Genome wide analysis of pathogenic SH2 domain mutations.
Lappalainen, Ilkka ; Thusberg, Janita ; Shen, Bairong and Vihinen, Mauno LU
(2008)
In Proteins
72(2).
p.779-792
- Abstract
- The authors have made a genome-wide analysis of mutations in Src homology 2 (SH2) domains associated with human disease. Disease-causing mutations have been detected in the SH2 domains of cytoplasmic signaling proteins Bruton tyrosine kinase (BTK), SH2D1A, Ras GTPase activating protein (RasGAP), ZAP-70, SHP-2, STAT1, STAT5B, and the p85alpha subunit of the PIP3. Mutations in the BTK, SH2D1A, ZAP70, STAT1, and STAT5B genes have been shown to cause diverse immunodeficiencies, whereas the mutations in RASA1 and PIK3R1 genes lead to basal carcinoma and diabetes, respectively. PTPN11 mutations cause Noonan sydrome and different types of cancer, depending mainly on whether the mutation is inherited or sporadic. We collected and analyzed all... (More)
- The authors have made a genome-wide analysis of mutations in Src homology 2 (SH2) domains associated with human disease. Disease-causing mutations have been detected in the SH2 domains of cytoplasmic signaling proteins Bruton tyrosine kinase (BTK), SH2D1A, Ras GTPase activating protein (RasGAP), ZAP-70, SHP-2, STAT1, STAT5B, and the p85alpha subunit of the PIP3. Mutations in the BTK, SH2D1A, ZAP70, STAT1, and STAT5B genes have been shown to cause diverse immunodeficiencies, whereas the mutations in RASA1 and PIK3R1 genes lead to basal carcinoma and diabetes, respectively. PTPN11 mutations cause Noonan sydrome and different types of cancer, depending mainly on whether the mutation is inherited or sporadic. We collected and analyzed all known pathogenic mutations affecting human SH2 domains by bioinformatics methods. Among the investigated protein properties are sequence conservation and covariance, structural stability, side chain rotamers, packing effects, surface electrostatics, hydrogen bond formation, accessible surface area, salt bridges, and residue contacts. The majority of the mutations affect positions essential for phosphotyrosine ligand binding and specificity. The structural basis of the SH2 domain diseases was elucidated based on the bioinformatic analysis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3635025
- author
- Lappalainen, Ilkka
; Thusberg, Janita
; Shen, Bairong
and Vihinen, Mauno
LU
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Protein-Tyrosine Kinases: chemistry, Protein-Tyrosine Kinases: genetics
- in
- Proteins
- volume
- 72
- issue
- 2
- pages
- 779 - 792
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:18260110
- scopus:46449121011
- pmid:18260110
- ISSN
- 0887-3585
- DOI
- 10.1002/prot.21970
- language
- English
- LU publication?
- no
- id
- 5e33d3ff-eb5d-4ae1-b3bf-b85c1cb53884 (old id 3635025)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18260110?dopt=Abstract
- date added to LUP
- 2016-04-04 09:44:48
- date last changed
- 2022-01-29 19:21:15
@article{5e33d3ff-eb5d-4ae1-b3bf-b85c1cb53884,
abstract = {{The authors have made a genome-wide analysis of mutations in Src homology 2 (SH2) domains associated with human disease. Disease-causing mutations have been detected in the SH2 domains of cytoplasmic signaling proteins Bruton tyrosine kinase (BTK), SH2D1A, Ras GTPase activating protein (RasGAP), ZAP-70, SHP-2, STAT1, STAT5B, and the p85alpha subunit of the PIP3. Mutations in the BTK, SH2D1A, ZAP70, STAT1, and STAT5B genes have been shown to cause diverse immunodeficiencies, whereas the mutations in RASA1 and PIK3R1 genes lead to basal carcinoma and diabetes, respectively. PTPN11 mutations cause Noonan sydrome and different types of cancer, depending mainly on whether the mutation is inherited or sporadic. We collected and analyzed all known pathogenic mutations affecting human SH2 domains by bioinformatics methods. Among the investigated protein properties are sequence conservation and covariance, structural stability, side chain rotamers, packing effects, surface electrostatics, hydrogen bond formation, accessible surface area, salt bridges, and residue contacts. The majority of the mutations affect positions essential for phosphotyrosine ligand binding and specificity. The structural basis of the SH2 domain diseases was elucidated based on the bioinformatic analysis.}},
author = {{Lappalainen, Ilkka and Thusberg, Janita and Shen, Bairong and Vihinen, Mauno}},
issn = {{0887-3585}},
keywords = {{Protein-Tyrosine Kinases: chemistry; Protein-Tyrosine Kinases: genetics}},
language = {{eng}},
number = {{2}},
pages = {{779--792}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Proteins}},
title = {{Genome wide analysis of pathogenic SH2 domain mutations.}},
url = {{http://dx.doi.org/10.1002/prot.21970}},
doi = {{10.1002/prot.21970}},
volume = {{72}},
year = {{2008}},
}