Golgi-associated RAB2 interactor protein 5A is a protein that in humans is encoded by the GARIN5A gene (previously FAM71E1). The GARIN5A protein is predicted to interact with RAB2B and participate in the innate immune system response to DNA viruses.
Gene Location The gene is located on the minus strand at 19q13.33 and spans from 50,466,643 to 50,476,753. It is 10,070 bp long.
Gene neighborhood In humans, the gene is flanked by the following genes:
SPIB: putative oncogene that is active in hematopoietic cells MYBPC2: encodes a structural protein and is actively expressed in striated muscle cells EMC10: encodes a protein of unknown function JOSD2: encodes a protein involved in de-ubiquitination
Promoter The promoter of FAM71E1 is located on the minus strand from 50,476,094 to 50,477,946 . It is 1,853 bp long.
Expression The gene seems to be ubiquitously expressed at low levels throughout the body but has prominent expression in the adult human testis, followed by lower expression levels in the sperm, oocyte, and brain. Age does not have an effect on its expression in the skeletal muscle of males or females. Its expression is elevated prior to the differentiation of embryonic stem cells into pancreatic islet-like cells.
Transcript
Isoforms The FAM71E1 gene produces two isoforms from alternative splicing. Isoform 1 is 1281 bp long, and isoform 2 is slightly shorter at 1233 bp long. Both transcript variants have 5 exons, 4 of which are coding exons. The third intron for the isoform 2 transcript is longer than the one found in isoform 1.
Regulation The FAM71E1 transcript is regulated by micro-RNAs, such as miR-149, miR-7, miR-125b, miR-125a-5p, miR192-5p, and miR-215.
Protein
Properties The protein from isoform 1 is 247 amino acids long with a molecular weight of 27.6 kDa. It has a charge of 5.0 and an isoelectric point of 8.9. It has a domain of unknown function (DUF3699), which is conserved in eukaryotes and has no known pairwise interactions with other domains. The structure of the protein has 3 alpha helices and 5 beta strands.
Localization The protein is predicted to localize to the nucleus and thought to be mainly associated with the nucleoli fibrillar center. It can also be exported to the cytoplasm.
Homologs
Paralogs The FAM71E1 gene is fast evolving. It has the following 8 paralogs: FAM71A, FAM71B, FAM71C, FAM71D, FAM71E2, FAM71F1, FAM71F2, and AC020922.1. FAM71D, FAM71E2 and AC0209221.1 are found in Amniotes and their last common ancestor with FAM71E1 was likely in the ancestor of the Sauria taxon, which includes reptiles and birds. The remaining paralogs are found in mammals and are expressed in organisms from the evolutionary descendants of the lobe-finned fish (Sarcopterygii). Their last common ancestor with FAM71E1 was Coelacanth (Latimeria chalumnae). + Overview of FAM71E1 ParalogsParalogAccession number Sequence length (aa) Sequence Identity (%) Sequence Similarity (%) FAM71E1NM_001308429247100100FAM71CNP_699195.124120.128.0FAM71F1NP_115988.134416.324.2FAM71F2NP_001012457.330915.423.8FAM71DNP_775797.242212.016.5AC020922.1Unavailable47211.116.3FAM71ANP_705834.259410.814.5FAM71BNP_570969.260510.213.9FAM71E2NP_001138874.19226.89.0
Orthologs Orthologs of FAM71E1 can be found only in vertebrates, primarily in placental mammals in the Boreoeutheria group and occasionally in a few reptilian species. Reptiles and marsupials are included in the distant homologs, while orthologs in placental animals such as rodents and primates are more closely related to FAM71E1. The gene history contains 27 duplication events and 1 splitting event. + Overview of FAM71E1 Orthologs Genus and species Common Name Accession number Length (aa) Identity (%) Similarity (%) Homo sapiensHumanNP_001295358247100100Pan troglodytesChimpanzeeXP_009434364 2479897Microcebus murinus Gray mouse lemur XP_012609669.1 2337982Mus musculus House mouseNP_082445.1 2126872Equus caballus HorseXP_023505998.1 1927679Bos taurus CattleXP_010813399 2277579Panthera pardus LeopardXP_019281103 2177176Trichechus manatus latirostris Florida manatee XP_004381904 2197376Phascolarctos cinereus KoalaXP_020827525 2316875Python bivittatus Burmese pythonXP_007423163 1675064Anolis carolinensisGreen anoleXP_0168501311313748
Clinical significance
Mutations There are no disease-causing mutations associated with this gene, and it is tolerant towards loss-of-function variants.
Disease associations FAM71E1 has reduced expression in Type 2 diabetes patients and is likely not involved in the disease's pathophysiology. Its expression is also altered in Parkinson's disease and several cancers, such as non-triple negative ductal carcinoma in situ, breast cancer, pancreatic adenocarcinoma, and colorectal carcinoma. It is a gene of interest in predicting susceptibility to pneumonia.
References