ARL4D

ARL4D
Identifiers
Aliases	ARL4D , ARF4L, ARL6, ADP ribosylation factor like GTPase 4D
External IDs	OMIM: 600732 MGI: 1933155 HomoloGene: 1255 GeneCards: ARL4D
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q21.31 Start 43,398,993 bp [1] End 43,401,137 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11|11 D Start 101,556,367 bp [2] End 101,558,658 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in vena cava oocyte parotid gland right lobe of liver left lobe of thyroid gland nipple right lobe of thyroid gland skin of abdomen kidney body of tongue Top expressed in medial ganglionic eminence seminal vesicula left lobe of liver yolk sac retinal pigment epithelium myocardium of ventricle islet of Langerhans olfactory tubercle uterus piriform cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding GTP binding protein binding GTPase activity Cellular component cytoplasm plasma membrane nucleolus intracellular anatomical structure membrane nucleus Biological process protein secretion intracellular protein transport vesicle-mediated transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 379 80981 Ensembl ENSG00000175906 ENSMUSG00000034936 UniProt P49703 Q99PE9 RefSeq (mRNA) NM_001661 NM_025404 RefSeq (protein) NP_001652 NP_079680 Location (UCSC) Chr 17: 43.4 – 43.4 Mb Chr 11: 101.56 – 101.56 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

ADP-ribosylation factor-like protein 4D is a protein that in humans is encoded by the ARL4D gene. ^{[5] [6]}

Function

ADP-ribosylation factor 4D is a member of the ADP-ribosylation factor family of GTP-binding proteins. ARL4D is closely similar to ARL4A and ARL4C and each has a nuclear localization signal and an unusually high guanine nucleotide exchange rate. This protein may play a role in membrane-associated intracellular trafficking. Mutations in this gene have been associated with Bardet–Biedl syndrome (BBS). ^[6]

Model organisms

Arl4d knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal [7]
Radiography	Abnormal [8]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Abnormal [9]
Micronucleus test	Normal
Heart weight	Abnormal [10]
Skin Histopathology	Normal
Brain histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Normal [11]
Citrobacter infection	Normal [12]
All tests and analysis from [13] [14]

Model organisms have been used in the study of ARL4D function. A conditional knockout mouse line, called Arl4d^{tm1a(EUCOMM)Wtsi [15] [16]} 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. ^{[17] [18] [19]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[13] [20]} Twenty five tests were carried out on mutant mice and significant abnormalities were observed. ^[13] Homozygous mutant females had decreased bone mineral content, heart weight, lean body mass and CD8-positive, alpha-beta memory T cell number. Males had abnormal rib morphology with vertebral transformation. Both sexes displayed a reduction in dorsal third ventricle area and hippocampal area. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000175906 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034936 - 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. Smith SA, Holik PR, Stevens J, Melis R, White R, Albertsen H (Jul 1995). "Isolation and mapping of a gene encoding a novel human ADP-ribosylation factor on chromosome 17q12-q21". Genomics. 28 (1): 113–5. doi:10.1006/geno.1995.1115. PMID   7590735.
6. "Entrez Gene: ARL4D ADP-ribosylation factor-like 4D".
7. "DEXA data for Arl4d". Wellcome Trust Sanger Institute.
8. "Radiography data for Arl4d". Wellcome Trust Sanger Institute.
9. "Peripheral blood lymphocytes data for Arl4d". Wellcome Trust Sanger Institute.
10. "Heart weight data for Arl4d". Wellcome Trust Sanger Institute.
11. "Salmonella infection data for Arl4d". Wellcome Trust Sanger Institute.
12. "Citrobacter infection data for Arl4d". Wellcome Trust Sanger Institute.
13. 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. S2CID   85911512.
14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
15. "International Knockout Mouse Consortium".
16. "Mouse Genome Informatics".
17. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
18. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
19. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC   3218837 . PMID   21722353.

External links

• Human ARL4D genome location and ARL4D gene details page in the UCSC Genome Browser .
• Human ARL6 genome location and ARL6 gene details page in the UCSC Genome Browser .

Further reading

• Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (Oct 1994). "A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1". Science. 266 (5182): 66–71. Bibcode:1994Sci...266...66M. doi: 10.1126/science.7545954 . PMID   7545954.
• Harshman K, Bell R, Rosenthal J, Katcher H, Miki Y, Swenson J, Gholami Z, Frye C, Ding W, Dayananth P (Aug 1995). "Comparison of the positional cloning methods used to isolate the BRCA1 gene". Human Molecular Genetics. 4 (8): 1259–66. doi:10.1093/hmg/4.8.1259. PMID   7581362.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Jacobs S, Schilf C, Fliegert F, Koling S, Weber Y, Schürmann A, Joost HG (Aug 1999). "ADP-ribosylation factor (ARF)-like 4, 6, and 7 represent a subgroup of the ARF family characterization by rapid nucleotide exchange and a nuclear localization signal". FEBS Letters. 456 (3): 384–8. doi: 10.1016/S0014-5793(99)00759-0 . PMID   10462049. S2CID   84422541.
• Ingley E, Williams JH, Walker CE, Tsai S, Colley S, Sayer MS, Tilbrook PA, Sarna M, Beaumont JG, Klinken SP (Oct 1999). "A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61beta subunit". FEBS Letters. 459 (1): 69–74. doi: 10.1016/S0014-5793(99)01188-6 . PMID   10508919. S2CID   30948975.
• Nonaka Y, Tsuda N, Shichijo S, Ito M, Maeda Y, Harada M, Kamura T, Shigemori M, Itoh K (Oct 2002). "Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients with brain tumors". Tissue Antigens. 60 (4): 319–27. doi:10.1034/j.1399-0039.2002.600406.x. PMID   12472661.
• Chiang AP, Nishimura D, Searby C, Elbedour K, Carmi R, Ferguson AL, Secrist J, Braun T, Casavant T, Stone EM, Sheffield VC (Sep 2004). "Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3)". American Journal of Human Genetics. 75 (3): 475–84. doi:10.1086/423903. PMC   1182025 . PMID   15258860.
• Fan Y, Esmail MA, Ansley SJ, Blacque OE, Boroevich K, Ross AJ, Moore SJ, Badano JL, May-Simera H, Compton DS, Green JS, Lewis RA, van Haelst MM, Parfrey PS, Baillie DL, Beales PL, Katsanis N, Davidson WS, Leroux MR (Sep 2004). "Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome". Nature Genetics. 36 (9): 989–93. doi: 10.1038/ng1414 . PMID   15314642.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Hofmann I, Thompson A, Sanderson CM, Munro S (Apr 2007). "The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane". Current Biology. 17 (8): 711–6. doi: 10.1016/j.cub.2007.03.007 . PMID   17398095. S2CID   1341183.