View source for ADAM (protein)

{{Use dmy dates|date=April 2016}}
{{For|the fictional biologically active substance called ADAM|BioShock}}
[[File:Ectodomain shedding en.svg|thumb|400px|right|Diagram of an ectodomain shedding ADAM metalloprotease.]]
{{Pfam box |Symbol = ADAM |Name = Disintegrin and metalloproteinase domain-containing proteins |Pfam = PF08516 |InterPro = IPR027053 |PROSITE =  |PDB = |Membranome family=538}}
'''ADAMs''' (short for '''a disintegrin and metalloproteinase''') are a family of single-pass transmembrane and secreted [[metalloendopeptidases]].<ref>{{cite journal|last=Brocker|first=C|author2=Vasiliou, V|author3= Nebert, DW|title=Evolutionary divergence and functions of the ADAM and ADAMTS gene families.|journal=Human Genomics|date=October 2009|volume=4|issue=1|pages=43–55|pmid=19951893|pmc=3500187|doi=10.1186/1479-7364-4-1-43|doi-access=free}}</ref><ref>{{cite journal |vauthors=Wolfsberg TG, Straight PD, Gerena RL |title=ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain |journal=Dev. Biol. |volume=169 |issue=1 |pages=378–383 |year=1995 |pmid=7750654 |doi=10.1006/dbio.1995.1152|display-authors=etal|doi-access=free }}</ref> All ADAMs are characterized by a particular [[protein domain|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.<ref name="IP">{{cite web|title=ADAM, cysteine-rich (IPR006586)|url=http://www.ebi.ac.uk/interpro/entry/IPR006586?q=adam%20type:domain|website=[[InterPro]]|access-date=18 February 2016}}</ref> Nonetheless, not all human ADAMs have a functional protease domain, which indicates that their biological function mainly depends on [[protein–protein interactions]].<ref name="ED">{{cite journal |vauthors=Edwards DR, Handsley MM, Pennington CJ |title=The ADAM metalloproteinases |journal=Mol. Aspects Med. |volume=29 |issue=5 |pages=258–89 |date=October 2008 |pmid=18762209 |doi=10.1016/j.mam.2008.08.001 |pmc=7112278 }}</ref> Those ADAMs which are active proteases are classified as [[sheddase]]s because they cut off or shed extracellular portions of [[transmembrane proteins]].<ref name="ED" /> For example, ADAM10 can cut off part of the [[HER2]] receptor, thereby activating it.<ref>{{cite journal | last = Liu | first = P.C. | title = Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells. | journal = Cancer Biology and Therapy | volume = 5 | pages = 657–664 | year = 2006 | pmid = 16627989 | issue = 6 | doi=10.4161/cbt.5.6.2708|display-authors=etal| doi-access = free }}</ref> ADAM genes are found in [[animals]], [[choanoflagellate]]s, [[fungi]] and some groups of [[green algae]]. Most [[green algae]] and all [[land plants]] probably had ADAM proteins but lost them.<ref name="ED2">{{cite journal |vauthors=Souza J, Lisboa A, Santos T, Andrade M, Neves V, Teles-Souza J, Jesus H, Bezerra T, Falcão V, Oliveira R, Del-Bem L |title=The evolution of ADAM gene family in eukaryotes |journal=Genomics | year = 2020 |volume=112 |issue=5 |pages=3108–3116 | doi=10.1016/j.ygeno.2020.05.010|pmid=32437852 |s2cid=218832838 |doi-access=free }}</ref>

ADAMs are categorized under the {{EC number|3.4.24.46}} enzyme group, and in the [[MEROPS]] peptidase family M12B.<ref name="IP" /> The terms '''adamalysin''' and '''MDC family''' (metalloproteinase-like, disintegrin-like, cysteine rich) have been used to refer to this family historically.<ref>{{cite journal|last1=Blobel|first1=CP|title=Metalloprotease-disintegrins: links to cell adhesion and cleavage of TNF alpha and Notch.|journal=Cell|date=22 August 1997|volume=90|issue=4|pages=589–92|pmid=9288739|doi=10.1016/s0092-8674(00)80519-x|s2cid=17710705|doi-access=free}}</ref>

