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    LCP2 lymphocyte cytosolic protein 2 [ Homo sapiens (human) ]

    Gene ID: 3937, updated on 4-Feb-2018
    Official Symbol
    LCP2provided by HGNC
    Official Full Name
    lymphocyte cytosolic protein 2provided by HGNC
    Primary source
    HGNC:HGNC:6529
    See related
    Ensembl:ENSG00000043462 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
    This gene encodes an adapter protein that acts as a substrate of the T cell antigen receptor (TCR)-activated protein tyrosine kinase pathway. The encoded protein associates with growth factor receptor bound protein 2, and is thought to play a role TCR-mediated intracellular signal transduction. A similar protein in mouse plays a role in normal T-cell development and activation. Mice lacking this gene show subcutaneous and intraperitoneal fetal hemorrhaging, dysfunctional platelets and impaired viability. [provided by RefSeq, Nov 2016]
    Expression
    Broad expression in bone marrow (RPKM 53.7), appendix (RPKM 44.7) and 19 other tissues See more
    Orthologs
    Location:
    5q35.1
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 5 NC_000005.10 (170248084..170297818, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (169675088..169724822, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene keratin 18 pseudogene 41 Neighboring gene long intergenic non-protein coding RNA 1187 Neighboring gene chromosome 5 open reading frame 58 Neighboring gene long intergenic non-protein coding RNA 1366 Neighboring gene uncharacterized LOC101928033 Neighboring gene potassium voltage-gated channel interacting protein 1 Neighboring gene potassium calcium-activated channel subfamily M regulatory beta subunit 1

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
    NHGRI GWA Catalog

    Replication interactions

    Interaction Pubs
    Knockdown of lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) (LCP2; SLP76) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed
    Knockdown of SLP76 by siRNA inhibits HIV-1 infection in MT4 cells and PBMCs PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of lymphocyte cytosolic protein 2 (LCP2, SLP76) in human B cells PubMed
    env Lck is recuited to a virological synapse (VS) interface and is highly colocalized with gp120 when cells interact with gp120+ICAM-1 bilayers, leading to activate ZAP70, LAT, SLP76, and PLCgamma PubMed
    Nef nef The association of HIV-1 Nef with Vav1, Pak2, and Nck1 is greatly reduced in SLP76-deficient T cells. SLP-76 associates with Nef and modulates actin cytoskeletal reorganization PubMed
    nef HIV-1 Nef inhibits colocalization of activated ZAP70 with SLP76 in microclusters (MCs) PubMed
    nef HIV-1 Nef potently inhibits formation of SLP76-containing microclusters (MCs) and causes disruption of the SLP76-containing MCs proliferation and translocation PubMed

    Go to the HIV-1, Human Interaction Database

    • 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...
    • DAP12 interactions, organism-specific biosystem (from REACTOME)
      DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
    • DAP12 signaling, organism-specific biosystem (from REACTOME)
      DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
    • FCERI mediated Ca+2 mobilization, organism-specific biosystem (from REACTOME)
      FCERI mediated Ca+2 mobilization, organism-specific biosystemIncrease of intracellular calcium in mast cells is most crucial for mast cell degranulation. Elevation of intracellular calcium is achieved by activation of PLC-gamma. Mast cells express both PLC-gam...
    • FCERI mediated MAPK activation, organism-specific biosystem (from REACTOME)
      FCERI mediated MAPK activation, organism-specific biosystemFormation of the LAT signaling complex leads to activation of MAPK and production of cytokines. The sequence of events that leads from LAT to cytokine production has not been as clearly defined as th...
    • 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 (FCERI) signaling, organism-specific biosystem (from REACTOME)
      Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...
    • 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...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • 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, organism-specific biosystem (from KEGG)
      Platelet activation, organism-specific biosystemPlatelets play a key and beneficial role for primary hemostasis on the disruption of the integrity of vessel wall. Platelet adhesion and activation at sites of vascular wall injury is initiated by ad...
    • 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...
    • Rap1 signaling pathway, organism-specific biosystem (from KEGG)
      Rap1 signaling pathway, organism-specific biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
    • Rap1 signaling pathway, conserved biosystem (from KEGG)
      Rap1 signaling pathway, conserved biosystemRap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an ac...
    • 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...
    • T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystem (from WikiPathways)
      T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
    • T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystem (from WikiPathways)
      T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystemThis pathway is based on Figure 4 of "A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus au...
    • 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
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    Fc-epsilon receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    T cell receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    cytokine secretion IEA
    Inferred from Electronic Annotation
    more info
     
    immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    mast cell activation IEA
    Inferred from Electronic Annotation
    more info
     
    platelet activation TAS
    Traceable Author Statement
    more info
     
    positive regulation of protein kinase activity IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    transmembrane receptor protein tyrosine kinase signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    TCR signalosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell-cell junction IEA
    Inferred from Electronic Annotation
    more info
     
    cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    plasma membrane raft IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    lymphocyte cytosolic protein 2
    Names
    76 kDa tyrosine phosphoprotein
    SH2 domain-containing leukocyte protein of 76 kDa
    SLP-76 tyrosine phosphoprotein

    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_005565.4NP_005556.1  lymphocyte cytosolic protein 2

      See identical proteins and their annotated locations for NP_005556.1

      Status: REVIEWED

      Source sequence(s)
      AC034199, AW291566, BC016618, BY995095, DB116470, U20158
      Consensus CDS
      CCDS47339.1
      UniProtKB/Swiss-Prot
      Q13094
      Related
      ENSP00000046794.5, OTTHUMP00000223178, ENST00000046794.9, OTTHUMT00000371727
      Conserved Domains (3) summary
      cd09522
      Location:1078
      SAM_SLP76; SAM domain of SLP76 subfamily
      cd09929
      Location:411531
      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)
      cl26464
      Location:130421
      Atrophin-1; Atrophin-1 family

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p7 Primary Assembly

      Range
      170248084..170297818 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018916.2 Alternate CHM1_1.1

      Range
      169107544..169157743 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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