| GLIPR1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | GLIPR1 , CRISP7, GLIPR, RTVP1, GLI pathogenesis related 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602692; MGI: 1920940; HomoloGene: 21357; GeneCards: GLIPR1; OMA:GLIPR1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Glioma pathogenesis-related protein 1 is a protein that in humans is encoded by the GLIPR1 gene. [5] [6] [7]
This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. [7]
The previous finding of RTVP1 (GLIPR1) as a p53 target gene with tumor suppressor functions prompted the researches to initiate a genome-wide sequence homology search for RTVP1/GLIPR1-like (GLIPR1L) genes. [8] p53, the tumor suppressor gene is the most commonly mutated gene in human cancer. [8] Mutation in p53 gene can lead to cellular malfunctions such as malignant growth and metastasis. [9] [10] [11] Human GLIPR1, was initially identified in human glioblastoma and was called as GLIPR1 (glioma pathogenesis-related protein 1) [12] or RTVP1 (related to testes-specific, vespid, and pathogenesis protein 1). [13] Furthermore, it was identified as a marker of myelomocytic differentiation in macrophage. [14] RTVP-1 cluster proteins share significant sequence homology with the members of (PR ) superfamily and CRISP Family proteins. [8]
Protein structure: GLIPR1 is in two isomeric form, identifier: P48060-1 and P48060-2, which encodes 266(30,366 da) and 236( 26, 919 Da ) amino acid. [15] The GLIPR1 proteins contains following domains:
• SCP: SCP-like extracellular protein domain •CAP: Cysteine-rich secretory protein family
These predicted transmembrane domains a makes them unique to mammalian CAP proteins and are not presented in any othert GLIPR1 isoforms. [16] CAP domain is 15 KDa structurally conserved cystine rich domain as was historically referred to as SCP, NCBI cd00168 pr Pfam00188. [8] [15]
GLIPR1L and Glipr1l genes are located very near RTVP1 within the range of 170 kb, in human it is in chromosome 12q21 and in chromosome 10D1 in mouse (Figs. 1A and 1B). [8] In human GLIPR1 gene is located on the long (q) arm of chromosome 12 from base pair 71500001-75700000 (Build GRCh37/hg19)(map) [17]
GlIPR1 is highly tissue specific with high mRNA, with the expression of GLIPR1L1 being with very high mRNA levels in testes but few traces in bladder followed by undetectable expression in prostate, kidney, lung, and bone marrow. [8] The expression GLIPR1L2 was similar to GLIPR1L1. [8]
Study showed human GLIPR1 promoter to be highly methylated in prostate cancer tissues compared to the normal prostate tissue correlating with the decreased level of GLIPR1 expression. Hence, GLIPR1 has been proposed to act as a tumor suppressor that undergoes epigenetic inactivation in prostate cancer. [18] [15] This unique property of GLIPR1 might be effective for the control of malignancies. [19] Preclinical studies has the significant suppression of tumor growth when AdGLIPR1 was directly injected into prostate cancer using an immunocompetent orthotopic mouse model. [19]
GLIPR1 exhibits 35% amino acid sequence identity with the tomato pathogenesis-related (PR) protein P14a, which has importance in plant defense mechanism. [20] Comparison of these two protein lead to the identification of a common partially solvent-exposed spatial cluster of four amino acid residues, His-69, Glu-88, Glu-110, and His-127 in the GliPR numeration which indicates a common putative active site for GliPR and PR-1 proteins making a functional link between the human immune system and a plant defense system. [20]
The graphical representation of number of positions affected by cancer type vs cancer type and number of cancer types vs postiiton in amino acid sequence is provided in the link.
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.
p73 is a protein related to the p53 tumor protein. Because of its structural resemblance to p53, it has also been considered a tumor suppressor. It is involved in cell cycle regulation, and induction of apoptosis. Like p53, p73 is characterized by the presence of different isoforms of the protein. This is explained by splice variants, and an alternative promoter in the DNA sequence.
Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate cancer. Genes corresponding to PTEN (orthologs) have been identified in most mammals for which complete genome data are available.
Zbtb7, whose protein product is also known as Pokemon, is a gene that functions as a regulator of cellular growth and a proto oncogene.
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.
Runt-related transcription factor 3 is a protein that in humans is encoded by the RUNX3 gene.
Krueppel-like factor 6 is a protein that in humans is encoded by the KLF6 gene.
Homeobox protein Nkx-3.1, also known as NKX3-1, NKX3, BAPX2, NKX3A and NKX3.1 is a protein that in humans is encoded by the NKX3-1 gene located on chromosome 8p. NKX3-1 is a prostatic tumor suppressor gene.
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the DNAJA3 gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers.
CD82, or KAI1, is a human protein encoded by the CD82 gene.
Inhibitor of growth protein 1 is a protein that in humans is encoded by the ING1 gene.
WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene.
5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73, is an enzyme that in humans is encoded by the NT5E gene. CD73 commonly serves to convert AMP to adenosine.
Hypermethylated in cancer 1 protein is a protein that in humans is encoded by the HIC1 gene.
Apoptosis regulatory protein Siva is a protein that in humans is encoded by the SIVA1 gene. This gene encodes a protein with an important role in the apoptotic pathway induced by the CD27 antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been described.
Large tumor suppressor kinase 2 (LATS2) is an enzyme that in humans is encoded by the LATS2 gene.
Receptor-type tyrosine-protein phosphatase kappa is an enzyme that in humans is encoded by the PTPRK gene. PTPRK is also known as PTPkappa and PTPκ.
Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule that is encoded by the myelin-related gene EMP3. EMP3 is a member of the peripheral myelin protein gene family 22-kDa (PMP22), which is mainly responsible for the formation of the sheath of compact myelin. Although the detailed functions and mechanisms of EMP3 still remain unclear, it is suggested that EMP3 is possibly epigenetically linked to certain carcinomas.
p53 apoptosis effector related to PMP-22 is a plasma membrane protein that, in humans, is encoded by the PERP gene.
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.
