SH2 domain

SH2ドメイン、SH2領域、Src相同性領域2

関

SH3 domain、Src homology domain

WordNet

1. territory over which rule or control is exercised; "his domain extended into Europe"; "he made it the law of the land" (同)demesne, land
2. (mathematics) the set of values of the independent variable for which a function is defined (同)domain of a function
3. the 19th letter of the Roman alphabet (同)s

PrepTutorEJDIC

1. (国の)領地,領土;(個人の)所有地 / (関心・活動などの)範囲,分野 / (個人・一族の)所有地 / (数学で)変域(関数の独立変数がとる値の集合)
2. sulfurの化学記号 / {略}South[ern]

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/10 17:57:59」(JST)

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Crystallographic structure of the SH2 domain. The structure consists of a large beta sheet (green) flanked by two alpha-helices (orange and blue).
Identifiers
Symbol	SH2
Pfam	PF00017
InterPro	IPR000980
SMART	SH2
PROSITE	PDOC50001
SCOP	1sha
SUPERFAMILY	1sha
OPM protein	1xa6
CDD	cd00173
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins. SH2 domains are commonly found in adapter proteins that aid in the signal transduction of receptor tyrosine kinase pathways.

Introduction

Protein-protein interactions play a major role in cellular growth and development. Modular domains, which are the subunits of a protein, moderate these protein interactions by identifying short peptide sequences. These peptide sequences determine the binding partners of each protein. One of the more prominent domains is the SH2 domain. SH2 domains play a vital role in cellular communication. Its length is approximately 100 amino acids long and it is found within 111 human proteins. Regarding its structure, it contains 2 alpha helices and 7 beta strands. Research has shown that it has a high affinity to phosphorylated tyrosine residues and it is known to identify a sequence of 3-6 amino acids within a peptide motif.

Binding and phosphorylation

SH2 domains typically bind a phosphorylated tyrosine residue in the context of a longer peptide motif within a target protein, and SH2 domains represent the largest class of known pTyr-recognition domains.

Phosphorylation of tyrosine residues in a protein occurs during signal transduction and is carried out by tyrosine kinases. In this way, phosphorylation of a substrate by tyrosine kinases acts as a switch to trigger binding to an SH2 domain-containing protein. Many tyrosine containing short linear motifs that bind to SH2 domains are conserved across a wide variety of higher Eukaryotes. The intimate relationship between tyrosine kinases and SH2 domains is supported by their coordinate emergence during eukaryotic evolution.

Diversity

SH2 domains are not present in yeast and appear at the boundary between protozoa and animalia in organisms such as the social amoeba Dictyostelium discoideum.

A detailed bioinformatic examination of SH2 domains of human and mouse reveals 120 SH2 domains contained within 115 proteins encoded by the human genome, representing a rapid rate of evolutionary expansion among the SH2 domains.

A large number of SH2 domain structures have been solved and many SH2 proteins have been knocked out in mice. Information generated on the Mouse Knockouts can be found on the sh2.uchicago.edu website.

Function

The function of SH2 domains is to specifically recognize the phosphorylated state of tyrosine residues, thereby allowing SH2 domain-containing proteins to localize to tyrosine-phosphorylated sites. This process constitutes the fundamental event of signal transduction through a membrane, in which a signal in the extracellular compartment is "sensed" by a receptor and is converted in the intracellular compartment to a different chemical form, i.e. that of a phosphorylated tyrosine. Tyrosine phosphorylation leads to activation of a cascade of protein-protein interactions whereby SH2 domain-containing proteins are recruited to tyrosine-phosphorylated sites. This process initiates a series of events which eventually result in altered patterns of gene expression or other cellular responses. The SH2 domain, which was first identified in the oncoproteins Src and Fps, is about 100 amino-acid residues long. It functions as a regulatory module of intracellular signaling cascades by interacting with high affinity to phosphotyrosine-containing target peptides in a sequence-specific and strictly phosphorylation-dependent manner.

Examples

Human proteins containing this domain include:

• ABL1; ABL2
• BCAR3; BLK; BLNK; BMX; BTK
• CHN2; CISH; CRK; CRKL; CSK
• DAPP1
• FER; FES; FGR; FRK; FYN
• GRAP; GRAP2; GRB10; GRB14; GRB2; GRB7
• HCK; HSH2D
• INPP5D; INPPL1; ITK; JAK2; LCK; LCP2; LYN
• MATK; NCK1; NCK2
• PIK3R1; PIK3R2; PIK3R3; PLCG1; PLCG2; PTK6; PTPN11; PTPN6; RASA1
• SH2B1; SH2B2; SH2B3; SH2D1A; SH2D1B; SH2D2A; SH2D3A; SH2D3C; SH2D4A; SH2D4B; SH2D5; SH2D6; SH3BP2; SHB; SHC1; SHC3; SHC4; SHD; SHE
• SLA; SLA2
• SOCS1; SOCS2; SOCS3; SOCS4; SOCS5; SOCS6; SOCS7
• SRC; SRMS
• STAT1; STAT2; STAT3; STAT4; STAT5A; STAT5B; STAT6
• SUPT6H; SYK
• TEC; TENC1; TNS; TNS1; TNS3; TNS4; TXK
• VAV1; VAV2; VAV3
• YES1; ZAP70

