CPNE1

Last updated
CPNE1
Identifiers
Aliases CPNE1 , COPN1, CPN1, copine 1
External IDs OMIM: 604205 MGI: 2386621 HomoloGene: 36501 GeneCards: CPNE1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_170588
NM_170590

RefSeq (protein)

NP_733467
NP_733469

Location (UCSC) Chr 20: 35.63 – 35.66 Mb Chr 2: 155.91 – 155.95 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Copine-1, is a protein that in humans is encoded by the CPNE1 gene. [5] [6]

Contents

CPNE is a highly homologous protein first discovered in nematodes and plants. Nine CPNEs were originally discovered (CPNE1-9) and only 8 CPNEs were found in mammals (CPNE1-8). CPNE1-3 are the most widely distributed and are found in most mammalian tissues, this includes but is not limited to, the testis, kidney, brain, lung, heart, and intestine. [7] (CPNE-1) was reported in 1998, where it was identified by isolating annexin in Paramecium. [8]

CPNE-1 is a highly conservedCalcium-dependent membrane-binding proteins in different eukaryotes. In humans the CPNE1 gene encodes the, calcium dependant, Copine-1 protein which has an integrin A doman and two N-terminal type II C2 domains. Where the C2 domains act as calcium dependent phospholipid binding motifs and can be included in cell signaling or membrane trafficking pathways. [9] However, the encoded protein does not contain a predicted signal sequence or transmembrane domains. CPNE-1 may also regulate molecular events at the interface of the cell membrane and cytoplasm. This protein has a broad tissue distribution and it may function in membrane trafficking. This gene and the gene for RNA binding motif protein 12 overlap at map location 20q11.21. Sequence analysis identified multiple alternatively spliced variants in the 5' UTR. All variants encode the same protein. [6]

Roles of CPNE1

CPNE1 has a general role in many biological processes, where it promotes the outgrowth of neurites by activating the AKT phosphorylation and plays an important role in the regulation of neural stem cell proliferation. New and old studies suggest that the important and dominant role of CPNE1 is in tumorigenesis and malignant progression. [10]

CPNE1 can regulate molecular events at the interface of the cell membrane and cytoplasm. [11] In brain cells, it is connected to the AKT signalling pathway, giving it importance in the neural stem cell functions in the course of brain development. Where it is detrimental in regulating the neural stem cell functions throughout the activation of the AKT-mTOR signalling pathway in the brain development phase. [12] It has an important role in the central nervous system as a regulator for neuronal differentiation of HiB5 cells. It does this by activating the AKT signalling pathway by its interactions with JAB-1 and 14-4-3 gamma (Kim et al., 2018). (The AKT Signaling pathway is a signal transduction pathway that helps the growth and survival in response to extracellular signals).

In addition to this role, CPNE1 has an important role in the presence and growth of different cancer types. Individuals with prostate cancer show a higher CPNE1 expression and this expression is affiliated with the stage and prognosis of patients with prostate cancer. This happens mechanistically when CPNE1 interacts with TRAF-2 (regulates a variety of different physiological roles, from inflammatory responses and T and B signalling to organogenesis and cell survival) To promote the progression of cancer. [13] In patients with osteosarcoma ( cancer that starts in the bone), CPNE1 has a role in increasing cell numbers and migration, it does this using the MAPK pathway (a pathway responsible for many pathological processes. All eukaryotic cells have multiple MAPK pathways that control gene expression, metabolism, survival, mitosis, motility, apoptosis, and differentiation. In addition to this there is the TGF-beta pathway (this pathway acts as a tumour suppressor, by mediating its anti-cell duplication effects in multiple different cell types). [14]

CPNE1 also has a role in promoting the progression of colorectal cancer and increases chemoresistance ( cancer affecting the colon or rectum, causing cells to grow out of control) [15] This happens due to the activation of the AKT-GLUT1/HK2 cascade (The AKT-glucose transporter 1-hexokinase2 pathway is responsible in regulating the glycolytic process in various cancer cells, due to colorectal cancer the AKT pathway increases the GLUT1 expression, CPNE1 activates the AKT to increase neuronal progenitor cell differentiation causing an implication in the regulation of the pathway.) [16]

In triple-negative breast cancer, CPNE1 increases tumorigenesis and radioresistance, due to the regulation of AKT activation. Due to this, it is possible to use the CPNE1 expression to sensitize the triple-negative breast cancer cells to therapy by radiation. In lung cancer, Non-Small Cell Lung Cancer (NSCLC) tissues have high demonstrations of CPNE1 which corresponds with lymph node metastasis (a serious condition in which the cancer invaded lymph nodes move to other organs) and less survival in patients. [17]

In hepatocellular carcinoma (HCC, is the most common type of primary liver cancer. It occurs in people with chronic liver diseases.) overexpressed CPNE1 is a regulator to the cell cycle process in order to mediate cell dedifferentiation. [18]

In gastric cancer (cancer that starts in the cells lining the stomach), [19] CPNE1 is upregulated (the process of increasing the response to a stimulus); This was identified using the Immunohistochemistry and Kaplan-Meier plotter database and the higher the CPNE1 the worse the prognosis. On the other hand, the proliferation of tumours can be suppressed, cell apoptosis can be accelerated and the cell cycle in vitro can enter arrest (in Vitro means in glass, it refers to tests, experiments, and medical procedures performed by researchers outside of living organisms) if the CPNE1 is silenced. In vivo experiments (in Vivo means within the living, it refers to tests, experiments, and medical procedures performed by researchers inside of living organisms)., [20] by using the Xenograft mouse model ( is a model based on the implantation of tumor cells from humans into mice that are immunocompromised in order to avoid graft versus host reaction of the mouse in opposition to the human tumor tissue [graft versus reaction is a systemic disorder that happens when the donated tissue cells think that the host is foreign and attacks the recipient's body cells], [21] tumor growth in vivo was found to be slowed down by the targeted inhibition of CPNE1. The specific inhibition of the DDIT3-FOS-MKNK2 axis has the ability to suppress the excessive cell duplication related to gastric cancer with the knockdown of CPNE1. [10] Overall, it is possible to use CPNE1 as a prognostic biomarker for cancers, however, they correlate with sex, age, cancer stage and tumour grade. Where an increased amount of CPNE1 leads to decreased survival chances and less CPNE1 leads to an increased chance of survival for the patient with cancer.

