Q9GZY6 (NTAL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Linker for activation of T-cells family member 2

Alternative name(s):
Linker for activation of B-cells
Membrane-associated adapter molecule
Non-T-cell activation linker
Williams-Beuren syndrome chromosomal region 15 protein
Williams-Beuren syndrome chromosomal region 5 protein

Gene names

Name:	LAT2
Synonyms:	LAB, NTAL, WBS15, WBSCR15, WBSCR5
ORF Names:	HSPC046

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	243 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2. Ref.3 Ref.4 Ref.11
Subunit structure	When phosphorylated, interacts with GRB2. May also interact with SOS1, GAB1 and CBL. Ref.3 Ref.4 Ref.12
Subcellular location	Cell membrane; Single-pass type III membrane protein. Note: Present in lipid rafts. Ref.3 Ref.4
Tissue specificity	Highly expressed in spleen, peripheral blood lymphocytes, and germinal centers of lymph nodes. Also expressed in placenta, lung, pancreas and small intestine. Present in B-cells, NK cells and monocytes. Absent from T-cells (at protein level). Ref.1 Ref.3 Ref.4 Ref.13
Post-translational modification	Phosphorylated on tyrosines following cross-linking of BCR in B-cells, FCGR1 in myeloid cells, or FCER1 in mast cells; which induces the recruitment of GRB2. Ref.3 Ref.4 Ref.12 Ref.14 Ref.15 May be polyubiquitinated.
Involvement in disease	Note=LAT2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of LAT2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. Ref.1 Ref.2 Ref.5
Sequence caution	The sequence AAF29018.1 differs from that shown. Reason: Frameshift at positions 82, 86, 130 and 221.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Mast cell degranulation
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Disease	Williams-Beuren syndrome
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	B cell activation Inferred from direct assay Ref.4. Source: HGNC B cell receptor signaling pathway Inferred from direct assay Ref.4. Source: HGNC calcium-mediated signaling Inferred from genetic interaction Ref.12. Source: HGNC mast cell degranulation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from genetic interaction Ref.12. Source: GOC membrane raft Inferred from direct assay Ref.3Ref.4. Source: HGNC plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	SH2 domain binding Inferred from mutant phenotype Ref.12. Source: HGNC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9GZY6-1)

