APLP1

Amyloid beta (A4) precursor-like protein 1
E2 domain of APLP1 PDB 3qmk
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3PMR​, 3Q7G​, 3Q7L​, 3QMK​, 4RD9​, 4RDA​
Identifiers
Symbols	APLP1 ; APLP
External IDs	OMIM: 104775 MGI: 88046 HomoloGene: 68447 GeneCards: APLP1 Gene
Gene ontology Molecular function • protein binding • heparin binding • alpha-2A adrenergic receptor binding • alpha-2B adrenergic receptor binding • alpha-2C adrenergic receptor binding • identical protein binding • transition metal ion binding Cellular component • basement membrane • plasma membrane • integral component of membrane • perinuclear region of cytoplasm Biological process • endocytosis • apoptotic process • cell adhesion • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway • nervous system development • organ morphogenesis • negative regulation of cAMP biosynthetic process • cellular response to norepinephrine stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	333	11803
Ensembl	ENSG00000105290	ENSMUSG00000006651
UniProt	P51693	Q03157
RefSeq (mRNA)	NM_001024807	NM_007467
RefSeq (protein)	NP_001019978	NP_031493
Location (UCSC)	Chr 19: 35.87 – 35.88 Mb	Chr 7: 30.43 – 30.45 Mb
PubMed search

Amyloid-like protein 1, also known as APLP1, is a protein that in humans is encoded by the APLP1 gene.^[1][2] APLP1 along with APLP2 are important modulators of glucose and insulin homeostasis.^[3]

Function

This gene encodes a member of the highly conserved amyloid precursor protein gene family. The encoded protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor protein cleavage. This cleavage liberates an intracellular cytoplasmic fragment that may act as a transcriptional activator. The encoded protein may also play a role in synaptic maturation during cortical development. Alternatively spliced transcript variants encoding different isoforms have been described.^[1]

APLP1 and APLP2 double knockout mice display hypoglycemia and hyperinsulinemia indicating that these two proteins are important modulators of glucose and insulin homeostasis.^[3]

References

1. "Entrez Gene: APLP1 amyloid beta (A4) precursor-like protein 1".
2. Wasco W, Brook JD, Tanzi RE (January 1993). "The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19". Genomics 15 (1): 237–9. doi:10.1006/geno.1993.1047. PMID 8432545.
3. Needham BE, Wlodek ME, Ciccotosto GD, Fam BC, Masters CL, Proietto J, Andrikopoulos S, Cappai R (June 2008). "Identification of the Alzheimer's disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth". J. Pathol. 215 (2): 155–63. doi:10.1002/path.2343. PMID 18393365.

Further reading

• Bayer TA, Cappai R, Masters CL; et al. (2000). "It all sticks together--the APP-related family of proteins and Alzheimer's disease.". Mol. Psychiatry 4 (6): 524–8. doi:10.1038/sj.mp.4000552. PMID 10578233.
• Kim TW, Wu K, Xu JL; et al. (1996). "Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density.". Brain Res. Mol. Brain Res. 32 (1): 36–44. doi:10.1016/0169-328X(95)00328-P. PMID 7494461.
• Bush AI, Pettingell WH, de Paradis M; et al. (1994). "The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily.". J. Biol. Chem. 269 (43): 26618–21. PMID 7929392.
• Wasco W, Brook JD, Tanzi RE (1993). "The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19.". Genomics 15 (1): 237–9. doi:10.1006/geno.1993.1047. PMID 8432545.
• Bressler SL, Gray MD, Sopher BL; et al. (1997). "cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein.". Hum. Mol. Genet. 5 (10): 1589–98. doi:10.1093/hmg/5.10.1589. PMID 8894693.
• Paliga K, Peraus G, Kreger S; et al. (1998). "Human amyloid precursor-like protein 1--cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid.". Eur. J. Biochem. 250 (2): 354–63. doi:10.1111/j.1432-1033.1997.0354a.x. PMID 9428684.
• Lenkkeri U, Kestilä M, Lamerdin J; et al. (1998). "Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1.". Hum. Genet. 102 (2): 192–6. doi:10.1007/s004390050676. PMID 9521588.
• McNamara MJ, Ruff CT, Wasco W; et al. (1998). "Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer disease and aged control brains.". Brain Res. 804 (1): 45–51. doi:10.1016/S0006-8993(98)00653-2. PMID 9729270.
• Tomita S, Ozaki T, Taru H; et al. (1999). "Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein.". J. Biol. Chem. 274 (4): 2243–54. doi:10.1074/jbc.274.4.2243. PMID 9890987.
• Homayouni R, Rice DS, Sheldon M, Curran T (1999). "Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1.". J. Neurosci. 19 (17): 7507–15. PMID 10460257.
• Simons A, Ruppert T, Schmidt C; et al. (2002). "Evidence for a copper-binding superfamily of the amyloid precursor protein.". Biochemistry 41 (30): 9310–20. doi:10.1021/bi0258647. PMID 12135352.
• Scheinfeld MH, Ghersi E, Laky K; et al. (2003). "Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription.". J. Biol. Chem. 277 (46): 44195–201. doi:10.1074/jbc.M208110200. PMID 12228233.
• 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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Walsh DM, Fadeeva JV, LaVoie MJ; et al. (2003). "gamma-Secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins.". Biochemistry 42 (22): 6664–73. doi:10.1021/bi027375c. PMID 12779321.
• Yamakami M, Yoshimori T, Yokosawa H (2004). "Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin.". J. Biol. Chem. 278 (52): 52865–72. doi:10.1074/jbc.M306740200. PMID 14563850.
• Adlerz L, Beckman M, Holback S; et al. (2004). "Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction.". Brain Res. Mol. Brain Res. 119 (1): 62–72. doi:10.1016/j.molbrainres.2003.08.014. PMID 14597230.
• Li Q, Südhof TC (2004). "Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1.". J. Biol. Chem. 279 (11): 10542–50. doi:10.1074/jbc.M310001200. PMID 14699153.
• 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.
• Eggert S, Paliga K, Soba P; et al. (2004). "The proteolytic processing of the amyloid precursor protein gene family members APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilon-like cleavages: modulation of APLP-1 processing by n-glycosylation.". J. Biol. Chem. 279 (18): 18146–56. doi:10.1074/jbc.M311601200. PMID 14970212.