kalirin; huntingtin-associated protein-interacting protein; protein duo; serine/threonine protein kinase with Dbl- & pleckstrin homology domain (KALRN, DUET, DUO, HAPIP, TRAD)

^[1]^[2]^[3]

Function

promotes the exchange of GDP by GTP
activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulateneuronal shape, growth, & plasticity, through effects on the actin cytoskeleton
induces lamellipodia independent of its GEF activity
autophosphorylated
interacts with the C-terminal of peptidylglycine alpha-amidating monooxygenase (PAM) & with the huntingtin-associated protein 1 (HAP1) (putative)

the two GEF domains catalyze nucleotide exchange for RAC1 & RhoA which are bound by DH1 & DH2 respectively
the two GEF domains appear to play differing roles in neuronal development & axonal outgrowth
SH3 1 binds to the first GEF domain inhibiting GEF activity only when in the presence of a PXXP peptide,suggesting that the SH3 domain/peptide interaction mediates binding to GEF1
CRK1 SH3 domain binds to & inhibits GEF1 activity (putative)
belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family
contains 1 CRAL-TRIO domain
contains 2 DH (DBL-homology) domains
contains 1 fibronectin F3 module
contains 1 Ig-like C2-type domain (immunoglobulin-like)
contains 2 PH domains
contains 1 protein kinase domain
contains 2 SH3 domains
contains 5 spectrin repeats

Alternative initiation; named isoforms=6

genetic variation in KALRN is associated with susceptibility to coronary heart disease type 5
neurofibrillary tangle burden & kalirin-mediated synaptic dysfunction may be neuropathologic components of psychosis in Alzheimer's disease

called DUO because the encoded protein is closely related to but shorter than TRIO