TMED5

TMED5
Identifiers
Aliases	TMED5, CGI-100, p28, p24g2, transmembrane p24 trafficking protein 5
External IDs	OMIM: 616876 MGI: 1921586 HomoloGene: 4996 GeneCards: TMED5
Gene location (Human) Chr. Chromosome 1 (human) Band 1p22.1 Start 93,149,742 bp End 93,180,516 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 F Start 108,254,232 bp End 108,280,486 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parietal pleura corpus epididymis sperm jejunal mucosa visceral pleura thoracic diaphragm retinal pigment epithelium superficial temporal artery kidney tubule lower lobe of lung Top expressed in intercostal muscle brown adipose tissue interventricular septum hair follicle seminal vesicula white adipose tissue left lobe of liver cumulus cell mammary gland subcutaneous adipose tissue More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding Cellular component integral component of membrane Golgi apparatus endoplasmic reticulum-Golgi intermediate compartment membrane endoplasmic reticulum-Golgi intermediate compartment endoplasmic reticulum exit site endoplasmic reticulum membrane cis-Golgi network membrane endoplasmic reticulum COPII-coated ER to Golgi transport vesicle Biological process protein transport Golgi ribbon formation intracellular protein transport endoplasmic reticulum to Golgi vesicle-mediated transport Golgi organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 50999 73130 Ensembl ENSG00000117500 ENSMUSG00000063406 UniProt Q9Y3A6 Q9CXE7 RefSeq (mRNA) NM_001167830 NM_016040 NM_028876 NM_001347383 NM_001361466 NM_001361467 RefSeq (protein) NP_001161302 NP_057124 NP_001334312 NP_083152 NP_001348395 NP_001348396 Location (UCSC) Chr 1: 93.15 – 93.18 Mb Chr 5: 108.25 – 108.28 Mb PubMed search
Wikidata
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Transmembrane emp24 domain-containing protein 5 is a protein that in humans is encoded by the TMED5 gene.

Gene

General properties

TMED5 (transmembrane emp24 domain-containing protein 5) is also known as p28, p24g2, and CGI-100. The human gene spans 30,775 base pairs over 4 exons and 3 introns for transcript variant 1, 5 exons and 4 introns for transcript variant 2, and it is located on the minus strand of chromosome 1, at 1p22.1.

Expression

TMED5 has ubiquitous expression with transcripts detected in 246 tissues.Androgen deprivation led to lower expression in mice splenocytes compared to the control. Human dendritic cells infected with Chlamydia pneumoniae showed an absence of TMED5 expression compared to uninfected dendritic cells which had moderate expression.

View of human TMED5 gene isoform 1 and 2 with promoter and exon locations.

Conceptual translation of TMED5. Labeled are the start and stop codon, exon splice sites, domains and motifs, polyadenylation signals, predicted RNA and miRNA binding proteins, and predicted post-translational modifications. Bolded amino acids and nucleotides represent highly conserved amongst distant orthologs.

mRNA transcript

TMED5 has two coding transcript variants and one non-coding transcript variant produced by alternative splicing.Isoform 1 has 4 exons and encodes a protein 229 amino acids. Isoform 2 has 5 exons and encodes a protein with a shorter C-terminus 193 amino acids due to an additional exon causing a frameshift.

Protein

General properties

TMED5 contains a signal peptide. After cleavage of the signal peptide, TMED5 isoform 1 is composed of 202 amino acids and has a molecular weight of ~23 kDa. The mature form of isoform 2 is composed of 166 amino acids and has a molecular weight of ~19 kDa. Both isoforms have an isolectric point of approximately 4.6.

Composition

Compared to the reference set of human proteins, TMED5 has fewer alanine and proline residues but more aspartic acid and phenylalanine residues. TMED5 isoform 1 has one hydrophobic segment that corresponds with its transmembrane region.

Domains and motifs

TMED5 protein isoform 1 visual made via Protter.

TMED5 protein isoform 2 visual made via Protter.

TMED5 isoform 1 is a single-pass transmembrane protein and is composed of a lumenal domain, one transmembrane (helical) domain, and a cytoplasmic domain.

TMED5 is part of the emp24/gp25L/p24 family/GOLD family protein.

TMED5 contains a di-lysine motif and predicted NLS in its cytoplasmic tail.

Structure

The structure of TMED5 isoform 1 consists of beta strands making up the lumenal region, disparate coil-coiled regions, alpha helices making up the transmembrane domain, and alpha helices making up some of the cytoplasmic domain.

Predicted tertiary structure of TMED5 generated by Phyre2. Signal peptide is highlighted in yellow. GOLD domain in the lumen is shown to be made up of beta sheets. Transmembrane domain is grayed out followed by the short cytosolic sequence.

Post-translational modifications

TMED5 has two predicted phosphorylation sites in the cytosolic region, Ser227 and Thr229.

Localization

TMED5's predicted location is in the plasma membrane, with an extracellular N-terminus and intracellular C-terminus. TMED5's localization is predicted to be cytoplasmic, but has been found in some tissues to be located in the nucleus.

Interacting proteins

The following table provides a list of proteins most likely to interact with TMED5. Not shown in the table are Wnt family proteins which are known to interact with the p24 protein family.

Function and clinical significance

TMED5 is a part of the p24 protein family whose general functions are protein trafficking for the secretory pathway. TMED5 is thought to be necessary in the formation of the Golgi into a ribbon.

Glycosylphosphatidylinositol-anchored proteins (GPI-AP) depend on p24 cargo receptors for transport from the ER to the Golgi. Knockdown of p24γ2 (a mouse ortholog of TMED5) in mice resulted in impaired transport of GPI-AP. The study concluded that the α-helical region of p24γ2 binds GPI which is necessary to incorporate it into COPII transport vesicles.

TMED5 is reported to be necessary for the secretion of Wnt ligands. TMED5 has been found to interact with WNT7B, activating the canonical WNT-CTNNB1/β-catenin signaling pathway. This pathway is linked to numerous cancers because upregulation of the Wnt/β-catenin signaling pathway leads to cytosolic accumulation of β-catenin, promoting cellular proliferation.

Research has identified bladder cancer to have a common chromosomal amplification at 1p21-22 and showed significant upregulation of TMED5.

Evolution

Homology

Paralogs

TMED5 paralogs include TMED1, TMED2, TMED3, TMED4, TMED6, TMED7, TMED8, TMED9, and TMED10. All paralogs share the conserved transmembrane domain and contain the characteristic GOLD domain as included in the emp24/gp25L/p24 family/GOLD family proteins.

TMED5 evolutionary graph shows evolutionary rate. Cytochrome C is shown to represent a slow-evolutionary rate and Fibrinogen alpha represents a fast-evolutionary rate. TMED5 is shown to have a fast-evolutionary rate similar to Fibrinogen alpha. Estimated date of divergence for paralogs were plotted: TMED1 diverged ~64 million years ago (MYA), TMED3 diverged ~118 MYA, and TMED7 diverged ~122 MYA.

Orthologs

TMED5 is found to be conserved in vertebrates, invertebrates, plants and fungi, and there are 243 known organisms that have orthologs with the gene. The following table provides a sample of the ortholog space of TMED5.