CDH1 (gene)
Encyclopedia
Cadherin-1 also known as CAM 120/80 or epithelial cadherin (E-cadherin) or uvomorulin is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the CDH1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. CDH1 has also been designated as CD324 (cluster of differentiation
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...

 324). It is a tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

.

Function

Cadherin-1 is a classical member of the cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

 superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail
Cadherin cytoplasmic region
In molecular biology, the cadherin cytoplasmic region is a conserved region found at the C-terminus of cadherin proteins. A key determinant to the strength of the binding that it is mediated by cadherins is the juxtamembrane region of the cadherin...

. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells, and the cytoplasmic domain is required for internalization. Identified transcript variants arise from mutation at consensus splice sites.

E-cadherin (epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

) is the most well-studied member of the cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

 family. It consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and an intracellular domain that binds p120-catenin and beta-catenin
Beta-catenin
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...

. The intracellular domain contains a highly-phosphorylated
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 region vital to beta-catenin binding and, therefore, to E-cadherin function. Beta-catenin can also bind to alpha-catenin. Alpha-catenin participates in regulation of actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

-containing cytoskeletal filaments. In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

.

E-cadherin is first expressed in the 2-cell stage of mammalian development, and becomes phosphorylated by the 8-cell stage, where it causes compaction. In adult tissues, E-cadherin is expressed in epithelial tissues, where it is constantly regenerated with a 5-hour half-life on the cell surface.

Clinical significance

Loss of E-cadherin function or expression has been implicated in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 progression and metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...

 and invade surrounding tissues.

E-cadherin is also used by pathologists to diagnose different kinds of breast cancer. When compared with invasive duct carcinoma, E-cadherin expression is markedly reduced or absent in the great majority of invasive lobular carcinomas when studied by immunohistochemistry.

Interactions

CDH1 (gene) has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with

  • CDC27
    CDC27
    Cell division cycle protein 27 homolog is a protein that in humans is encoded by the CDC27 gene.-Interactions:CDC27 has been shown to interact with ANAPC1, ANAPC4, ANAPC5, ANAPC11, FZR1, CDC20, CDH1, CDC23, PIN1, CDC16, ANAPC7, MAD2L1 and ANAPC10....

    ,
  • CDON
    CDON
    Cell adhesion molecule-related/down-regulated by oncogenes is a protein that in humans is encoded by the CDON gene.-Interactions:CDON has been shown to interact with CDH1 and BOC.-Further reading:...

    ,
  • CDH3
    CDH3 (gene)
    Cadherin-3 is a protein that in humans is encoded by the CDH3 gene.-Interactions:CDH3 has been shown to interact with CDH1, Beta-catenin, Plakoglobin, Nephrin and Catenin , alpha 1.-Further reading:...

    ,
  • C-Met
    C-MET
    c-Met is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor . The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity...

    ,


Cadherin-1 also known as CAM 120/80 or epithelial cadherin (E-cadherin) or uvomorulin is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the CDH1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. CDH1 has also been designated as CD324 (cluster of differentiation
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...

 324). It is a tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

.

Function

Cadherin-1 is a classical member of the cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

 superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail
Cadherin cytoplasmic region
In molecular biology, the cadherin cytoplasmic region is a conserved region found at the C-terminus of cadherin proteins. A key determinant to the strength of the binding that it is mediated by cadherins is the juxtamembrane region of the cadherin...

. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells, and the cytoplasmic domain is required for internalization. Identified transcript variants arise from mutation at consensus splice sites.

E-cadherin (epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

) is the most well-studied member of the cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

 family. It consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and an intracellular domain that binds p120-catenin and beta-catenin
Beta-catenin
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...

. The intracellular domain contains a highly-phosphorylated
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 region vital to beta-catenin binding and, therefore, to E-cadherin function. Beta-catenin can also bind to alpha-catenin. Alpha-catenin participates in regulation of actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

-containing cytoskeletal filaments. In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

.

E-cadherin is first expressed in the 2-cell stage of mammalian development, and becomes phosphorylated by the 8-cell stage, where it causes compaction. In adult tissues, E-cadherin is expressed in epithelial tissues, where it is constantly regenerated with a 5-hour half-life on the cell surface.

Clinical significance

Loss of E-cadherin function or expression has been implicated in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 progression and metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...

 and invade surrounding tissues.

E-cadherin is also used by pathologists to diagnose different kinds of breast cancer. When compared with invasive duct carcinoma, E-cadherin expression is markedly reduced or absent in the great majority of invasive lobular carcinomas when studied by immunohistochemistry.

Interactions

CDH1 (gene) has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with

  • CDC27
    CDC27
    Cell division cycle protein 27 homolog is a protein that in humans is encoded by the CDC27 gene.-Interactions:CDC27 has been shown to interact with ANAPC1, ANAPC4, ANAPC5, ANAPC11, FZR1, CDC20, CDH1, CDC23, PIN1, CDC16, ANAPC7, MAD2L1 and ANAPC10....

    ,
  • CDON
    CDON
    Cell adhesion molecule-related/down-regulated by oncogenes is a protein that in humans is encoded by the CDON gene.-Interactions:CDON has been shown to interact with CDH1 and BOC.-Further reading:...

    ,
  • CDH3
    CDH3 (gene)
    Cadherin-3 is a protein that in humans is encoded by the CDH3 gene.-Interactions:CDH3 has been shown to interact with CDH1, Beta-catenin, Plakoglobin, Nephrin and Catenin , alpha 1.-Further reading:...

