APLP1

APLP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3PMR, 3Q7G, 3Q7L, 3QMK, 4RD9, 4RDA
Identifiers
Aliases	APLP1 , APLP, amyloid beta precursor like protein 1
External IDs	OMIM: 104775; MGI: 88046; HomoloGene: 68447; GeneCards: APLP1; OMA:APLP1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19q13.12 Start 35,867,899 bp [1] End 35,879,792 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 B1|7 18.32 cM Start 30,134,407 bp [2] End 30,144,960 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in C1 segment inferior olivary nucleus middle frontal gyrus right frontal lobe prefrontal cortex caudate nucleus nucleus accumbens dorsal motor nucleus of vagus nerve amygdala hypothalamus Top expressed in nucleus accumbens nucleus of stria terminalis piriform cortex molar subiculum olfactory tubercle central gray substance of midbrain globus pallidus primary visual cortex superior colliculus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function alpha-2C adrenergic receptor binding heparin binding alpha-2B adrenergic receptor binding metal ion binding protein binding alpha-2A adrenergic receptor binding identical protein binding transition metal ion binding Cellular component cytoplasm integral component of membrane membrane plasma membrane basement membrane perinuclear region of cytoplasm Biological process endocytosis nervous system development cellular response to norepinephrine stimulus cell adhesion animal organ morphogenesis apoptotic process negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 333 11803 Ensembl ENSG00000105290 ENSMUSG00000006651 UniProt P51693 Q03157 RefSeq (mRNA) NM_005166 NM_001024807 NM_007467 RefSeq (protein) NP_001019978 NP_005157 NP_031493 Location (UCSC) Chr 19: 35.87 – 35.88 Mb Chr 7: 30.13 – 30.14 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Amyloid precursor like protein 1, also known as APLP1, is a protein encoded by the APLP1 gene in humans. ^{[5] [6]} APLP1 along with APLP2 are important modulators of glucose and insulin homeostasis. ^[7]

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. ^[5]

APLP1 and APLP2 double knockout mice display hypoglycemia and hyperinsulinemia indicating that these two proteins are important modulators of glucose and insulin homeostasis. ^[7]

APLP1 has also been implicated in the transmission pathologic α-synuclein in Parkinson's disease ^{[8] [9]}

References

1. GRCh38: Ensembl release 89: ENSG00000105290 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000006651 – 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.
5. "Entrez Gene: APLP1 amyloid beta (A4) precursor-like protein 1".
6. 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.
7. Needham BE, Wlodek ME, Ciccotosto GD, Fam BC, Masters CL, Proietto J, et al. (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. S2CID   1064378.
8. Mao X, Gu H, Kim D, Kimura Y, Wang N, Xu E, et al. (May 2024). "Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein". Nature Communications. 15 (1): 4663. doi:10.1038/s41467-024-49016-3. PMC   11143359 . PMID   38821932.
9. "New Study Suggests Cancer Drug Could Be Used to Target Protein Connection That Spurs Parkinson's Disease". Johns Hopkins Medicine. 17 June 2024.

Further reading

• Bayer TA, Cappai R, Masters CL, Beyreuther K, Multhaup G (November 1999). "It all sticks together--the APP-related family of proteins and Alzheimer's disease". Molecular Psychiatry. 4 (6): 524–528. doi: 10.1038/sj.mp.4000552 . PMID   10578233.
• Kim TW, Wu K, Xu JL, McAuliffe G, Tanzi RE, Wasco W, et al. (August 1995). "Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density". Brain Research. Molecular Brain Research. 32 (1): 36–44. doi:10.1016/0169-328X(95)00328-P. PMID   7494461.
• Bush AI, Pettingell WH, de Paradis M, Tanzi RE, Wasco W (October 1994). "The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily". The Journal of Biological Chemistry. 269 (43): 26618–26621. doi: 10.1016/S0021-9258(18)47062-7 . PMID   7929392.
• 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): 237–239. doi:10.1006/geno.1993.1047. PMID   8432545.
• Bressler SL, Gray MD, Sopher BL, Hu Q, Hearn MG, Pham DG, et al. (October 1996). "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". Human Molecular Genetics. 5 (10): 1589–1598. doi: 10.1093/hmg/5.10.1589 . PMID   8894693.
• Paliga K, Peraus G, Kreger S, Dürrwang U, Hesse L, Multhaup G, et al. (December 1997). "Human amyloid precursor-like protein 1--cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid". European Journal of Biochemistry. 250 (2): 354–363. doi: 10.1111/j.1432-1033.1997.0354a.x . PMID   9428684.
• Lenkkeri U, Kestilä M, Lamerdin J, McCready P, Adamson A, Olsen A, et al. (February 1998). "Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1". Human Genetics. 102 (2): 192–196. doi:10.1007/s004390050676. PMID   9521588. S2CID   709094.
• McNamara MJ, Ruff CT, Wasco W, Tanzi RE, Thinakaran G, Hyman BT (August 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 Research. 804 (1): 45–51. doi: 10.1016/S0006-8993(98)00653-2 . PMID   9729270. S2CID   25127562.
• Tomita S, Ozaki T, Taru H, Oguchi S, Takeda S, Yagi Y, et al. (January 1999). "Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein". The Journal of Biological Chemistry. 274 (4): 2243–2254. doi: 10.1074/jbc.274.4.2243 . PMID   9890987.
• Homayouni R, Rice DS, Sheldon M, Curran T (September 1999). "Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1". The Journal of Neuroscience. 19 (17): 7507–7515. doi:10.1523/JNEUROSCI.19-17-07507.1999. PMC   6782519 . PMID   10460257.
• Simons A, Ruppert T, Schmidt C, Schlicksupp A, Pipkorn R, Reed J, et al. (July 2002). "Evidence for a copper-binding superfamily of the amyloid precursor protein". Biochemistry. 41 (30): 9310–9320. 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.
• Walsh DM, Fadeeva JV, LaVoie MJ, Paliga K, Eggert S, Kimberly WT, et al. (June 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): 6664–6673. doi:10.1021/bi027375c. PMID   12779321.
• Yamakami M, Yoshimori T, Yokosawa H (December 2003). "Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin". The Journal of Biological Chemistry. 278 (52): 52865–52872. doi: 10.1074/jbc.M306740200 . PMID   14563850.
• Adlerz L, Beckman M, Holback S, Tehranian R, Cortés Toro V, Iverfeldt K (November 2003). "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 Research. Molecular Brain Research. 119 (1): 62–72. doi:10.1016/j.molbrainres.2003.08.014. PMID   14597230.
• Li Q, Südhof TC (March 2004). "Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1". The Journal of Biological Chemistry. 279 (11): 10542–10550. doi: 10.1074/jbc.M310001200 . PMID   14699153.
• Eggert S, Paliga K, Soba P, Evin G, Masters CL, Weidemann A, et al. (April 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". The Journal of Biological Chemistry. 279 (18): 18146–18156. doi: 10.1074/jbc.M311601200 . PMID   14970212.

External links

• Human APLP1 genome location and APLP1 gene details page in the UCSC Genome Browser .