ADAM12

Last updated
ADAM12
Identifiers
Aliases ADAM12 , ADAM12-OT1, CAR10, MCMP, MCMPMltna, MLTN, MLTNA, ADAM metallopeptidase domain 12
External IDs OMIM: 602714 MGI: 105378 HomoloGene: 74862 GeneCards: ADAM12
Orthologs
SpeciesHumanMouse
Entrez

8038

11489

Ensembl

ENSG00000148848

ENSMUSG00000054555

UniProt

O43184

Q61824

RefSeq (mRNA)

NM_021641
NM_001288973
NM_001288974
NM_001288975
NM_003474

Contents

NM_007400

RefSeq (protein)

NP_001275902
NP_001275903
NP_001275904
NP_003465
NP_067673

NP_031426

Location (UCSC) Chr 10: 126.01 – 126.39 Mb Chr 7: 133.48 – 133.83 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Disintegrin and metalloproteinase domain-containing protein 12 (previously Meltrin) is an enzyme that in humans is encoded by the ADAM12 gene. [5] [6] 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. [7]

Function

This gene encodes a member of the 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. This gene has two alternatively spliced transcripts: a shorter secreted form and a longer membrane-bound form. The shorter form is found to stimulate myogenesis. [8]

Clinical Significance

ADAM 12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early Down syndrome marker. Decreased levels of ADAM 12 may be detected in cases of trisomy 21 as early as 8 to 10 weeks gestation. Maternal serum ADAM 12 and PAPP-A levels at 8 to 9 weeks gestation in combination with maternal age yielded a 91% detection rate for Down syndrome at a 5% false-positive rate. When nuchal translucency data from approximately 12 weeks gestation was added, this increased the detection rate to 97%. [9]

ADAM12 has also been implicated in the development of pathology in various cancers, hypertension, liver fibrogenesis, and asthma. [10] In asthma, ADAM12 is upregulated in lung epithelium in response to TNF-alpha. [11]

In a study of about 1200 persons with extremely high intelligence (IQ about 170), variants of the gene were associated with high IQ compared with a general population. [12]

Interactions

ADAM12 has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">ADAM (protein)</span>

ADAMs are a family of single-pass transmembrane and secreted metalloendopeptidases. All ADAMs are characterized by a particular 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. Nonetheless, not all human ADAMs have a functional protease domain, which indicates that their biological function mainly depends on protein–protein interactions. Those ADAMs which are active proteases are classified as sheddases because they cut off or shed extracellular portions of transmembrane proteins. For example, ADAM10 can cut off part of the HER2 receptor, thereby activating it. ADAM genes are found in animals, choanoflagellates, fungi and some groups of green algae. Most green algae and all land plants likely lost ADAM proteins.

<span class="mw-page-title-main">Alpha secretase</span> Family of proteolytic enzymes

Alpha secretases are a family of proteolytic enzymes that cleave amyloid precursor protein (APP) in its transmembrane region. Specifically, alpha secretases cleave within the fragment that gives rise to the Alzheimer's disease-associated peptide amyloid beta when APP is instead processed by beta secretase and gamma secretase. The alpha-secretase pathway is the predominant APP processing pathway. Thus, alpha-secretase cleavage precludes amyloid beta formation and is considered to be part of the non-amyloidogenic pathway in APP processing. Alpha secretases are members of the ADAM family, which are expressed on the surfaces of cells and anchored in the cell membrane. Several such proteins, notably ADAM10, have been identified as possessing alpha-secretase activity. Upon cleavage by alpha secretases, APP releases its extracellular domain - a fragment known as APPsα - into the extracellular environment in a process known as ectodomain shedding.

<span class="mw-page-title-main">Nuclear receptor coactivator 2</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).

<span class="mw-page-title-main">PIK3R1</span> Protein-coding gene in the species Homo sapiens

Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.

<span class="mw-page-title-main">IGFBP3</span> Protein-coding gene in the species Homo sapiens

Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the IGFBP3 gene. IGFBP-3 is one of six IGF binding proteins that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes included in this family, shares neither the conserved structural features nor the high IGF affinity. Instead, IGFBP-7 binds IGF1R, which blocks IGF-1 and IGF-2 binding, resulting in apoptosis.

<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">Alpha-actinin-2</span> Protein-coding gene in the species Homo sapiens

Alpha-actinin-2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.

<span class="mw-page-title-main">Laminin subunit alpha-1</span> Protein-coding gene in the species Homo sapiens

Laminin subunit alpha-1 is a protein that in humans is encoded by the LAMA1 gene.

