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Gene Review

ADAMTS2  -  ADAM metallopeptidase with thrombospondin...

Homo sapiens

Synonyms: A disintegrin and metalloproteinase with thrombospondin motifs 2, ADAM-TS 2, ADAM-TS2, ADAMTS-2, ADAMTS-3, ...
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Disease relevance of ADAMTS2

  • Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene [1].
  • The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for [2].
  • We studied 20 patients and 20 age-matched control subjects with neuropsychiatric tests (Blessed, Cornell depression and NPI scores) and autonomic tests (Deep breath (HRdb), 30:15 ratio and orthostatic hypotension (Bpoh)) [3].
  • A standard clinical protocol including inclusion/exclusion criteria, collection of demographic and medical data, cognitive (Mini Mental State Examination: MMSE), motor (Unified Parkinson's Disease Rating Scale: UPDRS) and neuropsychiatric (Neuropsychiatric Inventory: NPI) examinations, was applied after obtaining informed consent [4].

Psychiatry related information on ADAMTS2

  • This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH) [5].
  • During follow-up, anxious children were more likely to develop new psychiatric disorders (30%), primarily new anxiety disorders (16%), than were NPI children (11% and 2%, respectively), but not psychopathological controls (42% and 10%, respectively) [6].
  • RESULTS: On univariate analysis, decreased quality of life was statistically significantly correlated with higher levels of behavioural and psychological disturbance (NPI total score and its agitation, depression, anxiety, disinhibition, and irritability subscales); younger age of the person with dementia; and poorer mental health of the carer [7].
  • Follow-up interviews assessed subjects' residential, educational, occupational, and marital status; utilization of mental health services; and psychological status RESULTS: Anxious subjects without histories of depression were less likely than NPI controls to be living independently [8].
  • METHOD: This 8-year prospective study compared psychosocial functioning in young adults (mean age 22 years) who had histories of early-onset anxiety disorders, comorbid anxiety and depressive disorders, or no history of psychiatric illness (NPI) [8].

High impact information on ADAMTS2

  • The pNPI enzyme is a metalloproteinase containing properdin repeats and a cysteine-rich domain with similarities to the disintegrin domain of reprolysins [9].
  • We also demonstrate that, despite similarities in NH2-terminal domain structures, pro-alpha2(V) NH2-terminal globular sequences are not cleaved by ADAMTS-2, the metalloproteinase that cleaves the N-propeptides of the major fibrillar procollagen chains [10].
  • Null mutations in procollagen I N-propeptidase (ADAMTS-2) cause dermatosparaxis in cattle and the Ehlers-Danlos syndrome (dermatosparactic type) in humans by preventing proteolytic excision of the N-propeptide of procollagen I [11].
  • Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function [1].
  • Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III [1].

Chemical compound and disease context of ADAMTS2


Biological context of ADAMTS2

  • All participants completed NPI I on their first or second postpartum day [13].
  • PI (normalized (NPI) for heart rate) and maximum, minimum and average velocities of the uterine artery were recorded and waveforms were qualitatively assessed using Goswamy and Steptoe's waveform classification [14].
  • The relationship between age and urodynamic parameters was studied cross-sectionally in a group of 28 women in whom clinically and urodynamically both stress incontinence and detrusor instability were excluded (no proven incontinence, NPI) and in a group, matched for age, with genuine stress incontinence (GSI) [15].
  • Presence and severity of psychosis was measured with a modification of the Neuropsychiatric Inventory (NPI; Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gorbein, J. (1994). The neuropsychiatric inventory: Comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308-2314) [16].