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 2 (identifier: Q9GZY6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     112-243: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 243	243	Linker for activation of T-cells family member 2		PRO_0000083334
Regions
	Topological domain	1 – 5	5	Extracellular Potential
	Transmembrane	6 – 26	21	Helical; Signal-anchor for type III membrane protein; Potential
	Topological domain	27 – 243	217	Cytoplasmic Potential
Amino acid modifications
	Modified residue	40	1	Phosphotyrosine By similarity
	Modified residue	44	1	Phosphoserine Ref.15
	Modified residue	58	1	Phosphotyrosine By similarity
	Modified residue	59	1	Phosphoserine By similarity
	Modified residue	92	1	Phosphoserine By similarity
	Modified residue	95	1	Phosphotyrosine By similarity
	Modified residue	135	1	Phosphoserine Ref.14 Ref.15
	Modified residue	136	1	Phosphotyrosine Probable
	Modified residue	193	1	Phosphotyrosine Probable
	Modified residue	233	1	Phosphotyrosine Ref.3 Ref.12
	Lipidation	25	1	S-palmitoyl cysteine Probable
	Lipidation	28	1	S-palmitoyl cysteine Probable
Natural variations
	Alternative sequence	112 – 243	132	Missing in isoform 2.		VSP_016643
Experimental info
	Mutagenesis	58	1	Y → F: No change in phosphorylation upon BCR activation. Ref.12
	Mutagenesis	84	1	Y → F: No change in phosphorylation upon BCR activation. Ref.12
	Mutagenesis	95	1	Y → F: Slightly reduces phosphorylation upon BCR activation. Ref.12
	Mutagenesis	110	1	Y → F: No change in phosphorylation upon BCR activation. Ref.12
	Mutagenesis	118	1	Y → F: No change in phosphorylation upon BCR activation. Ref.12
	Mutagenesis	136	1	Y → F: Slightly reduces phosphorylation upon BCR activation. Ref.12
	Mutagenesis	193	1	Y → F: Reduces phosphorylation upon BCR activation. Ref.12
	Mutagenesis	233	1	Y → F: Strongly reduces phosphorylation upon BCR activation. Ref.12
	Sequence conflict	39	1	I → M in BAF82763. Ref.7
	Sequence conflict	82	1	Q → A in AAF29018. Ref.6
	Sequence conflict	101	1	G → R in AAF29018. Ref.6
	Sequence conflict	221	1	V → M in AAF29018. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 222D2CCF3C71C503	FASTA	243	26,550
	10 20 30 40 50 60 MSSGTELLWP GAALLVLLGV AASLCVRCSR PGAKRSEKIY QQRSLREDQQ SFTGSRTYSL 70 80 90 100 110 120 VGQAWPGPLA DMAPTRKDKL LQFYPSLEDP ASSRYQNFSK GSRHGSEEAY IDPIAMEYYN 130 140 150 160 170 180 WGRFSKPPED DDANSYENVL ICKQKTTETG AQQEGIGGLC RGDLSLSLAL KTGPTSGLCP 190 200 210 220 230 240 SASPEEDEES EDYQNSASIH QWRESRKVMG QLQREASPGP VGSPDEEDGE PDYVNGEVAA TEA
	Isoform 2 [UniParc]. Checksum: 09540AE67B44F485	FASTA	111	12,255
	10 20 30 40 50 60 MSSGTELLWP GAALLVLLGV AASLCVRCSR PGAKRSEKIY QQRSLREDQQ SFTGSRTYSL 70 80 90 100 110 VGQAWPGPLA DMAPTRKDKL LQFYPSLEDP ASSRYQNFSK GSRHGSEEAY I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Divergent human and mouse orthologs of a novel gene (WBSCR15/Wbscr15) reside within the genomic interval commonly deleted in Williams syndrome." Doyle J.L., DeSilva U., Miller W., Green E.D. Cytogenet. Cell Genet. 90:285-290(2000) [PubMed: 11124535] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DISEASE, TISSUE SPECIFICITY.
[2]	"Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23." Martindale D.W., Wilson M.D., Wang D., Burke R.D., Chen X., Duronio V., Koop B.F. Mamm. Genome 11:890-898(2000) [PubMed: 11003705] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISEASE.
[3]	"Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling." Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O., Spicka J., Hilgert I., Luskova P., Draber P., Novak P., Engels N., Wienands J., Simeoni L., Oesterreicher J., Aguado E., Malissen M., Schraven B., Horejsi V. J. Exp. Med. 196:1617-1626(2002) [PubMed: 12486104] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH GRB2; SOS1; GAB1 AND CBL, TISSUE SPECIFICITY, PALMITOYLATION AT CYS-25 AND CYS-28, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-136; TYR-193 AND TYR-233, UBIQUITINATION, FUNCTION. Tissue: Leukocyte.
[4]	"LAB: a new membrane-associated adaptor molecule in B cell activation." Janssen E., Zhu M., Zhang W., Koonpaew S., Zhang W. Nat. Immunol. 4:117-123(2003) [PubMed: 12514734] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH GRB2, FUNCTION. Tissue: B-cell.
[5]	"A novel gene, WBS15, is deleted in patients with Williams syndrome." Tassabehji M., Heather L., Gladwin A., Metcalfe K., Donnai D., Read A., Wilmot C. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), DISEASE.
[6]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Umbilical cord blood.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Neutrophil, Placenta, Spleen and Substantia nigra.
[8]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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 1). Tissue: B-cell and Lymph.
[11]	"NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation." Tkaczyk C., Horejsi V., Iwaki S., Draber P., Samelson L.E., Satterthwaite A.B., Nahm D.H., Metcalfe D.D., Gilfillan A.M. Blood 104:207-214(2004) [PubMed: 15010370] [Abstract] Cited for: FUNCTION.
[12]	"The importance of three membrane-distal tyrosines in the adaptor protein NTAL/LAB." Koonpaew S., Janssen E., Zhu M., Zhang W. J. Biol. Chem. 279:11229-11235(2004) [PubMed: 14722116] [Abstract] Cited for: MUTAGENESIS OF TYR-58; TYR-84; TYR-95; TYR-110; TYR-118; TYR-136; TYR-193 AND TYR-233, PHOSPHORYLATION AT TYR-136; TYR-193 AND TYR-233, INTERACTION WITH GRB2.
[13]	"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.
[14]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed: 19367720] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-135, MASS SPECTROMETRY. Tissue: T-cell.
[15]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND SER-135, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF257135 mRNA. Translation: AAF91352.1.
AF045555 Genomic DNA. Translation: AAF74978.1.
AY190023 mRNA. Translation: AAO63155.1.
AF252611 mRNA. Translation: AAK37429.1.
AF252612 mRNA. Translation: AAK37430.1.
AF252613 mRNA. Translation: AAK37633.1.
AF252614 mRNA. Translation: AAK37431.1.
AF161531 mRNA. Translation: AAF29018.1. Frameshift.
AK002099 mRNA. Translation: BAA92084.1.
AK092904 mRNA. Translation: BAG52627.1.
AK290074 mRNA. Translation: BAF82763.1.
AK290916 mRNA. Translation: BAF83605.1.
AC005081 Genomic DNA. Translation: AAS07404.1.
AC005081 Genomic DNA. Translation: AAS07405.1.
CH471200 Genomic DNA. Translation: EAW69610.1.
CH471200 Genomic DNA. Translation: EAW69611.1.
CH471200 Genomic DNA. Translation: EAW69612.1.
CH471200 Genomic DNA. Translation: EAW69613.1.
BC001609 mRNA. Translation: AAH01609.1.
BC009204 mRNA. Translation: AAH09204.1.

