Glioma pathogenesis-related protein 1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''GLIPR1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

This gene encodes a protein with similarity to both the

pathogenesis-related protein Pathogenesis-related (PR) proteins are proteins produced in plants in the event of a pathogen attack. They are induced as part of systemic acquired resistance. Infections activate genes that produce PR proteins. Some of these proteins are antimicro ...

(PR) superfamily and the

cysteine-rich secretory protein Cysteine-rich secretory proteins, often abbreviated as CRISPs, are a group of glycoproteins. They are a subgroup of the CRISP, antigen 5 and Pr-1 (CAP) protein superfamily and also contain a domain related to the ShK toxins. They are substantially ...

(CRISP) family.

Discovery

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 Sequence homology is the homology (biology), biological homology between DNA sequence, DNA, RNA sequence, RNA, or Protein primary structure, protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments ...

search for RTVP1/GLIPR1-like (GLIPR1L) genes. p53, the

tumor suppressor gene A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), 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 ...

is the most commonly mutated gene in human cancer. Mutation in p53 gene can lead to cellular malfunctions such as

malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

growth and metastasis. Human GLIPR1, was initially identified in human

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...

and was called as GLIPR1 (glioma pathogenesis-related protein 1) or RTVP1 (related to testes-specific, vespid, and pathogenesis protein 1). Furthermore, it was identified as a marker of myelomocytic differentiation in

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

. RTVP-1 cluster proteins share significant sequence homology with the members of (PR ) superfamily and CRISP Family proteins.

Structure

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.
The GLIPR1 proteins contains following Protein domain, 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. CAP domain is 15 KDa structurally conserved

cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...

rich domain as was historically referred to as SCP, NCBI cd00168 pr Pfam00188.

Gene location

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 A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

10D1 in mouse (Figs. 1A and 1B). In human GLIPR1 gene is located on the long (q) arm of chromosome 12 from base pair 71500001-75700000 (Build GRCh37/hg1
(map)

Gene expression

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. The expression GLIPR1L2 was similar to GLIPR1L1.

Clinical significance

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 In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...

inactivation in prostate cancer. This unique property of GLIPR1 might be effective for the control of

malignancies Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...

. Preclinical studies has the significant suppression of tumor growth when AdGLIPR1 was directly injected into prostate cancer using an

immunocompetent In immunology, immunocompetence is the ability of the body to produce a normal immune response following exposure to an antigen. Immunocompetence is the opposite of immunodeficiency (also known as ''immuno-incompetence'' or being ''immuno-comprom ...

orthotopic Orthotopic procedures (from Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assu ...

mouse model.

Homology with plant defense mechanism

GLIPR1 exhibits 35% amino acid sequence identity with the tomato pathogenesis-related (PR) protein P14a, which has importance in plant defense mechanism. 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.

Cancer types/SNP positions

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 lin

SNP Position vs Freq

File:Cancer type vs frequency.png, Number of position affected by cancer types vs cancer type