RBCC

Full text data of LIME1

LIME1 (LIME) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Lck-interacting transmembrane adapter 1; Lck-interacting membrane protein (Lck-interacting molecule)

UniProt Q9H400
ID LIME1_HUMAN Reviewed; 295 AA.
AC Q9H400; E1P5K5; E1P5K6; Q5JWJ2; Q6XYB3; Q9NX69;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=Lck-interacting transmembrane adapter 1;
DE Short=Lck-interacting membrane protein;
DE AltName: Full=Lck-interacting molecule;
GN Name=LIME1; Synonyms=LIME; ORFNames=LP8067;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, INTERACTION WITH LCK AND CSK, PHOSPHORYLATION AT
RP TYR-167; TYR-200 AND TYR-254, PALMITOYLATION AT CYS-28 AND CYS-31,
RP MUTAGENESIS OF TYR-145; TYR-167; TYR-200; TYR-235 AND TYR-254, AND
RP FUNCTION.
RX PubMed=14610046; DOI=10.1084/jem.20031484;
RA Brdickova N., Brdicka T., Angelisova P., Horvath O., Spicka J.,
RA Hilgert I., Paces J., Simeoni L., Kliche S., Merten C., Schraven B.,
RA Horejsi V.;
RT "LIME: a new membrane raft-associated adaptor protein involved in CD4
RT and CD8 coreceptor signaling.";
RL J. Exp. Med. 198:1453-1462(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH LCK,
RP PHOSPHORYLATION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=14610044; DOI=10.1084/jem.20030232;
RA Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.;
RT "LIME, a novel transmembrane adaptor protein, associates with p56lck
RT and mediates T cell activation.";
RL J. Exp. Med. 198:1463-1473(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=16160011; DOI=10.1182/blood-2005-06-2273;
RA Tedoldi S., Paterson J.C., Hansmann M.-L., Natkunam Y., Rudiger T.,
RA Angelisova P., Du M.Q., Roberton H., Roncador G., Sanchez L.,
RA Pozzobon M., Masir N., Barry R., Pileri S., Mason D.Y., Marafioti T.,
RA Horejsi V.;
RT "Transmembrane adaptor molecules: a new category of lymphoid-cell
RT markers.";
RL Blood 107:213-221(2006).
CC -!- FUNCTION: Involved in BCR (B-cell antigen receptor)-mediated
CC signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-
CC cell signaling in T-cells. In absence of TCR signaling, may be
CC involved in CD4-mediated inhibition of T-cell activation. Couples
CC activation of these receptors and their associated kinases with
CC distal intracellular events such as calcium mobilization or MAPK
CC activation through the recruitment of PLCG2, GRB2, GRAP2, and
CC other signaling molecules.
CC -!- SUBUNIT: When phosphorylated in response to BCR activation,
CC interacts with LYN, PIK3R1, PLCG2, and GRB2 (By similarity). When
CC phosphorylated in response to TCR stimulation and/or CD4 co-
CC stimulation, interacts with LCK, CSK, FYN, PTPN11/SHP2, GRB2,
CC PIK3R1 and GRAP2.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type III membrane
CC protein. Note=Present in lipid rafts. Recruited to the
CC immunological synapse upon conjugation of T-cell with antigen-
CC presenting cell.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H400-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H400-2; Sequence=VSP_016642;
CC -!- TISSUE SPECIFICITY: Expressed in peripheral blood lymphocytes,
CC lymphoid tissues, and liver. Present in T-cells and plasma cells,
CC and in various hematopoietic cell lines (at protein level).
CC -!- PTM: Palmitoylation of Cys-28 and Cys-31 is required for raft
CC targeting.
CC -!- PTM: Phosphorylated on tyrosines upon TCR activation and/or CD4
CC coreceptor stimulation, or upon BCR stimulation; which leads to
CC the recruitment of SH2-containing proteins.
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DR EMBL; AY203957; AAP34480.1; -; mRNA.
DR EMBL; AK000413; BAA91148.1; -; mRNA.
DR EMBL; AL121845; CAC03671.1; -; Genomic_DNA.
