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

Summary

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; AllianceGenome:HGNC:6529
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: IMD81; 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: mouse all
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Genomic context

Location:: 5q35.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (170246233..170297777, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (170785090..170836631, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (169673237..169724781, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SLP76 Mutation Associated with Combined Immunodeficiency and EBV-Related Lymphoma.
Title: SLP76 Mutation Associated with Combined Immunodeficiency and EBV-Related Lymphoma.
STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease.
Title: STAT1 epigenetically regulates LCP2 and TNFAIP2 by recruiting EP300 to contribute to the pathogenesis of inflammatory bowel disease.
Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma.
Title: Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma.
A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8(+) T cells.
Title: A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8(+) T cells.
The 14-3-3/SLP76 protein-protein interaction in T-cell receptor signalling: a structural and biophysical characterization.
Title: The 14-3-3/SLP76 protein-protein interaction in T-cell receptor signalling: a structural and biophysical characterization.
Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis.
Title: Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis.
Findings reveal that ADAP acts upstream of SLP-76 to convert labile, Ca(2+)-competent microclusters into stable adhesive junctions with enhanced signaling potential.
Title: ADAP is an upstream regulator that precedes SLP-76 at sites of TCR engagement and stabilizes signaling microclusters.
a previously unappreciated role for PLC-gamma1 in the positive regulation of Zap-70 and T-cell receptor tyrosine phosphorylation. Conversely, PLC-gamma1 negatively regulated the phosphorylation of SLP-76-associated proteins, including previously established Lck substrate phosphorylation sites within this complex.
Title: A PLC-γ1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex.
These data are consistent with a model in which bivalent recruitment of a GADS/SLP-76 complex is required for costimulation by CD6.
Title: T Cell Costimulation by CD6 Is Dependent on Bivalent Binding of a GADS/SLP-76 Complex.
LAT and SLP-76 are randomly dispersed throughout the clusters that form upon T cell receptor engagement.
Title: Development of nanoscale structure in LAT-based signaling complexes.

Submit: New GeneRIF Correction See all GeneRIFs (58)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Immunodeficiency 81 MedGen: C5543540 OMIM: 619374 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70367 (e-PCR)
- UniSTS:11521

LCP2 (e-PCR)
- UniSTS:504848

SGC35415 (e-PCR)
- UniSTS:46888

STS-T25868 (e-PCR)
- UniSTS:66884

G58254 (e-PCR)
- UniSTS:135597

RH70635 (e-PCR)
- UniSTS:6579

RH79005 (e-PCR)
- UniSTS:1976

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in mast cell activation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein kinase activity	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
part_of TCR signalosome	IDA Inferred from Direct Assay more info	PubMed
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in plasma membrane raft	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: lymphocyte cytosolic protein 2

Names: 76 kDa tyrosine phosphoprotein; SH2 domain-containing leukocyte protein of 76 kDa; SLP-76 tyrosine phosphoprotein

NCBI Reference Sequences (RefSeq)

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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)

NM_005565.5 → NP_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

A8KA25, Q13094, Q53XV4

UniProtKB/TrEMBL

B4DT07

Related

ENSP00000046794.5, ENST00000046794.10

Conserved Domains (3) summary

cd09522
Location:10 → 78

SAM_SLP76; SAM domain of SLP76 subfamily

cd09929
Location:411 → 531

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:130 → 421

Atrophin-1; Atrophin-1 family