Disintegrin and metalloproteinase domain-containing protein 15 is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''ADAM15''

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

The protein encoded by this gene is a member of the

ADAM Adam is the name given in Genesis 1–5 to the first human. Adam is the first human-being aware of God, and features as such in various belief systems (including Judaism, Christianity, Gnosticism and Islam). According to Christianity, Adam ...

(a disintegrin and metalloproteinase) protein family. ADAM family members are type I

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

s known to be involved in

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as Cell_junction, cell junc ...

and proteolytic

ectodomain An ectodomain is the domain of a membrane protein that extends into the extracellular space (the space outside a cell). Ectodomains are usually the parts of proteins that initiate contact with surfaces, which leads to signal transduction. A n ...

processing of

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a

disintegrin Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Operation Disintegrins work by countering th ...

-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.

Clinical significance

Arthritis

ADAM15 has been associated with a number of diseases, most recently

Rheumatoid Arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress. ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.

Cancer

The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as

Breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

where the expression of the protein is increased in carcinoma in-situ, invasive carcinoma and metastatic breast cancer tissues Additionally, the alternative splice variant forms of ADAM15 have also been correlated with different prognosis in 48 breast cancer patients based upon their expression levels. ADAM15 has also been shown to have a role in

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

again through increased expression in neoplastic and metastatic tissues compared to normal prostate tissues and also through its modulation of

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

cell- tumour cell interactions.

Interactions

ADAM15 has been shown to interact with: *

Grb2 Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/ cell communication. In humans, the GRB2 protein is encoded by the ''GRB2'' gene. The protein encoded by this gene binds recepto ...

, * HCK, * Lck and *

SH3GL2 Endophilin-A1 is a protein that in humans is encoded by the ''SH3GL2'' gene. Interactions SH3GL2 has been shown to interact with DNM1, Amphiphysin, ADAM9 Disintegrin and metalloproteinase domain-containing protein 9 is an enzyme that in huma ...

, and *

SNX9 Sorting nexin-9 is a protein that in humans is encoded by the ''SNX9'' gene. This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved i ...

. The alternatively spliced isoforms have also been shown to exhibit different preferential interactions with proteins containing

SH3 domain The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of ph ...

References

External links

* The MEROPS online database for peptidases and their inhibitors
M12.215
* {{DEFAULTSORT:Adam15 Proteases Human proteins EC 3.4.24