# TMED5

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> Source: https://en.wikipedia.org/wiki/TMED5
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**Transmembrane emp24 domain-containing protein 5** is a [protein](/source/Protein) that in humans is encoded by the *TMED5* [gene](/source/Gene).[1]

## Gene

### General properties

*TMED5* (transmembrane emp24 domain-containing protein 5) is also known as *p28*, *p24g2*, and *CGI-100*.[1] The human gene spans 30,775 base pairs over 4 [exons](/source/Exon) and 3 [introns](/source/Intron) for transcript variant 1, 5 exons and 4 introns for transcript variant 2, and it is located on the minus strand of [chromosome 1](/source/Chromosome_1), at 1p22.1.[2]

### Expression

TMED5 has ubiquitous expression with transcripts detected in 246 tissues.[3] [Androgen deprivation](/source/Androgen_deprivation) led to lower expression in mice [splenocytes](/source/Splenocyte) compared to the control.[4] Human [dendritic cells](/source/Dendritic_cell) infected with *[Chlamydia pneumoniae](/source/Chlamydia_pneumoniae)* showed an absence of *TMED5* expression compared to uninfected dendritic cells which had moderate expression.[5]

## mRNA transcript

TMED5 has two coding transcript variants and one non-coding transcript variant produced by [alternative splicing](/source/Alternative_splicing).[3] [Isoform](/source/Protein_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.[1]

## Protein

### General properties

TMED5 contains a signal peptide.[6] After cleavage of the signal peptide, TMED5 isoform 1 is composed of 202 amino acids and has a molecular weight of ~23 kDa.[7] The mature form of isoform 2 is composed of 166 amino acids and has a molecular weight of ~19 kDa.[8] Both isoforms have an [isolectric point](/source/Isoelectric_point) of approximately 4.6.[9]

### Composition

Compared to the reference set of human proteins, TMED5 has fewer alanine and proline residues but more aspartic acid and phenylalanine residues.[10] TMED5 isoform 1 has one hydrophobic segment that corresponds with its transmembrane region.[10]

### Domains and motifs

TMED5 isoform 1 is a single-pass transmembrane protein and is composed of a lumenal domain, one transmembrane (helical) domain, and a cytoplasmic domain.[3]

TMED5 is part of the emp24/gp25L/p24 family/GOLD family protein.[3]

TMED5 contains a di-lysine motif and predicted [NLS](/source/Nuclear_localization_sequence) in its cytoplasmic tail.[11][12]

### 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.[13][14]

### Post-translational modifications

TMED5 has two predicted phosphorylation sites in the cytosolic region, Ser227 and Thr229.[15][16]

### 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.[12][17]

### 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](/source/Wnt_signaling_pathway) which are known to interact with the [p24 protein family](/source/P24_protein_family).[18]

Protein Name Protein Abrev DB Source Species Evidence Interaction PubMed ID Transmembrane emp24 domain-containing protein 2 TMED2 IntAct Homo sapiens Anti tag coimmunoprecipitation[19] Association 28514442 Transmembrane emp24 domain-containing protein 10 TMED10 IntAct Mus musculus Anti tag coimmunoprecipitation[20] Association 26496610 Protein ERGIC-53 LMAN1 MINT Homo sapiens Fluorescence microscopy[21] Colocalization 22094269 C-X-C motif chemokine 9 CXCL9 IntAct Homo sapiens Validated two hybrid[22] Physical Association 32296183 Protein arginine N-methyltransferase 6 PRMT6 MINT Homo sapiens Two hybrid[23] Physical Association 23455924 Phosphatidylethanolamine-binding protein 1 PEBP1 IntAct Homo sapiens Anti tag coimmunoprecipitation[24] Association 31980649 Kinase suppressor of Ras 1 KSR1 IntAct Homo sapiens Anti tag coimmunoprecipitation[25] Association 27086506 Endothelial lipase LIPG IntAct Mus musculus Anti tag coimmunoprecipitation[19] Association 28514442 Histone-lysine N-methyltransferase PRDM16 Prdm16 MINT Mus musculus Anti tag coimmunoprecipitation[26] Association 30462309 Intracellular growth locus, subunit C iglC2 MINT Francisella tularensis Two hybrid pooling approach[27] Physical Association 26714771 ORF9C ORF9C BioGRID SARS-Cov-2 Affinity Capture-MS[28] Association 32353859 Uncharacterized protein 14 ORF14 IntAct SARS-Cov-2 Pull down[28] Association 32353859

