Reviewed, UniProtKB/Swiss-Prot O43561 (LAT_HUMAN)

Names and origin

Protein names

Recommended name:
    Linker for activation of T-cells family member 1
Alternative name(s):
    36 kDa phospho-tyrosine adapter protein
    pp36
    p36-38

Gene names

Name:

LAT

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	262 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Ref.6
Subunit structure	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 MIST By similarity. Interacts with FCGR1A.
Subcellular location	Cell membrane; Single-pass type III membrane protein. Note= Present in lipid rafts. Ref.1 Ref.4
Tissue specificity	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). Ref.1 Ref.12
Post-translational modification	Phosphorylated on tyrosines by ZAP-70 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. Ref.1 Ref.9 Ref.13 Palmitoylation of Cys-26 and Cys-29 is required for raft targeting and efficient phosphorylation.
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.

Ontologies

Keywords
Biological process	Immune response Mast cell degranulation
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from mutant phenotype. Source: HGNC calcium-mediated signaling Inferred from mutant phenotype. Source: HGNC integrin-mediated signaling pathway Inferred from direct assay. Source: HGNC mast cell degranulation Inferred from electronic annotation. Source: UniProtKB-KW regulation of T cell activation Inferred from mutant phenotype. Source: HGNC
Cellular component	immunological synapse Inferred from direct assay. Source: HGNC integral to membrane Inferred from direct assay. Source: HGNC membrane raft Traceable author statement. Source: HGNC
Molecular function	SH3/SH2 adaptor activity Ref.1 Inferred from direct assay. Source: HGNC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FYN	P06241	1	EBI-1222766,EBI-515315
GRB2	P62993	1	EBI-1222766,EBI-401755
LCK	P06239	1	EBI-1222766,EBI-1348
PLCG1	P19174	1	EBI-1222766,EBI-79387

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: O43561-1)

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.

