AP4E1

AP4E1
Identifiers
Aliases	AP4E1, CPSQ4, SPG51, STUT1, adaptor related protein complex 4 epsilon 1 subunit, adaptor related protein complex 4 subunit epsilon 1
External IDs	OMIM: 607244 MGI: 1336993 HomoloGene: 22397 GeneCards: AP4E1
Gene location (Human)
Chr.	Chromosome 15 (human)[1]
End	51,005,895 bp[1]
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)[2]
End	127,067,909 bp[2]
Gene ontology
Molecular function	• GO:0001948 protein binding;
Cellular component	• membrane coat; • Golgi apparatus; • trans-Golgi network membrane; • endosome lumen; • membrane; • AP-4 adaptor complex;
Biological process	• protein transport; • intracellular protein transport; • vesicle-mediated transport; • protein targeting; • protein localization;
	Sources:Amigo / QuickGO
Orthologs
	23431
	108011
	ENSG00000081014
	ENSMUSG00000001998
	Q9UPM8
	Q80V94
	NM_001252127; NM_007347
	NM_175550
	NP_001239056; NP_031373
	NP_780759
	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.[5]

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).[5]

Clinical relevance

It is currently hypothesized that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning.[6]

Model organisms

*Ap4e1* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Abnormal[7]
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[8]
Haematology	Abnormal[9]
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Normal[10]
Citrobacter infection	Normal[11]
All tests and analysis from[12][13]

Model organisms have been used in the study of AP4E1 function. A conditional knockout mouse line, called Ap4e1^{tm1a(KOMP)Wtsi}[14][15] 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.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty four tests were carried out on homozygous mutant mice and four significant abnormalities were observed.[12] 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.[12]

References

GRCh38: Ensembl release 89: ENSG00000081014 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000001998 - 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.
"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.
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.

External links

Human AP4E1 genome location and AP4E1 gene details page in the UCSC Genome Browser.