## Function and clinical significance

TMED5 is a part of the [p24 protein family](/source/P24_protein_family) whose general functions are [protein trafficking](/source/Protein_trafficking) for the secretory pathway.[29] TMED5 is thought to be necessary in the formation of the [Golgi](/source/Golgi_apparatus) into a ribbon.[30]

[Glycosylphosphatidylinositol-anchored proteins](/source/Glycosylphosphatidylinositol) (GPI-AP) depend on p24 cargo receptors for transport from the [ER](/source/Endoplasmic_reticulum) to the [Golgi](/source/Golgi_apparatus).[31] Knockdown of *[p24γ2](https://www.ncbi.nlm.nih.gov/gene/73130)* (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](/source/COPII).[31]

TMED5 is reported to be necessary for the secretion of [Wnt ligands](/source/Wnt_signaling_pathway). TMED5 has been found to interact with WNT7B, activating the canonical WNT-CTNNB1/β-catenin signaling pathway.[32] 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.[33]

Research has identified [bladder cancer](/source/Bladder_cancer) to have a common chromosomal amplification at 1p21-22 and showed significant upregulation of *TMED5.*[34]

## Evolution

### Homology

#### Paralogs

TMED5 [paralogs](/source/Sequence_homology) include [TMED1](/source/TMED1), [TMED2](/source/TMED2), [TMED3](/source/TMED3), [TMED4](/source/TMED4), TMED6, TMED7, TMED8, TMED9, and [TMED10](/source/TMED10).[35] All paralogs share the conserved transmembrane domain and contain the characteristic GOLD domain as included in the emp24/gp25L/p24 family/GOLD family proteins.[3]

#### 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.[1] The following table provides a sample of the ortholog space of TMED5.

Genus and species NCBI Accession Number Date of Divergence (MYA)[36] Sequence length Sequence identity[35] Homo sapiens (Human) NP_057124.3 0 229 100 Pan troglodytes (Chimpanzee) XP_001154650.1 6 229 99.6 Mus musculus (Mouse) NP_083152.1 89 229 90 Monodelphis domestica (Gray short-tailed opossum) XP_016284519.1 160 228 84 Gallus gallus (Chicken) NP_001007957.1 318 226 83 Gekko japonicus (Gekko) XP_015268825.1 318 245 73.1 Xenopus tropicalis (Western clawed frog) XP_031755940.1 351 223 67.7 Danio rerio (Zebrafish) NP_956697.1 433 225 65.1 Rhincodon typus (Whale shark) XP_020385910.1 465 224 66.8 Octopus vulgaris (Octopus) XP_029646555.1 736 239 42.5 Cryptotermes secundus (Termite) XP_023712535.1 736 235 37.5 Caenorhabditis elegans (Roundworm) NP_502288.1 736 234 37.3 Drosophila mojavensis (Fruit fly) XP_002009472.2 736 239 36.3 Eufriesea mexicana (Orchid bee) XP_017762298.1 736 227 26.8 Trichoplax adhaerens XP_002108774.1 747 193 32.1 Rhizopus microsporus XP_023464765.1 1017 199 30.2 Coprinopsis cinerea (Gray shag mushroom) XP_001836898.2 1017 199 28.5 Kluyveromyces lactis XP_453709.1 1017 208 28.1 Rhodamnia argentea (Malletwood) XP_030545696.1 1275 217 28.9 Quercus suber (Cork oak) XP_023882547.1 1275 277 28.7 Vitis riparia (Riverbank grape) XP_034686416.1 1275 215 27.3

## References

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1. Weizmann Institute of Science. ["TMED5 Gene"](https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMED5&keywords=tmed5). *Gene Cards Human Gene Database*.

1. UniProt Consortium. ["*TMED5* gene"](https://www.uniprot.org/uniprot/Q9Y3A6). UniProtKB.

1. National Center for Biotechnology Information (NCBI). ["GDS5301 Expression Profile"](https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS5301:1424573_PM_at). *Gene Expression Omnibus Repository*.

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Adapted from the Wikipedia article [TMED5](https://en.wikipedia.org/wiki/TMED5) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/TMED5?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.