    ,
  • C-Met
    C-MET
    c-Met is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor . The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity...

    ,


Cadherin-1 also known as CAM 120/80 or epithelial cadherin (E-cadherin) or uvomorulin is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the CDH1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. CDH1 has also been designated as CD324 (cluster of differentiation
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...

 324). It is a tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

.

Function

Cadherin-1 is a classical member of the cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

 superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail
Cadherin cytoplasmic region
In molecular biology, the cadherin cytoplasmic region is a conserved region found at the C-terminus of cadherin proteins. A key determinant to the strength of the binding that it is mediated by cadherins is the juxtamembrane region of the cadherin...

. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells, and the cytoplasmic domain is required for internalization. Identified transcript variants arise from mutation at consensus splice sites.

E-cadherin (epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

) is the most well-studied member of the cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...

 family. It consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and an intracellular domain that binds p120-catenin and beta-catenin
Beta-catenin
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...

. The intracellular domain contains a highly-phosphorylated
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 region vital to beta-catenin binding and, therefore, to E-cadherin function. Beta-catenin can also bind to alpha-catenin. Alpha-catenin participates in regulation of actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

-containing cytoskeletal filaments. In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...

.

E-cadherin is first expressed in the 2-cell stage of mammalian development, and becomes phosphorylated by the 8-cell stage, where it causes compaction. In adult tissues, E-cadherin is expressed in epithelial tissues, where it is constantly regenerated with a 5-hour half-life on the cell surface.

Clinical significance

Loss of E-cadherin function or expression has been implicated in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 progression and metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...

 and invade surrounding tissues.

E-cadherin is also used by pathologists to diagnose different kinds of breast cancer. When compared with invasive duct carcinoma, E-cadherin expression is markedly reduced or absent in the great majority of invasive lobular carcinomas when studied by immunohistochemistry.

Interactions

CDH1 (gene) has been shown to interact
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with

  • CDC27
    CDC27
    Cell division cycle protein 27 homolog is a protein that in humans is encoded by the CDC27 gene.-Interactions:CDC27 has been shown to interact with ANAPC1, ANAPC4, ANAPC5, ANAPC11, FZR1, CDC20, CDH1, CDC23, PIN1, CDC16, ANAPC7, MAD2L1 and ANAPC10....

    ,
  • CDON
    CDON
    Cell adhesion molecule-related/down-regulated by oncogenes is a protein that in humans is encoded by the CDON gene.-Interactions:CDON has been shown to interact with CDH1 and BOC.-Further reading:...

    ,
  • CDH3
    CDH3 (gene)
    Cadherin-3 is a protein that in humans is encoded by the CDH3 gene.-Interactions:CDH3 has been shown to interact with CDH1, Beta-catenin, Plakoglobin, Nephrin and Catenin , alpha 1.-Further reading:...

    ,
  • C-Met
    C-MET
    c-Met is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor . The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity...

    ,
  • CTNND1
    CTNND1
    Catenin delta-1 is a protein that in humans is encoded by the CTNND1 gene.-Interactions:CTNND1 has been shown to interact with Beta-catenin, FYN, Collagen, type XVII, alpha 1, PTPN6, YES1, PTPRJ, VE-cadherin, MUC1, CDH1, CDH2, PTPRM, Cortactin, Nephrin, ZBTB33 and PSEN1.-Further reading:...

    ,
  • CTNNB1
    Beta-catenin
    Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...

    ,
  • CTNNA1
  • FOXM1
    FOXM1
    Forkhead box protein M1 is a protein that in humans is encoded by the FOXM1 gene. The protein encoded by this gene is a member of the FOX family of transcription factors...

    ,
  • HDAC1
    HDAC1
    Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...

    ,
  • HDAC2
    Histone deacetylase 2
    Histone deacetylase 2 is an enzyme that in humans is encoded by the HDAC2 gene.-Interactions:Histone deacetylase 2 has been shown to interact with CHD3, MTA1, FKBP3, CHD4, RCOR1, Retinoblastoma protein, CDC20, RBBP4, CDH1, EED, GTF2I, Host cell factor C1, PHF21A, BUB3, MXD1, HDAC10, RELA, Sp3...

    ,
  • IQGAP1
    IQGAP1
    Ras GTPase-activating-like protein IQGAP1 also known as p195 is a ubiquitously expressed protein that in humans is encoded by the IQGAP1 gene...

    ,
  • FYN
    FYN
    Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...

    ,
  • NEDD9
    NEDD9
    Enhancer of filamentation 1 is a protein that in humans is encoded by the NEDD9 gene.-Interactions:NEDD9 has been shown to interact with ID2, LYN, NCK1, MICAL1, CDH1, Abl gene, PTK2, CRKL, CRK and Mothers against decapentaplegic homolog 3....

    ,
  • Plakoglobin
    Plakoglobin
    Junction plakoglobin, also known as gamma-catenin or JUP, is a protein that in humans is encoded by the JUP gene.- Function :...

    ,
  • Vinculin
    Vinculin
    In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton...

    ,

  • PTPmu(PTPRM
    PTPRM
    Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene.- Function :The protein encoded by this gene is a member of the protein tyrosine phosphatase family. Protein tyrosine phosphatases are protein enzymes that remove phosphate moieties from tyrosine...

    )

External links

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