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TMED5
Identifiers
Aliases	TMED5, CGI-100, p28, p24g2, transmembrane p24 trafficking protein 5
External IDs	OMIM: 616876; MGI: 1921586; HomoloGene: 4996; GeneCards: TMED5; OMA:TMED5 - orthologs
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 Skeletal muscle tissue of biceps brachii parietal pleura corpus epididymis Epithelium of choroid plexus sperm mucosa of sigmoid colon jejunal mucosa visceral pleura decidua thoracic diaphragm Top expressed in intercostal muscle endothelial cell of lymphatic vessel brown adipose tissue interventricular septum hair follicle seminal vesicula white adipose tissue left lobe of liver cumulus cell gastrula 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.

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 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.

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.

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.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000117500 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000063406 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ National Center for Biotechnology Information. "Transmembrane p24 trafficking protein 5". NCBI Gene.
6. Weizmann Institute of Science. "TMED5 Gene". Gene Cards Human Gene Database.
7. ^ UniProt Consortium. "TMED5 gene". UniProtKB.
8. National Center for Biotechnology Information (NCBI). "GDS5301 Expression Profile". Gene Expression Omnibus Repository.
9. National Center for Biotechnology Information (NCBI). "GDS3573 Expression Profile". Gene Expression Omnibus Repository.
10. Center of Biological Sequential Analysis. "SignalP-5.0 Server". Prediction Servers.
11. National Center for Biotechnology Information. "Transmembrane emp24 domain-containing protein 5 isoform 1 precursor". NCBI Protein.
12. National Center for Biotechnology Information. "Transmembrane emp24 domain-containing protein 5 isoform 2 precursor". NCBI Protein.
13. Swiss Institute of Bioinformatics. "Compute pI/Mw Tool". ExPASy.
14. ^ European Molecular Biology Laboratory - European Bioinformatics Institute (EMBL-EBI). "Statistical Analysis of Protein Sequences (SAPS)".
15. ^ Protter: interactive protein feature visualization and integration with experimental proteomic data. Omasits U, Ahrens CH, Müller S, Wollscheid B. Bioinformatics. 2014 Mar 15;30(6):884-6. doi:10.1093/bioinformatics/btt607
16. The Eukaryotic Liner Motif (ELM) resource for Functional Sites in Proteins. "ELM prediction".
17. ^ Prediction of Protein Sorting Signals and Localization Sites in Amino Acid Sequences. "PSORT II Prediction". PSORT WWW Server.
18. Max Planck Institute (MPI) for Developmental Biology, Tübingen, Germany. "Ali2D". MPI Bioinformatics Toolkit.
19. University of Michigan. "I-TASSER Protein Structure & Function Predictions". Zhang Lab.
20. Kelley, L., Mezulis, S., Yates, C. et al. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10, 845–858 (2015). doi:10.1038/nprot.2015.053
21. Swiss Institute of Bioinformatics. "MyHits Motif Scan". ExPASy.
22. Blom, Nikolaj. "Net Phos 3.1 Server". DTU Bioinformatics.
23. Tissue Atlas. "Tissue expression of TMED5". The Human Protein Atlas.
24. Buechling, T., Chaudhary, V., Spirohn, K., Weiss, M. and Boutros, M. (2011), p24 proteins are required for secretion of Wnt ligands. EMBO reports, 12: 1265-1272. doi:10.1038/embor.2011.212
25. Huttlin, E. L., Bruckner, R. J., Paulo, J. A., Cannon, J. R., Ting, L., Baltier, K., Colby, G., Gebreab, F., Gygi, M. P., Parzen, H., Szpyt, J., Tam, S., Zarraga, G., Pontano-Vaites, L., Swarup, S., White, A. E., Schweppe, D. K., Rad, R., Erickson, B. K., Obar, R. A., … Harper, J. W. (2017). Architecture of the human interactome defines protein communities and disease networks. Nature, 545(7655), 505–509. doi:10.1038/nature22366
26. Hein, M. Y., Hubner, N. C., Poser, I., Cox, J., Nagaraj, N., Toyoda, Y., Gak, I. A., Weisswange, I., Mansfeld, J., Buchholz, F., Hyman, A. A., & Mann, M. (2015). A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell, 163(3), 712–723. doi:10.1016/j.cell.2015.09.053
27. Buechling, T., Chaudhary, V., Spirohn, K., Weiss, M., & Boutros, M. (2011). p24 proteins are required for secretion of Wnt ligands. EMBO reports, 12(12), 1265–1272. doi:10.1038/embor.2011.212
