LAX1_HUMAN
ID LAX1_HUMAN Reviewed; 398 AA.
AC Q8IWV1; B7Z744; J3KP69; Q6NSZ6; Q9NXB4;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Lymphocyte transmembrane adapter 1;
DE AltName: Full=Linker for activation of X cells;
DE AltName: Full=Membrane-associated adapter protein LAX;
GN Name=LAX1; Synonyms=LAX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, INTERACTION WITH GRB2; PIK3R1 AND GRAP2, PHOSPHORYLATION AT
RP TYR-193; TYR-268; TYR-294 AND TYR-373, AND FUNCTION.
RX PubMed=12359715; DOI=10.1074/jbc.m208946200;
RA Zhu M., Janssen E., Leung K., Zhang W.;
RT "Molecular cloning of a novel gene encoding a membrane-associated adaptor
RT protein (LAX) in lymphocyte signaling.";
RL J. Biol. Chem. 277:46151-46158(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INDUCTION.
RX PubMed=15843560; DOI=10.4049/jimmunol.174.9.5612;
RA Zhu M., Granillo O., Wen R., Yang K., Dai X., Wang D., Zhang W.;
RT "Negative regulation of lymphocyte activation by the adaptor protein LAX.";
RL J. Immunol. 174:5612-5619(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-345 AND TYR-373, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
CC -!- FUNCTION: Negatively regulates TCR (T-cell antigen receptor)-mediated
CC signaling in T-cells and BCR (B-cell antigen receptor)-mediated
CC signaling in B-cells. {ECO:0000269|PubMed:12359715}.
CC -!- SUBUNIT: When phosphorylated, interacts with GRB2, PIK3R1 and GRAP2.
CC {ECO:0000269|PubMed:12359715}.
CC -!- INTERACTION:
CC Q8IWV1; Q14451: GRB7; NbExp=4; IntAct=EBI-10232942, EBI-970191;
CC Q8IWV1; Q96FJ0: STAMBPL1; NbExp=3; IntAct=EBI-10232942, EBI-745021;
CC Q8IWV1-3; Q14451-3: GRB7; NbExp=3; IntAct=EBI-12327415, EBI-11991632;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12359715};
CC Single-pass type III membrane protein {ECO:0000269|PubMed:12359715}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IWV1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IWV1-2; Sequence=VSP_016641;
CC Name=3;
CC IsoId=Q8IWV1-3; Sequence=VSP_046972;
CC -!- TISSUE SPECIFICITY: Expressed in spleen, thymus, and peripheral blood
CC leukocytes. Expressed in several B-, T-, NK and monocyte cell lines.
CC {ECO:0000269|PubMed:12359715}.
CC -!- INDUCTION: Up-regulated in T-cells following TCR engagement.
CC {ECO:0000269|PubMed:15843560}.
CC -!- PTM: Phosphorylated on tyrosines by Syk, Lck or ZAP70 upon TCR or BCR
CC activation; which leads to the recruitment of GRB2, PIK3R1 and GRAP2.
CC {ECO:0000269|PubMed:12359715}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH69650.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY090784; AAM09818.1; -; mRNA.
DR EMBL; AK000347; BAA91101.1; -; mRNA.
DR EMBL; AK301421; BAH13480.1; -; mRNA.
DR EMBL; AC114402; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91491.1; -; Genomic_DNA.
DR EMBL; BC069650; AAH69650.1; ALT_INIT; mRNA.
DR EMBL; BC089408; AAH89408.1; -; mRNA.
DR CCDS; CCDS1441.2; -. [Q8IWV1-1]
DR CCDS; CCDS44297.1; -. [Q8IWV1-3]
DR RefSeq; NP_001129662.1; NM_001136190.1. [Q8IWV1-3]
DR RefSeq; NP_001269807.1; NM_001282878.1. [Q8IWV1-2]
DR RefSeq; NP_060243.2; NM_017773.3. [Q8IWV1-1]
DR RefSeq; XP_006711460.1; XM_006711397.3. [Q8IWV1-1]
DR AlphaFoldDB; Q8IWV1; -.
DR BioGRID; 120246; 8.
DR IntAct; Q8IWV1; 8.
DR MINT; Q8IWV1; -.
DR STRING; 9606.ENSP00000406970; -.
DR iPTMnet; Q8IWV1; -.
DR PhosphoSitePlus; Q8IWV1; -.
DR BioMuta; LAX1; -.
DR DMDM; 74728197; -.
DR CPTAC; CPTAC-1761; -.
DR MassIVE; Q8IWV1; -.
DR PaxDb; Q8IWV1; -.
DR PeptideAtlas; Q8IWV1; -.
DR PRIDE; Q8IWV1; -.
