This gene encodes a member of the KN motif and ankyrin repeat domains (KANK) family of proteins, which play a role in cytoskeletal formation by regulating actin polymerization. The encoded protein functions in the sequestration of steroid receptor coactivators and possibly other proteins. Mutations in this gene are associated with impaired kidney podocyte function and nephrotic syndrome, and keratoderma and woolly hair. [provided by RefSeq, Jul 2016]
Full Name
KN Motif And Ankyrin Repeat Domains 2
Function
Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3 (PubMed:17476305).
Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria (PubMed:22371500).
Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis (PubMed:22371500).
Involved in the negative control of vitamin D receptor signaling pathway (PubMed:24671081).
Involved in actin stress fibers formation through its interaction with ARHGDIA and the regulation of the Rho signaling pathway (PubMed:17996375, PubMed:25961457).
May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney (PubMed:25961457).
Through the Rho signaling pathway may also regulate cell proliferation (By similarity).
Biological Process
Apoptotic processIEA:UniProtKB-KW
Glomerular visceral epithelial cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Kidney epithelium developmentManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of intracellular estrogen receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of programmed cell deathManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of vitamin D receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of Rho protein signal transductionManual Assertion Based On ExperimentIMP:UniProtKB
Cellular Location
Cytoplasm; Mitochondrion
Involvement in disease
Palmoplantar keratoderma and woolly hair (PPKWH):
A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe.
Nephrotic syndrome 16 (NPHS16):
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS16 inheritance is autosomal recessive.
PTM
Phosphorylated by casein kinase II upon estrogen stimulation (PubMed:17476305).
Phosphorylation induces the release by KANK2 of NCOA1 and its translocation to the nucleus where NCOA1 can activate gene transcription (PubMed:17476305).