References

External links

• Eukaryotic Linear Motif resource motif class LIG_SH2_GRB2
• Eukaryotic Linear Motif resource motif class LIG_SH2_PTP2
• Eukaryotic Linear Motif resource motif class LIG_SH2_SRC
• Eukaryotic Linear Motif resource motif class LIG_SH2_STAT3
• Eukaryotic Linear Motif resource motif class LIG_SH2_STAT5
• Eukaryotic Linear Motif resource motif class LIG_SH2_STAT6
• Eukaryotic Linear Motif resource motif class MOD_TYR_ITAM
• Eukaryotic Linear Motif resource motif class MOD_TYR_ITIM
• Eukaryotic Linear Motif resource motif class MOD_TYR_ITSM

• Li S (2007). "SMALI site". University of Western Ontario. Retrieved 2009-01-08. 
• Mayer BJ (2007-10-23). "SH2 Domain Database link page". University of Connecticut. Retrieved 2009-01-08. 
• The Nash Lab (2005). "the SH2 domain". The Nash Lab. Retrieved 2012-12-13. 
• The Pawson Lab. "SH2 Domain". Mount Sinai Hospital, Ontario, Canada. Retrieved 2009-01-08. 
• Rose T, Waksman G (2000-02-29). "SH2 domains: Introduction and Overview". Washington University School of Medicine. Retrieved 2009-01-08. 

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English Journal

• The role of the Src Homology-2 domain containing protein B (SHB) in β cells.

• Welsh M1, Jamalpour M2, Zang G2, Åkerblom B2.
• Journal of molecular endocrinology.J Mol Endocrinol.2016 Jan;56(1):R21-31. doi: 10.1530/JME-15-0228. Epub 2015 Oct 21.
• This review will describe the SH2-domain signaling protein Src Homology-2 domain containing protein B (SHB) and its role in various physiological processes relating in particular to glucose homeostasis and β cell function. SHB operates downstream of several tyrosine kinase receptors and assembles s
• PMID 26489764

• Molecular characterization of SOCS gene and its expression analysis on Plasmodium berghei infection in Anopheles culicifacies.

• Dhawan R1, Gupta K1, Kajla M1, Kumar S1, Gakhar SK2, Kakani P1, Choudhury TP1, Gupta L3.
• Acta tropica.Acta Trop.2015 Dec;152:170-5. doi: 10.1016/j.actatropica.2015.09.014. Epub 2015 Sep 25.
• Anopheles culicifacies mosquitoes are able to transmit both falciparum and vivax malaria in India. More than 65% of malaria cases reported annually spread through this vector. Despite the fact that it poses major vectorial burden in India, the molecular basis of its immune role against Plasmodium de
• PMID 26407822

• Tensin1 positively regulates RhoA activity through its interaction with DLC1.

• Shih YP1, Sun P2, Wang A2, Lo SH2.
• Biochimica et biophysica acta.Biochim Biophys Acta.2015 Dec;1853(12):3258-65. doi: 10.1016/j.bbamcr.2015.09.028. Epub 2015 Sep 28.
• DLC1 is a RhoGAP-containing tumor suppressor and many of DLC1's functions are absolutely dependent on its RhoGAP activity. Through its RhoGAP domain, DLC1 inhibits the activity of RhoA GTPase, which regulates actin cytoskeleton networks and dis/assembly of focal adhesions. Tensin1 (TNS1) is a focal
• PMID 26427649

Japanese Journal

• An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe

• Saio Tomohide,Ogura Kenji,Shimizu Kazumi,Yokochi Masashi,Burke Terrence R. Jr.,Inagaki Fuyuhiko
• Journal of Biomolecular NMR 51(3), 395-408, 2011-11
• … The usefulness of this strategy was demonstrated in the case of the growth factor receptor-bound protein 2 (Grb2) Src homology 2 (SH2) domain and its low- and high-affinity ligands. …
• NAID 120003464639

• Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells.

• IKEDA Osamu,MIZUSHIMA Akihiro,SEKINE Yuichi,YAMAMOTO Chikako,MUROMOTO Ryuta,NANBO Asuka,ORITANI Kenji,YOSHIMURA Akihiko,MATSUDA Tadashi
• Cancer science 102(4), 756-761, 2011-04-10
• … Signal-transducing adaptor protein (STAP)-2 is a recently identified adaptor protein that contains Pleckstrin homology (PH) and Src homology 2 (SH2)-like domains, and is also known to be a substrate of breast tumor kinase (Brk). … Regarding the mechanism, the PH domain of STAP-2 is likely to participate in the process by which Brk phosphorylates and activates STAT5. …
• NAID 10029292209

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★リンクテーブル★

リンク元	「SH2領域」「SH3 domain」「Src homology domain」「Src相同性領域2」
拡張検索	「SH2 domain-containing protein tyrosine phosphatase」「SH2 domains」
関連記事	「domain」「S」「SH」「domains」

「SH2領域」

　　[★]

英

SH2 domain

関

Src相同性領域2、Src相同性領域3、Src相同性領域、SH2ドメイン

「SH3 domain」

　　[★]

SH3ドメイン、SH3領域、Src相同性領域3

関

SH2 domain、Src homology domain

「Src homology domain」

　　[★]

• Src相同領域、Src相同性領域

関

SH2 domain、SH3 domain

「Src相同性領域2」

　　[★]

英

SH2 domain

関

SH2領域、SH2ドメイン

「SH2 domain-containing protein tyrosine phosphatase」

　　[★]

SH2ドメイン含有タンパク質チロシンホスファターゼ

「SH2 domains」

　　[★]

関

See Src homology 2 (SH2) domains

同

Src homology 2

「domain」

　　[★]

• n.

• ドメイン、(分子内の)領域、分域

関

area、realm、region、regional、segregation、territory、universe

　 　 　

「S」

　　[★]

• セリン serine
• 胸骨上縁

　 　

「SH」

　　[★]

• チオール基、スルフヒドリル基

「domains」

　　[★]

関

See also specific type