Human ARH peptide (ab23072)

Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface.

Expressed at high levels in the kidney, liver, and placenta, with lower levels detectable in brain, heart, muscle, colon, spleen, intestine, lung, and leukocytes.

Defects in LDLRAP1 are the cause of autosomal recessive hypercholesterolemia (ARH) [MIM:603813]. ARH is a disorder caused by defective internalization of LDL receptors (LDLR) in the liver. ARH has the clinical features of familial hypercholesterolemia (FH) [MIM:143890] homozygotes, including severely elevated plasma LDL cholesterol, tuberous and tendon xanthomata, and premature atherosclerosis. LDL receptor (LDLR) activity measured in skin fibroblasts is normal, as the LDL binding ability.

Contains 1 PID domain.

The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1.

Phosphorylated upon DNA damage, probably by ATM or ATR.

Cytoplasm.