ADAM7

Last updated
ADAM7
Identifiers
Aliases ADAM7 , ADAM 7, ADAM-7, EAPI, GP-83, GP83, ADAM metallopeptidase domain 7
External IDs OMIM: 607310 MGI: 107247 HomoloGene: 2830 GeneCards: ADAM7
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003817

NM_007402

RefSeq (protein)

NP_003808

NP_031428

Location (UCSC) Chr 8: 24.44 – 24.53 Mb Chr 14: 68.73 – 68.77 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Disintegrin and metalloproteinase domain-containing protein 7 is a protein that in humans is encoded by the ADAM7 gene. [5] ADAM7 is an 85-kDa enzyme that is a member of the transmembrane ADAM (A Disintegrin and Metalloprotease) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. ADAM7 is important for the maturation of sperm cells in mammals. ADAM7 is also denoted as: ADAM_7, ADAM-7, EAPI, GP-83, and GP83.

Contents

Function

The functions of ADAM7 directly relate to sperm maturation and fertilization. Sperm are immobile until traversing the epididymis, in which the sperm interact with many proteins secreted by epithelial cells of the epididymis. [6] 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 and ADAM3 protein levels. [7] Complex formation between ADAM7, Calnexin, Hspa5, and Itm2b 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 leading to a conformation change in ADAM7. [7] 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. [6] Portions of the membrane are secreted as exosome vesicles. Secretion in this manner is an 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. [8] [9]

Physical characteristics

Human ADAM7 contains a sequence of 756 amino acids. [10] Numerous mammalian orthologs are currently known. [11] 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. [12]

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. [13] ADAM7 is also present in mature sperm cell membranes of mice. [14] Thus, ADAM7 is synthesized in the epididymis and transferred to the maturing sperm cell membrane. mRNA transcripts are highly expressed in testes leydig cells as well. [15]

Model Organisms

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

Related Research Articles

<span class="mw-page-title-main">Epididymis</span> Tube that connects a testicle to a vas deferens

The epididymis is an elongated tubular structure 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, 6 to 7 centimetres in length; uncoiled the tube would be approximately 6 m long. It connects the testicle to the vas deferens in the male reproductive system. The epididymis serves as an interconnection between the multiple efferent ducts at the rear of a testicle (proximally), and the vas deferens (distally). Its primary function is the storage, maturation and transport of sperm cells.

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. In vivo, capacitation occurs after ejaculation, when the spermatozoa leave the vagina and enter the upper female reproductive tract. The uterus aids in the steps of capacitation by secreting sterol-binding albumin, lipoproteins, and proteolytic and glycosidasic enzymes such as heparin.

<span class="mw-page-title-main">Disintegrin</span> Proteins from viper venom inhibiting platelets aggregation

Disintegrins are a family of small proteins from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion.

<span class="mw-page-title-main">ADAM12</span> Human protein-coding gene

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">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">ADAM33</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 33 is an enzyme that in humans is encoded by the ADAM33 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.

<span class="mw-page-title-main">CST8 (gene)</span> Protein-coding gene in the species Homo sapiens

Cystatin-8 is a protein that in humans is encoded by the CST8 gene.

<span class="mw-page-title-main">ADAM2</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 2 or Beta-fertilin is an enzyme that in humans is encoded by the ADAM2 gene.

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

Calcium-binding tyrosine phosphorylation-regulated protein is a protein that in humans is encoded by the CABYR 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">ADAM8</span> Protein-coding gene in the species Homo sapiens

A Disintegrin and metalloproteinase domain-containing protein 8 is an enzyme that in humans is encoded by the ADAM8 gene.

<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">CRISP1</span> Protein-coding gene in the species Homo sapiens

Cysteine-rich secretory protein 1 is a cysteine-rich secretory protein that in humans is encoded by the CRISP1 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">ADAM18</span> Protein-coding gene in the species Homo sapiens

Disintegrin and metalloproteinase domain-containing protein 18 is an enzyme that in humans is encoded by the ADAM18 gene.

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 membrane protein is critical for crucial steps in fertilization such as migration of sperm through the uterus to the oviduct as well as binding to the zona pellucida. Inactivation of ADAM3 is a cause of male infertility.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000069206 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022056 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: ADAM metallopeptidase domain 7".
  6. 1 2 Oh, Jeong Su; Han, Cecil; Cho, Chunghee (2009). "ADAM7 Is Associated with Epididymosomes and Integrated into Sperm Plasma Membrane". Molecules and Cells. 28 (5): 441–446. doi: 10.1007/s10059-009-0140-x . PMID   19855936. S2CID   591146.
  7. 1 2 Cho C (Oct 2012). "Testicular and epididymal ADAMs: expression and function during fertilization". Nature Reviews. Urology. 9 (10): 550–560. doi:10.1038/nrurol.2012.167. PMID   22926424. S2CID   23223954.
  8. Hermo, L; Jacks, D (2002). "Nature's ingenuity: bypassing the classical secretory route via apocrine secretion". Mol. Reprod. Dev. 63 (3): 394–410. doi:10.1002/mrd.90023. PMID   12237956. S2CID   22251485.
  9. Sullivan, R; Saez, F; Girouard, J; Frenette, G (2005). "Role of exosomes in sperm maturation during the transit along the male reproductive tract". Blood Cells Mol. Dis. 35 (1): 1–10. doi:10.1016/j.bcmd.2005.03.005. PMID   15893944.
  10. "Homo sapiens (human): 8756". www.genome.jp. Retrieved 9 March 2015.
  11. "ORTHOLOGY: K16071". www.genome.jp. Retrieved 9 March 2015.
  12. "Disintegrin and Metalloproteinase Domain-containing Protein 7". UniProt. Retrieved 29 April 2015.
  13. Oh J, Woo JM, Choi E, Kim T, Cho BN, Park ZY, Kim YC, Kim DH, Cho C (Jun 2005). "Molecular, biochemical, and cellular characterization of epididymal ADAMs, ADAM7 and ADAM28". Biochemical and Biophysical Research Communications. 331 (4): 1374–1383. doi:10.1016/j.bbrc.2005.04.067. PMID   15883027.
  14. Kim T, Oh J, Woo JM, Choi E, Im SH, Yoo YJ, Kim DH, Nishimura H, Cho C (Apr 2006). "Expression and relationship of male reproductive ADAMs in mouse". Biology of Reproduction. 74 (4): 744–750. doi: 10.1095/biolreprod.105.048892 . PMID   16407499.
  15. "Adam7 (ADAM metallopeptidase domain 7)". Biogps. Retrieved 12 May 2015.