Gene/Proteome Database (LMPD)
LMPD ID
LMP005380
Gene ID
Species
Homo sapiens (Human)
Gene Name
low density lipoprotein receptor adaptor protein 1
Gene Symbol
Synonyms
ARH; ARH1; ARH2; FHCB1; FHCB2
Chromosome
1
Map Location
1p36-p35
Summary
The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. [provided by RefSeq, Jul 2008]
Orthologs
Proteins
| low density lipoprotein receptor adapter protein 1 | |
|---|---|
| Refseq ID | NP_056442 |
| Protein GI | 132626790 |
| UniProt ID | Q5SW96 |
| mRNA ID | NM_015627 |
| Length | 308 |
| RefSeq Status | REVIEWED |
| MDALKSAGRALIRSPSLAKQSWGGGGRHRKLPENWTDTRETLLEGMLFSLKYLGMTLVEQPKGEELSAAAIKRIVATAKASGKKLQKVTLKVSPRGIILTDNLTNQLIENVSIYRISYCTADKMHDKVFAYIAQSQHNQSLECHAFLCTKRKMAQAVTLTVAQAFKVAFEFWQVSKEEKEKRDKASQEGGDVLGARQDCTPSLKSLVATGNLLDLEETAKAPLSTVSANTTNMDEVPRPQALSGSSVVWELDDGLDEAFSRLAQSRTNPQVLDTGLTAQDMHYAQCLSPVDWDKPDSSGTEQDDLFSF | |
Gene Information
Entrez Gene ID
Gene Name
low density lipoprotein receptor adaptor protein 1
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0030424 | ISS:BHF-UCL | C | axon |
| GO:0009925 | IDA:UniProtKB | C | basal plasma membrane |
| GO:0009898 | IDA:BHF-UCL | C | cytoplasmic side of plasma membrane |
| GO:0005829 | IDA:UniProtKB | C | cytosol |
| GO:0005769 | IDA:UniProtKB | C | early endosome |
| GO:0005883 | ISS:BHF-UCL | C | neurofilament |
| GO:0055037 | IDA:BHF-UCL | C | recycling endosome |
| GO:0035612 | IDA:BHF-UCL | F | AP-2 adaptor complex binding |
| GO:0001540 | IPI:BHF-UCL | F | beta-amyloid binding |
| GO:0035615 | IDA:BHF-UCL | F | clathrin adaptor activity |
| GO:0030276 | IDA:UniProtKB | F | clathrin binding |
| GO:0050750 | IPI:BHF-UCL | F | low-density lipoprotein particle receptor binding |
| GO:0005546 | IDA:BHF-UCL | F | phosphatidylinositol-4,5-bisphosphate binding |
| GO:0001784 | IDA:UniProtKB | F | phosphotyrosine binding |
| GO:0030159 | IMP:UniProtKB | F | receptor signaling complex scaffold activity |
| GO:0035591 | IDA:BHF-UCL | F | signaling adaptor activity |
| GO:0042982 | IMP:BHF-UCL | P | amyloid precursor protein metabolic process |
| GO:0042632 | IMP:BHF-UCL | P | cholesterol homeostasis |
| GO:0008203 | NAS:UniProtKB | P | cholesterol metabolic process |
| GO:0090205 | IC:BHF-UCL | P | positive regulation of cholesterol metabolic process |
| GO:0048260 | IMP:UniProtKB | P | positive regulation of receptor-mediated endocytosis |
| GO:0009967 | IDA:GOC | P | positive regulation of signal transduction |
| GO:0031623 | IMP:BHF-UCL | P | receptor internalization |
| GO:0006898 | IDA:BHF-UCL | P | receptor-mediated endocytosis |
| GO:0090118 | IMP:BHF-UCL | P | receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport |
| GO:0090003 | IMP:BHF-UCL | P | regulation of establishment of protein localization to plasma membrane |
| GO:0043393 | IMP:UniProtKB | P | regulation of protein binding |
| GO:0006810 | NAS:UniProtKB | P | transport |
KEGG Pathway Links
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_6841 | Chylomicron-mediated lipid transport |
| REACT_6934 | LDL-mediated lipid transport |
| REACT_602 | Lipid digestion, mobilization, and transport |
| REACT_6823 | Lipoprotein metabolism |
| REACT_111217 | Metabolism |
| REACT_22258 | Metabolism of lipids and lipoproteins |
Domain Information
UniProt Annotations
Entry Information
Gene Name
low density lipoprotein receptor adaptor protein 1
Protein Entry
ARH_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Disease | Hypercholesterolemia, autosomal recessive (ARH) [MIM:603813]: A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins. {ECO:0000269|PubMed:11326085}. Note=The disease is caused by mutations affecting the gene represented in this entry. |
| Domain | The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1. {ECO:0000269|PubMed:16516836}. |
| Function | 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. {ECO:0000269|PubMed:15728179}. |
| Interaction | P63010:AP2B1; NbExp=3; IntAct=EBI-747813, EBI-432924; |
| Similarity | Contains 1 PID domain. {ECO:0000255|PROSITE- ProRule:PRU00148}. |
| Subcellular Location | Cytoplasm {ECO:0000269|PubMed:12451172}. |
| Subunit | Interacts with LDLR. Binds to soluble clathrin trimers. Interacts with AP2B1; the interaction mediates the association with the AP-2 complex. Interacts with VLDLR (By similarity). {ECO:0000250}. |
| Tissue Specificity | Expressed at high levels in the kidney, liver, and placenta, with lower levels detectable in brain, heart, muscle, colon, spleen, intestine, lung, and leukocytes. |
Identical and Related Proteins
Unique RefSeq proteins for LMP005380 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 132626790 | RefSeq | NP_056442 | 308 | low density lipoprotein receptor adapter protein 1 |
Identical Sequences to LMP005380 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:132626790 | DBBJ | BAI46788.1 | 308 | low density lipoprotein receptor adaptor protein 1, partial [synthetic construct] |
| GI:132626790 | GenBank | AGB64043.1 | 308 | Sequence 5 from patent US 8288346 |
| GI:132626790 | SwissProt | Q5SW96.3 | 308 | RecName: Full=Low density lipoprotein receptor adapter protein 1; AltName: Full=Autosomal recessive hypercholesterolemia protein [Homo sapiens] |
Related Sequences to LMP005380 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:132626790 | DBBJ | BAG52309.1 | 308 | unnamed protein product [Homo sapiens] |
| GI:132626790 | EMBL | CAB56030.2 | 308 | hypothetical protein [Homo sapiens] |
| GI:132626790 | GenBank | AAQ90407.1 | 308 | LDL receptor adaptor protein [Homo sapiens] |
| GI:132626790 | GenBank | AAH29770.2 | 308 | Low density lipoprotein receptor adaptor protein 1 [Homo sapiens] |
| GI:132626790 | GenBank | JAA04603.1 | 308 | low density lipoprotein receptor adaptor protein 1 [Pan troglodytes] |
| GI:132626790 | GenBank | AHD69533.1 | 308 | Sequence 547 from patent US 8586006 |