNETi538.
MalaCardsiATP7A.
MIMi300489. phenotype.
304150. phenotype.
309400. phenotype.
Orphaneti565. Menkes disease.
198. Occipital horn syndrome.
139557. X-linked distal spinal muscular atrophy.
PharmGKBiPA72.

Chemistry databases

DrugBankiDB00958. Carboplatin.
DB00515. Cisplatin.
DB00526. Oxaliplatin.

Polymorphism and mutation databases

DMDMi223590241.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000463111 – 1500Copper-transporting ATPase 1Add BLAST1500

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei152PhosphothreonineCombined sources1
Modified residuei270PhosphoserineCombined sources1
Modified residuei327PhosphothreonineCombined sources1
Modified residuei339PhosphoserineCombined sources1
Modified residuei353PhosphoserineBy similarity1
Modified residuei357PhosphoserineCombined sources1
Modified residuei362PhosphoserineBy similarity1
Glycosylationi686N-linked (GlcNAc...)Sequence analysis1
Glycosylationi975N-linked (GlcNAc...)Sequence analysis1
Modified residuei1212PhosphothreonineBy similarity1
Modified residuei1430PhosphoserineCombined sources1
Modified residuei1432PhosphoserineCombined sources1
Modified residuei1460PhosphoserineCombined sources1
Modified residuei1463PhosphoserineCombined sources1
Modified residuei1466PhosphoserineCombined sources1
Modified residuei1469PhosphoserineCombined sources1
Modified residuei1473PhosphoserineCombined sources1
Modified residuei1476PhosphoserineBy similarity1
Modified residuei1486PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ04656.
PaxDbiQ04656.
PeptideAtlasiQ04656.
PRIDEiQ04656.

PTM databases

iPTMnetiQ04656.
PhosphoSitePlusiQ04656.

Expressioni

Tissue specificityi

Found in most tissues except liver. Isoform 3 is widely expressed including in liver cell lines. Isoform 1 is expressed in fibroblasts, choriocarcinoma, colon carcinoma and neuroblastoma cell lines. Isoform 2 is expressed in fibroblasts, colon carcinoma and neuroblastoma cell lines.

Gene expression databases

BgeeiENSG00000165240.
CleanExiHS_ATP7A.
GenevisibleiQ04656. HS.

Organism-specific databases

HPAiHPA012887.
HPA048107.

Interactioni

Subunit structurei

Monomer. Interacts with PDZD11. Interacts with ATOX1 and COMMD1 (PubMed:21667063).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PDZD11Q5EBL84EBI-7706409,EBI-1644207

GO - Molecular functioni

  • copper-dependent protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107020. 22 interactors.
IntActiQ04656. 4 interactors.
MINTiMINT-106053.
STRINGi9606.ENSP00000345728.

