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    LCP2 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) [ Homo sapiens ]

    Gene ID: 3937, updated on 12-May-2012
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    Summary

    Official Symbol
    LCP2provided by HGNC
    Official Full Name
    lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)provided by HGNC
    Primary source
    HGNC:6529
    See related
    Ensembl:ENSG00000043462; HPRD:03362; MIM:601603; Vega:OTTHUMG00000163121
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SLP76; SLP-76
    Summary
    SLP-76 was originally identified as a substrate of the ZAP-70 protein tyrosine kinase following T cell receptor (TCR) ligation in the leukemic T cell line Jurkat. The SLP-76 locus has been localized to human chromosome 5q33 and the gene structure has been partially characterized in mice. The human and murine cDNAs both encode 533 amino acid proteins that are 72% identical and comprised of three modular domains. The NH2-terminus contains an acidic region that includes a PEST domain and several tyrosine residues which are phosphorylated following TCR ligation. SLP-76 also contains a central proline-rich domain and a COOH-terminal SH2 domain. A number of additional proteins have been identified that associate with SLP-76 both constitutively and inducibly following receptor ligation, supporting the notion that SLP-76 functions as an adaptor or scaffold protein. Studies using SLP-76 deficient T cell lines or mice have provided strong evidence that SLP-76 plays a positive role in promoting T cell development and activation as well as mast cell and platelet function. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    5q35.1
    Sequence :
    Chromosome: 5; NC_000005.9 (169675088..169724822, complement)
    See LCP2 in Epigenomics, MapViewer

    Chromosome 5 - NC_000005.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100507267 Neighboring gene chromosome 5 open reading frame 58 Neighboring gene uncharacterized LOC100128059 Neighboring gene uncharacterized LOC257358

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. The adaptor protein SLP-76 regulates HIV-1 release and cell-to-cell transmission in T cells. Nagaraja T, et al. J Immunol, 2012 Mar 15. PMID 22323535.
    2. The SLP-76 Src homology 2 domain is required for T cell development and activation. Burns JC, et al. J Immunol, 2011 Nov 1. PMID 21949020.
    3. A directed protein interaction network for investigating intracellular signal transduction. Vinayagam A, et al. Sci Signal, 2011 Sep 6. PMID 21900206.
    4. Spatial association of signaling proteins and F-actin effects on cluster assembly analyzed via photoactivation localization microscopy in T cells. Hsu CJ, et al. PLoS One, 2011. PMID 21887278.
    5. Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells. Sela M, et al. EMBO J, 2011 Jul 1. PMID 21725281.

