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FLASH GENE

Symbol

LDLRAP1

contributors: mct - updated : 30-11-2021

HGNC name	low density lipoprotein receptor adaptor protein 1
HGNC id	18640

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ARH hypercholesterolemia, severe
Location	1p36.11      Physical location : 25.870.075 - 25.895.375
Synonym name	putative low density lipoprotein (LDL) receptor adaptor
	autosomal recessive hypercholesterolemia protein
Synonym symbol(s)	ARH2, FHCB1, FHCB2, MGC34705, LDLRA, ARH, ARH1, DKFZp586D0624

DNA

TYPE	functioning gene
STRUCTURE	46.81 kb     9 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

Map	pter - D1S2864 - D1S2698 - D1S2734 - [D1S1152 - D1S234 - D1S1676 - D1S2885 ] - D1S2749 - D1S2787 - cen
Authors	Garcia (01)
Text	[LDLRAP1 ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015627 9 - 2914 NP_056442 - 308 - 2020 32073192

EXPRESSION

Type

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen       lowly Cardiovascular heart       lowly Digestive intestine large intestine colon   lowly   liver       highly Endocrine pancreas           placenta       highly Nervous brain       lowly Reproductive male system prostate       Respiratory lung       lowly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Connective         Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol   digestive Blood/Hematopoietic leukocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text	placenta highly

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a phosphotyrosine binding (PTB/PID) domain

HOMOLOGY

interspecies	homolog to Drosophila lnk
	ortholog to murine LdlrA/arh
	ortholog to xenopus arh

Homologene

FAMILY

CATEGORY

adaptor , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic

basic FUNCTION	participating in the internalization of the LDL-LDLR complex, possibly enhancing the efficiency of the packaging into endocytic vesicles
	required for the efficient activity of low density lipoprotein receptor (LDLR) in selected tissues
	appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts
	endocytic sorting adaptor that actively participates in the internalization of the LDL-LDLR complex, possibly enhancing the efficiency of its packaging into the endocytic vesicles
	in addition to its role in endocytosis, cooperates with AP-1B in basolateral exocytosis of LDLR from recycling endosomes (REs)
	combination of LDLRAP1 and DAB2 is responsible for the majority of adaptor function in LDLR endocytosis and LDLR-mediated cholesterol homeostasis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

endocytosis transport , cellular trafficking transport

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding to the consensus sequence of several cell-surface receptors

RNA

small molecule	other,
	phosphoinositides

protein	binding to the cytoplasmic tail of the LDL receptor (consensus sequence NPXY)
	binding to soluble clathrin trimers and to the adapter protein complex 2 (AP-2, beta 2 subunit)
	escorting megalin yo and throuh endosomes
	KCNJ1 bound directly to the clathrin adaptor molecule autosomal recessive hypercholesterolemia (LDLRAP1) (LDLRAP1 marks KCNJ1 for clathrin-dependent endocytosis, in concert with the demands of potassium homeostasis)
	LDLRAP1 colocalizes and cooperates with AP1B1 in recycling endosomes (REs)
	LDLRAP1 may have additional roles in LRP2 trafficking
	in the absence of LDLRAP1, DAB2 in liver endothelial cells regulates cholesterol synthesis in hepatocytes

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

ARH

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

elimination of both Arh and Dab2 genes in mice resulted in profound hypercholesterolemia similar to that resulting from Ldlr homozygous deletion