HAP1 (huntingtin-associated protein 1) binds to huntingtin. Huntingtin is a protein that contains a polyglutamine region and when the number of glutamine repeats exceeds 35, the gene encodes a version of huntingtin that leads to Huntington’s disease (HD). The ability of HAP1 to bind to huntingtin is enhanced by an expanded polyglutamine repeat region. HAP1 shows neuronal localization and moves with huntingtin in nerve fibers. HAP1 is primarily expressed in brain tissue, with greater expression in the olfactory bulb and brain stem. Mouse HAP1 is localized to membrane-bound organelles including large endosomes, tubulovesicular structures and budding vesicles in neurons. Duo, also designated huntingtin-associated protein interacting protein or HAPIP, binds Huntingtin-associated protein 1 (HAP1) and may have a role in vesicle trafficking and cytoskeletal function.
Function:
Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity.
Subunit:
Interacts with the SLCterminal of peptidylglycine alpha-amidating monooxygenase (PAM) and with the huntingtin-associated protein 1 (HAP1) (By similarity). Interacts with FASLG.
Subcellular Location:
Cytoplasm. Cytoplasm, cytoskeleton. Note=Associated with the cytoskeleton.
Tissue Specificity:
Isoform 2 is brain specific. Highly expressed in cerebral cortex, putamen, amygdala, hippocampus and caudate nucleus. Weakly expressed in brain stem and cerebellum. Isoform 4 is expressed in skeletal muscle.
Post-translational modifications:
Autophosphorylated.
DISEASE:
Genetic variation in KALRN is associated with susceptibility to coronary heart disease type 5 (CHDS5) [MIM:608901]. CHD is the leading cause of death and disability worldwide. CHD is multifactorial disease with a strong genetic component. Classic epidemiologic studies have revealed many risk factors for CHD, including age, sex, hypertension, dyslipidemia, diabetes mellitus, smoking, and physical inactivity.
Similarity:
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 type-III domain.
Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
Contains 2 PH domains.
Contains 1 protein kinase domain.
Contains 2 SH3 domains.
Contains 5 spectrin repeats.
SWISS:
O60229
Gene ID:
8997
Database links:
Entrez Gene: 8997 Human
Entrez Gene: 545156 Mouse
Entrez Gene: 16809 Rat
Omim: 60925 Human
SwissProt: O60229 Human
SwissProt: A2CG49 Mouse
SwissProt: P97924 Rat
Unigene: 8004 Human
Unigene: 353103 Mouse
Unigene: 450612 Mouse
Unigene: 82274 Mouse
Unigene: 87882 Rat
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