Related Research Articles

<span class="mw-page-title-main">Signal transduction</span> Cascade of intracellular and molecular events for transmission/amplification of signals

Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Most commonly, protein phosphorylation is catalyzed by protein kinases, ultimately resulting in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.

<span class="mw-page-title-main">Uniporter</span>

Uniporters, also known as solute carriers or facilitated transporters, are a type of membrane transport protein that passively transports solutes across a cell membrane. It uses facilitated diffusion for the movement of solutes down their concentration gradient from an area of high concentration to an area of low concentration. Unlike active transport, it does not require energy in the form of ATP to function. Uniporters are specialized to carry one specific ion or molecule and can be categorized as either channels or carriers. Facilitated diffusion may occur through three mechanisms: uniport, symport, or antiport. The difference between each mechanism depends on the direction of transport, in which uniport is the only transport not coupled to the transport of another solute.

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

<span class="mw-page-title-main">P-glycoprotein</span> Mammalian protein found in Homo sapiens

P-glycoprotein 1 also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances.

<span class="mw-page-title-main">Protein kinase B</span> Set of three serine/threonine-specific protein kinases

Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.

A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that is transduced to the cell interior through second messengers which amplify the signal and transfer it to effector molecules, causing the cell to respond to the initial stimulus. Most biochemical cascades are series of events, in which one event triggers the next, in a linear fashion. At each step of the signaling cascade, various controlling factors are involved to regulate cellular actions, in order to respond effectively to cues about their changing internal and external environments.

<span class="mw-page-title-main">Nerve growth factor</span> Mammalian protein found in Homo sapiens

Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was one of the first to be described. Since it was first isolated by Nobel Laureates Rita Levi-Montalcini and Stanley Cohen in 1956, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system.

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The prolactin receptor (PRLR) is a type I cytokine receptor encoded in humans by the PRLR gene on chromosome 5p13-14. It is the receptor for prolactin (PRL). The PRLR can also bind to and be activated by growth hormone (GH) and human placental lactogen (hPL). The PRLR is expressed in the mammary glands, pituitary gland, and other tissues. It plays an important role in lobuloalveolar development of the mammary glands during pregnancy and in lactation.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 3</span> Protein-coding gene in humans

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The PHLPP isoforms are a pair of protein phosphatases, PHLPP1 and PHLPP2, that are important regulators of Akt serine-threonine kinases and conventional/novel protein kinase C (PKC) isoforms. PHLPP may act as a tumor suppressor in several types of cancer due to its ability to block growth factor-induced signaling in cancer cells.

Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. Trk receptors affect neuronal survival and differentiation through several signaling cascades. However, the activation of these receptors also has significant effects on functional properties of neurons.

<span class="mw-page-title-main">IQGAP1</span>

Ras GTPase-activating-like protein IQGAP1 (IQGAP1) also known as p195 is a ubiquitously expressed protein that in humans is encoded by the IQGAP1 gene. IQGAP1 is a scaffold protein involved in regulating various cellular processes ranging from organization of the actin cytoskeleton, transcription, and cellular adhesion to regulating the cell cycle.

<span class="mw-page-title-main">RhoC</span> Protein-coding gene in the species Homo sapiens

RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.

<span class="mw-page-title-main">RPS6KA2</span> Enzyme found in humans

Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene.

<span class="mw-page-title-main">CPNE4</span> Protein-coding gene in the species Homo sapiens

Copine-4 is a protein that in humans is encoded by the CPNE4 gene.

The Akt signaling pathway or PI3K-Akt signaling pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K and Akt.

<span class="mw-page-title-main">XB130</span> Protein-coding gene in the species Homo sapiens

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In molecular biology, copines is a name for the group of human proteins that includes members such as CPNE1, CPNE4, CPNE6, and CPNE8. These are highly conserved, calcium-dependent membrane proteins found in a variety of eukaryotes. The domain structure of these 55 kDa proteins suggests that they may have a role in membrane trafficking in some prokaryotes as well as eukaryotes. Copines contains two C2 domains which play a role in signal transduction by binding to calcium, phospholipids, or polyphosphates. Both domains are located at the N-terminal portion of the protein which is not the case for most other double C2 domain proteins, and their role is most similar to that carried out by proteins that exhibit a single C2 domain. The core domain located at the C-terminus part of the copine is found to have a unique and conserved primary sequence. The function of the core domain is still uncertain, however, researchers believe it has a similar function to the "A domain" in integrins. This similarity in function involves serving as a binding site for target proteins, and is supported by evidence that the copine core domain exhibits secondary and tertiary structures comparable to the integrin A domain.

Membrane progesterone receptors (mPRs) are a group of cell surface receptors and membrane steroid receptors belonging to the progestin and adipoQ receptor (PAQR) family which bind the endogenous progestogen and neurosteroid progesterone, as well as the neurosteroid allopregnanolone. Unlike the progesterone receptor (PR), a nuclear receptor which mediates its effects via genomic mechanisms, mPRs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades. The mPRs mediate important physiological functions in male and female reproductive tracts, liver, neuroendocrine tissues, and the immune system as well as in breast and ovarian cancer.

References

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Further reading