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Genetics Home Reference: your guide to understanding genetic conditions
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SH2 domain containing gene family

Reviewed December 2013

What are the SH2 domain containing genes?

Genes in the SH2 domain containing family provide instructions for making proteins that contain one or more regions called Src homology 2 (SH2) domains. These domains, which are made up of similar sequences of protein building blocks (amino acids), were originally identified in a protein called Src. More than 100 proteins in humans are currently thought to contain at least one SH2 domain.

Proteins with SH2 domains are involved in the transmission of chemical signals from a cell's surroundings to the interior of the cell, a process called signal transduction. Proteins with SH2 domains help start, stop, or regulate various signal transduction pathways by interacting with other proteins, especially enzymes called tyrosine kinases. These interactions occur when an SH2 domain attaches (binds) to a particular location on the tyrosine kinase or other protein. Specifically, SH2 domains bind to a protein building block (amino acid) called tyrosine that has been modified by the addition of a cluster of phosphorus and oxygen atoms (a phosphate group).

SH2 domain containing genes are critical for many cell activities, and mutations in these genes have wide-ranging health effects. Mutations in more than a dozen SH2 domain containing genes have been found to cause disorders characterized by immune system malfunction, hormone abnormalities, problems with development, or cancer. Changes in SH2 domain containing genes have also been associated with autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs.

Which genes are included in the SH2 domain containing gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides a list of genes in the SH2 domain containing family (http://www.genenames.org/genefamilies/SH2D).

Genetics Home Reference summarizes the normal function and health implications of these members of the SH2 domain containing gene family: BTK, CHN1, JAK2, PIK3R1, PTPN11, RASA1, SH2D1A, SH3BP2, STAT3, STAT4, and ZAP70.

What conditions are related to genes in the SH2 domain containing gene family?

Genetics Home Reference includes these conditions related to genes in the SH2 domain containing gene family:

  • capillary malformation-arteriovenous malformation syndrome
  • cherubism
  • essential thrombocythemia
  • isolated Duane retraction syndrome
  • isolated growth hormone deficiency
  • Job syndrome
  • juvenile idiopathic arthritis
  • multiple lentigines syndrome
  • Noonan syndrome
  • Parkes Weber syndrome
  • polycythemia vera
  • primary myelofibrosis
  • rheumatoid arthritis
  • short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay
  • systemic lupus erythematosus
  • systemic scleroderma
  • X-linked agammaglobulinemia
  • X-linked lymphoproliferative disease
  • ZAP70-related severe combined immunodeficiency

Where can I find additional information about the SH2 domain containing gene family?

You may find the following resources about the SH2 domain containing gene family helpful.

  • SH2base: Database for Pathogenic SH2 Domain Mutations (http://structure.bmc.lu.se/idbase/SH2base/)
  • Pawson Lab: SH2 Domain (http://pawsonlab.mshri.on.ca/index.php?option=com_content&task=view&Itemid=64&id=178)
  • SH2 Domain Website from the Nash Lab and the Pawson Lab (https://sites.google.com/site/sh2domain/)
  • Molecular Biology of the Cell (fourth edition, 2002): Phosphorylated Tyrosines Serve as Docking Sites For Proteins With SH2 Domains (http://www.ncbi.nlm.nih.gov/books/NBK26822/)

What glossary definitions help with understanding the SH2 domain containing gene family?

acids ; acute ; amino acid ; autoimmune ; cancer ; cell ; domain ; homology ; hormone ; immune system ; kinase ; oxygen ; phosphatase ; phosphate ; phosphorus ; protein ; RAS ; receptor ; signal transduction ; subunit ; transcription ; transduction ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

These sources were used to develop the Genetics Home Reference summary for the SH2 domain containing gene family.

  • Filippakopoulos P, Müller S, Knapp S. SH2 domains: modulators of nonreceptor tyrosine kinase activity. Curr Opin Struct Biol. 2009 Dec;19(6):643-9. doi: 10.1016/j.sbi.2009.10.001. Epub 2009 Nov 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19926274?dopt=Abstract)
  • Lappalainen I, Thusberg J, Shen B, Vihinen M. Genome wide analysis of pathogenic SH2 domain mutations. Proteins. 2008 Aug;72(2):779-92. doi: 10.1002/prot.21970. (http://www.ncbi.nlm.nih.gov/pubmed/18260110?dopt=Abstract)
  • Waksman G, Kumaran S, Lubman O. SH2 domains: role, structure and implications for molecular medicine. Expert Rev Mol Med. 2004 Jan 30;6(3):1-18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14987415?dopt=Abstract)
  • Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, Roberts T, Ratnofsky S, Lechleider RJ, et al. SH2 domains recognize specific phosphopeptide sequences. Cell. 1993 Mar 12;72(5):767-78. (http://www.ncbi.nlm.nih.gov/pubmed/7680959?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2013
Published: December 16, 2014