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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ADAM7

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 ...

. ADAM7 is an 85-kDa

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 is a member of the transmembrane

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 ...

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 ...

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 myoge ...

)

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 th ...

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

matrix Matrix (: matrices or matrixes) or MATRIX may refer to: Science and mathematics * Matrix (mathematics), a rectangular array of numbers, symbols or expressions * Matrix (logic), part of a formula in prenex normal form * Matrix (biology), the m ...

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

sperm Sperm (: sperm or sperms) is the male reproductive Cell (biology), 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 ...

cells in

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

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

Tissue distribution

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.

Structure

Human ADAM7 contains a sequence of 756

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

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.

Function

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

epididymis The epididymis (; : epididymides or ) is an elongated tubular genital organ attached to the posterior side of each one of the two male reproductive glands, the testicles. It is a single, narrow, tightly coiled tube in adult humans, in length; ...

, 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 protein levels. Complex formation between ADAM7,

Calnexin Calnexin (CNX) is a 67kDa integral 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 calciu ...

, Hspa5, and

Itm2b Integral membrane protein 2B (ITM2B or BRI2) is a protein that in humans is encoded by the ''ITM2B'' gene. ''ITM2B'' or ''BRI2'' is a gene located on chromosome 13. The gene is connected to familial Danish dementia and familial British dement ...

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 can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...

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

apocrine Apocrine () is a term used to classify the mode of secretion of exocrine glands. In apocrine secretion, secretory cells accumulate material at their apical ends, often forming blebs or "snouts", and this material then buds off from the cells ...

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.

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 inhibito ...

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