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Protein

Linker for activation of T-cells family member 1

Gene

LAT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development. Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules.1 Publication

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • SH3/SH2 adaptor activity Source: HGNC

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • calcium-mediated signaling Source: HGNC
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • gene expression Source: Ensembl
  • immune response Source: HGNC
  • inflammatory response Source: Ensembl
  • integrin-mediated signaling pathway Source: HGNC
  • intracellular signal transduction Source: HGNC
  • lymphocyte homeostasis Source: Ensembl
  • MAPK cascade Source: Reactome
  • mast cell degranulation Source: UniProtKB-KW
  • platelet activation Source: Reactome
  • positive regulation of protein kinase activity Source: CACAO
  • Ras protein signal transduction Source: HGNC
  • regulation of T cell activation Source: HGNC
  • T cell activation Source: UniProtKB
  • T cell receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Adaptive immunity, Immunity, Mast cell degranulation

Enzyme and pathway databases

ReactomeiR-HSA-114604. GPVI-mediated activation cascade.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-2424491. DAP12 signaling.
R-HSA-2454202. Fc epsilon receptor (FCERI) signaling.
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-5673001. RAF/MAP kinase cascade.
SignaLinkiO43561.
SIGNORiO43561.

Names & Taxonomyi

Protein namesi
Recommended name:
Linker for activation of T-cells family member 1
Alternative name(s):
36 kDa phospho-tyrosine adapter protein
Short name:
pp36
p36-38
Gene namesi
Name:LAT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:18874. LAT.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 44ExtracellularSequence analysis
Transmembranei5 – 2723Helical; Signal-anchor for type III membrane proteinSequence analysisAdd
BLAST
Topological domaini28 – 262235CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • COP9 signalosome Source: UniProtKB
  • immunological synapse Source: HGNC
  • integral component of membrane Source: HGNC
  • mast cell granule Source: GOC
  • membrane raft Source: HGNC
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi26 – 261C → A: Reduces palmitoylation; abolishes localization to lipid rafts. 1 Publication
Mutagenesisi29 – 291C → A: Reduces palmitoylation; impairs localization to lipid rafts. 1 Publication
Mutagenesisi161 – 1611Y → F: Abolishes interaction with PLCG1. 1 Publication
Mutagenesisi200 – 2001Y → F: Abolishes interaction with GRB2 and PIK3R1; when associated with F-220. 1 Publication
Mutagenesisi220 – 2201Y → F: Abolishes interaction with GRB2 and PIK3R1; when associated with F-200. 1 Publication

Organism-specific databases

PharmGKBiPA38728.

Chemistry

ChEMBLiCHEMBL5779.

Polymorphism and mutation databases

BioMutaiLAT.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 262262Linker for activation of T-cells family member 1PRO_0000083325Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi26 – 261S-palmitoyl cysteine1 Publication
Lipidationi29 – 291S-palmitoyl cysteine1 Publication
Modified residuei39 – 391PhosphothreonineCombined sources
Modified residuei40 – 401PhosphoserineCombined sources
Modified residuei41 – 411PhosphoserineCombined sources
Modified residuei43 – 431PhosphoserineCombined sources
Modified residuei84 – 841PhosphoserineCombined sources
Modified residuei101 – 1011PhosphoserineCombined sources
Modified residuei106 – 1061PhosphoserineCombined sources
Modified residuei109 – 1091PhosphoserineBy similarity
Modified residuei110 – 1101PhosphotyrosineCurated
Modified residuei156 – 1561PhosphotyrosineCurated
Modified residuei161 – 1611PhosphotyrosineCurated
Modified residuei200 – 2001Phosphotyrosine1 Publication
Modified residuei220 – 2201PhosphotyrosineCurated
Modified residuei224 – 2241PhosphoserineCombined sources
Modified residuei240 – 2401PhosphoserineCombined sources
Modified residuei241 – 2411PhosphoserineCombined sources
Modified residuei255 – 2551PhosphotyrosineCombined sources

Post-translational modificationi

Phosphorylated on tyrosines by ZAP70 upon TCR activation, or by SYK upon other immunoreceptor activation; which leads to the recruitment of multiple signaling molecules. Is one of the most prominently tyrosine-phosphorylated proteins detected following TCR engagement. May be dephosphorylated by PTPRJ. Phosphorylated by ITK leading to the recruitment of VAV1 to LAT-containing complexes.
Palmitoylation of Cys-26 and Cys-29 is required for raft targeting and efficient phosphorylation.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiO43561.
PeptideAtlasiO43561.
PRIDEiO43561.

PTM databases

iPTMnetiO43561.
PhosphoSiteiO43561.
SwissPalmiO43561.

Expressioni

Tissue specificityi

Expressed in thymus, T-cells, NK cells, mast cells and, at lower levels, in spleen. Present in T-cells but not B-cells (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000213658.
CleanExiHS_LAT.
ExpressionAtlasiO43561. baseline and differential.
GenevisibleiO43561. HS.

Organism-specific databases

HPAiCAB002223.
CAB012978.
HPA011157.

