Biology:ARL4D

Generic protein structure example

ADP-ribosylation factor-like protein 4D is a protein that in humans is encoded by the ARL4D gene.

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).

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
Radiography	Abnormal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Abnormal
Micronucleus test	Normal
Heart weight	Abnormal
Skin Histopathology	Normal
Brain histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

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

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and significant abnormalities were observed. 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.

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

• "A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1". Science 266 (5182): 66–71. Oct 1994. doi:10.1126/science.7545954. PMID 7545954. Bibcode: 1994Sci...266...66M. 
• "Comparison of the positional cloning methods used to isolate the BRCA1 gene". Human Molecular Genetics 4 (8): 1259–66. Aug 1995. doi:10.1093/hmg/4.8.1259. PMID 7581362. 
• "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. Sep 1996. doi:10.1101/gr.6.9.791. PMID 8889548. 
• "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. Aug 1999. doi:10.1016/S0014-5793(99)00759-0. PMID 10462049. 
• "A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61beta subunit". FEBS Letters 459 (1): 69–74. Oct 1999. doi:10.1016/S0014-5793(99)01188-6. PMID 10508919. 
• "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. Oct 2002. doi:10.1034/j.1399-0039.2002.600406.x. PMID 12472661. 
• "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. Sep 2004. doi:10.1086/423903. PMID 15258860. 
• "Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome". Nature Genetics 36 (9): 989–93. Sep 2004. doi:10.1038/ng1414. PMID 15314642. 
• "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. Oct 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R. 
• "The Arl4 family of small G proteins can recruit the cytohesin Arf6 exchange factors to the plasma membrane". Current Biology 17 (8): 711–6. Apr 2007. doi:10.1016/j.cub.2007.03.007. PMID 17398095.