Low-density lipoprotein receptor adapter protein 1

LDLRAP1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2G30
Identifiers
Aliases	LDLRAP1 , ARH, ARH1, ARH2, FHCB1, FHCB2, low density lipoprotein receptor adaptor protein 1, FHCL4
External IDs	OMIM: 605747 MGI: 2140175 HomoloGene: 9219 GeneCards: LDLRAP1
Gene location (Human)
Chr.	Chromosome 1 (human)
End	25,568,886 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	134,768,024 bp
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• AP-2 adaptor complex binding ; • clathrin adaptor activity ; • phosphotyrosine residue binding ; • clathrin binding ; • amyloid-beta binding ; • signaling adaptor activity ; • low-density lipoprotein particle receptor binding ; • GO:0001948 protein binding ; • phosphatidylinositol-4,5-bisphosphate binding ; • signaling receptor complex adaptor activity ; • AP-1 adaptor complex binding ;
Cellular component	• cytoplasm ; • AP-1 adaptor complex ; • recycling endosome ; • cytosol ; • basal plasma membrane ; • cytoplasmic side of plasma membrane ; • AP-2 adaptor complex ; • neurofilament ; • axon ; • early endosome ; • plasma membrane ; • clathrin-coated vesicle membrane ;
Biological process	• positive regulation of receptor-mediated endocytosis ; • steroid metabolic process ; • endocytosis ; • receptor-mediated endocytosis involved in cholesterol transport ; • lipid metabolism ; • receptor internalization ; • amyloid precursor protein metabolic process ; • receptor-mediated endocytosis ; • positive regulation of cholesterol metabolic process ; • cholesterol homeostasis ; • regulation of protein binding ; • cholesterol metabolic process ; • positive regulation of signal transduction ; • low-density lipoprotein particle clearance ; • membrane organization ; • positive regulation of receptor-mediated endocytosis involved in cholesterol transport ; • regulation of protein localization to plasma membrane ; • cholesterol transport ; • cellular response to cytokine stimulus ; • positive regulation of vascular associated smooth muscle cell proliferation ; • positive regulation of low-density lipoprotein particle clearance ;
	Sources:Amigo / QuickGO
Orthologs
	26119
	100017
	ENSG00000157978
	ENSMUSG00000037295
	Q5SW96
	Q8C142
	NM_015627
	NM_145554
	NP_056442
	NP_663529
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated September 09, 2021

Low-density lipoprotein receptor adapter protein 1 is a protein that in humans is encoded by the LDLRAP1 gene.^[5]

The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTB) domain. The PTB 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.^[5]

Interactions

LDLRAP1 has been shown to interact with AP2B1 ^[6]^[7] and LRP2.^[8]

Related Research Articles

Apolipoprotein B (ApoB) is a protein that in humans is encoded by the APOB gene.

The low-density lipoprotein receptor gene family codes for a class of structurally related cell surface receptors that fulfill diverse biological functions in different organs, tissues, and cell types. The role that is most commonly associated with this evolutionarily ancient family is cholesterol homeostasis. In humans, excess cholesterol in the blood is captured by low-density lipoprotein (LDL) and removed by the liver via endocytosis of the LDL receptor. Recent evidence indicates that the members of the LDL receptor gene family are active in the cell signalling pathways between specialized cells in many, if not all, multicellular organisms.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein, in the blood and early cardiovascular disease.The most common mutations diminish the number of functional LDL receptors in the liver. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.

Low density lipoprotein receptor-related protein 2 also known as LRP2 or megalin is a protein which in humans is encoded by the LRP2 gene.

C-jun-amino-terminal kinase-interacting protein 1 is an enzyme that in humans is encoded by the MAPK8IP1 gene.

AP-2 complex subunit alpha-1 is a protein that in humans is encoded by the AP2A1 gene.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (orthologs) are found across many species. As with many proteins, PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.

Clathrin heavy chain 1 is a protein that in humans is encoded by the CLTC gene.

Arrestin, beta 1, also known as ARRB1, is a protein which in humans is encoded by the ARRB1 gene.

Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP gene.

Macrophage scavenger receptor 1, also known as MSR1, is a protein which in humans is encoded by the MSR1 gene. MSR1 has also been designated CD204.

AP-1 complex subunit beta-1 is a protein that in humans is encoded by the AP1B1 gene.

AP-2 complex subunit beta is a protein that in humans is encoded by the AP2B1 gene.

Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.

Sorting nexin-9 is a protein that in humans is encoded by the SNX9 gene.

Conserved oligomeric Golgi complex subunit 7 is a protein that in humans is encoded by the COG7 gene.

Low-density lipoprotein receptor-related protein 1B is a protein that in humans is encoded by the LRP1B gene.

Myosin regulatory light chain interacting protein, also known as MYLIP, is a protein that in humans is encoded by the MYLIP gene.

AP-4 complex subunit mu-1 is a protein that in humans is encoded by the AP4M1 gene.

Cubilin is a protein that in humans is encoded by the CUBN gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000157978 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000037295 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 "Entrez Gene: LDLRAP1 low density lipoprotein receptor adaptor protein 1".
↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . England. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
↑ He, Guocheng; Gupta Sarita; Yi Ming; Michaely Peter; Hobbs Helen H; Cohen Jonathan C (Nov 2002). "ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2". J. Biol. Chem. United States. 277 (46): 44044–9. doi: 10.1074/jbc.M208539200 . ISSN 0021-9258. PMID 12221107.
↑ Nagai, Masaaki; Meerloo Timo; Takeda Tetsuro; Farquhar Marilyn Gist (Dec 2003). "The adaptor protein ARH escorts megalin to and through endosomes". Mol. Biol. Cell. United States. 14 (12): 4984–96. doi:10.1091/mbc.E03-06-0385. ISSN 1059-1524. PMC 284800 . PMID 14528014.

