ADAM (protein)

Last updated

Diagram of an ectodomain shedding ADAM metalloprotease. Ectodomain shedding en.svg
Diagram of an ectodomain shedding ADAM metalloprotease.
Disintegrin and metalloproteinase domain-containing proteins
Identifiers
SymbolADAM
Pfam PF08516
InterPro IPR027053
Membranome 538
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

ADAMs (short for a disintegrin and metalloproteinase) are a family of single-pass transmembrane and secreted metalloendopeptidases. [1] [2] All ADAMs are characterized by a particular domain organization featuring a pro-domain, a metalloprotease, a disintegrin, a cysteine-rich, an epidermal-growth factor like and a transmembrane domain, as well as a C-terminal cytoplasmic tail. [3] Nonetheless, not all human ADAMs have a functional protease domain, which indicates that their biological function mainly depends on protein–protein interactions. [4] Those ADAMs which are active proteases are classified as sheddases because they cut off or shed extracellular portions of transmembrane proteins. [4] For example, ADAM10 can cut off part of the HER2 receptor, thereby activating it. [5] ADAM genes are found in animals, choanoflagellates, fungi and some groups of green algae. Most green algae and all land plants likely lost ADAM proteins. [6]

Contents

ADAMs are categorized under the EC 3.4.24.46 enzyme group, and in the MEROPS peptidase family M12B. [3] The terms adamalysin and MDC family (metalloproteinase-like, disintegrin-like, cysteine rich) have been used to refer to this family historically. [7]

ADAM family members

ProteinDescription
ADAM1 ADAM1 (fertilin α) is a subunit of an integral sperm membrane heterodimeric glycoprotein called fertilin, which plays an important role in sperm-egg interactions.
ADAM2 ADAM2 (fertilin β) is a subunit of an integral sperm membrane heterodimeric glycoprotein called fertilin, which plays an important role in sperm-egg interactions. [8]
ADAM7 ADAM7 is a transmembrane protein important for the maturation of sperm cells in mammals. ADAM7 is also denoted as: ADAM_7, ADAM-7, EAPI, GP-83, and GP83. [9]
ADAM8 The ADAM8 protein encoded by this gene may be involved in cell adhesion during neurodegeneration. [10]
ADAM9 The ADAM9 protein encoded by this gene interacts with SH3 domain-containing proteins, binds mitotic arrest deficient 2 beta protein, and is also involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. [11]
ADAM10 ADAM10 (EC#: 3.4.24.81) is a sheddase, and has a broad specificity for peptide hydrolysis reactions. [12]
ADAM11 The ADAM11 gene represents a candidate tumor suppressor gene for human breast cancer based on its location within a minimal region of chromosome 17q21 previously defined by tumor deletion mapping. [13]
ADAM12 ADAM12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early Down syndrome marker. [14]
ADAM15 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-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. [15]
ADAM17 ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha (TNF-α) at the surface of the cell, and from within the intracellular membranes of the trans-Golgi network. ADAM17 also has a role in the shedding of L-selectin, a cellular adhesion molecule. [16]
ADAM18 The protein encoded by this gene is a sperm surface protein. [17] Synonymous with ADAM27.
ADAM19 This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has also been demonstrated to be an active metalloproteinase, which may be involved in normal physiological and pathological processes such as cells migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. [18]
ADAM20 Exclusively expressed in the testes.
ADAM21 Note: Synonymous with ADAM31.
ADAM22 This gene is highly expressed in the brain and may function as an integrin ligand in the brain. [19]
ADAM23 This gene is highly expressed in the brain and may function as an integrin ligand in the brain. [20]
ADAM28 The protein encoded by this gene is a lymphocyte-expressed ADAM protein. [21]
ADAM29
ADAM30
ADAM33 This protein is a type I transmembrane protein implicated in asthma and bronchial hyperresponsiveness. [22]

Medicine

Therapeutic ADAM inhibitors might potentiate anti-cancer therapy. [23]

See also

Related Research Articles

<span class="mw-page-title-main">Sheddase</span> Enzyme family

Sheddases are membrane-bound enzymes that cleave extracellular portions of transmembrane proteins, releasing the soluble ectodomains from the cell surface. Many sheddases are members of the ADAM or aspartic protease (BACE) protein families.

