CDD: smart00248.5, ANK
PFAM: PF00023
InterPro: IPR002110
SMART: SM0248
 

Homo sapiens ankyrin repeat domain of Bcl-3
Authors:   F. Michel, M. Soler-Lopez, C. Petosa, P. Cramer, U. Siebenlist, C. W. Mueller
pdb file: 1K1A
jpeg generated from pdb file 1K1A using Chime
 

Description

Ankyrin repeat domains consist of  repeated sequences approximately 33 amino acids long.  These sequences have been known to occur in several consecutive copies as shown above.  Ankyrin repeats are characterized as L-shaped in structure, consisting of a b-hairpin and two a-helices.

Ankyrin repeat regions are known to function as interactive domains between proteins.  They have been described in a large number of functionally diverse proteins found mainly in eukaryotes.  Ankyrin repeats are incorporated in several diverse families of proteins including ankyrins, which link integral membrane proteins to the spectrin-actin cytoskeleton and have involvement in cell motility, activation, proliferation, and contact.

A few known examples have also been isolated in prokaryotes and viruses and are suspected of originating as the result of horizontal gene transfers.
 

Examples of proteins containing the ANK domain

ANK1
Also known as ankyrinR.  This membrane protein attaches cytoskeletal components to the plasma membrane.  This protein was first isolated in human erythrocytes and later found in the brain and muscle tissue.
PubMed: 9235914
LocusLink: 286

ANK3
Also known as ankyrinG.  This protein links the plasma membrane to cytoskeletal proteins.  Ankyrin 3 was originally found at the axonal initial segment and nodes of Ranvier of neurons in the CNS and PNS.
PubMed: 9060470
LocusLink: 288

53BP2
A p53 binding protein that may have a role in p53 related signal transduction pathways and BCL2, a regulator of programmed cell death.
PubMed: 97035414
LocusLink: 7159

p19INK4d
A cyclin-dependent kinase inhibitor that inhibits CDK4. This protein is a member of the INK4 family of cyclin-dependent kinase inhibitors.  It prevents the action of of the CDK kinases and controls cell cycle G1 progression.  Also known as CDKN2D.
PubMed: 98013176
LocusLink: 1032

GABP-a/b
GABP (growth-associated binding protein) is a transcription factor with roles in development, in some cases interacting with members of the Sp-family of transcription factors.  It is a heterodimer.  GABP -a is a member of the ETS-family of transcription factors, whereas GABP-b consists of ankyrin repeats.
PubMed: 98128030
PubMed: 10934247
LocusLink 2552

NOTCH3
Third discovered human homologue of Drosophila melanogaster type I membrane protein notch.  This protein interacts with cell-bound ligands and establishes an intercellular signalling pathway that is key to neural development in Drosophila.  The homologue of this protein in humans has an undetermined function, but is associated with certain inherited dementias (OMIM: 125310).
PubMed: 7835890
LocusLink: 4854

Human Disease

Hereditary spherocytosis (OMIM: 182900)

Characterized as one of the most common hereditary hemolytic anemias among whites of northern European descent.  HS is an autosomal deficiency characterized by spectrin deficient red blood cells resulting from a mutation in the alpha- and beta-spectrin loci on chromosome 1 and 14 and/or a deletion of an ankyrin 1 copy on chromosome 8 (SPH2).  Hereditary spherocytosis red cells are characterized as spectrin deficient from both dominant and recessive variants.  Human erythrocyte ankyrin links beta-spectrin to an anion exchange protein AE1.  Chromosome mapping shows that the gene for ankyrin 1 maps to chromosome 8p11.2 and that one copy was absent from the DNA of two unrelated individuals characterized with severe HS (Lux et al. (1990) PubMed: 90294909).  The affected red cells in these individuals are also ankyrin-deficient.  Data from Lux et al. suggest that deficiency of ankyrin are responsible for HS at the SPH2 locus. Coetzer et. al. (1988) also described similar deficiencies in ankyrin in two patients with severe HS (PubMed: 2961992). Delaunay  also attributes mutations in the genes encoding ANK1 as a source of HS (PubMed: 12432217).
 

Submitted by:
Matthew Cambell
Kyle Lorditch
Cell Biology Class
Shippensburg University
11/20/02

Edited by William J. Patrie
12/13/02