    See all (91) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. our studies demonstrate a novel role for the adaptor molecule SLP-76 in regulating HIV-1 infection in T cells
      Title: The adaptor protein SLP-76 regulates HIV-1 release and cell-to-cell transmission in T cells.
    2. Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant demonstrates that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes.
      Title: The SLP-76 Src homology 2 domain is required for T cell development and activation.
    3. The spatial correlation between kinase ZAP70 and adaptor SLP76 microclusters (MC) at the cell periphery and the effects of F-actin on MC assembly, were analysed.
      Title: Spatial association of signaling proteins and F-actin effects on cluster assembly analyzed via photoactivation localization microscopy in T cells.
    4. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to PLC-gamma1.
      Title: Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells.
    5. findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo
      Title: Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses.
    6. LAT recruits Src homology 2 domain-containing leukocyte 76 kDa protein (SLP-76) following T-cell receptor ligation and membrane translocation of Akt and phosphatidylinositol 3-kinase (PI3K)phosphorylation in Jurkat cells, activating Akt signaling.
      Title: Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells.
    7. Results define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex, which is crucial for regulation of the actin machinery after T-cell activation.
      Title: Cooperative interactions at the SLP-76 complex are critical for actin polymerization.
    8. T-cell receptor (TCR)-induced association between ITK and SLP-76, recruitment and transphosphorylation of ITK, actin polarization at the T-cell contact site, and expression of Th2 cytokines
      Title: In vivo significance of ITK-SLP-76 interaction in cytokine production.
    9. findings reconfigure the TCR signaling pathway by showing SLP-76 back-regulation of ZAP-70, an event that could ensure that signaling components are in balance for optimal T cell activation
      Title: SH2 domain containing leukocyte phosphoprotein of 76-kDa (SLP-76) feedback regulation of ZAP-70 microclustering.
    10. The results show that Bcr-Abl regulates the actin cytoskeleton and non-apoptotic membrane blebbing via a GADS/Slp-76/Nck1 adaptor protein pathway.
      Title: The Bcr-Abl kinase regulates the actin cytoskeleton via a GADS/Slp-76/Nck1 adaptor protein pathway.
    Submit: New GeneRIF Correction See all (32)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_005556.1 NP_004801.1 GRAP2    BIND  PubMed SLP-76 interacts with Gads. 
    NP_005556.1 NP_006144.1 NCK1    BIND  PubMed Nck interacts with SLP-76. 
    Q13094 Q8WV28 BLNK    HPRD  PubMed  
    Q13094 P22681 CBL    HPRD  PubMed  
    Q13094 P20273 CD22    HPRD  PubMed  
    Q13094 Q7Z7G1 CLNK    HPRD  PubMed  
    Q13094 O15117 FYB    HPRD  PubMed  
    Q13094 P06241 FYN    HPRD  PubMed  
    Q13094 O75791 GRAP2    HPRD  PubMed  
    Q13094 P62993 GRB2    HPRD  PubMed  
    Q13094 P08631 HCK    HPRD  PubMed  
    Q13094 Q08881 ITK    HPRD  PubMed  
    Q13094 O43561 LAT    HPRD  PubMed  
    Q13094 P06239 LCK    HPRD  PubMed  
    Q13094 P07948 LYN    HPRD  PubMed  
    Q13094 Q92918 MAP4K1    HPRD  PubMed  
    Q13094 P16333 NCK1    HPRD  PubMed  
    Q13094 Q9NWQ8 PAG1    HPRD  PubMed  
    Q13094 P19174 PLCG1    HPRD  PubMed  
    Q13094 P16885 PLCG2    HPRD  PubMed  
    Q13094 Q96QH2 PRAM1    HPRD  PubMed  
    Q13094 P29350 PTPN6    HPRD  PubMed  
    Q13094 P08575 PTPRC    HPRD  PubMed  
    Q13094 Q15464 SHB    HPRD  PubMed  
    Q13094 P29353 SHC1    HPRD  PubMed  
    Q13094 P43405 SYK    HPRD  PubMed  
    Q13094 P42681 TXK    HPRD  PubMed  
    Q13094 P15498 VAV1    HPRD  PubMed  
    Q13094 Q9UKW4 VAV3    HPRD  PubMed  
    Q13094 P42768 WAS    HPRD  PubMed  
    Q13094 P43403 ZAP70    HPRD  PubMed  
    BioGRID:110129 BioGRID:107315 CBL    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110129 BioGRID:204772 Fyb    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110129 BioGRID:114799 GRAP2    BioGRID  PubMed Affinity Capture-Western; Phenotypic Enhancement; Reconstituted Complex; Two-hybrid 
    BioGRID:110129 BioGRID:109142 GRB2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:110129 BioGRID:109907 ITK    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110129 BioGRID:110245 LYN    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110129 BioGRID:110770 NCK1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110129 BioGRID:120931 PAG1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110129 BioGRID:111313 PIK3R1    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:110129 BioGRID:111351 PLCG1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110129 BioGRID:123894 PRAM1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110129 BioGRID:111742 PTPN6    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110129 BioGRID:112353 SH3GL2    BioGRID  PubMed Two-hybrid 
    BioGRID:110129 BioGRID:112358 SHB    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110129 BioGRID:119154 TRAT1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110129 BioGRID:113252 VAV1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110129 BioGRID:113293 WAS    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110129 BioGRID:113366 YWHAZ    BioGRID  PubMed Two-hybrid 
    BioGRID:110129 BioGRID:113367 ZAP70    BioGRID  PubMed Biochemical Activity 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      B Cell Receptor Signaling Pathway, organism-specific biosystemThe B cell receptor includes membrane ?? heavy chain molecules bound to a light chain and an Ig alpha (CD79A)/Ig beta (CD79B) heterodimer. Activation of the B cell receptor involves phosphorylation o...
    • Fc epsilon RI signaling pathway, organism-specific biosystem (from KEGG)
      Fc epsilon RI signaling pathway, organism-specific biosystemFc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation...
    • Fc epsilon RI signaling pathway, conserved biosystem (from KEGG)
      Fc epsilon RI signaling pathway, conserved biosystemFc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation...
    • Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem (from Pathway Interaction Database)
      Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem
      Fc-epsilon receptor I signaling in mast cells
    • GPVI-mediated activation cascade, organism-specific biosystem (from REACTOME)
      GPVI-mediated activation cascade, organism-specific biosystemThe GPVI receptor is a complex of the GPVI protein with Fc epsilon R1 gamma (FcR). The Src family kinases Fyn and Lyn constitutively associate with the GPVI-FcR complex in platelets and initiate plat...
    • Generation of second messenger molecules, organism-specific biosystem (from REACTOME)
      Generation of second messenger molecules, organism-specific biosystemIn addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have be...
    • Hemostasis, organism-specific biosystem (from REACTOME)
      Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • JNK signaling in the CD4+ TCR pathway, organism-specific biosystem (from Pathway Interaction Database)
      JNK signaling in the CD4+ TCR pathway, organism-specific biosystem
      JNK signaling in the CD4+ TCR pathway
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Osteoclast differentiation, organism-specific biosystem (from KEGG)
      Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
    • Osteoclast differentiation, conserved biosystem (from KEGG)
      Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
    • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
      Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
    • T Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      T Cell Receptor Signaling Pathway, organism-specific biosystem
      T Cell Receptor Signaling Pathway
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • TCR signaling, organism-specific biosystem (from REACTOME)
      TCR signaling, organism-specific biosystemThe TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen p...
    • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
      TCR signaling in naive CD4+ T cells, organism-specific biosystem
      TCR signaling in naive CD4+ T cells
    • TCR signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
      TCR signaling in naive CD8+ T cells, organism-specific biosystem
      TCR signaling in naive CD8+ T cells