28. Luck, K., Kim, D. K., Lambourne, L., Spirohn, K., Begg, B. E., Bian, W., Brignall, R., Cafarelli, T., Campos-Laborie, F. J., Charloteaux, B., Choi, D., Coté, A. G., Daley, M., Deimling, S., Desbuleux, A., Dricot, A., Gebbia, M., Hardy, M. F., Kishore, N., Knapp, J. J., … Calderwood, M. A. (2020). A reference map of the human binary protein interactome. Nature, 580(7803), 402–408. doi:10.1038/s41586-020-2188-x
29. Weimann, M., Grossmann, A., Woodsmith, J., Özkan, Z., Birth, P., Meierhofer, D., Benlasfer, N., Valovka, T., Timmermann, B., Wanker, E. E., Sauer, S., & Stelzl, U. (2013). A Y2H-seq approach defines the human protein methyltransferase interactome. Nature methods, 10(4), 339–342. doi:10.1038/nmeth.2397
30. Kennedy, S. A., Jarboui, M. A., Srihari, S., Raso, C., Bryan, K., Dernayka, L., Charitou, T., Bernal-Llinares, M., Herrera-Montavez, C., Krstic, A., Matallanas, D., Kotlyar, M., Jurisica, I., Curak, J., Wong, V., Stagljar, I., LeBihan, T., Imrie, L., Pillai, P., Lynn, M. A., … Kolch, W. (2020). Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D. Nature communications, 11(1), 499. doi:10.1038/s41467-019-14224-9
31. Bryan, K., Jarboui, M. A., Raso, C., Bernal-Llinares, M., McCann, B., Rauch, J., Boldt, K., & Lynn, D. J. (2016). HiQuant: Rapid Postquantification Analysis of Large-Scale MS-Generated Proteomics Data. Journal of proteome research, 15(6), 2072–2079. doi:10.1021/acs.jproteome.5b01008
32. Huttlin, E. L., Bruckner, R. J., Paulo, J. A., Cannon, J. R., Ting, L., Baltier, K., Colby, G., Gebreab, F., Gygi, M. P., Parzen, H., Szpyt, J., Tam, S., Zarraga, G., Pontano-Vaites, L., Swarup, S., White, A. E., Schweppe, D. K., Rad, R., Erickson, B. K., Obar, R. A., … Harper, J. W. (2017). Architecture of the human interactome defines protein communities and disease networks. Nature, 545(7655), 505–509. doi:10.1038/nature22366
33. Ivanochko, D., Halabelian, L., Henderson, E., Savitsky, P., Jain, H., Marcon, E., Duan, S., Hutchinson, A., Seitova, A., Barsyte-Lovejoy, D., Filippakopoulos, P., Greenblatt, J., Lima-Fernandes, E., & Arrowsmith, C. H. (2019). Direct interaction between the PRDM3 and PRDM16 tumor suppressors and the NuRD chromatin remodeling complex. Nucleic acids research, 47(3), 1225–1238. doi:10.1093/nar/gky1192
34. Wallqvist, A., Memišević, V., Zavaljevski, N., Pieper, R., Rajagopala, S. V., Kwon, K., Yu, C., Hoover, T. A., & Reifman, J. (2015). Using host-pathogen protein interactions to identify and characterize Francisella tularensis virulence factors. BMC genomics, 16, 1106. doi:10.1186/s12864-015-2351-1
35. ^ Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White, K. M., O'Meara, M. J., Rezelj, V. V., Guo, J. Z., Swaney, D. L., Tummino, T. A., Hüttenhain, R., Kaake, R. M., Richards, A. L., Tutuncuoglu, B., Foussard, H., Batra, J., Haas, K., Modak, M., Kim, M., … Krogan, N. J. (2020). A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583(7816), 459–468. doi:10.1038/s41586-020-2286-9
36. Pastor-Cantizano, N., Montesinos, J.C., Bernat-Silvestre, C. et al. p24 family proteins: key players in the regulation of trafficking along the secretory pathway. Protoplasma 253, 967–985 (2016).doi:10.1007/s00709-015-0858-6
37. Koegler, E., Bonnon, C., Waldmeier, L., Mitrovic, S., Halbeisen, R. and Hauri, H.‐P. (2010), p28, A Novel ERGIC/cis Golgi Protein, Required for Golgi Ribbon Formation. Traffic, 11: 70-89. doi:10.1111/j.1600-0854.2009.01009.x
38. ^ Theiler, R., Fujita, M., Nagae, M., Yamaguchi, Y., Maeda, Y., & Kinoshita, T. (2014). The α-helical region in p24γ2 subunit of p24 protein cargo receptor is pivotal for the recognition and transport of glycosylphosphatidylinositol-anchored proteins. The Journal of biological chemistry, 289(24), 16835–16843. doi:10.1074/jbc.M114.568311
39. Zhen Yang, Qi Sun, Junfei Guo, Shixing Wang, Ge Song, Weiying Liu, Min Liu & Hua Tang (2019) GRSF1-mediated MIR-G-1 promotes malignant behavior and nuclear autophagy by directly upregulating TMED5 and LMNB1 in cervical cancer cells, Autophagy, 15:4, 668-685, doi:10.1080/15548627.2018.1539590
40. Pai, S.G., Carneiro, B.A., Mota, J.M. et al. Wnt/beta-catenin pathway: modulating anticancer immune response. J Hematol Oncol 10, 101 (2017). doi:10.1186/s13045-017-0471-6
41. Scaravilli, M., Asero, P., Tammela, T.L. et al. Mapping of the chromosomal amplification 1p21-22 in bladder cancer. BMC Res Notes 7, 547 (2014). doi:10.1186/1756-0500-7-547
42. ^ National Center for Biotechnology Information. "Standard Protein BLAST".
43. Temple University Center of Biodiversity. "Pairwise Divergence Time". Timetree: The Timescale of Life.

• Genes on human chromosome 1
• Proteins