Structurei

Secondary structure

11500
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni4 – 6Combined sources3
Beta strandi8 – 14Combined sources7
Helixi20 – 31Combined sources12
Beta strandi33 – 35Combined sources3
Beta strandi36 – 42Combined sources7
Turni43 – 46Combined sources4
Beta strandi47 – 52Combined sources6
Turni54 – 56Combined sources3
Helixi59 – 68Combined sources10
Beta strandi73 – 77Combined sources5
Beta strandi165 – 169Combined sources5
Beta strandi171 – 177Combined sources7
Turni180 – 182Combined sources3
Helixi187 – 194Combined sources8
Beta strandi199 – 204Combined sources6
Turni207 – 209Combined sources3
Beta strandi210 – 215Combined sources6
Turni217 – 219Combined sources3
Helixi222 – 231Combined sources10
Beta strandi236 – 238Combined sources3
Turni242 – 244Combined sources3
Beta strandi277 – 285Combined sources9
Helixi288 – 299Combined sources12
Beta strandi305 – 311Combined sources7
Turni312 – 315Combined sources4
Beta strandi316 – 321Combined sources6
Beta strandi324 – 326Combined sources3
Helixi329 – 336Combined sources8
Turni340 – 342Combined sources3
Beta strandi344 – 346Combined sources3
Beta strandi377 – 384Combined sources8
Helixi388 – 400Combined sources13
Beta strandi408 – 411Combined sources4
Turni412 – 415Combined sources4
Beta strandi416 – 421Combined sources6
Turni423 – 425Combined sources3
Helixi428 – 438Combined sources11
Beta strandi441 – 446Combined sources6
Beta strandi488 – 495Combined sources8
Helixi497 – 499Combined sources3
Helixi502 – 510Combined sources9
Beta strandi513 – 518Combined sources6
Turni523 – 526Combined sources4
Beta strandi527 – 532Combined sources6
Turni534 – 536Combined sources3
Helixi539 – 549Combined sources11
Beta strandi553 – 557Combined sources5
Beta strandi566 – 571Combined sources6
Turni575 – 577Combined sources3
Helixi578 – 586Combined sources9
Beta strandi592 – 598Combined sources7
Turni599 – 602Combined sources4
Beta strandi603 – 608Combined sources6
Turni610 – 613Combined sources4
Helixi614 – 626Combined sources13
Beta strandi628 – 633Combined sources6
Helixi808 – 814Combined sources7
Beta strandi818 – 824Combined sources7
Beta strandi826 – 828Combined sources3
Beta strandi833 – 838Combined sources6
Turni839 – 841Combined sources3
Beta strandi847 – 849Combined sources3
Beta strandi860 – 862Combined sources3
Beta strandi868 – 870Combined sources3
Turni872 – 875Combined sources4
Beta strandi887 – 889Combined sources3
Beta strandi894 – 898Combined sources5
Beta strandi901 – 904Combined sources4
Turni908 – 910Combined sources3
Helixi912 – 919Combined sources8
Turni920 – 923Combined sources4
Beta strandi1055 – 1061Combined sources7
Turni1065 – 1067Combined sources3
Helixi1070 – 1079Combined sources10
Helixi1080 – 1082Combined sources3
Beta strandi1083 – 1085Combined sources3
Helixi1087 – 1100Combined sources14
Beta strandi1112 – 1114Combined sources3
Turni1115 – 1117Combined sources3
Beta strandi1118 – 1123Combined sources6
Helixi1127 – 1129Combined sources3
Turni1135 – 1139Combined sources5
Turni1150 – 1153Combined sources4
Beta strandi1161 – 1166Combined sources6
Turni1167 – 1171Combined sources5
Helixi1172 – 1174Combined sources3
Beta strandi1178 – 1183Combined sources6
Helixi1185 – 1191Combined sources7
Helixi1197 – 1208Combined sources12
Beta strandi1212 – 1218Combined sources7
Beta strandi1221 – 1229Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AW0NMR-A375-446[»]
1KVINMR-A1-79[»]
1KVJNMR-A1-79[»]
1Q8LNMR-A164-246[»]
1S6ONMR-A169-240[»]
1S6UNMR-A169-240[»]
1Y3JNMR-A486-558[»]
1Y3KNMR-A486-558[»]
1YJRNMR-A562-633[»]
1YJTNMR-A562-633[»]
1YJUNMR-A562-633[»]
1YJVNMR-A562-633[»]
2AW0NMR-A375-446[»]
2G9ONMR-A275-352[»]
2GA7NMR-A275-352[»]
2K1RNMR-A5-77[»]
2KIJNMR-A806-924[»]
2KMVNMR-A1051-1231[»]
2KMXNMR-A1051-1231[»]
3CJKX-ray1.80B7-77[»]
5T7LX-ray2.83B7-77[»]
DisProtiDP00282.
ProteinModelPortaliQ04656.
SMRiQ04656.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04656.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 75HMA 1PROSITE-ProRule annotationAdd BLAST67
Domaini172 – 238HMA 2PROSITE-ProRule annotationAdd BLAST67
Domaini278 – 344HMA 3PROSITE-ProRule annotationAdd BLAST67
Domaini378 – 444HMA 4PROSITE-ProRule annotationAdd BLAST67
Domaini489 – 555HMA 5PROSITE-ProRule annotationAdd BLAST67
Domaini565 – 631HMA 6PROSITE-ProRule annotationAdd BLAST67

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1486 – 1500PDZD11-bindingAdd BLAST15

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1487 – 1488Endocytosis signal2

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi355 – 362Poly-Ser8

Domaini

The C-terminal di-leucine, 1487-Leu-Leu-1488, 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.

Sequence similaritiesi

Contains 6 HMA domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0207. Eukaryota.
COG2217. LUCA.
HOGENOMiHOG000250397.
HOVERGENiHBG050616.
InParanoidiQ04656.
KOiK17686.
OrthoDBiEOG091G022E.
PhylomeDBiQ04656.
TreeFamiTF300460.

