Disintegrin and metalloproteinase domain-containing protein 7 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ADAM7

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. ADAM7 is an 85-kDa

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that is a member of the transmembrane

ADAM Adam; el, Ἀδάμ, Adám; la, Adam is the name given in Genesis 1-5 to the first human. Beyond its use as the name of the first man, ''adam'' is also used in the Bible as a pronoun, individually as "a human" and in a collective sense as " ...

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 the blo ...

and

Metalloprotease A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example is ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myogen ...

)

family. Members of this family are membrane-anchored proteins structurally related to snake venom

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 the blo ...

s, and have been implicated in a variety of biological processes involving cell-cell and cell-

matrix Matrix most commonly refers to: * ''The Matrix'' (franchise), an American media franchise ** ''The Matrix'', a 1999 science-fiction action film ** "The Matrix", a fictional setting, a virtual reality environment, within ''The Matrix'' (franchis ...

interactions, including fertilization, muscle development, and neurogenesis. ADAM7 is important for the maturation of

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...

cells in

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s. ADAM7 is also denoted as: ADAM_7, ADAM-7, EAPI, GP-83, and GP83.

Function

The functions of ADAM7 directly relate to sperm maturation and fertilization. Sperm are immobile until traversing the

epididymis The epididymis (; plural: epididymides or ) is a tube that connects a testicle to a vas deferens in the male reproductive system. It is a single, narrow, tightly-coiled tube in adult humans, in length. It serves as an interconnection between the ...

, in which the sperm interact with many proteins secreted by epithelial cells of the epididymis. Lacking protease activity, ADAM7 may play roles in protein-protein interactions and cell adhesion processes including sperm-egg fusion. ADAM7 is secreted by epididymis cells and transferred to the maturing sperm's surface. As determined through mouse gene knock-out studies, the amount of ADAM7 secreted is directly linked to

ADAM2 Disintegrin and metalloproteinase domain-containing protein 2 or Beta-fertilin is an enzyme that in humans is encoded by the ''ADAM2'' gene. Function This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Me ...

and

ADAM3 A disintegrin and metalloprotease 3, or ADAM3, belongs to a family of peptidase proteins referred to as ADAMs. Many of these are solely found in spermatogenic cells, specifically in the anterior portion of capacitated spermatozoa heads. This membr ...

protein levels. Complex formation between ADAM7,

Calnexin Calnexin (CNX) is 67kDaintegral protein (that appears variously as a 90kDa, 80kDa, or 75kDa band on western blotting depending on the source of the antibody) of the endoplasmic reticulum (ER). It consists of a large (50 kDa) N-terminal calcium- bi ...

, Hspa5, and

Itm2b Integral membrane protein 2B (ITM2B or BRI2) is a protein that in humans is encoded by the ''ITM2B'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meani ...

have been shown to act as a molecular chaperone after ADAM7 is incorporated into the membrane of sperm cells. Furthermore, complex formation with Itm2b is increased during sperm

capacitation Capacitation is the penultimate step in the maturation of mammalian spermatozoa and is required to render them competent to fertilize an oocyte. This step is a biochemical event; the sperm move normally and look mature prior to capacitation. ''I ...

leading to a conformation change in ADAM7. As such, the ADAM7 protein plays an important function involved in sperm capacitation, although this function is not entirely understood.

Mechanism of secretion and membrane transfer

ADAM7 is synthesized in epididymis cells and transferred to the membrane of immature sperm cells as they traverse the epididymis during sperm maturation. Epithelial cells of the epididymis incorporate ADAM7 into their membrane normally like other

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signi ...

. Portions of the membrane are secreted as exosome vesicles. Secretion in this manner is an

apocrine Apocrine () glands are a type of exocrine gland, which are themselves a type of gland, i.e. a group of cells specialized for the release of secretions. Exocrine glands secrete by one of three means: holocrine, merocrine and apocrine. In apocrine ...

secretion in which apical blebs containing a portion of the epididymis cell are released from the cell. The apical blebs then encounter the immature sperm cell membrane within the convoluted tubules of the epididymis. The apical bleb and immature sperm cell membrane then fuse, ultimately incorporating ADAM7 into the sperm cell membrane.

Physical characteristics

Human ADAM7 contains a sequence of 756

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s. Numerous mammalian

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

are currently known. The largest portion of ADAM7 resides in the extracellular space. A short helical transmembrane sequence anchors the sequence while a short cytoplasmic sequence exists. This is consistent and expected as the protein has a secretory function.

Localization

ADAM7 expression is localized in mammalian epididymis cells. Expression of ADAM7 is higher in the head (''Caput'') of the epididymis and decreases in cells towards the distal epididymis. ADAM7 is also present in mature sperm cell membranes of mice. Thus, ADAM7 is synthesized in the epididymis and transferred to the maturing sperm cell membrane. mRNA transcripts are highly expressed in testes

leydig cell Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...

s as well.

Model Organisms

Due to the large mammalian homology, ADAM7 is primarily studied in ''Mus Musculus''.

References

External links

* The

MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibitor ...

online database for peptidases and their inhibitors
M12.956Endocrinology Journal
* Gene expression/activity chart via biogps
mRNA Tissue Expression
* {{Metalloproteinases Proteases Human proteins