SH2D1B

Gene Summary

Gene:SH2D1B; SH2 domain containing 1B
Aliases: EAT2
Location:1q23.3
Summary:By binding phosphotyrosines through its free SRC (MIM 190090) homology-2 (SH2) domain, EAT2 regulates signal transduction through receptors expressed on the surface of antigen-presenting cells (Morra et al., 2001 [PubMed 11689425]).[supplied by OMIM, Mar 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:SH2 domain-containing protein 1B
HPRD
Source:NCBIAccessed: 17 August, 2015

Ontology:

What does this gene/protein do?
Show (5)
Pathways:What pathways are this gene/protein implicaed in?
Show (1)

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 17 August 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • CD99 (MIC2)
  • CD Antigens
  • Cancer Gene Expression Regulation
  • Ewing's Sarcoma
  • Oncogene Fusion Proteins
  • Base Sequence
  • Cell Adhesion Molecules
  • Recombinant Fusion Proteins
  • Transcription Factors
  • src Homology Domains
  • Chromosome 1
  • Monoclonal Antibodies
  • Oncogenic Retroviridae Proteins
  • EWSR1-FLI fusion protein
  • RAS Genes
  • Trans-Activators
  • Chromosome Mapping
  • RNA-Binding Protein EWS
  • Phosphotyrosine
  • Fli1 protein, mouse
  • Immunohistochemistry
  • Ribonucleoproteins
  • Neoplastic Cell Transformation
  • Bone Cancer
  • Polymerase Chain Reaction
  • Transcription
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Molecular Sequence Data
  • Signal Transducing Adaptor Proteins
  • FLI1
  • EWS-ETV1 fusion
  • DNA-Binding Proteins
  • SH2D1B
  • Signal Transduction
  • 3T3 Cells
  • Sh2d1b1 protein, mouse
  • Proto-Oncogene Proteins
  • oncogene proteins v-ets
  • Up-Regulation
  • Phenotype
Tag cloud generated 17 August, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (2)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Ewing's SarcomaSH2D1B (EAT2) is Upregulated by Ewing's Sarcoma EWS/FLI1 Fusion Genes
In a study of genes up regulated by EWS/FLI1 but not by full-length FLI1 (Thompson et al, 1996) characterised a novel gene EAT2 which was cloned from a mouse cDNA library. EAT2 expression correlated with transformation of NIH3T3 cells by EWS/FLI1chimeric proteins but not by unrelated genes. They identified a homologous sequence in humans mapped to chromosome 1q22 and detected human EAT-2 transcripts in Ewing's sarcoma cell lines by RT-PCR. In a later report (Thompson, 1999) the variant EWS/ETV1 translocation was also shown to upregulate EAT2.
View Publications4
Bone Cancer (primary)SH2D1B and Bone Cancer View Publications1

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: SH2D1B (cancer-related)

Morra M, Howie D, Grande MS, et al.
X-linked lymphoproliferative disease: a progressive immunodeficiency.
Annu Rev Immunol. 2001; 19:657-82 [PubMed] Related Publications
Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years. The gene that is altered in the condition (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least two sets of target molecules for this small SH2 domain-containing protein have been identified: A family of hematopoietic cell surface receptors, i.e. the SLAM family, and a second molecule, which is a phosphorylated adapter. A SAP-like protein, EAT-2, has also been found to interact with this family of surface receptors. Several lines of evidence, including structural studies and analyses of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a natural inhibitor of SH2-domain-dependent interactions with members of the SLAM family. However, details of its role in signaling mechanisms are yet to be unravelled. Further analyses of the SAP/SH2D1A gene in XLP patients have made it clear that the development of dys-gammaglobulinemia and B cell lymphoma can occur without evidence of prior EBV infection. Moreover, preliminary results of virus infections of a mouse in which the SAP/SH2D1A gene has been disrupted suggest that EBV infection is not per se critical for the development of XLP phenotypes. It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM family of surface receptors and thus may play a fundamental role in T cell and APC interactions during viral infections.

