| TMED5 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | TMED5 , CGI-100, p28, p24g2, transmembrane p24 trafficking protein 5 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 616876 MGI: 1921586 HomoloGene: 4996 GeneCards: TMED5 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Transmembrane emp24 domain-containing protein 5 is a protein that in humans is encoded by the TMED5 gene. [5]
TMED5 (transmembrane emp24 domain-containing protein 5) is also known as p28, p24g2, and CGI-100. [5] 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. [6]
TMED5 has ubiquitous expression with transcripts detected in 246 tissues. [7] Androgen deprivation led to lower expression in mice splenocytes compared to the control. [8] Human dendritic cells infected with Chlamydia pneumoniae showed an absence of TMED5 expression compared to uninfected dendritic cells which had moderate expression. [9]
TMED5 has two coding transcript variants and one non-coding transcript variant produced by alternative splicing. [7] 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. [5]
TMED5 contains a signal peptide. [10] After cleavage of the signal peptide, TMED5 isoform 1 is composed of 202 amino acids and has a molecular weight of ~23 kDa. [11] The mature form of isoform 2 is composed of 166 amino acids and has a molecular weight of ~19 kDa. [12] Both isoforms have an isolectric point of approximately 4.6. [13]
Compared to the reference set of human proteins, TMED5 has fewer alanine and proline residues but more aspartic acid and phenylalanine residues. [14] TMED5 isoform 1 has one hydrophobic segment that corresponds with its transmembrane region. [14]
TMED5 isoform 1 is a single-pass transmembrane protein and is composed of a lumenal domain, one transmembrane (helical) domain, and a cytoplasmic domain. [7]
TMED5 is part of the emp24/gp25L/p24 family/GOLD family protein. [7]
TMED5 contains a di-lysine motif and predicted NLS in its cytoplasmic tail. [16] [17]
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. [18] [19]
TMED5 has two predicted phosphorylation sites in the cytosolic region, Ser227 and Thr229. [21] [22]
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. [17] [23]
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. [24]
| Protein Name | Protein Abrev | DB Source | Species | Evidence | Interaction | PubMed ID |
|---|---|---|---|---|---|---|
| Transmembrane emp24 domain-containing protein 2 | TMED2 | IntAct | Homo sapiens | Anti tag coimmunoprecipitation [25] | Association | 28514442 |
| Transmembrane emp24 domain-containing protein 10 | TMED10 | IntAct | Mus musculus | Anti tag coimmunoprecipitation [26] | Association | 26496610 |
| Protein ERGIC-53 | LMAN1 | MINT | Homo sapiens | Fluorescence microscopy [27] | Colocalization | 22094269 |
| C-X-C motif chemokine 9 | CXCL9 | IntAct | Homo sapiens | Validated two hybrid [28] | Physical Association | 32296183 |
| Protein arginine N-methyltransferase 6 | PRMT6 | MINT | Homo sapiens | Two hybrid [29] | Physical Association | 23455924 |
| Phosphatidylethanolamine-binding protein 1 | PEBP1 | IntAct | Homo sapiens | Anti tag coimmunoprecipitation [30] | Association | 31980649 |
| Kinase suppressor of Ras 1 | KSR1 | IntAct | Homo sapiens | Anti tag coimmunoprecipitation [31] | Association | 27086506 |
| Endothelial lipase | LIPG | IntAct | Mus musculus | Anti tag coimmunoprecipitation [32] | Association | 28514442 |
| Histone-lysine N-methyltransferase PRDM16 | Prdm16 | MINT | Mus musculus | Anti tag coimmunoprecipitation [33] | Association | 30462309 |
| Intracellular growth locus, subunit C | iglC2 | MINT | Francisella tularensis | Two hybrid pooling approach [34] | Physical Association | 26714771 |
| ORF9C | ORF9C | BioGRID | SARS-Cov-2 | Affinity Capture-MS [35] | Association | 32353859 |
| Uncharacterized protein 14 | ORF14 | IntAct | SARS-Cov-2 | Pull down [35] | Association | 32353859 |
TMED5 is a part of the p24 protein family whose general functions are protein trafficking for the secretory pathway. [36] TMED5 is thought to be necessary in the formation of the Golgi into a ribbon. [37]
Glycosylphosphatidylinositol-anchored proteins (GPI-AP) depend on p24 cargo receptors for transport from the ER to the Golgi. [38] 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. [38]
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. [39] 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. [40]
Research has identified bladder cancer to have a common chromosomal amplification at 1p21-22 and showed significant upregulation of TMED5. [41]
TMED5 paralogs include TMED1, TMED2, TMED3, TMED4, TMED6, TMED7, TMED8, TMED9, and TMED10. [42] All paralogs share the conserved transmembrane domain and contain the characteristic GOLD domain as included in the emp24/gp25L/p24 family/GOLD family proteins. [7]
TMED5 is found to be conserved in vertebrates, invertebrates, plants and fungi, and there are 243 known organisms that have orthologs with the gene. [5] The following table provides a sample of the ortholog space of TMED5.
| Genus and Species | NCBI Accession Number | Date of Divergence (MYA) [43] | Sequence Length | Sequence Identity [42] |
|---|---|---|---|---|
| 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 |
Transmembrane protein 8B is a protein that in humans is encoded by the TMEM8B gene. It encodes for a transmembrane protein that is 338 amino acids long, and is located on human chromosome 9. Aliases associated with this gene include C9orf127, NAG-5, and NGX61.
The TCF/LEF family is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain. They are involved in the Wnt signaling pathway, particularly during embryonic and stem-cell development, but also had been found to play a role in cancer and diabetes. TCF/LEF factors recruit the coactivator beta-catenin to enhancer elements of genes they target. They can also recruit members of the Groucho family of corepressors.
UPF0172 protein FAM158A, also known as c14orf122 or CGI112, is a protein that in humans is encoded by the FAM158A gene located on chromosome 14q11.2.
Transmembrane protein 131-like, alternatively named uncharacterized protein KIAA0922, is an integral transmembrane protein encoded by the human gene KIAA0922 that is significantly conserved in eukaryotes, at least through protists. Although the function of this gene is not yet fully elucidated, initial microarray evidence suggests that it may be involved in immune responses. Furthermore, its paralog, prolyl endopeptidase (PREP) whose function is known, provides clues as to the function of TMEM131L.
Solute carrier family 46 member 3 (SLC46A3) is a protein that in humans is encoded by the SLC46A3 gene. Also referred to as FKSG16, the protein belongs to the major facilitator superfamily (MFS) and SLC46A family. Most commonly found in the plasma membrane and endoplasmic reticulum (ER), SLC46A3 is a multi-pass membrane protein with 11 α-helical transmembrane domains. It is mainly involved in the transport of small molecules across the membrane through the substrate translocation pores featured in the MFS domain. The protein is associated with breast and prostate cancer, hepatocellular carcinoma (HCC), papilloma, glioma, obesity, and SARS-CoV. Based on the differential expression of SLC46A3 in antibody-drug conjugate (ADC)-resistant cells and certain cancer cells, current research is focused on the potential of SLC46A3 as a prognostic biomarker and therapeutic target for cancer. While protein abundance is relatively low in humans, high expression has been detected particularly in the liver, small intestine, and kidney.
DEP Domain Containing Protein 1B also known as XTP1, XTP8, HBV XAg-Transactivated Protein 8, [formerly referred to as BRCC3] is a human protein encoded by a gene of similar name located on chromosome 5.
TMEM143 is a protein that in humans is encoded by TMEM143 gene. TMEM143, a dual-pass protein, is predicted to reside in the mitochondria and high expression has been found in both human skeletal muscle and the heart. Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.
Transmembrane and coiled-coil domain 6, TMCO6, is a protein that in humans is encoded by the TMCO6 gene with aliases of PRO1580, HQ1580 or FLJ39769.1.
C12orf40, also known as Chromosome 12 Open Reading Frame 40, HEL-206, and Epididymis Luminal Protein 206 is a protein that in humans is encoded by the C12orf40 gene.
Transmembrane Protein 217 is a protein encoded by the gene TMEM217. TMEM217 has been found to have expression correlated with the lymphatic system and endothelial tissues and has been predicted to have a function linked to the cytoskeleton.
Ring finger protein 43 is a protein that in humans is encoded by the RNF43 gene.
Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene.
C2orf16 is a protein that in humans is encoded by the C2orf16 gene. Isoform 2 of this protein is 1,984 amino acids long. The gene contains 1 exon and is located at 2p23.3. Aliases for C2orf16 include Open Reading Frame 16 on Chromosome 2 and P-S-E-R-S-H-H-S Repeats Containing Sequence.
WD Repeat and Coiled-coiled containing protein (WDCP) is a protein which in humans is encoded by the WDCP gene. The function of the protein is not completely understood, but WDCP has been identified in a fusion protein with anaplastic lymphoma kinase found in colorectal cancer. WDCP has also been identified in the MRN complex, which processes double-stranded breaks in DNA.
Serum amyloid A-like 1 is a protein in humans encoded by the SAAL1 gene.
Transmembrane protein 101 (TMEM101) is a protein that in humans is encoded by the TMEM101 gene. The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have been linked to breast cancer.
TBC1D30 is a gene in the human genome that encodes the protein of the same name. This protein has two domains, one of which is involved in the processing of the Rab protein. Much of the function of this gene is not yet known, but it is expressed mostly in the brain and adrenal cortex.
Transmembrane protein 212 is a protein that in humans is encoded by the TMEM212 gene. The protein consists of five transmembrane domains and localizes in the plasma membrane and endoplasmic reticulum. TMEM212 has orthologs in vertebrates but not invertebrates. TMEM212 has been associated with sporadic Parkinson's disease, facial processing, and adiposity in African Americans.
Transmembrane Protein 144 (TMEM144) is a protein in humans encoded by the TMEM144 gene.
Armadillo-like Helical Domain Containing 1 (ARMH1) is a protein which in humans is encoded by chromosome 1 open reading frame 228, also known as the ARMH1 gene. The gene shows expression levels significantly higher in bone marrow, lymph nodes, and testis. Currently the function of the gene and subsequent protein is still uncertain.
