ADAMs

ADAMs (a disintegrin and metalloproteases) are a family of transmembrane metalloproteinases that function as proteases and/or adhesion molecules. They are members of the M12B adamalysin protease subfamily, which also includes reprolysins and ADAMTs.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
3995 GI 254023X
Selective ADAM10 metalloprotease inhibitor
5960 TMI 1
Adam 17 (TACE) and MMP inhibitor; orally bioavailable

ADAMs (a disintegrin and metalloproteases) are a family of transmembrane metalloproteinases that function as proteases and/or adhesion molecules. They are members of the M12B adamalysin protease subfamily, which also includes reprolysins and ADAMTs. There have been 25 human ADAM genes identified to date, 21 of them are functional, and 13 have proteolytic activity. The ADAMs with proteolytic activity are ADAMDEC-1, ADAM-8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30 and 33, while ADAM-2, 7, 11, 18, 22, 23, 29 and 32 are catalytically inactive, and have roles in protein folding and protein-protein interaction.

The ADAM family has a varied tissue distribution profile. ADAM-2, 18, 20, 21, 29 and 30 are primarily expressed in the testes and have been associated with fertility, consistent with their role in spermatogenesis and sperm-egg interaction. The other ADAMs are expressed in a variety of tissues and have been associated with biological processes such as cell fate determination in the nervous system, axon guidance, cell migration, muscle development, immunity and wound healing.

Proteolytic ADAMs function by cleaving transmembrane proteins, such as cytokines, chemokines and growth factors, to modulate their activity. Cleavage of the protein's ectodomain, a process termed 'shedding', results in the transmembrane and cytoplasmic domains being released into the cytoplasm. This mechanism regulates substrate activity by either resulting in a non-functional cell surface molecule, or inducing signal transduction through the release of intracellular or extracellular components. Non-proteolytic ADAMs interact with integrins to either positively or negatively regulate cell-cell adhesion. ADAM activity is regulated endogenously by TIMPs (tissue inhibitors of metalloproteinases), although ADAM-8, 9 and 19 are insensitive to TIMP inhibition.

ADAM substrates include EGF, TNF-α, Notch and amyloid precursor protein (APP). EGF and TNF-α require cleavage by ADAM-17 before being released from the cell membrane and binding to their receptors to initiate signaling. Following ligand binding Notch is cleaved by ADAM-10 and then γ-secretase, releasing the intracellular component of Notch, and initiating Notch signaling. ADAM-10 and 17 have been shown to act as α-secretases, and are therefore able to cleave APP to form soluble APPsα. Overexpression of ADAM-10 has been shown to reduce amyloid plaque formation and improve cognitive deficits in a mouse model of Alzheimer's disease (AD).

ADAMs have been implicated in cancer, being involved in the promotion of tumor invasion and metastasis, as well as having a role in breast cancer through the initiation of EGF receptor signaling. ADAMs may also be important in the pathology of neurological and cardiovascular diseases, including AD and atherosclerosis, as well as in asthma, inflammation, rheumatoid arthritis and diabetes.

External sources of pharmacological information for ADAMs :

    Literature for ADAMs

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    ADAM Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    ADAM2 Human ADAM2 NM_001464 Q99965
    Mouse Adam2 NM_009618 Q60718
    Rat Adam2 NM_020077 NP_064462
    ADAM7 Human ADAM7 NM_003817 Q9H2U9
    Mouse Adam7 NM_007402 O35227
    Rat Adam7 NM_020301 NP_064697
    ADAM8 Human ADAM8 NM_001109 P78325
    Mouse Adam8 NM_007403 Q05910
    Rat Adam8
    ADAM9 Human ADAM9 XM_017013942 Q13443
    Mouse Adam9 NM_001270996 Q61072
    Rat Adam9 NM_001014772 NP_001014772
    ADAM10 Human ADAM10 NM_001110 O14672
    Mouse Adam10 NM_007399 Q6NZC0
    Rat Adam10 NM_019254 NP_062127
    ADAM11 Human ADAM11 NM_002390 O75078
    Mouse Adam11 NM_001110778 Q9R1V4
    Rat Adam11 NM_001108300 NP_001101770
    ADAM12 Human ADAM12 XM_017016705 O43184
    Mouse Adam12 NM_007400 Q61824
    Rat Adam12
    ADAM15 Human ADAM15 NM_003815 Q13444
    Mouse Adam15 NM_001037722 O88839
    Rat Adam15 NM_020308 Q9QYV0
    ADAM17 Human ADAM17 XM_011510375 P78536
    Mouse Adam17 NM_009615 Q9Z0F8
    Rat Adam17 NM_020306 NP_064702
    ADAM18 Human ADAM18 NM_014237 Q9Y3Q7
    Mouse Adam18 NM_010084 Q9R157
    Rat Adam18
    ADAM19 Human ADAM19 NM_033274 Q9H013
    Mouse Adam19 NM_009616 O35674
    Rat Adam19 NM_001160228 NP_001153700
    ADAM20 Human ADAM20 XM_005268151 O43506
    Mouse Adam20 NM_001009548 Q7M763
    Rat Adam20 XM_001056657 XP_006253165
    ADAM21 Human ADAM21 NM_003813 Q9UKJ8
    Mouse Adam21 NM_020330 Q9JI76
    Rat Adam21 XM_003751594 XP_003751642
    ADAM22 Human ADAM22 NM_021723 Q9P0K1
    Mouse Adam22 NM_001007220 Q9R1V6
    Rat Adam22 XM_002726324 XP_002726370
    ADAM23 Human ADAM23 NM_003812 O75077
    Mouse Adam23 NM_011780 Q9R1V7
    Rat Adam23 NM_001029899 NP_001025070
    ADAM28 Human ADAM28 NM_021778 Q9UKQ2
    Mouse Adam28 NM_010082 Q9JLN6
    Rat Adam28 NM_181693 NP_859044
    ADAM29 Human ADAM29 NM_014269 Q9UKF5
    Mouse Adam29 NM_175939 Q811Q4
    ADAM30 Human ADAM30 NM_021794 Q9UKF2
    Mouse Adam30 NM_027665 Q811Q3
    Rat Adam30 NM_001109600 NP_001103070
    ADAM32 Human ADAM32 NM_145004 Q8TC27
    Mouse Adam32 NM_153397 Q8K410
    Rat Adam32 NM_001170582 NP_001164053
    ADAM33 Human ADAM33 NM_025220 Q9BZ11
    Mouse Adam33 NM_033615 Q923W9
    Rat Adam33 NM_001107776 XP_003749622
    ADAMDEC1 Human ADAMDEC1 NM_014479 O15204
    Mouse Adamdec1 NM_021475 Q9R0X2
    Rat Adamdec1 NM_001106046 NP_001099516