Anatomical context of ADAMTS2


Associations of ADAMTS2 with chemical compounds

  • CONCLUSIONS: Nifedipine induces a reversible decrease in NPI and an increase in blood flow velocities in the uterine artery in prematurely menopausal women [14].
  • RESULTS: Patients treated with memantine had significantly lower NPI total scores than patients treated with placebo [19].
  • METHODS: Based on the Croatian Institute for Health Insurance data for 2003, the number of prescriptions per insured individual (NPI) was calculated for employed and unemployed persons, as well as for different subsets according to the region (Zagreb, Split, Rijeka, Osijek), age, gender, and prescribed drug category [20].
  • Compared with placebo, the use of trazodone was not associated with statistically significant benefits for behavioural manifestations as measured by various rating scales (ABID, CERAD-BRSD,CMAI, NPI) [21].

Other interactions of ADAMTS2

  • Abnormal dentin structure in two novel gene mutations [COL1A1, Arg134Cys] and [ADAMTS2, Trp795-to-ter] causing rare type I collagen disorders [12].
  • We investigated the mRNA expression of ADAM-8, -17, -19, -28, ADAM-TS1, and ADAM-TS2 in paired tissue samples from cancerous and non-cancerous parts of the kidneys of 27 patients with RCC who underwent tumour nephrectomy [22].
  • ADAM-8 and ADAM-TS2 over expression as well as decreased hepsin expression were associated with shorter patient survival [23].

Analytical, diagnostic and therapeutic context of ADAMTS2

  • Like the animal model dermatosparaxis, EDS type VIIC results from the absence of activity of procollagen I N-proteinase (pNPI), the enzyme that excises the N-propeptide of type I and type II procollagens [9].
  • On NPI II a significantly positive change in perception was found for the experimental group, but not for the control group [13].
  • Neuropsychiatric symptom profiles differ among dementia syndromes, and the NPI provides a means of assessing neuropsychiatric symptoms that may aid in differential diagnosis [18].
  • METHODS: On admission and on discharge, a multidimensional evaluation was performed assessing mental and functional status, BPSD (Neuropsychiatric Inventory, NPI), somatic health status, and pharmacotherapy [24].