DR EMBL; AL121845; CAI21882.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75213.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75214.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75215.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75216.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75217.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75218.1; -; Genomic_DNA.
DR EMBL; BC017016; AAH17016.1; -; mRNA.
DR RefSeq; NP_060276.2; NM_017806.2.
DR RefSeq; XP_005260270.1; XM_005260213.1.
DR RefSeq; XP_005260271.1; XM_005260214.1.
DR RefSeq; XP_005260272.1; XM_005260215.1.
DR UniGene; Hs.233220; -.
DR ProteinModelPortal; Q9H400; -.
DR IntAct; Q9H400; 1.
DR STRING; 9606.ENSP00000309521; -.
DR PhosphoSite; Q9H400; -.
DR DMDM; 74752630; -.
DR PaxDb; Q9H400; -.
DR PRIDE; Q9H400; -.
DR Ensembl; ENST00000309546; ENSP00000309521; ENSG00000203896.
DR GeneID; 54923; -.
DR KEGG; hsa:54923; -.
DR UCSC; uc002ygp.4; human.
DR CTD; 54923; -.
DR GeneCards; GC20P062366; -.
DR HGNC; HGNC:26016; LIME1.
DR HPA; CAB015363; -.
DR MIM; 609809; gene.
DR neXtProt; NX_Q9H400; -.
DR PharmGKB; PA142671551; -.
DR eggNOG; NOG77780; -.
DR HOGENOM; HOG000231956; -.
DR HOVERGEN; HBG080499; -.
DR InParanoid; Q9H400; -.
DR OMA; VAEYACI; -.
DR OrthoDB; EOG780RNR; -.
DR GeneWiki; LIME1; -.
DR GenomeRNAi; 54923; -.
DR NextBio; 58007; -.
DR PRO; PR:Q9H400; -.
DR Bgee; Q9H400; -.
DR CleanEx; HS_LIME1; -.
DR Genevestigator; Q9H400; -.
DR GO; GO:0019815; C:B cell receptor complex; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0043405; P:regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0042345; P:regulation of NF-kappaB import into nucleus; IEA:Ensembl.
DR GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase cascade; IEA:Ensembl.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:InterPro.
DR InterPro; IPR026072; Lime1.
DR Pfam; PF15332; LIME1; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane;
KW Complete proteome; Immunity; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Polymorphism; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 295 Lck-interacting transmembrane adapter 1.
FT /FTId=PRO_0000083332.
FT TOPO_DOM 1 6 Extracellular (Potential).
FT TRANSMEM 7 27 Helical; Signal-anchor for type III
FT membrane protein; (Potential).
FT TOPO_DOM 28 295 Cytoplasmic (Potential).
FT REGION 145 148 Interaction with GRB2 (By similarity).
FT REGION 167 170 Interaction with CSK.
FT REGION 200 203 Interaction with CSK.
FT REGION 235 238 Interaction with LCK and PIK3R1 (By
FT similarity).
FT REGION 254 257 Interaction with LCK, PLCG2 and PIK3R1
FT (By similarity).
FT MOD_RES 167 167 Phosphotyrosine (Probable).
FT MOD_RES 200 200 Phosphotyrosine.
FT MOD_RES 254 254 Phosphotyrosine; by LCK (Probable).
FT LIPID 28 28 S-palmitoyl cysteine (Probable).
FT LIPID 31 31 S-palmitoyl cysteine (Probable).
FT VAR_SEQ 1 95 Missing (in isoform 2).
FT /FTId=VSP_016642.
FT VARIANT 211 211 P -> L (in dbSNP:rs1151625).
FT /FTId=VAR_053918.
FT MUTAGEN 145 145 Y->F: No change in binding to LCK, CSK or
FT FYN.
FT MUTAGEN 167 167 Y->F: Abolishes binding to CSK.
FT MUTAGEN 200 200 Y->F: Reduces binding to CSK.
FT MUTAGEN 235 235 Y->F: No change in binding to LCK, CSK or
FT FYN.
FT MUTAGEN 254 254 Y->F: Abolishes binding to LCK and
FT reduces binding to FYN.
FT CONFLICT 246 246 D -> G (in Ref. 4; BAA91148).
SQ SEQUENCE 295 AA; 31288 MW; D85ACE978F2DC99E CRC64;
MGLPVSWAPP ALWVLGCCAL LLSLWALCTA CRRPEDAVAP RKRARRQRAR LQGSATAAEA
SLLRRTHLCS LSKSDTRLHE LHRGPRSSRA LRPASMDLLR PHWLEVSRDI TGPQAAPSAF
PHQELPRALP AAAATAGCAG LEATYSNVGL AALPGVSLAA SPVVAEYARV QKRKGTHRSP
QEPQQGKTEV TPAAQVDVLY SRVCKPKRRD PGPTTDPLDP KGQGAILALA GDLAYQTLPL
RALDVDSGPL ENVYESIREL GDPAGRSSTC GAGTPPASSC PSLGRGWRPL PASLP
//