DR ProteomicsDB; 70902; -. [Q8IWV1-1]
DR ProteomicsDB; 70903; -. [Q8IWV1-2]
DR Antibodypedia; 1184; 253 antibodies from 29 providers.
DR DNASU; 54900; -.
DR Ensembl; ENST00000367217.5; ENSP00000356186.5; ENSG00000122188.13. [Q8IWV1-3]
DR Ensembl; ENST00000442561.7; ENSP00000406970.2; ENSG00000122188.13. [Q8IWV1-1]
DR GeneID; 54900; -.
DR KEGG; hsa:54900; -.
DR MANE-Select; ENST00000442561.7; ENSP00000406970.2; NM_017773.4; NP_060243.2.
DR UCSC; uc001haa.4; human. [Q8IWV1-1]
DR CTD; 54900; -.
DR DisGeNET; 54900; -.
DR GeneCards; LAX1; -.
DR HGNC; HGNC:26005; LAX1.
DR HPA; ENSG00000122188; Tissue enriched (lymphoid).
DR MIM; 619622; gene.
DR neXtProt; NX_Q8IWV1; -.
DR OpenTargets; ENSG00000122188; -.
DR PharmGKB; PA142671569; -.
DR VEuPathDB; HostDB:ENSG00000122188; -.
DR eggNOG; ENOG502SP30; Eukaryota.
DR GeneTree; ENSGT00390000014063; -.
DR HOGENOM; CLU_058345_0_0_1; -.
DR InParanoid; Q8IWV1; -.
DR OMA; RDYINVP; -.
DR OrthoDB; 1008191at2759; -.
DR PhylomeDB; Q8IWV1; -.
DR TreeFam; TF337411; -.
DR PathwayCommons; Q8IWV1; -.
DR SignaLink; Q8IWV1; -.
DR BioGRID-ORCS; 54900; 13 hits in 1068 CRISPR screens.
DR ChiTaRS; LAX1; human.
DR GenomeRNAi; 54900; -.
DR Pharos; Q8IWV1; Tbio.
DR PRO; PR:Q8IWV1; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8IWV1; protein.
DR Bgee; ENSG00000122188; Expressed in lymph node and 111 other tissues.
DR Genevisible; Q8IWV1; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IDA:HGNC-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0019901; F:protein kinase binding; IDA:HGNC-UCL.
DR GO; GO:0042169; F:SH2 domain binding; IDA:HGNC-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0050851; P:antigen receptor-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0042113; P:B cell activation; IDA:HGNC-UCL.
DR GO; GO:0006955; P:immune response; IDA:HGNC-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:HGNC-UCL.
DR GO; GO:0046649; P:lymphocyte activation; IBA:GO_Central.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:HGNC-UCL.
DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:HGNC-UCL.
DR InterPro; IPR031393; LAX.
DR PANTHER; PTHR24091; PTHR24091; 1.
DR Pfam; PF15681; LAX; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane; Immunity; Membrane;
KW Phosphoprotein; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..398
FT /note="Lymphocyte transmembrane adapter 1"
FT /id="PRO_0000083329"
FT TOPO_DOM 1..37
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 38..58
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 228..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 347..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 316..330
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 193
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12359715"
FT MOD_RES 268
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12359715"
FT MOD_RES 294
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12359715"
FT MOD_RES 345
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 373
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12359715,
FT ECO:0007744|PubMed:19690332"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_016641"
FT VAR_SEQ 1..29
FT /note="MDGVTPTLSTIRGRTLESSTLHVTPRSLD -> MRSHFLQWALATS (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046972"
FT CONFLICT 152
FT /note="V -> A (in Ref. 2; BAA91101)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="I -> V (in Ref. 2; BAA91101)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="H -> R (in Ref. 2; BAH13480)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 398 AA; 44085 MW; 16FD4D8A56CEA980 CRC64;
MDGVTPTLST IRGRTLESST LHVTPRSLDR NKDQITNIFS GFAGLLAILL VVAVFCILWN
WNKRKKRQVP YLRVTVMPLL TLPQTRQRAK NIYDILPWRQ EDLGRHESRS MRIFSTESLL
SRNSESPEHV PSQAGNAFQE HTAHIHATEY AVGIYDNAMV PQMCGNLTPS AHCINVRASR
DCASISSEDS HDYVNVPTAE EIAETLASTK SPSRNLFVLP STQKLEFTEE RDEGCGDAGD
CTSLYSPGAE DSDSLSNGEG SSQISNDYVN MTGLDLSAIQ ERQLWVAFQC CRDYENVPAA
DPSGSQQQAE KDVPSSNIGH VEDKTDDPGT HVQCVKRTFL ASGDYADFQP FTQSEDSQMK
HREEMSNEDS SDYENVLTAK LGGRDSEQGP GTQLLPDE