  1. Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene. Colige, A., Nuytinck, L., Hausser, I., van Essen, A.J., Thiry, M., Herens, C., Adès, L.C., Malfait, F., Paepe, A.D., Franck, P., Wolff, G., Oosterwijk, J.C., Smitt, J.H., Lapière, C.M., Nusgens, B.V. J. Invest. Dermatol. (2004) [Pubmed]
  2. Contribution of vascular endothelial growth factor to the Nottingham prognostic index in node-negative breast cancer. Coradini, D., Boracchi, P., Daidone, M.G., Pellizzaro, C., Miodini, P., Ammatuna, M., Tomasic, G., Biganzoli, E. Br. J. Cancer (2001) [Pubmed]
  3. Association between neuropsychiatric and autonomic dysfunction in Alzheimer's disease. Idiaquez, J., Sandoval, E., Seguel, A. Clin. Auton. Res. (2002) [Pubmed]
  4. Dementia with lewy bodies: findings from an international multicentre study. Del Ser, T., McKeith, I., Anand, R., Cicin-Sain, A., Ferrara, R., Spiegel, R. International journal of geriatric psychiatry. (2000) [Pubmed]
  5. The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer's disease. Clark, W.S., Street, J.S., Feldman, P.D., Breier, A. The Journal of clinical psychiatry. (2001) [Pubmed]
  6. A prospective study of childhood anxiety disorders. Last, C.G., Perrin, S., Hersen, M., Kazdin, A.E. Journal of the American Academy of Child and Adolescent Psychiatry. (1996) [Pubmed]
  7. Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia. Banerjee, S., Smith, S.C., Lamping, D.L., Harwood, R.H., Foley, B., Smith, P., Murray, J., Prince, M., Levin, E., Mann, A., Knapp, M. J. Neurol. Neurosurg. Psychiatr. (2006) [Pubmed]
  8. Anxious children in adulthood: a prospective study of adjustment. Last, C.G., Hansen, C., Franco, N. Journal of the American Academy of Child and Adolescent Psychiatry. (1997) [Pubmed]
  9. Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Colige, A., Sieron, A.L., Li, S.W., Schwarze, U., Petty, E., Wertelecki, W., Wilcox, W., Krakow, D., Cohn, D.H., Reardon, W., Byers, P.H., Lapière, C.M., Prockop, D.J., Nusgens, B.V. Am. J. Hum. Genet. (1999) [Pubmed]
  10. Biosynthetic processing of the Pro-alpha1(V)Pro-alpha2(V)Pro-alpha3(V) procollagen heterotrimer. Gopalakrishnan, B., Wang, W.M., Greenspan, D.S. J. Biol. Chem. (2004) [Pubmed]
  11. Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis. Fernandes, R.J., Hirohata, S., Engle, J.M., Colige, A., Cohn, D.H., Eyre, D.R., Apte, S.S. J. Biol. Chem. (2001) [Pubmed]
  12. Abnormal dentin structure in two novel gene mutations [COL1A1, Arg134Cys] and [ADAMTS2, Trp795-to-ter] causing rare type I collagen disorders. De Coster, P.J., Cornelissen, M., De Paepe, A., Martens, L.C., Vral, A. Arch. Oral Biol. (2007) [Pubmed]
  13. Effect of teaching on primiparas' perceptions of their newborn. Hall, L.A. Nursing research. (1980) [Pubmed]
  14. Acute efficacy of a sublingual dose of nifedipine on uterine arterial blood flow: preliminary data in prematurely menopausal women. Huissoud, C., Hadj, S., Bied-Damon, V., Benchaïb, M., Salle, B. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. (2004) [Pubmed]
  15. Compensatory mechanisms which prevent urinary incontinence in aging women. Wijma, J., Tinga, D.J., Visser, G.H. Gynecol. Obstet. Invest. (1992) [Pubmed]
  16. Neuropsychological functioning of dementia patients with psychosis. Hopkins, M.W., Libon, D.J. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists. (2005) [Pubmed]
  17. Activated Leukocyte Cell Adhesion Molecule (ALCAM) is associated with suppression of breast cancer cells invasion. Jezierska, A., Olszewski, W.P., Pietruszkiewicz, J., Olszewski, W., Matysiak, W., Motyl, T. Med. Sci. Monit. (2006) [Pubmed]
  18. Neuropsychiatric assessment of Alzheimer's disease and related dementias. Cummings, J.L., McPherson, S. Aging (Milan, Italy) (2001) [Pubmed]
  19. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Cummings, J.L., Schneider, E., Tariot, P.N., Graham, S.M. Neurology (2006) [Pubmed]
  20. Socioeconomic stress and drug consumption: unemployment as an adverse health factor in Croatia. Dragun, A., Russo, A., Rumboldt, M. Croat. Med. J. (2006) [Pubmed]
  21. Trazodone for agitation in dementia. Martinon-Torres, G., Fioravanti, M., Grimley, E.J. Cochrane database of systematic reviews (Online) (2004) [Pubmed]
  22. Increased mRNA expression of ADAMs in renal cell carcinoma and their association with clinical outcome. Roemer, A., Schwettmann, L., Jung, M., Roigas, J., Kristiansen, G., Schnorr, D., Loening, S.A., Jung, K., Lichtinghagen, R. Oncol. Rep. (2004) [Pubmed]
  23. The membrane proteases adams and hepsin are differentially expressed in renal cell carcinoma. Are they potential tumor markers? Roemer, A., Schwettmann, L., Jung, M., Stephan, C., Roigas, J., Kristiansen, G., Loening, S.A., Lichtinghagen, R., Jung, K. J. Urol. (2004) [Pubmed]
  24. Effect of high climate temperature on the behavioral and psychological symptoms of dementia. Cornali, C., Franzoni, S., Riello, R., Ghianda, D., Frisoni, G.B., Trabucchi, M. Journal of the American Medical Directors Association. (2004) [Pubmed]
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