Thompson AD, Teitell MA, Arvand A, Denny CT
Divergent Ewing's sarcoma EWS/ETS fusions confer a common tumorigenic phenotype on NIH3T3 cells.
Oncogene. 1999; 18(40):5506-13 [PubMed] Related Publications
Ewing's sarcomas express chimeric transcription factors resulting from a fusion of the amino terminus of the EWS gene to the carboxyl terminus of one of five ETS proteins. While the majority of tumors express EWS/FLI1 fusions, some Ewing's tumors contain variant chimeras such as EWS/ETV1 that have divergent ETS DNA-binding domains. In spite of their structural differences, both EWS/ETS fusions up regulate EAT-2, a previously described EWS/FLI1 target gene. In contrast to EWS/FLI1, NIH3T3 cells expressing EWS/ETV1 cannot form colonies in soft agar though coexpression of a dominant negative truncated ETV1 construct attenuates EWS/FLI1 mediated anchorage independent growth. When EWS/ETV1 or EWS/FLI1 expressing NIH3T3 cells are injected into SCID mice, tumors form more often and faster than with NIH-3T3 cells with empty vector controls. The tumorigenic potency of each EWS/ETS fusion is linked to its C-terminal structure, with the FLI1 C-terminus confering a greater tumorigenic potential than the corresponding ETV1 domain. The resulting EWS/ETV1 and EWS/FLI1 tumors closely resemble each other at both a macroscopic and a microscopic level. These tumors differ greatly from tumors formed by NIH3T3 cells expressing activated RAS. These data indicate that in spite of their structural differences, EWS/ETV1 and EWS/FLI1 promote oncogenesis via similar biologic pathways.

Thompson AD, Braun BS, Arvand A, et al.
EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's sarcoma EWS/FLI1 fusion gene.
Oncogene. 1996; 13(12):2649-58 [PubMed] Related Publications
The EWS/FLI1 fusion protein is created by the translocation between chromosomes 11 and 22 that appears in most Ewing's sarcomas. This chimeric protein has been demonstrated to be an aberrant transcription factor. Genes up regulated by EWS/FLI1 but not by full-length FLI1 were identified by representational difference analysis (RDA). We have characterized a novel gene, EWS/FLI1 activated transcript 2 (EAT-2) that was cloned from a murine cDNA library using a differentially expressed RDA fragment. EAT-2 expression is seen within 4-8 h of EWS/FLI1 induction. Its expression correlates with transformation of NIH3T3 cells by chimeric proteins related to EWS/FLI1 but not by unrelated genes. EAT-2 is expressed in normal murine tissues and contains a unique but biochemically functional SH2 domain. An homologous sequence in the human genome has been identified and mapped to chromosome 1q22. Human EAT-2 transcripts were identified by reverse transcriptase-polymerase chain reaction (RT-PCR) in Ewing's sarcoma cell tumour cell lines. EAT-2's unique structure and correlation with transformation make it a candidate for playing a role in the transformation of NIH3T3 cells and the oncogenesis of Ewing's sarcoma.

Lee CS, Southey MC, Waters K, et al.
EWS/FLI-1 fusion transcript detection and MIC2 immunohistochemical staining in the diagnosis of Ewing's sarcoma.
Pediatr Pathol Lab Med. 1996 May-Jun; 16(3):379-92 [PubMed] Related Publications
Ewing's sarcoma (ES) and other primitive peripheral neuroectodermal tumors (pPNETs) can present a significant diagnostic problem, as they may morphologically resemble other small round cell tumors (SRCTs) of childhood. However, ES/pPNET is known to carry a characteristic t(11;22)(q24;q12), the detection of which may aid diagnosis. The recent identification of the EWS and FLI-1 genes flanking the translocation break point has enabled reverse transcriptase-polymerase chain reaction (RT-PCR) to be used to detect the putative chimeric transcription factor mRNA produced by the fusion gene. We have assessed the RT-PCR method of detection by examining 40 cases of ES for the presence of EWS/FLI-1 transcripts. Twenty-six (76%) of the 34 cases with intact mRNA yielded fusion transcripts. Four different transcript sizes were detected and two tumors contained two transcripts of different size. No transcripts were detected in a control group of non-ES/pPNET SRCTs. Eight cases with intact mRNA were transcript negative. The MIC2 cell surface antigen, which is reported to be present in over 95% of ES/pPNETs, was present in 32 of 33 tumors (97%), including all 24 EWS/FLI-1 transcript-positive cases examined. Hence MIC2 is a useful screen for ES, with RT-PCR detection of t(11;22) being the optimal method for confirming the diagnosis.

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Cite this page: Cotterill SJ. SH2D1B (EAT2), Cancer Genetics Web: http://www.cancer-genetics.org/EAT2.htm Accessed:

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