Top Qs
Timeline
Chat
Perspective
TMED5
Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
Remove ads
Transmembrane emp24 domain-containing protein 5 is a protein that in humans is encoded by the TMED5 gene.[5]
Remove ads
Gene
General properties
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]
Expression
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]
Remove ads
mRNA transcript
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]
Protein
Summarize
Perspective
General properties
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]
Composition
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]
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.[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]
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.[18][19]
Post-translational modifications
TMED5 has two predicted phosphorylation sites in the cytosolic region, Ser227 and Thr229.[21][22]
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.[17][23]
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.[24]
Remove ads
Function and clinical significance
TMED5 is a part of the p24 protein family whose general functions are protein trafficking for the secretory pathway.[35] TMED5 is thought to be necessary in the formation of the Golgi into a ribbon.[36]
Glycosylphosphatidylinositol-anchored proteins (GPI-AP) depend on p24 cargo receptors for transport from the ER to the Golgi.[37] 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.[37]
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.[38] 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.[39]
Research has identified bladder cancer to have a common chromosomal amplification at 1p21-22 and showed significant upregulation of TMED5.[40]
Remove ads
Evolution
Summarize
Perspective
Homology
Paralogs
TMED5 paralogs include TMED1, TMED2, TMED3, TMED4, TMED6, TMED7, TMED8, TMED9, and TMED10.[41] 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]
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.[5] The following table provides a sample of the ortholog space of TMED5.
Remove ads
References
Wikiwand - on
Seamless Wikipedia browsing. On steroids.
Remove ads