2kmv: Difference between revisions

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[[Image:2kmv.png|left|200px]]
{{STRUCTURE_2kmv|  PDB=2kmv  |  SCENE=  }}  
{{STRUCTURE_2kmv|  PDB=2kmv  |  SCENE=  }}  
===Solution structure of the nucleotide binding domain of the human Menkes protein in the ATP-free form===
{{ABSTRACT_PUBMED_19917612}}


===Solution structure of the nucleotide binding domain of the human Menkes protein in the ATP-free form===
==Disease==
[[http://www.uniprot.org/uniprot/ATP7A_HUMAN ATP7A_HUMAN]] Defects in ATP7A are the cause of Menkes disease (MNKD) [MIM:[http://omim.org/entry/309400 309400]]; also known as kinky hair disease. MNKD is an 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.<ref>PMID:10079817</ref><ref>PMID:7977350</ref><ref>PMID:8981948</ref><ref>PMID:10401004</ref><ref>PMID:10319589</ref><ref>PMID:11241493</ref><ref>PMID:11350187</ref><ref>PMID:15981243</ref><ref>PMID:22992316</ref>  Defects in ATP7A are the cause of occipital horn syndrome (OHS) [MIM:[http://omim.org/entry/304150 304150]]; also known as X-linked cutis laxa. OHS is an X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities included 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.<ref>PMID:9246006</ref><ref>PMID:17108763</ref>  Defects in ATP7A are a cause of distal spinal muscular atrophy X-linked type 3 (DSMAX3) [MIM:[http://omim.org/entry/300489 300489]]. DSMAX3 is a 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.<ref>PMID:20170900</ref>


{{ABSTRACT_PUBMED_19917612}}
==Function==
[[http://www.uniprot.org/uniprot/ATP7A_HUMAN ATP7A_HUMAN]] 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.


==About this Structure==
==About this Structure==
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==Reference==
==Reference==
<ref group="xtra">PMID:019917612</ref><references group="xtra"/>
<ref group="xtra">PMID:019917612</ref><references group="xtra"/><references/>
[[Category: Copper-exporting ATPase]]
[[Category: Copper-exporting ATPase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]

Revision as of 20:13, 24 March 2013

Template:STRUCTURE 2kmv

Solution structure of the nucleotide binding domain of the human Menkes protein in the ATP-free formSolution structure of the nucleotide binding domain of the human Menkes protein in the ATP-free form

Template:ABSTRACT PUBMED 19917612

DiseaseDisease

[ATP7A_HUMAN] Defects in ATP7A are the cause of Menkes disease (MNKD) [MIM:309400]; also known as kinky hair disease. MNKD is an 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.[1][2][3][4][5][6][7][8][9] Defects in ATP7A are the cause of occipital horn syndrome (OHS) [MIM:304150]; also known as X-linked cutis laxa. OHS is an X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities included 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.[10][11] Defects in ATP7A are a cause of distal spinal muscular atrophy X-linked type 3 (DSMAX3) [MIM:300489]. DSMAX3 is a 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.[12]

FunctionFunction

[ATP7A_HUMAN] 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.

About this StructureAbout this Structure

2kmv is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

See AlsoSee Also

ReferenceReference

[xtra 1]

  1. ↑ Banci L, Bertini I, Cantini F, Inagaki S, Migliardi M, Rosato A. The binding mode of ATP revealed by the solution structure of the N-domain of human ATP7A. J Biol Chem. 2010 Jan 22;285(4):2537-44. Epub 2009 Nov 16. PMID:19917612 doi:10.1074/jbc.M109.054262
  1. ↑ Tumer Z, Moller LB, Horn N. Mutation spectrum of ATP7A, the gene defective in Menkes disease. Adv Exp Med Biol. 1999;448:83-95. PMID:10079817
  2. ↑ Das S, Levinson B, Whitney S, Vulpe C, Packman S, Gitschier J. Diverse mutations in patients with Menkes disease often lead to exon skipping. Am J Hum Genet. 1994 Nov;55(5):883-9. PMID:7977350
  3. ↑ Tumer Z, Lund C, Tolshave J, Vural B, Tonnesen T, Horn N. Identification of point mutations in 41 unrelated patients affected with Menkes disease. Am J Hum Genet. 1997 Jan;60(1):63-71. PMID:8981948
  4. ↑ Ambrosini L, Mercer JF. Defective copper-induced trafficking and localization of the Menkes protein in patients with mild and copper-treated classical Menkes disease. Hum Mol Genet. 1999 Aug;8(8):1547-55. PMID:10401004
  5. ↑ Ogawa A, Yamamoto S, Takayanagi M, Kogo T, Kanazawa M, Kohno Y. Identification of three novel mutations in the MNK gene in three unrelated Japanese patients with classical Menkes disease. J Hum Genet. 1999;44(3):206-9. PMID:10319589 doi:10.1007/s100380050144
  6. ↑ Gu YH, Kodama H, Murata Y, Mochizuki D, Yanagawa Y, Ushijima H, Shiba T, Lee CC. ATP7A gene mutations in 16 patients with Menkes disease and a patient with occipital horn syndrome. Am J Med Genet. 2001 Mar 15;99(3):217-22. PMID:11241493
  7. ↑ Hahn S, Cho K, Ryu K, Kim J, Pai K, Kim M, Park H, Yoo O. Identification of four novel mutations in classical Menkes disease and successful prenatal DNA diagnosis. Mol Genet Metab. 2001 May;73(1):86-90. PMID:11350187 doi:10.1006/mgme.2001.3169
  8. ↑ Moller LB, Bukrinsky JT, Molgaard A, Paulsen M, Lund C, Tumer Z, Larsen S, Horn N. Identification and analysis of 21 novel disease-causing amino acid substitutions in the conserved part of ATP7A. Hum Mutat. 2005 Aug;26(2):84-93. PMID:15981243 doi:10.1002/humu.20190
  9. ↑ Leon-Garcia G, Santana A, Villegas-Sepulveda N, Perez-Gonzalez C, Henrriquez-Esquiroz JM, de Leon-Garcia C, Wong C, Baeza I. The T1048I mutation in ATP7A gene causes an unusual Menkes disease presentation. BMC Pediatr. 2012 Sep 19;12:150. doi: 10.1186/1471-2431-12-150. PMID:22992316 doi:10.1186/1471-2431-12-150
  10. ↑ Ronce N, Moizard MP, Robb L, Toutain A, Villard L, Moraine C. A C2055T transition in exon 8 of the ATP7A gene is associated with exon skipping in an occipital horn syndrome family. Am J Hum Genet. 1997 Jul;61(1):233-8. PMID:9246006 doi:10.1016/S0002-9297(07)64297-9
  11. ↑ Tang J, Robertson S, Lem KE, Godwin SC, Kaler SG. Functional copper transport explains neurologic sparing in occipital horn syndrome. Genet Med. 2006 Nov;8(11):711-8. PMID:17108763 doi:10.109701.gim.0000245578.94312.1e
  12. ↑ Kennerson ML, Nicholson GA, Kaler SG, Kowalski B, Mercer JF, Tang J, Llanos RM, Chu S, Takata RI, Speck-Martins CE, Baets J, Almeida-Souza L, Fischer D, Timmerman V, Taylor PE, Scherer SS, Ferguson TA, Bird TD, De Jonghe P, Feely SM, Shy ME, Garbern JY. Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. Am J Hum Genet. 2010 Mar 12;86(3):343-52. doi: 10.1016/j.ajhg.2010.01.027. Epub, 2010 Feb 18. PMID:20170900 doi:10.1016/j.ajhg.2010.01.027

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