Human Gene LCP2 (uc003man.1) Description and Page Index
  Description: Homo sapiens lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) (LCP2), mRNA.
RefSeq Summary (NM_005565): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: BC016618.1, SRR1163658.196053.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000046794.10/ ENSP00000046794.5 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr5:169,675,088-169,724,822 Size: 49,735 Total Exon Count: 21 Strand: -
Coding Region
   Position: hg19 chr5:169,675,701-169,724,615 Size: 48,915 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:169,675,088-169,724,822)mRNA (may differ from genome)Protein (533 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: LCP2_HUMAN
DESCRIPTION: RecName: Full=Lymphocyte cytosolic protein 2; AltName: Full=SH2 domain-containing leukocyte protein of 76 kDa; AltName: Full=SLP-76 tyrosine phosphoprotein; Short=SLP76;
FUNCTION: Involved in T-cell antigen receptor mediated signaling.
SUBUNIT: Interacts with SLA. Interacts with CBLB (By similarity). Interacts with the adapter proteins GRB2 and FYB. Interacts with SHB. Interacts with PRAM1.
INTERACTION: Q8IVH8:MAP4K3; NbExp=5; IntAct=EBI-346946, EBI-1758170; Q99JP0:Map4k3 (xeno); NbExp=2; IntAct=EBI-346946, EBI-5324222;
SUBCELLULAR LOCATION: Cytoplasm (Probable).
TISSUE SPECIFICITY: Highly expressed in spleen, thymus and peripheral blood leukocytes. Highly expressed also in T-cell and monocytic cell lines, expressed at lower level in B-cell lines. Not detected in fibroblast or neuroblastoma cell lines.
DOMAIN: The SH2 domain mediates interaction with SHB.
PTM: Phosphorylated after T-cell receptor activation by ZAP70, ITK and TXK, which leads to the up-regulation of Th1 preferred cytokine IL-2. SYK-dependent phosphorylation is required for recruitment of PI3K signaling components.
SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
SIMILARITY: Contains 1 SH2 domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): LCP2
CDC HuGE Published Literature: LCP2
Positive Disease Associations: Exercise Test
Related Studies:
  1. Exercise Test
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.

-  MalaCards Disease Associations
  MalaCards Gene Search: LCP2
Diseases sorted by gene-association score: b cell linker protein deficiency (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 46.92 RPKM in Whole Blood
Total median expression: 208.89 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -75.20207-0.363 Picture PostScript Text
3' UTR -133.29613-0.217 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001660 - SAM
IPR013761 - SAM/pointed
IPR011510 - SAM_2
IPR000980 - SH2

Pfam Domains:
PF00017 - SH2 domain
PF07647 - SAM domain (Sterile alpha motif)

SCOP Domains:
47769 - SAM/Pointed domain
55550 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1H3H
- NMR MuPIT

1YWO
- X-ray

2EAP
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2ROR - NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q13094
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding

Biological Process:
GO:0006955 immune response
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0030168 platelet activation
GO:0035556 intracellular signal transduction
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0045576 mast cell activation
GO:0045860 positive regulation of protein kinase activity
GO:0050663 cytokine secretion
GO:0050852 T cell receptor signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005911 cell-cell junction
GO:0036398 TCR signalosome
GO:0044853 plasma membrane raft


