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Ankyrin

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ANK1, erythrocytic
Ribbon diagram of a fragment of the membrane-binding domain of ankyrin R.[1]
Identifiers
SymbolANK1
Alt. symbolsAnkyrinR, Band2.1
NCBI gene286
HGNC492
OMIM182900
PDB1N11
RefSeqNM_000037
UniProtP16157
Other data
LocusChr. 8 p21.1-11.2
Search for
StructuresSwiss-model
DomainsInterPro
Ankyrin repeat
Identifiers
SymbolAnk
PfamPF00023
InterProIPR002110
SMARTSM00248
PROSITEPDOC50088
SCOP21awc / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
ANK2, neuronal
Identifiers
SymbolANK2
Alt. symbolsAnkyrinB
NCBI gene287
HGNC493
OMIM106410
RefSeqNM_001148
UniProtQ01484
Other data
LocusChr. 4 q25-q27
Search for
StructuresSwiss-model
DomainsInterPro
ANK3, node of Ranvier
Identifiers
SymbolANK3
Alt. symbolsAnkyrinG
NCBI gene288
HGNC494
OMIM600465
RefSeqNM_020987
UniProtQ12955
Other data
LocusChr. 10 q21
Search for
StructuresSwiss-model
DomainsInterPro

Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane cytoskeleton.[2] Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channels, ion exchangers and ion transporters in the plasma membrane. The name is derived from the Greek word for "fused".

Structure

Ankyrins contain four functional domains: an N-terminal domain that contains 24 tandem ankyrin repeats, a central domain that binds to spectrin, a death domain that binds to proteins involved in apoptosis, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins.[2]

Subtypes

Ankyrins are encoded by three genes (ANK1, ANK2 and ANK3) in mammals. Each gene in turn produces multiple proteins through alternative splicing.

ANK1

The ANK1 gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1.[3] AnkyrinR enables erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form of hemolytic anemia termed hereditary spherocytosis.[4] In erythrocytes, AnkyrinR links the membrane skeleton to the Cl/HCO3 anion exchanger.[5]

Ankyrin 1 links membrane receptor CD44 to the inositol triphosphate receptor and the cytoskeleton.[6]

It has been suggested that Ankyrin 1 interacts with KAHRP (shown via selective pull-downs, SPR and ELISA).[7]

ANK2

Subsequently, ankyrinB proteins (products of the ANK2 gene[8]) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na+/K+ ATPase, the voltage gated Na+ channel and the Na+/Ca2+ exchanger.

ANK3

AnkyrinG proteins (products of the ANK3 gene[9]) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3 is involved in bipolar disorder.[10][11]

See also

  • DARPin (designed ankyrin repeat protein), an engineered antibody mimetic based on the structure of ankyrin repeats

References

  1. ^ PDB: 1N11​; Michaely P, Tomchick DR, Machius M, Anderson RG (December 2002). "Crystal structure of a 12 ANK repeat stack from human ankyrinR". EMBO J. 21 (23): 6387–96. doi:10.1093/emboj/cdf651. PMC 136955. PMID 12456646.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b Bennett V, Baines AJ (1 July 2001). "Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues". Physiol. Rev. 81 (3): 1353–92. PMID 11427698.
  3. ^ Bennett V, Stenbuck PJ (10 April 1979). "Identification and partial purification of ankyrin, the high affinity membrane attachment site for human erythrocyte spectrin". J Biol Chem. 254 (7): 2533–41. PMID 372182.
  4. ^ Lux SE, Tse WT, Menninger JC, John KM, Harris P, Shalev O, Chilcote RR, Marchesi SL, Watkins PC, Bennett V (1990). "Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8". Nature. 345 (6277): 736–9. doi:10.1038/345736a0. PMID 2141669.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Bennett V, Stenbuck PJ (1979). "The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes". Nature. 280 (5722): 468–73. doi:10.1038/280468a0. PMID 379653.
  6. ^ Singleton PA, Bourguignon LY (2004). "CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation". Exp Cell Res. 295 (1): 102–18. doi:10.1016/j.yexcr.2003.12.025. PMID 15051494.
  7. ^ Weng, H; Guo, X; Papoin, J; Wang, J; Coppel, R; Mohandas, N; An, X (2014). "Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1838 (1 Pt B): 185–92. doi:10.1016/j.bbamem.2013.09.014. PMID 24090929.
  8. ^ Schott JJ, Charpentier F, Peltier S; et al. (November 1995). "Mapping of a Gene for Long QT Syndrome to Chromosome 4q25-27". Am. J. Hum. Genet. 57 (5): 1114–22. PMC 1801360. PMID 7485162.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Kapfhamer D, Miller DE, Lambert S, Bennett V, Glover TW, Burmeister M (May 1995). "Chromosomal localization of the ankyrinG gene (ANK3/Ank3) to human 10q21 and mouse 10". Genomics. 27 (1): 189–91. doi:10.1006/geno.1995.1023. PMID 7665168.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Ferreira MA, O'Donovan MC, Meng YA; et al. (August 2008). "Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder". Nat. Genet. 40 (9): 1056–8. doi:10.1038/ng.209. PMC 2703780. PMID 18711365.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ "Channeling Mental Illness: GWAS Links Ion Channels, Bipolar Disorder". Schizophrenia Research Forum: News. schizophreniaforum.org. 2008-08-19. Retrieved 2008-08-21.