| CKLF | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | CKLF , C32, CKLF1, CKLF2, CKLF3, CKLF4, UCK-1, HSPC224, chemokine-like factor, chemokine like factor | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 616074 MGI: 1922708 HomoloGene: 9663 GeneCards: CKLF | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Chemokine-like factor (CKLF) is a member of the CKLF-like MARVEL transmembrane domain-containing family of proteins that in humans is encoded by the CKLF gene. [5] [6] This gene is located on band 22.1 in the long (i.e. "q") arm of chromosome 16. [7]
Through the process of alternative splicing, the CKLF gene encodes 4 CKLF protein isoforms, i.e. proteins made from different areas of the same gene. These isoforms are 1) CKLF1 and CKLF3 proteins that consist of 99 and 67 amino acids, respectively, and are secreted from their parent cells and 2) CKLF2 (which is the full-length product of the CKLF gene) and CKLF4 proteins which consist of 152 and 120 amino acids, respectively, and are located in the membranes of their parent cells.
CKLF1 is the first member of the CKLF-like MARVEL transmembrane domain-containing family of proteins to be defined and the most investigated of its four isoforms. [8] Studies conducted in freshly isolated cells, cultured cells, animals, and tissue samples indicate that CKLF1 is a chemokine-like chemotactic factor that acts through the CCR4 receptors on human CD4+ Th2 lymphocytes, neutrophils, monocytes, macrophages, dendritic cells, and perhaps other CCR4-receptor bearing cells. Preliminary findings suggest that the actions of CKLF1 on these CCR4-bearing cells may contribute to the maturation of various tissues such as blood cells and skeletal muscle from their precursor cells and the regulation of allergic (e.g. asthma), autoimmune (e.g. rheumatoid arthritis and the antiphospholipid syndrome), and inflammatory (e.g. acute respiratory distress syndrome) disorders. [7] Other studies have found that: 1) the benign fibrous skin tumor, keloids, had higher levels of CKLF1 and CKLF1 mRNA than nearby normal skin tissues; [9] 2) CKLF1 levels were higher in ovarian carcinoma tissues than nearby normal ovary tissues and patients with higher levels of CKLF1 in their ovarian cancer tissues had a more aggressive cancer than patients with lover levels of the protein in their ovarian cancer tissues; [9] [10] and 3) the levels of CKLF1 protein were higher in cancerous than nearby normal liver tissues in patients with hepatocellular carcinoma (HCC) and patients with higher HCC tissue levels of CKLF1 had poorer overall survival times than patients with lower levels of this protein in their HCC tissues. [11] [12] These results suggest that high levels of CKLF1 promote the development and/or progression of these three neoplasms although further studies are required to further define these relationships and to determine if CKLF1 can be used as a marker for their severity and/or a therapeutic target for treating them. [9] [10] [11]
Relative little is known about the normal functions and pathological actions of the CKLF2, CKLF3, and CKLF4 isoforms. [7] [9]
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 is a protein that in humans is encoded by the CXCR4 gene. The protein is a CXC chemokine receptor.
The activin A receptor also known as ACVR1C or ALK-7 is a protein that in humans is encoded by the ACVR1C gene. ACVR1C is a type I receptor for the TGFB family of signaling molecules.
CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.
Chemokine-binding protein 2 is a protein that in humans is encoded by the CCBP2 gene.
Retrotransposon-derived protein PEG10 is a protein that in humans is encoded by the PEG10 gene.
PNKD is the abbreviation for a human neurological movement disorder paroxysmal nonkinesiogenic dyskinesia. Like many other human genetics disorders, PNKD also refers to the disease, the disease gene and the encoded protein. (PNKD) is a protein that in humans is encoded by the PNKD gene. Alternative splicing results in the transcription of three isoforms. The mouse ortholog is called brain protein 17 (Brp17).
Opioid-binding protein/cell adhesion molecule is a protein that in humans is encoded by the OPCML gene.
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.
Matrilin-2 is a matrilin protein that in humans is encoded by the MATN2 gene.
Eukaryotic translation initiation factor 5A-2 is a protein that in humans is encoded by the EIF5A2 gene.
CKLF-like MARVEL transmembrane domain-containing protein 2, previously termed chemokine-like factor superfamily 2, is a member of the CKLF-like MARVEL transmembrane domain-containing family (CMTM) of proteins. In humans, it is encoded by the CMTM2 gene located in band 22 on the long arm of chromosome 16. CMTM2 protein is expressed in the bone marrow and various circulating blood cells. It is also highly expressed in testicular tissues: The CMTM2 gene and CMTM2 protein, it is suggested, may play an important role in testicular development.
