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
Gene location (Human)
Chr.	Chromosome 19 (human)
End	35,879,792 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	30,144,960 bp
RNA expression pattern
	Top expressed in
	inferior olivary nucleus; ; middle frontal gyrus; ; prefrontal cortex; ; caudate nucleus; ; nucleus accumbens; ; amygdala; ; hypothalamus; ; Brodmann area 10; ; inferior ganglion of vagus nerve; ; corpus callosum;
	Top expressed in
	nucleus accumbens; ; piriform cortex; ; molar; ; subiculum; ; olfactory tubercle; ; globus pallidus; ; superior colliculus; ; superior frontal gyrus; ; temporal lobe; ; prefrontal cortex;
	More reference expression data
	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
	333
	11803
	ENSG00000105290
	ENSMUSG00000006651
	P51693
	Q03157
	NM_005166 ; NM_001024807
	NM_007467
	NP_001019978 ; NP_005157
	NP_031493
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 29, 2023

Amyloid-like protein 1, also known as APLP1, is a protein that in humans is encoded by the APLP1 gene.^[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]

Related Research Articles

Beta-secretase 2 is an enzyme that cleaves Glu-Val-Asn-Leu!Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein. BACE2 is a close homolog of BACE1.

Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity, and iron export. It is coded for by the gene APP and regulated by substrate presentation. APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.

Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is encoded by the BACE1 gene. Expression of BACE1 is observed mainly in neurons.

<span class="mw-page-title-main">Gamma secretase</span>

Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when cleaved by both gamma and beta secretase, produces a short 37-43 amino acid peptide called amyloid beta whose abnormally folded fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Gamma secretase is also critical in the related processing of several other type I integral membrane proteins, such as Notch, ErbB4, E-cadherin, N-cadherin, ephrin-B2, or CD44.

Presenilin-1(PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.

Presenilin-2 is a protein that is encoded by the PSEN2 gene.

Amyloid beta A4 precursor protein-binding family B member 1 is a protein that in humans is encoded by the APBB1 gene.

Laminin subunit alpha-1 is a protein that in humans is encoded by the LAMA1 gene.

Amyloid beta A4 precursor protein-binding family A member 1 is a protein that in humans is encoded by the APBA1 gene.

Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene.

Thimet oligopeptidase is an enzyme that in humans is encoded by the THOP1 gene.

NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.

Integral membrane protein 2B is a protein that in humans is encoded by the ITM2B gene.

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

Amyloid beta A4 precursor protein-binding family A member 3 is a protein that in humans is encoded by the APBA3 gene.

Amyloid beta A4 precursor protein-binding family B member 2 is a protein that in humans is encoded by the APBB2 gene.

N-terminal EF-hand calcium-binding protein 3 is a protein that in humans is encoded by the NECAB3 gene.

Amyloid beta A4 precursor protein-binding family B member 3 is a protein that in humans is encoded by the APBB3 gene.

Collagen alpha-1(XXV) chain is a protein that in humans is encoded by the COL25A1 gene.

Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP), also known as APBB1-interacting protein 1 or Rap1-GTP-interacting adapter molecule (RIAM) is a protein that in humans is encoded by the APBB1IP gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000105290 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000006651 - 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: APLP1 amyloid beta (A4) precursor-like protein 1".
↑ 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.
1 2 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. S2CID 1064378.

External links

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

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. doi: 10.1016/S0021-9258(18)47062-7 . 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. S2CID 709094.
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. S2CID 25127562.
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. doi:10.1523/JNEUROSCI.19-17-07507.1999. PMC 6782519 . 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. Bibcode:2002PNAS...9916899M. 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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000105290 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[entrez-5] 1 2 "Entrez Gene: APLP1 amyloid beta (A4) precursor-like protein 1".

[pmid8432545-6] 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.

[pmid18393365-7] 1 2 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. S2CID 1064378.

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APLP1

Contents

Function

Related Research Articles

References

External links

Further reading