==ADAM family members==
{{clear}}
{| class="wikitable"
! Protein !! Description 
|-
|[[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.<ref name="entrez">{{cite web | title = Entrez Gene: ADAM2 ADAM metallopeptidase domain 2 (fertilin beta)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2515}}</ref>
|-
|[[ADAM7]] || ADAM7 is a transmembrane protein important for the maturation of [[sperm]] cells in [[mammal]]s. ADAM7 is also denoted as: ADAM_7, ADAM-7, EAPI, GP-83, and GP83.<ref name="ADAM7">{{cite web | title = Entrez Gene: ADAM metallopeptidase domain 7 | url = https://www.ncbi.nlm.nih.gov/gene/8756 }}</ref>
|-
| [[ADAM8]] || The ADAM8 protein encoded by this gene may be involved in [[cell adhesion]] during [[neurodegeneration]].<ref name="ADAM8">{{cite web | title = Entrez Gene: ADAM8 ADAM metallopeptidase domain 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=101}}</ref>
|-
| [[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.<ref name="ADAM9">{{cite web | title = Entrez Gene: ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8754}}</ref>
|-
| [[ADAM10]] || ADAM10 (EC#: 3.4.24.81) is a [[sheddase]], and has a broad specificity for peptide hydrolysis reactions.<ref name="Brenda Database">{{cite web | title = Entry of ADAM10 endopeptidase (EC-Number 3.4.24.81 )| url = http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.81}}</ref>
|-
| [[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.<ref name="ADAM11">{{cite web | title = Entrez Gene: ADAM11 ADAM metallopeptidase domain 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4185}}</ref>
|-
| [[ADAM12]] || ADAM12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early [[Down syndrome]] marker.<ref>Danforth's Obstetrics and Gynecology, 10th Edition; Copyright 2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113</ref>
|-
| [[ADAM15]] || Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, [[CD61|beta 3]]. It also interacts with [[tyrosine-protein kinase CSK|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.<ref name="ADAM15">{{cite web | title = Entrez Gene: ADAM15 ADAM metallopeptidase domain 15 (metargidin)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8751}}</ref>
|-
| [[ADAM17]] || ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha ([[TNF-α]]) at the surface of the [[Cell (biology)|cell]], and from within the [[intracellular membranes]] of the [[trans-Golgi network]]. ADAM17 also has a role in the shedding of [[L-selectin]], a [[Cell adhesion molecule|cellular adhesion molecule]].<ref name="pmid16735599">{{cite journal | vauthors = Li Y, Brazzell J, Herrera A, Walcheck B | title = ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding | journal = Blood | volume = 108 | issue = 7 | pages = 2275–9 | date = October 2006 | pmid = 16735599 | pmc = 1895557 | doi = 10.1182/blood-2006-02-005827 }}</ref>
|-
| [[ADAM18]] || The protein encoded by this gene is a sperm surface protein.<ref name="ADAM18">{{cite web | title = Entrez Gene: ADAM18 ADAM metallopeptidase domain 18| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8749}}</ref> 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.<ref name="ADAM19">{{cite web | title = Entrez Gene: ADAM19 ADAM metallopeptidase domain 19 (meltrin beta)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8728}}</ref>
|-
| [[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.<ref name="ADAM22">{{cite web | title = Entrez Gene: ADAM22 ADAM metallopeptidase domain 22| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=53616}}</ref>
|-
| [[ADAM23]] || This gene is highly expressed in the brain and may function as an integrin ligand in the brain.<ref name="ADAM23">{{cite web | title = Entrez Gene: ADAM23 ADAM metallopeptidase domain 23| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8745}}</ref>
|-
| [[ADAM28]] || The protein encoded by this gene is a [[lymphocyte]]-expressed ADAM protein.<ref name="ADAM28">{{cite web | title = Entrez Gene: ADAM28 ADAM metallopeptidase domain 28| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10863}}</ref>
|-
| [[ADAM29]] || 
|-
| [[ADAM30]] || 
|-
| [[ADAM33]] || This protein is a type I [[transmembrane protein]] implicated in [[asthma]] and [[bronchial hyperresponsiveness]].<ref name="ADAM33">{{cite web | title = Entrez Gene: ADAM33 ADAM metallopeptidase domain 33| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80332}}</ref>
|}

==Medicine==
Therapeutic ADAM inhibitors might potentiate anti-cancer therapy.<ref>{{cite journal|last1=Guo|first1=Zhen|last2=Jin|first2=Xunbo|last3=Jia|first3=Haiyan|title=Inhibition of ADAM-17 more effectively down-regulates the Notch pathway than that of γ-secretase in renal carcinoma|journal=Journal of Experimental & Clinical Cancer Research|date=2013|volume=32|issue=1|pages=26|doi=10.1186/1756-9966-32-26|pmid=23659326|pmc=3662624 |doi-access=free }}</ref>

==See also==
* [[ADAMTS]] (A disintegrin and metalloproteinase with thrombospondin motifs) family
* [[Ectodomain shedding]]

==References==
{{reflist|2}}

==External links==
* {{MeshName|ADAM+Proteins}}
* http://www.healthvalue.net/sheddase.html {{Webarchive|url=https://web.archive.org/web/20190619070701/http://www.healthvalue.net/sheddase.html |date=19 June 2019 }}

{{Glycoproteins}}
{{Metalloendopeptidases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

{{DEFAULTSORT:ADAM protein}}
[[Category:Protein families]]
[[Category:Single-pass transmembrane proteins]]
[[Category:Proteases]]
[[Category:EC 3.4.24]]