Family and domain databases

CDDicd00371. HMA. 6 hits.
Gene3Di2.70.150.10. 1 hit.
3.40.1110.10. 2 hits.
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. 6 hits.
[Graphical view]
SUPFAMiSSF55008. SSF55008. 6 hits.
SSF56784. SSF56784. 2 hits.
SSF81660. SSF81660. 2 hits.
TIGRFAMsiTIGR01525. ATPase-IB_hvy. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
TIGR00003. TIGR00003. 6 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
PS01047. HMA_1. 6 hits.
PS50846. HMA_2. 6 hits.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 4 (identifier: Q04656-1) [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
MDPSMGVNSV TISVEGMTCN SCVWTIEQQI GKVNGVHHIK VSLEEKNATI
60 70 80 90 100
IYDPKLQTPK TLQEAIDDMG FDAVIHNPDP LPVLTDTLFL TVTASLTLPW
110 120 130 140 150
DHIQSTLLKT KGVTDIKIYP QKRTVAVTII PSIVNANQIK ELVPELSLDT
160 170 180 190 200
GTLEKKSGAC EDHSMAQAGE VVLKMKVEGM TCHSCTSTIE GKIGKLQGVQ
210 220 230 240 250
RIKVSLDNQE ATIVYQPHLI SVEEMKKQIE AMGFPAFVKK QPKYLKLGAI
260 270 280 290 300
DVERLKNTPV KSSEGSQQRS PSYTNDSTAT FIIDGMHCKS CVSNIESTLS
310 320 330 340 350
ALQYVSSIVV SLENRSAIVK YNASSVTPES LRKAIEAVSP GLYRVSITSE
360 370 380 390 400
VESTSNSPSS SSLQKIPLNV VSQPLTQETV INIDGMTCNS CVQSIEGVIS
410 420 430 440 450
KKPGVKSIRV SLANSNGTVE YDPLLTSPET LRGAIEDMGF DATLSDTNEP
460 470 480 490 500
LVVIAQPSSE MPLLTSTNEF YTKGMTPVQD KEEGKNSSKC YIQVTGMTCA
510 520 530 540 550
SCVANIERNL RREEGIYSIL VALMAGKAEV RYNPAVIQPP MIAEFIRELG
560 570 580 590 600
FGATVIENAD EGDGVLELVV RGMTCASCVH KIESSLTKHR GILYCSVALA
610 620 630 640 650
TNKAHIKYDP EIIGPRDIIH TIESLGFEAS LVKKDRSASH LDHKREIRQW
660 670 680 690 700
RRSFLVSLFF CIPVMGLMIY MMVMDHHFAT LHHNQNMSKE EMINLHSSMF
710 720 730 740 750
LERQILPGLS VMNLLSFLLC VPVQFFGGWY FYIQAYKALK HKTANMDVLI
760 770 780 790 800
VLATTIAFAY SLIILLVAMY ERAKVNPITF FDTPPMLFVF IALGRWLEHI
810 820 830 840 850
AKGKTSEALA KLISLQATEA TIVTLDSDNI LLSEEQVDVE LVQRGDIIKV
860 870 880 890 900
VPGGKFPVDG RVIEGHSMVD ESLITGEAMP VAKKPGSTVI AGSINQNGSL
910 920 930 940 950
LICATHVGAD TTLSQIVKLV EEAQTSKAPI QQFADKLSGY FVPFIVFVSI
960 970 980 990 1000
ATLLVWIVIG FLNFEIVETY FPGYNRSISR TETIIRFAFQ ASITVLCIAC
1010 1020 1030 1040 1050
PCSLGLATPT AVMVGTGVGA QNGILIKGGE PLEMAHKVKV VVFDKTGTIT
1060 1070 1080 1090 1100
HGTPVVNQVK VLTESNRISH HKILAIVGTA ESNSEHPLGT AITKYCKQEL
1110 1120 1130 1140 1150
DTETLGTCID FQVVPGCGIS CKVTNIEGLL HKNNWNIEDN NIKNASLVQI
1160 1170 1180 1190 1200
DASNEQSSTS SSMIIDAQIS NALNAQQYKV LIGNREWMIR NGLVINNDVN
1210 1220 1230 1240 1250
DFMTEHERKG RTAVLVAVDD ELCGLIAIAD TVKPEAELAI HILKSMGLEV
1260 1270 1280 1290 1300
VLMTGDNSKT ARSIASQVGI TKVFAEVLPS HKVAKVKQLQ EEGKRVAMVG
1310 1320 1330 1340 1350
DGINDSPALA MANVGIAIGT GTDVAIEAAD VVLIRNDLLD VVASIDLSRE
1360 1370 1380 1390 1400
TVKRIRINFV FALIYNLVGI PIAAGVFMPI GLVLQPWMGS AAMAASSVSV
1410 1420 1430 1440 1450
VLSSLFLKLY RKPTYESYEL PARSQIGQKS PSEISVHVGI DDTSRNSPKL
1460 1470 1480 1490 1500
GLLDRIVNYS RASINSLLSD KRSLNSVVTS EPDKHSLLVG DFREDDDTAL
Length:1,500
Mass (Da):163,374
Last modified:February 10, 2009 - v3
Checksum:iCF8FF9EA061D463B
GO
Isoform 1 (identifier: Q04656-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRKLSIRKRDNNLLK

Show »
Length:1,514
Mass (Da):165,110
Checksum:iB4FFD7472742EB62
GO
Isoform 2 (identifier: Q04656-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRKLSIRKRD...EELAVHNECY

Show »
Length:1,581
Mass (Da):172,078
Checksum:iFDE210402FD79C4B
GO
Isoform 3 (identifier: Q04656-4) [UniParc]FASTAAdd to basket
Also known as: 2-16

The sequence of this isoform differs from the canonical sequence as follows:
     42-1038: Missing.

Note: Lacks 6 transmembrane regions and 5 heavy-metal-associated (HMA) domains.
Show »
Length:503
Mass (Da):54,318
Checksum:iB81B1F9FFB00B832
GO
Isoform 5 (identifier: Q04656-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     725-802: Missing.

Note: Lacks the transmembrane domains 3 and 4. Expressed at a low level in several tissues of normal individuals and is the only isoform found in patients with OHS.
Show »
Length:1,422
Mass (Da):154,357
Checksum:iEEB740B5F6841813
GO
Isoform 6 (identifier: Q04656-6) [UniParc]FASTAAdd to basket
Also known as: NML45

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRKLSIRKRDNNLLKECNEEIK
     53-81: DPKLQTPKTLQEAIDDMGFDAVIHNPDPL → AHWFGFAALDGICSNGCFICFCSTFFSSL
     82-1499: Missing.