<span class="mw-page-title-main">ADAMTS1</span> Protein-coding gene in the species Homo sapiens

A disintegrin and metalloproteinase with thrombospondin motifs 1 is an enzyme that in humans is encoded by the ADAMTS1 gene.

<span class="mw-page-title-main">GIT1</span> Mammalian protein found in Homo sapiens

ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene.

<span class="mw-page-title-main">SH3GL2</span> Protein-coding gene in the species Homo sapiens

Endophilin-A1 is a protein that in humans is encoded by the SH3GL2 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">Laminin, beta 2</span> Protein-coding gene in the species Homo sapiens

Laminin subunit beta-2 is a protein that in humans is encoded by the LAMB2 gene.

<span class="mw-page-title-main">CLEC3B</span> Protein-coding gene in the species Homo sapiens

Tetranectin is a protein that in humans is encoded by the CLEC3B gene.

<span class="mw-page-title-main">SNX9</span> Protein-coding gene in the species Homo sapiens

Sorting nexin-9 is a protein that in humans is encoded by the SNX9 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">Integrin alpha 9</span> Protein-coding gene in the species Homo sapiens

Integrin alpha-9 is a protein that in humans is encoded by the ITGA9 gene. Cytogenetic location: 3p22.2

<span class="mw-page-title-main">PACSIN3</span> Protein-coding gene in the species Homo sapiens

Protein kinase C and casein kinase substrate in neurons protein 3 is an enzyme that in humans is encoded by the PACSIN3 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.

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: ENSG00000148848 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000054555 – 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. ↑ Gilpin BJ, Loechel F, Mattei MG, Engvall E, Albrechtsen R, Wewer UM (Feb 1998). "A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo". J. Biol. Chem. 273 (1): 157–66. doi: 10.1074/jbc.273.1.157 . PMID   9417060.
  6. ↑ Kveiborg M, Albrechtsen R, Couchman JR, Wewer UM (Jun 2008). "Cellular roles of ADAM12 in health and disease". Int. J. Biochem. Cell Biol. 40 (9): 1685–702. doi:10.1016/j.biocel.2008.01.025. PMID   18342566.
  7. ↑ Yagami-Hiromasa T, Sato T, Kurisaki T, Kamijo K, Nabeshima Y, Fujisawa-Sehara A (1995). "A metalloprotease-disintegrin participating in myoblast fusion". Nature. 377 (6550): 652–6. Bibcode:1995Natur.377..652Y. doi:10.1038/377652a0. PMID   7566181. S2CID   4348744.
  8. ↑ "Entrez Gene: ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha)".
  9. ↑ Danforth's Obstetrics and Gynecology, 10th Edition; Copyright ©2008 Lippincott Williams & Wilkins; Chapter 7: Prenatal Diagnosis, Page 113
  10. ↑ Nyren-Erickson EK, Jones JM, Srivastava DK, Mallik S (2013). "A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications". Biochim. Biophys. Acta. 1830 (10): 4445–55. doi:10.1016/j.bbagen.2013.05.011. PMC   3740046 . PMID   23680494.
  11. ↑ Estrella C, Rocks N, Paulissen G, Quesada-Calvo F, Noel A, Vilain E, Lassalle P, Tillie-Leblond I, Cataldo D, Gosset P (2009). "Role of a disintegrin and metalloprotease-12 in neutrophil recruitment induced by airway epithelium". Am. J. Respir. Cell Mol. Biol. 41 (4): 449–58. doi:10.1165/rcmb.2008-0124OC. hdl:2268/5767. PMID   19213876.
  12. ↑ Dzirasa K (2017-08-02). "A brilliant approach to study the basis of intelligence?". Science Translational Medicine. 9 (401). doi:10.1126/scitranslmed.aao0978. ISSN   1946-6234. S2CID   44125138.
  13. ↑ Galliano MF, Huet C, Frygelius J, Polgren A, Wewer UM, Engvall E (May 2000). "Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion". J. Biol. Chem. 275 (18): 13933–9. doi: 10.1074/jbc.275.18.13933 . PMID   10788519.
  14. ↑ Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (Jun 2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. 275 (24): 18574–80. doi: 10.1074/jbc.M002172200 . PMID   10849447.
  15. ↑ Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (Nov 2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. 278 (3): 511–5. doi:10.1006/bbrc.2000.3835. PMID   11095942.
  16. ↑ Kang Q, Cao Y, Zolkiewska A (Jul 2001). "Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells". J. Biol. Chem. 276 (27): 24466–72. doi: 10.1074/jbc.M101162200 . PMID   11313349.

Further reading

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