Interactioni

Subunit structurei

When phosphorylated, interacts directly with the PIK3R1 subunit of phosphoinositide 3-kinase and the SH2 domains of GRB2, GRAP, GRAP2, PLCG1 and PLCG2. Interacts indirectly with CBL, SOS, VAV, and LCP2. Interacts with SHB, SKAP2 and CLNK (By similarity). Interacts with FCGR1A. Interacts with GRB2, PLCG1 and THEMIS upon TCR activation in thymocytes (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
EGFRP005332EBI-1222766,EBI-297353
GRB2P6299312EBI-1222766,EBI-401755
LCKP062392EBI-1222766,EBI-1348
PIK3R1P279864EBI-1222766,EBI-79464
PLCG1P084874EBI-8070286,EBI-8013886From a different organism.
PLCG1P191747EBI-1222766,EBI-79387
PTPN1P180313EBI-1222766,EBI-968788
SGTAO437653EBI-1222766,EBI-347996

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • SH3/SH2 adaptor activity Source: HGNC

Protein-protein interaction databases

BioGridi117971. 35 interactions.
DIPiDIP-29231N.
IntActiO43561. 19 interactions.
MINTiMINT-2836977.

Structurei

3D structure databases

ProteinModelPortaliO43561.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni161 – 1644Interaction with PLCG1
Regioni200 – 2034Interaction with GRB2, GRAP2 and PIK3R1
Regioni220 – 2234Interaction with GRB2, GRAP2 and PIK3R1

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00390000014223.
HOGENOMiHOG000081810.
HOVERGENiHBG018198.
InParanoidiO43561.
KOiK07362.
OMAiGSHRMPS.
OrthoDBiEOG091G0QKO.
PhylomeDBiO43561.

Family and domain databases

InterProiIPR008359. Linker_for_activat_Tcells_prot.
[Graphical view]
PANTHERiPTHR15586. PTHR15586. 1 hit.
PfamiPF15234. LAT. 1 hit.
[Graphical view]
PRINTSiPR01781. LATPROTEIN.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43561-1) [UniParc]FASTAAdd to basket
Also known as: Long

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEEAILVPCV LGLLLLPILA MLMALCVHCH RLPGSYDSTS SDSLYPRGIQ
60 70 80 90 100
FKRPHTVAPW PPAYPPVTSY PPLSQPDLLP IPRSPQPLGG SHRTPSSRRD
110 120 130 140 150
SDGANSVASY ENEGASGIRG AQAGWGVWGP SWTRLTPVSL PPEPACEDAD
160 170 180 190 200
EDEDDYHNPG YLVVLPDSTP ATSTAAPSAP ALSTPGIRDS AFSMESIDDY
210 220 230 240 250
VNVPESGESA EASLDGSREY VNVSQELHPG AAKTEPAALS SQEAEEVEEE
260
GAPDYENLQE LN
Length:262
Mass (Da):27,930
Last modified:June 1, 1998 - v1
Checksum:iBCD80AE7DCA64153
GO
Isoform 2 (identifier: O43561-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     114-142: Missing.

Show »
Length:233
Mass (Da):24,985
Checksum:i0832E2D2B4220BC6
GO
Isoform 3 (identifier: O43561-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MEATAASWQVAVPVLGGASRPLGPRGAASLLRAPLQM
     114-142: Missing.

Note: Gene prediction based on EST data.
Show »
Length:269
Mass (Da):28,568
Checksum:i00A1E5FD10A258FE
GO
Isoform 4 (identifier: O43561-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-83: Missing.
     114-142: Missing.

Show »
Length:232
Mass (Da):24,829
Checksum:iAFA91E716FEBE1CE
GO
Isoform 5 (identifier: O43561-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-83: Missing.

Show »
Length:261
Mass (Da):27,774
Checksum:i0108E1F423BFE30E
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MEATAASWQVAVPVLGGASR PLGPRGAASLLRAPLQM in isoform 3. CuratedVSP_054758
Alternative sequencei83 – 831Missing in isoform 4 and isoform 5. 1 PublicationVSP_054759
Alternative sequencei114 – 14229Missing in isoform 2, isoform 3 and isoform 4. 3 PublicationsVSP_004303Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036906 mRNA. Translation: AAC39637.1.
AF036905 mRNA. Translation: AAC39636.1.
AJ223280 mRNA. Translation: CAA11218.1.
FN432832 mRNA. Translation: CBA11533.1.
AC109460 Genomic DNA. No translation available.
CH471267 Genomic DNA. Translation: EAW52027.1.
CH471267 Genomic DNA. Translation: EAW52028.1.
BC011563 mRNA. Translation: AAH11563.1.
CCDSiCCDS10647.1. [O43561-1]
CCDS32425.1. [O43561-2]
CCDS45455.1. [O43561-4]
CCDS53999.1. [O43561-3]
RefSeqiNP_001014987.1. NM_001014987.1. [O43561-2]
NP_001014988.1. NM_001014988.1. [O43561-4]
NP_001014989.2. NM_001014989.1. [O43561-3]
NP_055202.1. NM_014387.3. [O43561-1]
UniGeneiHs.632179.

Genome annotation databases

EnsembliENST00000360872; ENSP00000354119; ENSG00000213658. [O43561-1]
ENST00000395456; ENSP00000378841; ENSG00000213658. [O43561-2]
ENST00000395461; ENSP00000378845; ENSG00000213658. [O43561-3]
ENST00000454369; ENSP00000398793; ENSG00000213658. [O43561-4]
ENST00000564277; ENSP00000457036; ENSG00000213658. [O43561-4]
ENST00000566177; ENSP00000456761; ENSG00000213658. [O43561-5]
GeneIDi27040.
KEGGihsa:27040.
UCSCiuc002dsb.4. human. [O43561-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF036906 mRNA. Translation: AAC39637.1.
AF036905 mRNA. Translation: AAC39636.1.
AJ223280 mRNA. Translation: CAA11218.1.
FN432832 mRNA. Translation: CBA11533.1.
AC109460 Genomic DNA. No translation available.
CH471267 Genomic DNA. Translation: EAW52027.1.
CH471267 Genomic DNA. Translation: EAW52028.1.
BC011563 mRNA. Translation: AAH11563.1.
CCDSiCCDS10647.1. [O43561-1]
CCDS32425.1. [O43561-2]
CCDS45455.1. [O43561-4]
CCDS53999.1. [O43561-3]
RefSeqiNP_001014987.1. NM_001014987.1. [O43561-2]
NP_001014988.1. NM_001014988.1. [O43561-4]
NP_001014989.2. NM_001014989.1. [O43561-3]
NP_055202.1. NM_014387.3. [O43561-1]
UniGeneiHs.632179.

3D structure databases

ProteinModelPortaliO43561.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117971. 35 interactions.
DIPiDIP-29231N.
IntActiO43561. 19 interactions.
MINTiMINT-2836977.

Chemistry

ChEMBLiCHEMBL5779.

PTM databases

iPTMnetiO43561.
PhosphoSiteiO43561.
SwissPalmiO43561.

Polymorphism and mutation databases

BioMutaiLAT.

Proteomic databases

MaxQBiO43561.
PeptideAtlasiO43561.
PRIDEiO43561.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360872; ENSP00000354119; ENSG00000213658. [O43561-1]
ENST00000395456; ENSP00000378841; ENSG00000213658. [O43561-2]
ENST00000395461; ENSP00000378845; ENSG00000213658. [O43561-3]
ENST00000454369; ENSP00000398793; ENSG00000213658. [O43561-4]
ENST00000564277; ENSP00000457036; ENSG00000213658. [O43561-4]
ENST00000566177; ENSP00000456761; ENSG00000213658. [O43561-5]
GeneIDi27040.
KEGGihsa:27040.
UCSCiuc002dsb.4. human. [O43561-1]

Organism-specific databases

CTDi27040.
GeneCardsiLAT.
HGNCiHGNC:18874. LAT.
HPAiCAB002223.
CAB012978.
HPA011157.
MIMi602354. gene.
neXtProtiNX_O43561.
PharmGKBiPA38728.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00390000014223.
HOGENOMiHOG000081810.
HOVERGENiHBG018198.
InParanoidiO43561.
KOiK07362.
OMAiGSHRMPS.
OrthoDBiEOG091G0QKO.
PhylomeDBiO43561.

Enzyme and pathway databases

ReactomeiR-HSA-114604. GPVI-mediated activation cascade.
R-HSA-202433. Generation of second messenger molecules.
R-HSA-2424491. DAP12 signaling.
R-HSA-2454202. Fc epsilon receptor (FCERI) signaling.
R-HSA-2871796. FCERI mediated MAPK activation.
R-HSA-2871809. FCERI mediated Ca+2 mobilization.
R-HSA-5673001. RAF/MAP kinase cascade.
SignaLinkiO43561.
SIGNORiO43561.

Miscellaneous databases

GeneWikiiLinker_of_activated_T_cells.
GenomeRNAii27040.
PROiO43561.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213658.
CleanExiHS_LAT.
ExpressionAtlasiO43561. baseline and differential.
GenevisibleiO43561. HS.

Family and domain databases

InterProiIPR008359. Linker_for_activat_Tcells_prot.
[Graphical view]
PANTHERiPTHR15586. PTHR15586. 1 hit.
PfamiPF15234. LAT. 1 hit.
[Graphical view]
PRINTSiPR01781. LATPROTEIN.
ProtoNetiSearch...

Entry informationi

Entry nameiLAT_HUMAN
AccessioniPrimary (citable) accession number: O43561
Secondary accession number(s): B7WPI0
, C7C5T6, G5E9K3, O43919
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: June 1, 1998
Last modified: September 7, 2016
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Engagement of killer inhibitory receptors (KIR) disrupts the interaction of PLCG1 with LAT and blocks target cell-induced activation of PLC, maybe by inducing the dephosphorylation of LAT.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.