Note: Lacks all transmembrane regions and 5 heavy-metal-associated (HMA) domains, but has a putative nuclear localization signal attached at the N-terminus.
Show »
Length:103
Mass (Da):11,522
Checksum:i1F3873EFB0EA6CC2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10V → A no nucleotide entry (PubMed:9693104).Curated1
Sequence conflicti36V → E in AAA16974 (PubMed:8490647).Curated1
Sequence conflicti336E → V in AAA35580 (PubMed:8490659).Curated1
Sequence conflicti336E → V in AAA96010 (PubMed:7490081).Curated1
Sequence conflicti446D → G in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti624S → G in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti725F → V in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti833S → R in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti1099E → K no nucleotide entry (PubMed:9693104).Curated1
Sequence conflicti1171N → S in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti1178Y → C no nucleotide entry (PubMed:9693104).Curated1
Sequence conflicti1178Y → H in AAA35580 (PubMed:8490659).Curated1
Sequence conflicti1178Y → H in CAB94714 (PubMed:7607665).Curated1
Sequence conflicti1178Y → H in AAA96010 (PubMed:7490081).Curated1
Sequence conflicti1220D → G in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti1295R → W no nucleotide entry (PubMed:9693104).Curated1
Sequence conflicti1313N → D no nucleotide entry (PubMed:9693104).Curated1
Sequence conflicti1336N → D in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti1350E → K in AAA35580 (PubMed:8490659).Curated1
Sequence conflicti1350E → K in CAB94714 (PubMed:7607665).Curated1
Sequence conflicti1350E → K in AAA96010 (PubMed:7490081).Curated1
Sequence conflicti1376V → M in CAB08162 (PubMed:15772651).Curated1
Sequence conflicti1396S → P no nucleotide entry (PubMed:9693104).Curated1
Sequence conflicti1409L → R in CAB08160 (PubMed:15772651).Curated1
Sequence conflicti1455R → W no nucleotide entry (PubMed:9693104).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000699629A → P in MNKD. 1 Publication1
Natural variantiVAR_009999637S → L in OHS. 1 PublicationCorresponds to variant rs28936068dbSNPEnsembl.1
Natural variantiVAR_016119669I → T.2 PublicationsCorresponds to variant rs2234935dbSNPEnsembl.1
Natural variantiVAR_016120703R → H.Corresponds to variant rs2234936dbSNPEnsembl.1
Natural variantiVAR_023261706L → R in MNKD. 1 Publication1
Natural variantiVAR_000700727G → R in MNKD. 1 Publication1
Natural variantiVAR_010000767V → L.1 PublicationCorresponds to variant rs2227291dbSNPEnsembl.1
Natural variantiVAR_023262844R → H in MNKD. 1 Publication1
Natural variantiVAR_023263853G → R in MNKD. 1 Publication1
Natural variantiVAR_023264860G → V in MNKD. 1 Publication1
Natural variantiVAR_010001873L → R in MNKD; increased protein abundance; does not affect interaction with ATOX1; does not affect interaction with COMMD1; increased localization at the plasma membrane; does not cycle back to TGN under conditions of copper depletion. 2 Publications1
Natural variantiVAR_010002876G → E in MNKD. 1 Publication1
Natural variantiVAR_023265876G → R in MNKD. 1 Publication1
Natural variantiVAR_023266924Q → R in MNKD. 1 Publication1
Natural variantiVAR_063882994T → I in DSMAX3; demonstrates impaired intracellular trafficking compared to control with some of the mutant protein remaining in the Golgi apparatus after exposure to copper. 1 Publication1
Natural variantiVAR_0100031000C → R in MNKD; decreased protein abundance; increased protein degradation; does not affect interaction with ATOX1; does not affect interaction with COMMD1; subcellular location restricted to TGN; does not localizes to the plasma membrane in response to elevated copper levels. 2 Publications1
Natural variantiVAR_0007011006L → P in MNKD. 1 Publication1
Natural variantiVAR_0232671007A → V in MNKD. 1 Publication1
Natural variantiVAR_0232681015G → D in MNKD. 1 Publication1
Natural variantiVAR_0007021019G → D in MNKD. 1 Publication1
Natural variantiVAR_0232691044D → G in MNKD. 1 Publication1
Natural variantiVAR_0688311048T → I in MNKD. 1 Publication1
Natural variantiVAR_0232701100L → P in MNKD. 1 Publication1
Natural variantiVAR_0232711118G → D in MNKD. 1 Publication1
Natural variantiVAR_0232721255G → R in MNKD. 1 Publication1
Natural variantiVAR_0232731282K → E in MNKD. 1 Publication1
Natural variantiVAR_0100041300G → E in MNKD. 1 Publication1
Natural variantiVAR_0100051302G → R in MNKD. 1 Publication1
Natural variantiVAR_0100061302G → V in MNKD. 1 Publication1
Natural variantiVAR_0232741304N → K in MNKD. 1 Publication1
Natural variantiVAR_0638831304N → S in OHS; has approximately 33% residual copper transport; increased protein abundance; increased localization at the plasma membrane; does not cycle back to TGN under conditions of copper depletion; does not affect interaction with ATOX1; does not affect interaction with COMMD1. 2 Publications1
Natural variantiVAR_0100071305D → A in MNKD. 1 Publication1
Natural variantiVAR_0232751315G → R in MNKD. 1 Publication1
Natural variantiVAR_0232761325A → V in MNKD. 1 Publication1
Natural variantiVAR_0232771344S → R in MNKD. 1 Publication1
Natural variantiVAR_0232781345I → F in MNKD. 1 Publication1
Natural variantiVAR_0100081362A → V in MNKD; decreased protein abundance; increased protein degradation; does not affect interaction with ATOX1; does not affect interaction with COMMD1; subcellular location restricted to TGN; does not localizes to the plasma membrane in response to elevated copper levels. 2 Publications1
Natural variantiVAR_0232791369G → R in MNKD. 1 Publication1
Natural variantiVAR_0638841386P → S in DSMAX3; demonstrates impaired intracellular trafficking compared to control with some mutant protein remaining in the Golgi apparatus after exposure to copper. 1 Publication1
Natural variantiVAR_0232801397S → F in MNKD. 1 Publication1
Natural variantiVAR_0161211464I → V.Corresponds to variant rs2234938dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0004191M → MRKLSIRKRDNNLLK in isoform 1. 1 Publication1
Alternative sequenceiVSP_0004201M → MRKLSIRKRDNNLLKPSSAS SLGIAVSLGRPVLSRSSSGT VNLLEEVGLHIRDTAFSSTK LLEAISTVSAQVEELAVHNE CY in isoform 2. 1 Publication1
Alternative sequenceiVSP_0004211M → MRKLSIRKRDNNLLKECNEE IK in isoform 6. Curated1
Alternative sequenceiVSP_00042442 – 1038Missing in isoform 3. 2 PublicationsAdd BLAST997
Alternative sequenceiVSP_00042253 – 81DPKLQ…NPDPL → AHWFGFAALDGICSNGCFIC FCSTFFSSL in isoform 6. CuratedAdd BLAST29
Alternative sequenceiVSP_00042382 – 1499Missing in isoform 6. CuratedAdd BLAST1418
Alternative sequenceiVSP_000425725 – 802Missing in isoform 5. CuratedAdd BLAST78

