AP4E1
| AP4E1 | ||||||
|---|---|---|---|---|---|---|
| Identifiers | ||||||
| Aliases | AP4E1, CPSQ4, SPG51, STUT1, adaptor related protein complex 4 epsilon 1 subunit | |||||
| External IDs | MGI: 1336993 HomoloGene: 22397 GeneCards: AP4E1 | |||||
| Orthologs | ||||||
| Species | Human | Mouse | ||||
| Entrez | ||||||
| Ensembl | ||||||
| UniProt | ||||||
| RefSeq (mRNA) | ||||||
| RefSeq (protein) | ||||||
| Location (UCSC) | Chr 15: 50.91 – 51.01 Mb | Chr 2: 127.01 – 127.07 Mb | ||||
| PubMed search | [1] | [2] | ||||
| Wikidata | ||||||
| View/Edit Human | View/Edit Mouse |
AP-4 complex subunit epsilon-1 is a protein that in humans is encoded by the AP4E1 gene.[3]
Function
The heterotetrameric adaptor protein (AP) complexes sort integral membrane proteins at various stages of the endocytic and secretory pathways. AP4 is composed of 2 large chains, beta-4 (AP4B1) and epsilon-4 (AP4E1; this gene), a medium chain, mu-4 (AP4M1), and a small chain, sigma-4 (AP4S1).[3]
Clinical relevance
It is currently hypothesized that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning.[4]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Abnormal[5] |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal[6] |
| Haematology | Abnormal[7] |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Brain histopathology | Abnormal |
| Eye Histopathology | Normal |
| Salmonella infection | Normal[8] |
| Citrobacter infection | Normal[9] |
| All tests and analysis from[10][11] |
Model organisms have been used in the study of AP4E1 function. A conditional knockout mouse line, called Ap4e1tm1a(KOMP)Wtsi[12][13] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[14][15][16]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty four tests were carried out on homozygous mutant mice and four significant abnormalities were observed.[10] Females displayed decreased vertical activity in an open field test, had an abnormal complete blood count, hypoferremia, and a decreased corpus callosum size and enlarged lateral ventricles.[10]
References
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- 1 2 "Entrez Gene: adaptor-related protein complex 4".
- ↑ Abou Jamra R, Philippe O, Raas-Rothschild A, Eck SH, Graf E, Buchert R, Borck G, Ekici A, Brockschmidt FF, Nöthen MM, Munnich A, Strom TM, Reis A, Colleaux L (May 2011). "Adaptor Protein Complex 4 Deficiency Causes Severe Autosomal-Recessive Intellectual Disability, Progressive Spastic Paraplegia, Shy Character, and Short Stature". Am J Hum Genet. 88 (6): 788–95. doi:10.1016/j.ajhg.2011.04.019. PMC 3113253
. PMID 21620353. - ↑ "Anxiety data for Ap4e1". Wellcome Trust Sanger Institute.
- ↑ "Clinical chemistry data for Ap4e1". Wellcome Trust Sanger Institute.
- ↑ "Haematology data for Ap4e1". Wellcome Trust Sanger Institute.
- ↑ "Salmonella infection data for Ap4e1". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Ap4e1". Wellcome Trust Sanger Institute.
- 1 2 3 4 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Further reading
- Dell'Angelica EC, Mullins C, Bonifacino JS (1999). "AP-4, a novel protein complex related to clathrin adaptors.". J. Biol. Chem. 274 (11): 7278–85. doi:10.1074/jbc.274.11.7278. PMID 10066790.
- Hirst J, Bright NA, Rous B, Robinson MS (1999). "Characterization of a fourth adaptor-related protein complex.". Mol. Biol. Cell. 10 (8): 2787–802. doi:10.1091/mbc.10.8.2787. PMC 25515. PMID 10436028.
- Takatsu H, Futatsumori M, Yoshino K, et al. (2001). "Similar subunit interactions contribute to assembly of clathrin adaptor complexes and COPI complex: analysis using yeast three-hybrid system.". Biochem. Biophys. Res. Commun. 284 (4): 1083–9. doi:10.1006/bbrc.2001.5081. PMID 11409905.
- Boehm M, Aguilar RC, Bonifacino JS (2001). "Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs).". EMBO J. 20 (22): 6265–76. doi:10.1093/emboj/20.22.6265. PMC 125733. PMID 11707398.