IPI

IPI00032447.
IPI00395993.

RefSeq

NP_054865.2. NM_014146.3.
NP_115852.1. NM_032463.2.
NP_115853.2. NM_032464.2.

UniGene

Hs.726075.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MAZ	X-ray	1.90	B	133-141	[»]

ProteinModelPortal

Q9GZY6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9GZY6. 1 interaction.

MINT

MINT-2864124.

STRING

Q9GZY6.

PTM databases

PhosphoSite

Q9GZY6.

Proteomic databases

PRIDE

Q9GZY6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000275635; ENSP00000275635; ENSG00000086730.
ENST00000344995; ENSP00000344881; ENSG00000086730.
ENST00000398475; ENSP00000381492; ENSG00000086730.
ENST00000398479; ENSP00000381496; ENSG00000086730.
ENST00000460943; ENSP00000420494; ENSG00000086730.

GeneID

7462.

KEGG

hsa:7462.

UCSC

uc003uag.1. human.

Organism-specific databases

CTD

7462.

GeneCards

GC07P073613.

H-InvDB

HIX0006764.

HGNC

HGNC:12749. LAT2.

HPA

HPA003462.

MIM

605719. gene.

neXtProt

NX_Q9GZY6.

Orphanet

904. Williams syndrome.

PharmGKB

PA37356.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20062.

GeneTree

ENSGT00390000006821.

HOGENOM

HBG283125.

HOVERGEN

HBG082063.

InParanoid

Q9GZY6.

OMA

RSEKIYQ.

Enzyme and pathway databases

Pathway_Interaction_DB

fcer1pathway. Fc-epsilon receptor I signaling in mast cells.

Gene expression databases

ArrayExpress

Q9GZY6.

Bgee

Q9GZY6.

CleanEx

HS_LAT2.

Genevestigator

Q9GZY6.

GermOnline

ENSG00000086730. Homo sapiens.

Family and domain databases

ProtoNet

Search...

Other

NextBio

29222.

SOURCE

Search...

Entry information

Entry name

NTAL_HUMAN

Accession

Primary (citable) accession number: Q9GZY6
Secondary accession number(s): A6NFK6 , A8K209, A8K4F1, D3DXF9, Q9BXX8, Q9NZY9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 20, 2005
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.