<span class="mw-page-title-main">ADAM17</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloprotease 17 (ADAM17), also called TACE, is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases.

<span class="mw-page-title-main">Alpha secretase</span> Family of proteolytic enzymes

Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer's disease-associated peptide amyloid beta when APP is instead processed by beta secretase and gamma secretase. The alpha-secretase pathway is the predominant APP processing pathway. Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway in APP processing. Alpha secretases are members of the ADAM family, which are expressed on the surfaces of cells and anchored in the cell membrane. Several such proteins, notably ADAM10, have been identified as possessing alpha-secretase activity. Upon cleavage by alpha secretases, APP releases its extracellular domain - a fragment known as APPsα - into the extracellular environment in a process known as ectodomain shedding.

<span class="mw-page-title-main">ADAMTS4</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 4 is an enzyme that in humans is encoded by the ADAMTS4 gene.

<span class="mw-page-title-main">ADAM12</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 12 is an enzyme that in humans is encoded by the ADAM12 gene. ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.

<span class="mw-page-title-main">ADAM15</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.

<span class="mw-page-title-main">ADAM10</span> Protein-coding gene in the species Homo sapiens

A Disintegrin and metalloproteinase domain-containing protein 10, also known as ADAM10 or CDw156 or CD156c is a protein that in humans is encoded by the ADAM10 gene.

<span class="mw-page-title-main">ADAMTS1</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 1 is an enzyme that in humans is encoded by the ADAMTS1 gene.

<span class="mw-page-title-main">ADAM9</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 9 is an enzyme that in humans is encoded by the ADAM9 gene.

<span class="mw-page-title-main">ADAM19</span> Protein-coding gene in the species Homo sapiens

ADAM19 , is a human gene.

<span class="mw-page-title-main">ADAM22</span> Enzyme found in humans

Disintegrin and metalloproteinase domain-containing protein 22 also known as ADAM22 is an enzyme that in humans is encoded by the ADAM22 gene.

ADAMTS is a family of multidomain extracellular protease enzymes. 19 members of this family have been identified in humans, the first of which, ADAMTS1, was described in 1997. Known functions of the ADAMTS proteases include processing of procollagens and von Willebrand factor as well as cleavage of aggrecan, versican, brevican and neurocan, making them key remodeling enzymes of the extracellular matrix. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration. Homologous subfamily of ADAMTSL (ADAMTS-like) proteins, which lack enzymatic activity, has also been described. Most cases of thrombotic thrombocytopenic purpura arise from autoantibody-mediated inhibition of ADAMTS13.

<span class="mw-page-title-main">ADAMTS8</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 8 is an enzyme that in humans is encoded by the ADAMTS8 gene.

<span class="mw-page-title-main">ADAMTS10</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 10 is an enzyme that in humans is encoded by the ADAMTS10 gene.

<span class="mw-page-title-main">ADAM23</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 23 is a non-catalytic protein that in humans is encoded by the ADAM23 gene. It is a member of the ADAM family of extracellular matrix metalloproteinases.

<span class="mw-page-title-main">ADAM28</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 28 is an enzyme that in humans is encoded by the ADAM28 gene.

<span class="mw-page-title-main">ADAM11</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 11 is an enzyme that in humans is encoded by the ADAM11 gene.

<span class="mw-page-title-main">ADAMTS3</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 3 is an enzyme that in humans is encoded by the ADAMTS3 gene. The protein encoded by this gene is the major procollagen II N-propeptidase.

<span class="mw-page-title-main">ADAMTS12</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 12 is an enzyme that in humans is encoded by the ADAMTS12 gene.

Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.

References

  1. ↑ Brocker, C; Vasiliou, V; Nebert, DW (October 2009). "Evolutionary divergence and functions of the ADAM and ADAMTS gene families". Human Genomics. 4 (1): 43–55. doi:10.1186/1479-7364-4-1-43. PMC   3500187 . PMID   19951893.
  2. ↑ Wolfsberg TG, Straight PD, Gerena RL, et al. (1995). "ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain". Dev. Biol. 169 (1): 378–383. doi: 10.1006/dbio.1995.1152 . PMID   7750654.
  3. 1 2 "ADAM, cysteine-rich (IPR006586)". InterPro . Retrieved 18 February 2016.
  4. 1 2 Edwards DR, Handsley MM, Pennington CJ (October 2008). "The ADAM metalloproteinases". Mol. Aspects Med. 29 (5): 258–89. doi:10.1016/j.mam.2008.08.001. PMC   7112278 . PMID   18762209.
  5. ↑ Liu, P.C.; et al. (2006). "Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells". Cancer Biology and Therapy. 5 (6): 657–664. doi: 10.4161/cbt.5.6.2708 . PMID   16627989.
  6. ↑ Souza J, Lisboa A, Santos T, Andrade M, Neves V, Teles-Souza J, Jesus H, Bezerra T, Falcão V, Oliveira R, Del-Bem L (2020). "The evolution of ADAM gene family in eukaryotes". Genomics. 112 (5): 3108–3116. doi: 10.1016/j.ygeno.2020.05.010 . PMID   32437852. S2CID   218832838.
  7. ↑ Blobel, CP (22 August 1997). "Metalloprotease-disintegrins: links to cell adhesion and cleavage of TNF alpha and Notch". Cell. 90 (4): 589–92. doi: 10.1016/s0092-8674(00)80519-x . PMID   9288739. S2CID   17710705.
  8. ↑ "Entrez Gene: ADAM2 ADAM metallopeptidase domain 2 (fertilin beta)".
  9. ↑ "Entrez Gene: ADAM metallopeptidase domain 7".
  10. ↑ "Entrez Gene: ADAM8 ADAM metallopeptidase domain 8".
  11. ↑ "Entrez Gene: ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma)".
  12. ↑ "Entry of ADAM10 endopeptidase (EC-Number 3.4.24.81 )".
  13. ↑ "Entrez Gene: ADAM11 ADAM metallopeptidase domain 11".
  14. ↑ Danforth's Obstetrics and Gynecology, 10th Edition; Copyright 2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113
  15. ↑ "Entrez Gene: ADAM15 ADAM metallopeptidase domain 15 (metargidin)".
  16. ↑ Li Y, Brazzell J, Herrera A, Walcheck B (October 2006). "ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding". Blood. 108 (7): 2275–9. doi:10.1182/blood-2006-02-005827. PMC   1895557 . PMID   16735599.
  17. ↑ "Entrez Gene: ADAM18 ADAM metallopeptidase domain 18".
  18. ↑ "Entrez Gene: ADAM19 ADAM metallopeptidase domain 19 (meltrin beta)".
  19. ↑ "Entrez Gene: ADAM22 ADAM metallopeptidase domain 22".
  20. ↑ "Entrez Gene: ADAM23 ADAM metallopeptidase domain 23".
  21. ↑ "Entrez Gene: ADAM28 ADAM metallopeptidase domain 28".
  22. ↑ "Entrez Gene: ADAM33 ADAM metallopeptidase domain 33".
  23. ↑ Guo, Zhen; Jin, Xunbo; Jia, Haiyan (2013). "Inhibition of ADAM-17 more effectively down-regulates the Notch pathway than that of γ-secretase in renal carcinoma". Journal of Experimental & Clinical Cancer Research. 32 (1): 26. doi:10.1186/1756-9966-32-26. PMC   3662624 . PMID   23659326.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.