Abstract
The HCP5 RNA gene (NCBI ID: 10866) is located centromeric of the HLA-B gene and between the MICA and MICB genes within the major histocompatibility complex (MHC) class I region. It is a human species-specific gene that codes for a long noncoding RNA (lncRNA), composed mostly of an ancient ancestral endogenous antisense 3′ long terminal repeat (LTR, and part of the internal pol antisense sequence of endogenous retrovirus (ERV) type 16 linked to a human leukocyte antigen (HLA) class I promoter and leader sequence at the 5′-end. Since its discovery in 1993, many disease association and gene expression studies have shown that HCP5 is a regulatory lncRNA involved in adaptive and innate immune responses and associated with the promotion of some autoimmune diseases and cancers. The gene sequence acts as a genomic anchor point for binding transcription factors, enhancers, and chromatin remodeling enzymes in the regulation of transcription and chromatin folding. The HCP5 antisense retroviral transcript also interacts with regulatory microRNA and immune and cellular checkpoints in cancers suggesting its potential as a drug target for novel antitumor therapeutics.
Highlights
The human major histocompatibility complex (MHC), known as the human leukocyte antigen (HLA), covers 0.13% of the human genome and spans ~4 Mbp on the short arm of chromosome six at position 6p21 within a region that contains more than 250 annotated genes and pseudogenes [1,2].The classical class I and class II regions within the MHC have extensive patterns of linkage disequilibrium (LD), and a high degree of single nucleotide polymorphisms (SNPs) at the HLA genes can differentiate worldwide populations [1,3,4,5]
Karim et al [44] showed that episomal copies of HPV16 and HPV18 in undifferentiated keratinocytes downregulated the expression of HCP5 and the HLA-A, -B, -C, and -G
A number of different Single Nucleotide Variant (SNV) located in the MICA and MICB genes and in the genomic region between them have been associated with cancer
Summary
The human major histocompatibility complex (MHC), known as the human leukocyte antigen (HLA), covers 0.13% of the human genome and spans ~4 Mbp on the short arm of chromosome six at position 6p21 within a region that contains more than 250 annotated genes and pseudogenes [1,2]. 2019) and by its location on the GRCh38.p12 assembly (annotation release 109 in March 2018) at chr6:31,463,180–31,465,809 (NC_000006.12) with a transcript length of 2547 bp, including eight adenines of the RNA polyA tail (NCBI ncRNA reference sequence NR_040662.1) It spans 2630 bp of a 5153 bp (nt positions from 717 to 3346) extended HCP5 gene reference with 50 and 30 noncoding regions (GenBank AB088109.1) and the chromosome six reference sequence NC_000006.12. The gene structure of HCP5 is unusual because it is a hybrid sequence of an HLA class I gene fragment in exon 1 and the fragmented portions of the 30 LTR and internal sequence of ERV16 in exon 2 [30], annotated by RepeatMasker as 30 LTR16B and complementary (minus strand) ERV3-16A3.
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