CKLF like MARVEL transmembrane domain-containing 7, previously termed chemokine-like factor superfamily 7, is a protein that in humans is encoded by the CMTM7 gene. This gene, which is located in band 22 on the short arm of chromosome 3, and the protein that it encodes belong to the CKLF-like MARVEL transmembrane domain-containing family. Through the process of alternative splicing, the CMTM7 gene encodes two isoforms, CMTM7-v1 and CMTM7-v2, with CMTM7-v1 being the main form expressed and studied. CMTM7 proteins are widely expressed in normal human tissues.
CKLF like MARVEL transmembrane domain-containing 6, previously termed chemokine-like factor superfamily 6, is a transmembrane protein encoded in humans by the CMTM6 gene. This gene is located in band 22.3 on the short arm of chromosome 3. CMTM6 protein belongs to the CKLF-like MARVEL transmembrane domain-containing family of proteins. This family consist of 9 member proteins: CKLF and CMTM1 through CMTM8. The CMTM family proteins are involved in autoimmune diseases, cardiovascular diseases, the male reproductive system, haematopoiesis, and cancer development. CMTM6 protein regulates immune responses to normal and abnormal cells.
CKLF-like MARVEL transmembrane domain-containing protein 3, also termed chemokine-like factor superfamily 3, is a member of the CKLF-like MARVEL transmembrane domain-containing family of proteins. In humans, CMTM2 protein is encoded by the CMTM3 gene located in band 22.1 on the long arm of chromosome 16. This protein is expressed in a wide range of tissues, including fetal tissues. It is highly expressed in the male reproductive system, particularly testicular tissues and may play a role in the development of this tissue. It is also highly expressed in the immune system including circulating blood cells, i.e. B lymphocytes, CD4+ T lymphocytes, and monocytes. However, CMTM3 protein is weakly expressed or unexpressed in the malignant tissues of several types of cancers. In many but not all of theses cancers, this decreased or lack of expression appears due to methylation of the GpC islands in the promoter region, and thereby the silencing, of the CMTM3 gene.
Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene.
The CKLF-like MARVEL transmembrane domain-containing family (CMTM), previously termed the chemokine-like factor superfamily (CKLFSF), consists of 9 proteins, some of which have various isoforms due to alternative splicing of their respective genes. These proteins along with their isoforms are:
CKLF-like MARVEL transmembrane domain-containing 5 (CMTM5), previously termed chemokine-like factor superfamily 5, designates any one of the six protein isoforms encoded by six different alternative splices of its gene, CMTM5; CMTM5-v1 is the most studied of these isoforms. The CMTM5 gene is located in band 11.2 on the long arm of chromosome 14.
CKLF like MARVEL transmembrane domain-containing 8, previously termed chemokine-like factor superfamily 8 has at least two isoforms, the CMTM8 and CMTM8-v2 proteins. Protein isoforms are variant products that are made by the alternative splicing of a single gene. The gene for these isoforms, CMTM8, is located in band 22 on the short arm of chromosome 3. The CMTM8 gene and its CMTM8 and CMTM8-v2 proteins belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins. The CMTM8 protein is the full-length and predominant product of the CMTM8 gene. This protein is expressed in a wide range of normal adult and fetal tissues while relatively little is known about the CMTM8-v2 protein. Studies suggest that the CMTM8 protein may be involved in the development of various cancers.
CKLF like MARVEL transmembrane domain-containing 1, formerly termed chemokine-like factor superfamily 1, has 23 known isoforms, the CMTM1-v1 to CMTM1-v23 proteins. Protein isoforms are variant products that are made by alternative splicing of a single gene. The gene for these isoforms, CMTM1, is located in band 22 on the long arm of chromosome 16. The CMTM1 gene and its 23 isoforms belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins. CMTM1 proteins are weakly express in a wide range of normal tissues but are far more highly expressed in normal testes as well as the malignant cells of certain types of cancer.
CKLF like MARVEL transmembrane domain-containing 4, formerly termed chemokine-like factor superfamily 4, is a small transmembrane protein which passes the plasma membrane four times. It has 3 known isoforms, the CMTM4-v1 to CMTM4-v3 proteins. Protein isoforms are variant products that are made by alternative splicing of a single gene. The gene for the CMTM4 isoforms is located in band 22 on the long arm of chromosome 16. The CMTM4 gene and its 3 isoform proteins belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins. CMTM4-v1 and CMTM4-v2 are widely expressed in multiple human tissue while CMTM4-v3 has been detected only in the kidney and placental tissues.
