Kank proteins: structure, functions and diseases

Abstract

The Kank family of proteins, Kank1-Kank4, are characterized by their unique structure, coiled-coil motifs in the N-terminal region, and ankyrin-repeats in the C-terminal region, with an additional motif, the KN motif, at the N-terminus. Kank1 was obtained by positional cloning of a tumor suppressor gene in renal cell carcinoma, while the other members were found by homology search. The family is involved in the regulation of actin polymerization and cell motility through signaling pathways containing PI3K/Akt and/or unidentified modulators/effectors. Their relationship to diseases such as cancer, and to neuronal and developmental disorders, will be an important subject of future study.

KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia

“…3 Notably, the 8.1 AH is implicated in the risk of numerous autoimmune conditions, including those associated with NHL (for example, systemic lupus erythematosus and Sjogren's syndrome). [3][4][5] It remains unknown, however, whether the association reported for TNF-308A is due to or independent from HLA alleles and/or haplotypes.…”

“…In line with several previously reported PDGFRb hybrids, KANK1-PDGFRb (KPb) contains three coiled-coil domains of KANK1, which may mediate the oligomerization of the hybrid protein, as shown for wild-type KANK1. 5 It also includes the fifth immunoglobulin (Ig)-like extracellular domain, the transmembrane domain and the kinase domain of PDGFRb (Figure 1e). …”

“…The 9p chromosomal region, including KANK1, is also deleted in various cancers, such as in acute lymphocytic leukemia and in other diseases. 5 The concomitant disruption of a tumor suppressor and activation of a receptor tyrosine kinase by translocation has been suggested in other cases, such as ETV6-PDGFRB.…”

“…Furthermore, KANK1 was shown to inhibit cell migration and actin polymerization through the modulation of Rho GTPases. 5 As Rho GTPases and the actin cytoskeleton have important functions during megakaryopoiesis, KANK1 might regulate thrombocyte production.…”

Translocation t(1;16)(p31;q24) rearranging CBFA2T3 is specific for acute erythroid leukemia

“…12 KANK4 is one of the genes encoding the Kank family of proteins which are characterized by their unique structure, coiled-coil motif in the N-terminal region and ankyrin-repeats in the C-terminal region, with an additional motif, KN, at the N-terminus. 13 Whereas the human Kank1 gene (KANK1) was found as a candidate tumor suppressor gene for renal cell carcinoma mapping to chromosome band 9p24, the other members were discovered on the basis of domain and phylogenetic analyses. Deletions of the KANK1 locus have been reported in renal cell carcinoma, cervical carcinoma, bladder cancer, hepatocellular carcinoma, pancreatic carcinoma, lung cancer, acute lymphocytic leukemia and breast cancer.…”