Isoform Short (identifier: O43561-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 262	262	Linker for activation of T-cells family member 1		PRO_0000083325
Regions
	Topological domain	1 – 4	4	Extracellular Potential
	Transmembrane	5 – 27	23	Signal-anchor for type III membrane protein Potential
	Topological domain	28 – 262	235	Cytoplasmic Potential
	Region	161 – 164	4	Interaction with PLCG1
	Region	200 – 203	4	Interaction with GRB2, GRAP2 and PIK3R1
	Region	220 – 223	4	Interaction with GRB2, GRAP2 and PIK3R1
Amino acid modifications
	Modified residue	39	1	Phosphothreonine Ref.13
	Modified residue	84	1	Phosphoserine Ref.13
	Modified residue	101	1	Phosphoserine Ref.13
	Modified residue	109	1	Phosphoserine Ref.13
	Modified residue	110	1	Phosphotyrosine Probable
	Modified residue	156	1	Phosphotyrosine Probable
	Modified residue	161	1	Phosphotyrosine Probable
	Modified residue	200	1	Phosphotyrosine Ref.1
	Modified residue	220	1	Phosphotyrosine Probable
	Modified residue	224	1	Phosphoserine Ref.13
	Modified residue	255	1	Phosphotyrosine Probable
	Lipidation	26	1	S-palmitoyl cysteine Ref.4
	Lipidation	29	1	S-palmitoyl cysteine Ref.4
Natural variations
	Alternative sequence	114 – 142	29	Missing in isoform Short.		VSP_004303
Experimental info
	Mutagenesis	26	1	C → A: Reduces palmitoylation; abolishes localization to lipid rafts Ref.4
	Mutagenesis	29	1	C → A: Reduces palmitoylation; impairs localization to lipid rafts Ref.4
	Mutagenesis	161	1	Y → F: Abolishes interaction with PLCG1 Ref.10
	Mutagenesis	200	1	Y → F: Abolishes interaction with GRB2 and PIK3R1; when associated with F-220 Ref.1
	Mutagenesis	220	1	Y → F: Abolishes interaction with GRB2 and PIK3R1; when associated with F-200 Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified June 1, 1998. Version 1. Checksum: BCD80AE7DCA64153	FASTA	262	27,930
	10 20 30 40 50 60 MEEAILVPCV LGLLLLPILA MLMALCVHCH RLPGSYDSTS SDSLYPRGIQ FKRPHTVAPW 70 80 90 100 110 120 PPAYPPVTSY PPLSQPDLLP IPRSPQPLGG SHRTPSSRRD SDGANSVASY ENEGASGIRG 130 140 150 160 170 180 AQAGWGVWGP SWTRLTPVSL PPEPACEDAD EDEDDYHNPG YLVVLPDSTP ATSTAAPSAP 190 200 210 220 230 240 ALSTPGIRDS AFSMESIDDY VNVPESGESA EASLDGSREY VNVSQELHPG AAKTEPAALS 250 260 SQEAEEVEEE GAPDYENLQE LN
	Isoform Short. Checksum: 0832E2D2B4220BC6		233	24,985
	10 20 30 40 50 60 MEEAILVPCV LGLLLLPILA MLMALCVHCH RLPGSYDSTS SDSLYPRGIQ FKRPHTVAPW 70 80 90 100 110 120 PPAYPPVTSY PPLSQPDLLP IPRSPQPLGG SHRTPSSRRD SDGANSVASY ENEEPACEDA 130 140 150 160 170 180 DEDEDDYHNP GYLVVLPDST PATSTAAPSA PALSTPGIRD SAFSMESIDD YVNVPESGES 190 200 210 220 230 AEASLDGSRE YVNVSQELHP GAAKTEPAAL SSQEAEEVEE EGAPDYENLQ ELN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation." Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E. Cell 92:83-92(1998) [PubMed: 9489702] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), PROTEIN SEQUENCE OF 32-47 AND 219-233, PHOSPHORYLATION AT TYR-200, MASS SPECTROMETRY, MUTAGENESIS OF TYR-200 AND TYR-220, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH PIK3R1; GRB2; GRAP AND PLCG1. Tissue: Leukemia.
[2]	"Molecular cloning of the cDNA encoding pp36, a tyrosine-phosphorylated adaptor protein selectively expressed by T cells and natural killer cells." Weber J.R., Orstavik S., Torgersen K.M., Danbolt N.C., Berg S.F., Ryan J.C., Tasken K., Imboden J.B., Vaage J.T. J. Exp. Med. 187:1157-1161(1998) [PubMed: 9529333] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Tissue: Thymus.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT). Tissue: Colon.
[4]	"LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation." Zhang W., Trible R.P., Samelson L.E. Immunity 9:239-246(1998) [PubMed: 9729044] [Abstract] Cited for: SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-26 AND CYS-29, MUTAGENESIS OF CYS-26 AND CYS-29.
[5]	"Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells." Lindholm C.K., Gylfe E., Zhang W., Samelson L.E., Welsh M. J. Biol. Chem. 274:28050-28057(1999) [PubMed: 10488157] [Abstract] Cited for: INTERACTION WITH SHB.
[6]	"A role for the adaptor protein LAT in human NK cell-mediated cytotoxicity." Jevremovic D., Billadeau D.D., Schoon R.A., Dick C.J., Irvin B.J., Zhang W., Samelson L.E., Abraham R.T., Leibson P.J. J. Immunol. 162:2453-2456(1999) [PubMed: 10072481] [Abstract] Cited for: FUNCTION IN NK CELLS, INTERACTION WITH PLCG1.
[7]	"Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling." Zhang W., Trible R.P., Zhu M., Liu S.K., McGlade C.J., Samelson L.E. J. Biol. Chem. 275:23355-23361(2000) [PubMed: 10811803] [Abstract] Cited for: INTERACTION WITH GRB2; GRAP2 AND PLCG1.
[8]	"The adapter protein LAT enhances fcgamma receptor-mediated signal transduction in myeloid cells." Tridandapani S., Lyden T.W., Smith J.L., Carter J.E., Coggeshall K.M., Anderson C.L. J. Biol. Chem. 275:20480-20487(2000) [PubMed: 10781611] [Abstract] Cited for: INTERACTION WITH FCGR1A.
[9]	"Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin." Asazuma N., Wilde J.I., Berlanga O., Leduc M., Leo A., Schweighoffer E., Tybulewicz V., Bon C., Liu S.K., McGlade C.J., Schraven B., Watson S.P. J. Biol. Chem. 275:33427-33434(2000) [PubMed: 10942756] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH LCP2; SKAP2; GRB2; PLCG2 AND CBL.
[10]	"Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells." Paz P.E., Wang S., Clarke H., Lu X., Stokoe D., Abo A. Biochem. J. 356:461-471(2001) [PubMed: 11368773] [Abstract] Cited for: INTERACTION WITH PIK3R1 AND PLCG1, MUTAGENESIS OF TYR-161.
[11]	"LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways." Sommers C.L., Samelson L.E., Love P.E. Bioessays 26:61-67(2004) [PubMed: 14696041] [Abstract] Cited for: REVIEW ON FUNCTION IN T-CELLS.
[12]	"Transmembrane adaptor molecules: a new category of lymphoid-cell markers." Tedoldi S., Paterson J.C., Hansmann M.-L., Natkunam Y., Rudiger T., Angelisova P., Du M.Q., Roberton H., Roncador G., Sanchez L., Pozzobon M., Masir N., Barry R., Pileri S., Mason D.Y., Marafioti T., Horejsi V. Blood 107:213-221(2006) [PubMed: 16160011] [Abstract] Cited for: TISSUE SPECIFICITY.
[13]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-39; SER-84; SER-101; SER-109 AND SER-224, MASS SPECTROMETRY. Tissue: Platelet.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF036906 mRNA. Translation: AAC39637.1. AF036905 mRNA. Translation: AAC39636.1. AJ223280 mRNA. Translation: CAA11218.1. BC011563 mRNA. Translation: AAH11563.1.
RefSeq	NP_001014987.1. NP_001014988.1. NP_001014989.1. NP_055202.1.
UniGene	Hs.632179
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O43561. 6 interactions.
PTM databases
PhosphoSite	O43561.
Genome annotation databases
Ensembl	ENSG00000213658. Homo sapiens. [Contig view]
GeneID	27040.
KEGG	hsa:27040.
Organism-specific databases
GeneCards	GC16P028903.
H-InvDB	HIX0013329.
HGNC	HGNC:18874. LAT.
HPA	CAB002223. CAB012978. HPA011157.
MIM	602354. gene.
PharmGKB	PA27350.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O43561.
Gene expression databases
ArrayExpress	O43561.
CleanEx	HS_LAT.
GermOnline	ENSG00000169682. Homo sapiens.
Family and domain databases
InterPro	IPR008359. LAT. [Graphical view]
PRINTS	PR01781. LATPROTEIN.
ProtoNet	Search...
Other Resources
NextBio	49608.
SOURCE	Search...

Entry information

Entry name

LAT_HUMAN

Accession

Primary (citable) accession number: O43561
Secondary accession number(s): O43919

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	June 1, 1998
Last modified:	December 16, 2008
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)