-  Descriptions from all associated GenBank mRNAs
  AK122637 - Homo sapiens cDNA FLJ16062 fis, clone THYMU2000120, highly similar to Homo sapiens lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) (LCP2).
BC016618 - Homo sapiens lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa), mRNA (cDNA clone MGC:21114 IMAGE:4476274), complete cds.
AK292890 - Homo sapiens cDNA FLJ76481 complete cds, highly similar to Homo sapiens lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) (LCP2), mRNA.
AK296098 - Homo sapiens cDNA FLJ57378 complete cds, highly similar to Lymphocyte cytosolic protein 2.
AK300000 - Homo sapiens cDNA FLJ58407 complete cds, highly similar to Lymphocyte cytosolic protein 2.
U20158 - Homo sapiens SLP-76 mRNA, complete cds.
JD529318 - Sequence 510342 from Patent EP1572962.
JD204030 - Sequence 185054 from Patent EP1572962.
JD399762 - Sequence 380786 from Patent EP1572962.
JD396550 - Sequence 377574 from Patent EP1572962.
JD169969 - Sequence 150993 from Patent EP1572962.
JD499415 - Sequence 480439 from Patent EP1572962.
BT007273 - Homo sapiens lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) mRNA, complete cds.
FN432830 - Homo sapiens mRNA for lymphocyte cytosolic protein 2 (LCP2 gene), transcript variant Ins80.
DQ890681 - Synthetic construct clone IMAGE:100003311; FLH165053.01X; RZPDo839F03158D lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) (LCP2) gene, encodes complete protein.
KJ891538 - Synthetic construct Homo sapiens clone ccsbBroadEn_00932 LCP2 gene, encodes complete protein.
DQ893863 - Synthetic construct Homo sapiens clone IMAGE:100008323; FLH165049.01L; RZPDo839F03157D lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) (LCP2) gene, encodes complete protein.
AB527802 - Synthetic construct DNA, clone: pF1KB5922, Homo sapiens LCP2 gene for lymphocyte cytosolic protein 2, without stop codon, in Flexi system.
AK310369 - Homo sapiens cDNA, FLJ17411.
JD414658 - Sequence 395682 from Patent EP1572962.
JD119514 - Sequence 100538 from Patent EP1572962.
JD405650 - Sequence 386674 from Patent EP1572962.
JD436248 - Sequence 417272 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04650 - Natural killer cell mediated cytotoxicity
hsa04660 - T cell receptor signaling pathway
hsa04664 - Fc epsilon RI signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q13094 (Reactome details) participates in the following event(s):

R-HSA-430135 p-SLP-76 binds ADAP
R-HSA-430158 p-SLP-76 binds VAV
R-HSA-430190 p-SLP-76 binds NCK
R-HSA-429449 Syk activation leads to SLP-76 activation
R-HSA-202241 Recruitment of SLP-76 to Gads
R-HSA-202331 Recruitment of PLC-gamma1 to SLP-76
R-HSA-202375 Recruitment of ITK to SLP-76
R-HSA-202216 Phosphorylation of SLP-76
R-HSA-213407 Disassociation of PLC-gamma1 from SLP-76
R-HSA-430201 p-SLP-76:ADAP binds Ena/VASP
R-HSA-430180 NCK recruits WASP
R-HSA-430183 NCK binds PAK
R-HSA-2396561 Recruitment of GADS:SLP-76 to p-5Y-LAT
R-HSA-2424485 Release of p-PLCG1
R-HSA-2424481 Recruitment of VAV and BTK to p-SLP-76
R-HSA-2730892 Recruitment of VAV to p-SLP-76
R-HSA-2396594 Phosphorylation of SLP-76 by p-SYK
R-HSA-2730851 Phosphorylation of SLP-76 by p-SYK
R-HSA-2396606 Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT
R-HSA-202248 Phosphorylation of PLC-gamma1
R-HSA-2424487 Phosphorylation of PLC-gamma by p-BTK/p-SYK
R-HSA-2424484 Phosphorylation of BTK by p-SYK
R-HSA-2424486 Phosphorylation and activation of VAV2/VAV3 by SYK
R-HSA-2730888 Phosphorylation of PLC-gamma
R-HSA-2730858 Autophosphorylation of BTK/ITK
R-HSA-2730840 Activation of RAC1 by VAV
R-HSA-2730841 Phosphorylation and activation of VAV
R-HSA-2730885 Recruitment of TEC kinases to p-SLP-76
R-HSA-2730833 Phosphorylation of TEC kinases by p-SYK
R-HSA-2730889 Recruitment of PAK to the membrane by binding active RAC1
R-HSA-2730856 Autophosphorylation of PAK
R-HSA-2424476 Activation of RAC1 by VAV2/3
R-HSA-2730847 Hydrolysis of PIP2 by PLCG
R-HSA-202433 Generation of second messenger molecules
R-HSA-114604 GPVI-mediated activation cascade
R-HSA-202403 TCR signaling
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-2424491 DAP12 signaling
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-1280218 Adaptive Immune System
R-HSA-109582 Hemostasis
R-HSA-2172127 DAP12 interactions
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-168256 Immune System
R-HSA-168249 Innate Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: LCP2_HUMAN, NM_005565, NP_005556, Q13094, Q53XV4
UCSC ID: uc003man.1
RefSeq Accession: NM_005565
Protein: Q13094 (aka LCP2_HUMAN)
CCDS: CCDS47339.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005565.3
exon count: 21CDS single in 3' UTR: no RNA size: 2472
ORF size: 1602CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3374.00frame shift in genome: no % Coverage: 97.98
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.