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06133 mRNA. Translation: AAA35580.1.
X82336
, X82337, X82338, X82339, X82340, X82341, X82342, X82343, X82344, X82345, X82346, X82347, X82348, X82349, X82350, X82351, X82352, X82353, X82354, X82355, X82356 Genomic DNA. Translation: CAB94714.1.
AL645821 Genomic DNA. Translation: CAI42806.1.
CH471104 Genomic DNA. Translation: EAW98605.1.
U27381
, U27361, U27362, U27363, U27365, U27366, U27367, U27368, U27369, U27370, U27371, U27372, U27373, U27374, U27375, U27376, U27377, U27378, U27379, U27380 Genomic DNA. Translation: AAA96010.1.
X69208 mRNA. Translation: CAA49145.1.
L06476 mRNA. Translation: AAA16974.1.
Z94801 Genomic DNA. Translation: CAB08162.2.
Z94753 Genomic DNA. Translation: CAB08160.1.
AY011418 Genomic DNA. Translation: AAG47452.1.
CCDSiCCDS35339.1. [Q04656-1]
CCDS75997.1. [Q04656-5]
PIRiS36149.
RefSeqiNP_000043.4. NM_000052.6.
NP_001269153.1. NM_001282224.1.
UniGeneiHs.496414.
Hs.733232.

Genome annotation databases

EnsembliENST00000341514; ENSP00000345728; ENSG00000165240.
ENST00000343533; ENSP00000343026; ENSG00000165240.
ENST00000350425; ENSP00000343678; ENSG00000165240.
GeneIDi538.
KEGGihsa:538.
UCSCiuc004ecx.6. human. [Q04656-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

Heavy metal - Issue 79 of February 2007

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06133 mRNA. Translation: AAA35580.1.
X82336
, X82337, X82338, X82339, X82340, X82341, X82342, X82343, X82344, X82345, X82346, X82347, X82348, X82349, X82350, X82351, X82352, X82353, X82354, X82355, X82356 Genomic DNA. Translation: CAB94714.1.
AL645821 Genomic DNA. Translation: CAI42806.1.
CH471104 Genomic DNA. Translation: EAW98605.1.
U27381
, U27361, U27362, U27363, U27365, U27366, U27367, U27368, U27369, U27370, U27371, U27372, U27373, U27374, U27375, U27376, U27377, U27378, U27379, U27380 Genomic DNA. Translation: AAA96010.1.
X69208 mRNA. Translation: CAA49145.1.
L06476 mRNA. Translation: AAA16974.1.
Z94801 Genomic DNA. Translation: CAB08162.2.
Z94753 Genomic DNA. Translation: CAB08160.1.
AY011418 Genomic DNA. Translation: AAG47452.1.
CCDSiCCDS35339.1. [Q04656-1]
CCDS75997.1. [Q04656-5]
PIRiS36149.
RefSeqiNP_000043.4. NM_000052.6.
NP_001269153.1. NM_001282224.1.
UniGeneiHs.496414.
Hs.733232.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AW0NMR-A375-446[»]
1KVINMR-A1-79[»]
1KVJNMR-A1-79[»]
1Q8LNMR-A164-246[»]
1S6ONMR-A169-240[»]
1S6UNMR-A169-240[»]
1Y3JNMR-A486-558[»]
1Y3KNMR-A486-558[»]
1YJRNMR-A562-633[»]
1YJTNMR-A562-633[»]
1YJUNMR-A562-633[»]
1YJVNMR-A562-633[»]
2AW0NMR-A375-446[»]
2G9ONMR-A275-352[»]
2GA7NMR-A275-352[»]
2K1RNMR-A5-77[»]
2KIJNMR-A806-924[»]
2KMVNMR-A1051-1231[»]
2KMXNMR-A1051-1231[»]
3CJKX-ray1.80B7-77[»]
5T7LX-ray2.83B7-77[»]
DisProtiDP00282.
ProteinModelPortaliQ04656.
SMRiQ04656.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107020. 22 interactors.
IntActiQ04656. 4 interactors.
MINTiMINT-106053.
STRINGi9606.ENSP00000345728.

