FAM71E1

FAM71E1, also known as Family With Sequence Similarity 71 Member E1, is a protein that in humans is encoded by the FAM71E1 gene.^[5][6] It is thought to be ubiquitously expressed at low levels throughout the body, and it is conserved in vertebrates, particularly mammals and some reptiles. The protein is localized to the nucleus and can be exported to the cytoplasm.

GARIN5A
Identifiers
Aliases	GARIN5A, family with sequence similarity 71 member E1, GARIL5, golgi associated RAB2 interactor 5A, FAM71E1
External IDs	MGI: 1922788; HomoloGene: 19259; GeneCards: GARIN5A; OMA:GARIN5A - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.33 Start 50,466,785 bp[1] End 50,476,848 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B3 Start 44,146,005 bp[2] End 44,150,910 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left testis right testis sperm oocyte testicle gonad secondary oocyte prefrontal cortex endothelial cell hypothalamus Top expressed in seminiferous tubule spermatid spermatocyte neural layer of retina lens embryo neural tube ventricular zone epithelium of lens genital tubercle More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 112703 75538 Ensembl ENSG00000142530 ENSMUSG00000051113 UniProt Q6IPT2 A1L3C1 RefSeq (mRNA) NM_001308429 NM_138411 NM_028169 NM_001357650 NM_001357651 NM_001368290 NM_001368291 NM_001368292 RefSeq (protein) NP_001295358 NP_612420 NP_082445 NP_001344579 NP_001344580 NP_001355219 NP_001355220 NP_001355221 Location (UCSC) Chr 19: 50.47 – 50.48 Mb Chr 7: 44.15 – 44.15 Mb PubMed search [3] [4]
Wikidata
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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.^[5][6]

Gene Neighborhood

In humans, the gene is flanked by the following genes:^[5][6]

• SPIB: putative oncogene that is active in hematopoietic cells ^[7]
• MYBPC2: encodes a structural protein and is actively expressed in striated muscle cells ^[8]
• EMC10: encodes a protein of unknown function ^[9]
• JOSD2: encodes a protein involved in de-ubiquitination^[10]

Location of FAM71E1 on minus f Chromstrand oosome 19 at q13.33.

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.^[11]

Expression

The gene seems to be ubiquitously expressed at low levels throughout the body ^[12][13][14] but has prominent expression in the adult human testis,^[15] followed by lower expression levels in the sperm, oocyte, and brain.^{[16][17][18][19][20]} Age does not have an effect on its expression in the skeletal muscle of males or females.^[21] Its expression is elevated prior to the differentiation of embryonic stem cells into pancreatic islet-like cells.^[22]

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.^[23] 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.^[24]

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.^[25]

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.^[24] It has a domain of unknown function (DUF3699), which is conserved in eukaryotes and has no known pairwise interactions with other domains.^[26] 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.^[27] It can also be exported to the cytoplasm.^[14]

Homologs

Evolutionary tree of FAM71E1 paralogs and their associated peptide length^[28]

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).^[29]

Overview of FAM71E1 Paralogs^[30]

Paralog	Accession number	Sequence length (aa)	Sequence Identity (%)	Sequence Similarity (%)
FAM71E1	NM_001308429	247	100	100
FAM71C	NP_699195.1	241	20.1	28.0
FAM71F1	NP_115988.1	344	16.3	24.2
FAM71F2	NP_001012457.3	309	15.4	23.8
FAM71D	NP_775797.2	422	12.0	16.5
AC020922.1	Unavailable	472	11.1	16.3
FAM71A	NP_705834.2	594	10.8	14.5
FAM71B	NP_570969.2	605	10.2	13.9
FAM71E2	NP_001138874.1	922	6.8	9.0

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.^[29]

Overview of FAM71E1 Orthologs^[30]

Genus and species	Common Name	Accession number	Length (aa)	Identity (%)	Similarity (%)
Homo sapiens	Human	NP_001295358	247	100	100
Pan troglodytes	Chimpanzee	XP_009434364	247	98	97
Microcebus murinus	Gray mouse lemur	XP_012609669.1	233	79	82
Mus musculus	House mouse	NP_082445.1	212	68	72
Equus caballus	Horse	XP_023505998.1	192	76	79
Bos taurus	Cattle	XP_010813399	227	75	79
Panthera pardus	Leopard	XP_019281103	217	71	76
Trichechus manatus latirostris	Florida manatee	XP_004381904	219	73	76
Phascolarctos cinereus	Koala	XP_020827525	231	68	75
Python bivittatus	Burmese python	XP_007423163	167	50	64
Anolis carolinensis	Green anole	XP_016850131	131	37	48

Clinical Significance

Mutations

There are no disease-causing mutations associated with this gene,^[31] and it is tolerant towards loss-of-function variants.^[32]

Disease Associations

FAM71E1 has reduced expression in Type 2 diabetes patients and is likely not involved in the disease's pathophysiology.^[33] Its expression is also altered in Parkinson's disease^[34] and several cancers, such as non-triple negative ductal carcinoma in situ,^[35] breast cancer,^[36] pancreatic adenocarcinoma, and colorectal carcinoma.^[34] It is a gene of interest in predicting susceptibility to pneumonia.^[37]