MIM 609809
*RECORD*
*FIELD* NO
609809
*FIELD* TI
*609809 LCK-INTERACTING TRANSMEMBRANE ADAPTOR 1; LIME1
;;LIME
*FIELD* TX

DESCRIPTION
read more
LIME1 is a raft-associated transmembrane adaptor phosphoprotein that is
preferentially expressed in hemopoietic cells, particularly T cells
(Brdickova et al., 2003; Hur et al., 2003).

CLONING

By searching databases for proteins with structural features
characteristic of raft-targeted transmembrane adaptor proteins,
Brdickova et al. (2003) identified LIME. The predicted 295-amino acid
type III protein has a 4-amino acid extracellular peptide, a 23-amino
acid transmembrane domain that is followed immediately by a potential
palmitoylation motif (CxxC) and 2 arg residues, and a cytoplasmic domain
with 5 potential tyrosine phosphorylation sites. RT-PCR analysis
detected expression of LIME in liver, thymus, peripheral blood
lymphocytes (PBLs), and other lymphoid tissues. Western blot analysis
showed that, within PBLs, LIME was predominantly expressed in CD4
(186940) and CD8 (see 186910) T cells, and it was downmodulated after
T-cell activation. Confocal microscopy, biosynthetic labeling, and
Western blot analysis demonstrated membrane expression and association
with lipid rafts.

Using yeast 2-hybrid analysis with the SH2 and kinase domains of LCK
(153390) as bait, Hur et al. (2003) cloned mouse Lime. They obtained the
human sequence by database analysis. Northern blot analysis of mouse
tissues revealed expression in spleen and lung, and Northern blot
analysis of human tissues showed expression in spleen and PBLs. Western
blot analysis detected an approximately 30-kD protein.
Immunofluorescence microscopy showed that LIME localized to membrane
rafts and was distributed within the immunologic synapse upon contact
with antigen-presenting cells.

GENE FUNCTION

Brdickova et al. (2003) found that engagement of CD4 or CD8 receptors
induced tyrosine phosphorylation of LIME that was mediated by Src
kinases, principally LCK or LYN (165120). They concluded that LIME is
involved in the regulation of T-cell activation by coreceptors.

Using Western blot analysis, Hur et al. (2003) demonstrated that LIME
was involved in activation of the ERK (see 176948) and JNK (see 601158)
pathways in T cells. Moreover, overexpression of LIME in T cells induced
IL2 (147680) promoter activity. Hur et al. (2003) concluded that LIME is
a raft-associated transmembrane adaptor protein that links T-cell
receptor stimuli to downstream signaling pathways via associations with
LCK.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the LIME1
gene to chromosome 20 (TMAP RH75350).

*FIELD* RF
1. Brdickova, N.; Brdicka, T.; Angelisova, P.; Horvath, O.; Spicka,
J.; Hilgert, I.; Paces, J.; Simeoni, L.; Kliche, S.; Merten, C.; Schraven,
B.; Horejsi, V.: LIME: a new membrane raft-associated adaptor protein
involved in CD4 and CD8 coreceptor signaling. J. Exp. Med. 198:
1453-1462, 2003.

2. Hur, E. M.; Son, M.; Lee, O.-H.; Choi, Y. B.; Park, C.; Lee, H.;
Yun, Y.: LIME, a novel transmembrane adaptor protein, associates
with p56-lck and mediates T cell activation. J. Exp. Med. 198: 1463-1473,
2003.

*FIELD* CD
Paul J. Converse: 12/22/2005

*FIELD* ED
mgross: 12/22/2005

RBCC Red Blood Cell Collection

Full text data of LIME1