 | This article may be too technical for most readers to understand.(December 2023) |
Highly Expressed In Immature Dendritic Cell Transcript 1 (HIDE1) is a protein encoded by chromosome 19 open reading frame 38 (C19orf38) gene in humans. [1] There are no other aliases used for the gene. C19orf38 is only expressed in white blood cells, of the innate immune system. HIDE1 protein has been found to play a role in immune escape of tumors and diet induced obesity.
There are five risk associated variants found within the c19orf38 gene. Three of which lead to a significant increase in low density lipoprotein cholesterol. [2] [3] One variant is associated with prevalence of coronary artery disease. [4] And the fifth identified risk variant is associated with increased reporting of Idiopathic knee osteoarthritis. [5]
C19orf38 can be alternatively spliced to form three distinct mRNA products. Both isoform's 1 and 2 differ only via the 5' UTR. Isoform 3 has a different protein product in that the mRNA transcript does not contain exon 2 or exon 3, however, isoform 3 is not expressed in humans.
C19orf38 transcript is found at the highest amount in bone marrow, with less than a fifth of the transcript amount in the spleen, testis, appendix, and lymph nodes, with little to no transcript in other tissue types. Tissues with the transcript have a high leukocyte presence. [6] It is exclusively present in the following cell types: monocytes, peripheral blood mononuclear cells, eosinophils and basophil's, so any expression in tissues comes from innate immune cells, or granulocytes. [7] Transcript is not present in neutrophils. C19orf38 transcript is not found in macrophages, despite, classical monocyte expression. [8]
The promoter region of C19orf38 contains two transcription factor binding domains that are particularly important for innate immune system development: Spi-C Transcription Factor (SPIC) and E74 Like ETS Transcription Factor 3 (ELF3). Both are transcription factors are only present in leukocytes are involved in the negative transcription of genes for the development of macrophages, which coincides with cellular localization of C19orf38. [9]
HIDE1 is a 230 amino acid transmembrane protein, anchored via ɑ-helix transmembrane region. F-box only protein 2 (FBXO2) binds in an extracellular region to glycosylated arginine amino acids found at positions 48 and 97. [11] The extracellular region also contains a highly conserved signal peptide sequence, which leads the protein to the membrane space. Additionally, HIDE1 protein contains a disordered region in its intracellular region. TNPO3 and XPO-4 are known to interact with HIDE1. [12]
Human HIDE1 protein is largely confirmed to be a signal protein existing either embedded within the cellular membrane or in a secreted form. Deeploc signal analysis predicts a signal peptide region at the start of its translation. [13] Furthermore, PSORT2 k-NN prediction finds the protein to be localized extracellularly 34.8% of the time, 30.4% in the plasma membrane, 21.7% in the endoplasmic reticulum, and 13.0% in the golgi bodies. [14]
HIDE1 protein contains an ig-like domain and signal peptide in its extracellular region as well as multiple lipidification sites to assist with membrane association. [15] [16] Additionally, N-linked glycosylation sites can be found in the luminal side. The intracellular/cytoplasmic region contains multiple phosphorylation sites and calpain cleavage locations. [17]
Orthologs are found in the following taxon classes: Mammalia, Reptilia, Aves, and Amphibia. There are no orthologs found in either class Insecta or Actinopterygii. C19orf38 is only present in jawed vertebrates which coincides with the divergence of adaptive immune systems 550 MYA between jawed and jawless vertebrates.
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C19orf38 mutation rate is found to be less than that of fibrinogen alpha, but is high in comparison to other human proteins, especially, immune proteins which are highly conserved in jawed vertebrates. [20]
HIDE1 shows no significant association with any cancer. [21]
CD58, or lymphocyte function-associated antigen 3 (LFA-3), is a cell adhesion molecule expressed on Antigen Presenting Cells (APCs), particularly macrophages, and other tissue cells.
The granulocyte-macrophage colony-stimulating factor receptor, also known as CD116, is a receptor for granulocyte-macrophage colony-stimulating factor, which stimulates the production of white blood cells. In contrast to M-CSF and G-CSF which are lineage specific, GM-CSF and its receptor play a role in earlier stages of development. The receptor is primarily located on neutrophils, eosinophils and monocytes/macrophages, it is also on CD34+ progenitor cells (myeloblasts) and precursors for erythroid and megakaryocytic lineages, but only in the beginning of their development.
CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.
Signaling lymphocytic activation molecule 1 is a protein that in humans is encoded by the SLAMF1 gene. Recently SLAMF1 has also been designated CD150.
C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.
V-type proton ATPase subunit G 2 is an enzyme that in humans is encoded by the ATP6V1G2 gene.
Fc fragment of IgG receptor IIb is a low affinity inhibitory receptor for the Fc region of immunoglobulin gamma (IgG). FCGR2B participates in the phagocytosis of immune complexes and in the regulation of antibody production by B lymphocytes.
Triggering receptor expressed on myeloid cells 2(TREM2) is a protein that in humans is encoded by the TREM2 gene. TREM2 is expressed on macrophages, immature monocyte-derived dendritic cells, osteoclasts, and microglia, which are immune cells in the central nervous system. In the liver, TREM2 is expressed by several cell types, including macrophages, that respond to injury. In the intestine, TREM2 is expressed by myeloid-derived dendritic cells and macrophage. TREM2 is overexpressed in many tumor types and has anti-inflammatory activities. It might therefore be a good therapeutic target.
The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
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.
Chromosome 1 open reading frame 141, or C1orf141 is a protein which, in humans, is encoded by gene C1orf141. It is a precursor protein that becomes active after cleavage. The function is not yet well understood, but it is suggested to be active during development
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.
Family with Sequence Similarity 155 Member B is a protein in humans that is encoded by the FAM155B gene. It belongs to a family of proteins whose function is not yet well understood by the scientific community. It is a transmembrane protein that is highly expressed in the heart, thyroid, and brain.
Transmembrane protein 39B (TMEM39B) is a protein that in humans is encoded by the gene TMEM39B. TMEM39B is a multi-pass membrane protein with eight transmembrane domains. The protein localizes to the plasma membrane and vesicles. The precise function of TMEM39B is not yet well-understood by the scientific community, but differential expression is associated with survival of B cell lymphoma, and knockdown of TMEM39B is associated with decreased autophagy in cells infected with the Sindbis virus. Furthermore, the TMEM39B protein been found to interact with the SARS-CoV-2 ORF9C protein. TMEM39B is expressed at moderate levels in most tissues, with higher expression in the testis, placenta, white blood cells, adrenal gland, thymus, and fetal brain.
C2orf74, also known as LOC339804, is a protein encoding gene located on the short arm of chromosome 2 near position 15 (2p15). Isoform 1 of the gene is 19,713 base pairs long. C2orf74 has orthologs in 135 different species, including primarily placental mammals and some marsupials.
Family with Sequence Similarity 166, member C (FAM166C), is a protein encoded by the FAM166C gene. The protein FAM166C is localized in the nucleus. It has a calculated molecular weight of 23.29 kDa. It also contains DUF2475, a protein of unknown function from amino acid 19–85. The FAM166C protein is nominally expressed in the testis, stomach, and thyroid.
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