Barbagallo CM, Emmanuele G, Cefalù AB, et al. (2003). "Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene". Atherosclerosis. 166 (2): 395–400. doi:10.1016/S0021-9150(02)00379-9. PMID 12535754.
Garcia CK, Wilund K, Arca M, et al. (2001). "Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein". Science. 292 (5520): 1394–8. Bibcode:2001Sci...292.1394G. doi:10.1126/science.1060458. PMID 11326085. S2CID 18718435.
Arca M, Zuliani G, Wilund K, et al. (2002). "Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis". Lancet. 359 (9309): 841–7. doi:10.1016/S0140-6736(02)07955-2. PMID 11897284. S2CID 10028777.
Al-Kateb H, Bähring S, Hoffmann K, et al. (2002). "Mutation in the ARH gene and a chromosome 13q locus influence cholesterol levels in a new form of digenic-recessive familial hypercholesterolemia". Circ. Res. 90 (9): 951–8. doi: 10.1161/01.RES.0000018002.43041.08 . PMID 12016260.
He G, Gupta S, Yi M, et al. (2003). "ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2". J. Biol. Chem. 277 (46): 44044–9. doi: 10.1074/jbc.M208539200 . PMID 12221107.
Wilund KR, Yi M, Campagna F, et al. (2003). "Molecular mechanisms of autosomal recessive hypercholesterolemia". Hum. Mol. Genet. 11 (24): 3019–30. doi: 10.1093/hmg/11.24.3019 . PMID 12417523.
Mishra SK, Watkins SC, Traub LM (2003). "The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery". Proc. Natl. Acad. Sci. U.S.A. 99 (25): 16099–104. Bibcode:2002PNAS...9916099M. doi: 10.1073/pnas.252630799 . PMC 138571 . PMID 12451172.
Eden ER, Patel DD, Sun XM, et al. (2003). "Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1". J. Clin. Invest. 110 (11): 1695–702. doi:10.1172/JCI16445. PMC 151635 . PMID 12464675.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC 139241 . PMID 12477932.
Jones C, Hammer RE, Li WP, et al. (2003). "Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia". J. Biol. Chem. 278 (31): 29024–30. doi: 10.1074/jbc.M304855200 . PMID 12746448.
Harada-Shiba M, Takagi A, Miyamoto Y, et al. (2003). "Clinical features and genetic analysis of autosomal recessive hypercholesterolemia". J. Clin. Endocrinol. Metab. 88 (6): 2541–7. doi: 10.1210/jc.2002-021487 . PMID 12788851.
Nagai M, Meerloo T, Takeda T, Farquhar MG (2004). "The adaptor protein ARH escorts megalin to and through endosomes". Mol. Biol. Cell. 14 (12): 4984–96. doi:10.1091/mbc.E03-06-0385. PMC 284800 . PMID 14528014.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID 14702039.
Michaely P, Li WP, Anderson RG, et al. (2004). "The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits". J. Biol. Chem. 279 (32): 34023–31. doi: 10.1074/jbc.M405242200 . PMID 15166224.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928 . PMID 15489334.
Canizales-Quinteros S, Aguilar-Salinas CA, Huertas-Vázquez A, et al. (2005). "A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia". Hum. Genet. 116 (1–2): 114–20. doi:10.1007/s00439-004-1192-9. PMID 15599766. S2CID 19424659.
Mishra SK, Keyel PA, Edeling MA, et al. (2005). "Functional dissection of an AP-2 beta2 appendage-binding sequence within the autosomal recessive hypercholesterolemia protein". J. Biol. Chem. 280 (19): 19270–80. doi: 10.1074/jbc.M501029200 . PMID 15728179.
Sirinian MI, Belleudi F, Campagna F, et al. (2006). "Adaptor protein ARH is recruited to the plasma membrane by low density lipoprotein (LDL) binding and modulates endocytosis of the LDL/LDL receptor complex in hepatocytes". J. Biol. Chem. 280 (46): 38416–23. doi: 10.1074/jbc.M504343200 . PMID 16129683.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by expanding it.

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000157978 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000037295 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: LDLRAP1 low density lipoprotein receptor adaptor protein 1".

[pmid16189514-6] Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . England. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[pmid12221107-7] He, Guocheng; Gupta Sarita; Yi Ming; Michaely Peter; Hobbs Helen H; Cohen Jonathan C (Nov 2002). "ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2". J. Biol. Chem. United States. 277 (46): 44044–9. doi: 10.1074/jbc.M208539200 . ISSN 0021-9258. PMID 12221107.

[pmid14528014-8] Nagai, Masaaki; Meerloo Timo; Takeda Tetsuro; Farquhar Marilyn Gist (Dec 2003). "The adaptor protein ARH escorts megalin to and through endosomes". Mol. Biol. Cell. United States. 14 (12): 4984–96. doi:10.1091/mbc.E03-06-0385. ISSN 1059-1524. PMC 284800 . PMID 14528014.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

Low-density lipoprotein receptor adapter protein 1

Contents

Interactions

Related Research Articles

References

Further reading