Chemistry databases

DrugBankiDB00958. Carboplatin.
DB00515. Cisplatin.
DB00526. Oxaliplatin.

Protein family/group databases

TCDBi3.A.3.5.6. the p-type atpase (p-atpase) superfamily.

PTM databases

iPTMnetiQ04656.
PhosphoSitePlusiQ04656.

Polymorphism and mutation databases

DMDMi223590241.

Proteomic databases

MaxQBiQ04656.
PaxDbiQ04656.
PeptideAtlasiQ04656.
PRIDEiQ04656.

Protocols and materials databases

DNASUi538.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341514; ENSP00000345728; ENSG00000165240.
ENST00000343533; ENSP00000343026; ENSG00000165240.
ENST00000350425; ENSP00000343678; ENSG00000165240.
GeneIDi538.
KEGGihsa:538.
UCSCiuc004ecx.6. human. [Q04656-1]

Organism-specific databases

CTDi538.
DisGeNETi538.
GeneCardsiATP7A.
GeneReviewsiATP7A.
HGNCiHGNC:869. ATP7A.
HPAiHPA012887.
HPA048107.
MalaCardsiATP7A.
MIMi300011. gene.
300489. phenotype.
304150. phenotype.
309400. phenotype.
neXtProtiNX_Q04656.
Orphaneti565. Menkes disease.
198. Occipital horn syndrome.
139557. X-linked distal spinal muscular atrophy.
PharmGKBiPA72.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0207. Eukaryota.
COG2217. LUCA.
HOGENOMiHOG000250397.
HOVERGENiHBG050616.
InParanoidiQ04656.
KOiK17686.
OrthoDBiEOG091G022E.
PhylomeDBiQ04656.
TreeFamiTF300460.

Enzyme and pathway databases

BioCyciZFISH:HS09205-MONOMER.
BRENDAi3.6.3.4. 2681.
ReactomeiR-HSA-3299685. Detoxification of Reactive Oxygen Species.
R-HSA-6803544. Ion influx/efflux at host-pathogen interface.
R-HSA-936837. Ion transport by P-type ATPases.
SABIO-RKQ04656.

Miscellaneous databases

ChiTaRSiATP7A. human.
EvolutionaryTraceiQ04656.
GeneWikiiATP7A.
GenomeRNAii538.
PROiQ04656.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165240.
CleanExiHS_ATP7A.
GenevisibleiQ04656. HS.

Family and domain databases

CDDicd00371. HMA. 6 hits.
Gene3Di2.70.150.10. 1 hit.
3.40.1110.10. 2 hits.
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. 6 hits.
[Graphical view]
SUPFAMiSSF55008. SSF55008. 6 hits.
SSF56784. SSF56784. 2 hits.
SSF81660. SSF81660. 2 hits.
TIGRFAMsiTIGR01525. ATPase-IB_hvy. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
TIGR00003. TIGR00003. 6 hits.
PROSITEiPS00154. ATPASE_E1_E2. 1 hit.
PS01047. HMA_1. 6 hits.
PS50846. HMA_2. 6 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATP7A_HUMAN
AccessioniPrimary (citable) accession number: Q04656
Secondary accession number(s): B1AT72
, O00227, O00745, Q9BYY8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 10, 2009
Last modified: November 30, 2016
This is version 198 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. 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.