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FLASH GENE

Symbol

SH2D2A

contributors: mct - updated : 06-04-2014

HGNC name	SH2 domain protein 2A
HGNC id	10821

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen           thymus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Lymphoid/Immune B cell Mus musculus Lymphoid/Immune T cell Mus musculus Fetal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal SRC homology 2 domain
	putative SH3 domain
	two phosphotyrosine binding sites (NPXY motifs)
	lacking a catalytic domain

conjugated

PhosphoP

HOMOLOGY

Homologene

FAMILY

T-cell-specific adapter (TSAd) proteins family

CATEGORY

adaptor , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm

basic FUNCTION	adaptor protein involved in T cell signaling
	SH2D2A and HSH2D are adaptors related by structure and sequence, coexpressed in T cells
	SH2D2A and HSH2D have nonredundant functions in lymphocytes
	its expression of SH2D2A is important for proper activation of T-cells
	adapter protein playing key roles in intracellular signal transduction through complex formation with catalytically active signaling molecules
	promote migration of Jurkat T cells through interaction with the G protein beta subunit
	required for VEGF-induced, SRC-mediated regulation of endothelial cell junctions and for vascular permeability
	possible modulatory role for SH2D2A in T cell mediated immune surveillance of cancer
	modulates signaling downstream of the T cell receptor (TCR)
	contains several protein interaction domains, and is merging as a modulator of T cell activation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacts with SMAD2 and SMAD3
	upon TCR plus integrin costimulation, SH2D2A associates with RPSA and mediates T lymphocyte migration
	required for tyrosine phosphorylation of the LCK substrate ITK
	through its interaction with both ITK and LCK, primes ITK for LCK mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements
	KDR induces SRC signaling and vascular permeability in vivo via the adaptor protein SH2D2A
	novel interactions between the SH2D2A SH2 domain and CD6 phosphotyrosine (pTyr)629 and linker of activated T cells (LAT) pTyr171 , pTyr191 and pTyr226

cell & other

REGULATION

induced by

induced after T cell activation

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

to Guillain-Barré syndrome multiple sclerosis

Variant & Polymorphism other	association with a homozygous genotype for a low repeat number of tandem GA in the SH2D2A gene in Guillain-Barré syndrome

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Tsad-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses