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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

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.

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

Keywordsi

Biological processAdaptive 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

EuPathDBiHostDB:ENSG00000213658.10.
HGNCiHGNC:18874. LAT.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 4ExtracellularSequence analysis4
Transmembranei5 – 27Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST23
Topological domaini28 – 262CytoplasmicSequence analysisAdd BLAST235

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi26C → A: Reduces palmitoylation; abolishes localization to lipid rafts. 1 Publication1
Mutagenesisi29C → A: Reduces palmitoylation; impairs localization to lipid rafts. 1 Publication1
Mutagenesisi161Y → F: Abolishes interaction with PLCG1. 1 Publication1
Mutagenesisi200Y → F: Abolishes interaction with GRB2 and PIK3R1; when associated with F-220. 1 Publication1
Mutagenesisi220Y → F: Abolishes interaction with GRB2 and PIK3R1; when associated with F-200. 1 Publication1

Organism-specific databases

DisGeNETi27040.
OpenTargetsiENSG00000213658.
PharmGKBiPA38728.

Chemistry databases

ChEMBLiCHEMBL5779.

Polymorphism and mutation databases

BioMutaiLAT.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000833251 – 262Linker for activation of T-cells family member 1Add BLAST262

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi26S-palmitoyl cysteine1 Publication1
Lipidationi29S-palmitoyl cysteine1 Publication1
Modified residuei39PhosphothreonineCombined sources1
Modified residuei40PhosphoserineCombined sources1
Modified residuei41PhosphoserineCombined sources1
Modified residuei43PhosphoserineCombined sources1
Modified residuei84PhosphoserineCombined sources1
Modified residuei101PhosphoserineCombined sources1
Modified residuei106PhosphoserineCombined sources1
Modified residuei109PhosphoserineBy similarity1
Modified residuei110PhosphotyrosineCurated1
Modified residuei156PhosphotyrosineCurated1
Modified residuei161PhosphotyrosineCurated1
Modified residuei200Phosphotyrosine1 Publication1
Modified residuei220PhosphotyrosineCurated1
Modified residuei224PhosphoserineCombined sources1
Modified residuei240PhosphoserineCombined sources1
Modified residuei241PhosphoserineCombined sources1
Modified residuei255PhosphotyrosineCombined sources1

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.
PhosphoSitePlusiO43561.
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

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi117971. 38 interactors.
CORUMiO43561.
DIPiDIP-29231N.
IntActiO43561. 36 interactors.
MINTiMINT-2836977.

Structurei

3D structure databases

ProteinModelPortaliO43561.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni161 – 164Interaction with PLCG14
Regioni200 – 203Interaction with GRB2, GRAP2 and PIK3R11 Publication4
Regioni220 – 223Interaction with GRB2, GRAP2 and PIK3R11 Publication4

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR008359. Linker_for_activat_Tcells_prot.
PANTHERiPTHR15586. PTHR15586. 1 hit.
PfamiView protein in Pfam
PF15234. LAT. 1 hit.
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0547581M → MEATAASWQVAVPVLGGASR PLGPRGAASLLRAPLQM in isoform 3. Curated1
Alternative sequenceiVSP_05475983Missing in isoform 4 and isoform 5. 1 Publication1
Alternative sequenceiVSP_004303114 – 142Missing in isoform 2, isoform 3 and isoform 4. 3 PublicationsAdd BLAST29

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

Similar proteinsi

Entry informationi

Entry nameiLAT_HUMAN
AccessioniPrimary (citable) accession number: O43561
Secondary accession number(s): B7WPI0
, C7C5T6, G5E9K3, O43919
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: June 1, 1998
Last modified: October 25, 2017
This is version 163 of the entry and version 1 of the sequence. See 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

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