Receptor expression-enhancing protein 5 is a protein that in humans is encoded by the REEP5 gene.^[5][6][7] Receptor Expression Enhancing Protein is a protein encoded for in Humans by the REEP5 gene.

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REEP5
Identifiers
Aliases	REEP5, C5orf18, D5S346, DP1, TB2, YOP1, Yip2e, receptor accessory protein 5, POB16
External IDs	OMIM: 125265 MGI: 1270152 HomoloGene: 68479 GeneCards: REEP5
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q22.2 Start 112,876,385 bp[1] End 112,922,289 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18|18 B1 Start 34,477,938 bp[2] End 34,507,123 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus endothelial cell Brodmann area 23 pons spinal ganglia orbitofrontal cortex superior vestibular nucleus parietal lobe superior frontal gyrus Brodmann area 46 Top expressed in lacrimal gland salivary gland parotid gland submandibular gland ascending aorta subcutaneous adipose tissue white adipose tissue pyloric antrum aortic valve adrenal gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding molecular function Cellular component integral component of membrane membrane endoplasmic reticulum endoplasmic reticulum tubular network Biological process biological process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7905 13476 Ensembl ENSG00000129625 ENSMUSG00000005873 UniProt Q00765 Q60870 RefSeq (mRNA) NM_005669 NM_007874 RefSeq (protein) NP_005660 n/a Location (UCSC) Chr 5: 112.88 – 112.92 Mb Chr 18: 34.48 – 34.51 Mb PubMed search [3] [4]
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REEP5 is located on chromosome 5 between base pairs 112876385 to 112922289 on the minus strand.^[8] The gene includes five exons.^[8] The genes DCP2 and SRP19 are located upstream and downstream of REEP5 in humans.^[9]

The protein is a member of the REEP family, which generally facilitate intracellular trafficking through alterations to the endoplasmic reticulum, and which have the ability to enhance activity of G-protein coupled receptors.^[10] The human protein is 189 amino acids in length, containing two transmembrane regions and one named region- TB2_DP1_HVA22,^[11] The pre-modification protein mass is 21.5 kdal.^[12] Compared to the SwissProt collection of human proteins, REEP5 is composed of normal percentages of all amino acids.^[12] Aside from a long stretch of electrically neutral amino acids, no significant patterns appear.^[12] A second isoform exists in humans, and is 131 amino acids in length as the result of a change after the 117th amino acid.^[13] Most of the fifth exon is not included.

REEP5 interacts with a number of proteins, including Regulator of G Protein signalling 2, which was detected using Yeast 2 Hybridization. RGS2 plays a role in G protein signalling 2 pathways and the contraction of smooth muscle tissues. Derlin 2 (Derl2) interacts with REEP5 as detected by anti-tag coimmunoprecipation and degrades misfolded glycoproteins in the endoplasmic reticulum.^[26] Cholinergic Receptor Muscarinic 5 was detected as an interactant by ubiquitin reconstruction.^[27] CHRM5 binds acetylcholine, and can impact the function of the central and peripheral nervous systems.^[28]

Regulator of G Protein Signaling 2 was also detected with Yeast 2 Hybridization and is a regulator of G-protein receptor which may be involved with the contraction of smooth vascular muscle.^[27][29]

Four proteins were experimentally detected across several papers.^[30] Three of them, Atlastin GTPase 1, Atlastin GTPase 2, and Zinc Finger FYVE-Type Containing 27 are related to the structuring of the endoplasmic reticulum (tubules in particular), the development of axons, or neuron growth.^[17][31] The fourth is REEP6, which is responsible for transporting receptors to the cell surface, as well as regulating endoplasmic reticulum structure.^[32]

Research has linked REEP5 to several diseases and disorders.

In colon cancer, expression of REEP5 enhances activity of CXCR1, a protein receptor which contributes to the growth and spread of cancer cells. Researchers have found that under expression of REEP5 reduces the efficiency of CXRC1, and reduces the ability of lung cancer cells to metastasize.^[10] This provides both a potential target for cancer therapy and further evidence of REEP5 having function as a protein which increases activity of other receptor proteins. Another type of cancer related to REEP5 is colon cancer, in which the protein normally interacts with and neutralizes HCCR1, a protein which would otherwise interfere with P53 and contribute to the progression of cancer.^[34]

REEP5 has also been linked to heart disorders, and research into the connection has revealed that it helps organize the junctional Sarcoplasmic Reticulum in myocytes. REEP5 aligns the junctional SR to T-tubules, which promotes effective release of Calcium ions. When protein function is disrupted the junction becomes misaligned and Calcium ion release becomes less effective. Given the importance of Calcium ions to the muscle contractions which power the heart, targeting REEP5 has the potential to be a therapeutic option in some disorders.^[35]

Additionally, there is some statistical evidence linking certain SNPs found within REEP5 mRNA to Major Depressive Disorder.^[36] However, a biological mechanism has not been confirmed, and the study only looked at a limited population.^[36]