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    blood coagulation TAS
    Traceable Author Statement
    more info
    		  
    cytokine secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    mast cell activation IEA
    Inferred from Electronic Annotation
    more info
    		  
    platelet activation TAS
    Traceable Author Statement
    more info
    		  
    transmembrane receptor protein tyrosine kinase signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
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    General protein information

    Preferred Names
    lymphocyte cytosolic protein 2
    Names
    lymphocyte cytosolic protein 2
    76 kDa tyrosine phosphoprotein
    SLP-76 tyrosine phosphoprotein
    SH2 domain-containing leukocyte protein of 76kD
    SH2 domain-containing leukocyte protein of 76 kDa
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_005565.3 → NP_005556.1  lymphocyte cytosolic protein 2

      Status: REVIEWED

      Source sequence(s)
      BC016618, BG911397, U20158
      Consensus CDS
      CCDS47339.1
      UniProtKB/Swiss-Prot
      Q13094
      Related
      ENSP00000046794, OTTHUMP00000223178, ENST00000046794, OTTHUMT00000371727
      Conserved Domains (4) summary
      PHA03247
      Location:219 – 369
      Blast Score: 96
      PHA03247; large tegument protein UL36; Provisional
      cd09522
      Location:10 – 78
      Blast Score: 337
      SAM_SLP76; SAM domain of SLP76 subfamily
      cd09929
      Location:412 – 531
      Blast Score: 524
      SH2_BLNK_SLP-76; Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76)
      pfam07647
      Location:12 – 76
      Blast Score: 136
      SAM_2; SAM domain (Sterile alpha motif)

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000005.9 Reference GRCh37.p5 Primary Assembly

      Range
      169675088..169724822, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000137.1 Alternate HuRef

      Range
      164773564..164823697, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC034199.6 (17056..66790) None
    genomic CH471062.2 EAW61478.1
      EAW61479.1
      EAW61480.1
    genomic U44065.1 AAA93308.1
    mRNA AK122637.1 None
    mRNA AK292890.1 BAF85579.1
    mRNA AK296098.1 BAG58851.1
    mRNA AK300000.1 BAG61819.1
    mRNA AK310369.1 None
    mRNA BC016618.1 AAH16618.1
    mRNA BG911397.1 None
    mRNA BT007273.1 AAP35937.1
    mRNA FN432830.1 CBA11531.1
    mRNA U20158.1 AAC50135.1
    other-genetic DQ890681.2 ABM81607.1
    other-genetic DQ893863.2 ABM84789.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13094.1 GenPept UniProtKB/Swiss-Prot:Q13094
    Q14759 GenPept UniProtKB/TrEMBL:Q14759
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
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