ID CD244_MOUSE Reviewed; 397 AA. AC Q07763; O88654; Q3UV86; Q9JIE0; DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 24-JAN-2024, entry version 161. DE RecName: Full=Natural killer cell receptor 2B4; DE AltName: Full=NK cell type I receptor protein 2B4; DE Short=NKR2B4; DE AltName: Full=Non-MHC restricted killing associated; DE AltName: Full=SLAM family member 4; DE Short=SLAMF4; DE AltName: Full=Signaling lymphocytic activation molecule 4; DE AltName: CD_antigen=CD244; DE Flags: Precursor; GN Name=Cd244; Synonyms=2b4, Nmrk; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; RX PubMed=8228228; RA Mathew P.A., Garni-Wagner B.A., Land K., Takashima A., Stoneman E., RA Bennett M., Kumar V.; RT "Cloning and characterization of the 2B4 gene encoding a molecule RT associated with non-MHC-restricted killing mediated by activated natural RT killer cells and T cells."; RL J. Immunol. 151:5328-5337(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=A.CA; RX PubMed=10941850; DOI=10.1007/s002510000198; RA Kumaresan P.R., Huynh V.T., Mathew P.A.; RT "Polymorphism in the 2B4 gene of inbred mouse strains."; RL Immunogenetics 51:758-761(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; RA Stepp S.E., Schatzle J.D., Bennett M., Kumar V., Mathew P.A.; RT "Characterization of genomic structure and alternative splicing of the RT murine NK cell receptor 2B4."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Bone; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=8326140; RA Garni-Wagner B.A., Purohit A., Mathew P.A., Bennett M., Kumar V.; RT "A novel function-associated molecule related to non-MHC-restricted RT cytotoxicity mediated by activated natural killer cells and T cells."; RL J. Immunol. 151:60-70(1993). RN [6] RP INTERACTION WITH CD48. RX PubMed=9841922; DOI=10.1084/jem.188.11.2083; RA Brown M.H., Boles K., van der Merwe P.A., Kumar V., Mathew P.A., RA Barclay A.N.; RT "2B4, the natural killer and T cell immunoglobulin superfamily surface RT protein, is a ligand for CD48."; RL J. Exp. Med. 188:2083-2090(1998). RN [7] RP FUNCTION. RX PubMed=11739483; DOI=10.4049/jimmunol.167.12.6706; RA Kambayashi T., Assarsson E., Chambers B.J., Ljunggren H.G.; RT "Regulation of CD8(+) T cell proliferation by 2B4/CD48 interactions."; RL J. Immunol. 167:6706-6710(2001). RN [8] RP FUNCTION. RX PubMed=12734329; DOI=10.4049/jimmunol.170.10.4881; RA Lee K.M., Bhawan S., Majima T., Wei H., Nishimura M.I., Yagita H., RA Kumar V.; RT "The NK cell receptor 2B4 augments antigen-specific T cell cytotoxicity RT through CD48 ligation on neighboring T cells."; RL J. Immunol. 170:4881-4885(2003). RN [9] RP FUNCTION, DOMAIN ITSM MOTIF, PHOSPHORYLATION AT TYR-266; TYR-325; TYR-344 RP AND TYR-369, AND MUTAGENESIS OF TYR-266; TYR-325; TYR-344 AND TYR-369. RX PubMed=15169881; DOI=10.1128/mcb.24.12.5144-5156.2004; RA Chen R., Relouzat F., Roncagalli R., Aoukaty A., Tan R., Latour S., RA Veillette A.; RT "Molecular dissection of 2B4 signaling: implications for signal RT transduction by SLAM-related receptors."; RL Mol. Cell. Biol. 24:5144-5156(2004). RN [10] RP FUNCTION. RX PubMed=15998796; DOI=10.1084/jem.20050449; RA Bloch-Queyrat C., Fondaneche M.C., Chen R., Yin L., Relouzat F., RA Veillette A., Fischer A., Latour S.; RT "Regulation of natural cytotoxicity by the adaptor SAP and the Src-related RT kinase Fyn."; RL J. Exp. Med. 202:181-192(2005). RN [11] RP FUNCTION, AND INTERACTION WITH SH2D1A; SH2D1B AND SH2D1B2. RX PubMed=16127454; DOI=10.1038/ni1242; RA Roncagalli R., Taylor J.E., Zhang S., Shi X., Chen R., Cruz-Munoz M.E., RA Yin L., Latour S., Veillette A.; RT "Negative regulation of natural killer cell function by EAT-2, a SAP- RT related adaptor."; RL Nat. Immunol. 6:1002-1010(2005). RN [12] RP FUNCTION, AND INTERACTION WITH CD48. RX PubMed=15905190; DOI=10.1182/blood-2005-01-0185; RA Lee K.M., Forman J.P., McNerney M.E., Stepp S., Kuppireddi S., Guzior D., RA Latchman Y.E., Sayegh M.H., Yagita H., Park C.K., Oh S.B., Wuelfing C., RA Schatzle J., Mathew P.A., Sharpe A.H., Kumar V.; RT "Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in RT the generation of NK effector functions."; RL Blood 107:3181-3188(2006). RN [13] RP FUNCTION. RC STRAIN=129/SvJ, and C57BL/6J; RX PubMed=16425036; DOI=10.1007/s00251-005-0056-3; RA Calpe S., Erdos E., Liao G., Wang N., Rietdijk S., Simarro M., Scholtz B., RA Mooney J., Lee C.H., Shin M.S., Rajnavoelgyi E., Schatzle J., RA Morse H.C. III, Terhorst C., Lanyi A.; RT "Identification and characterization of two related murine genes, Eat2a and RT Eat2b, encoding single SH2-domain adapters."; RL Immunogenetics 58:15-25(2006). RN [14] RP FUNCTION. RX PubMed=19648922; DOI=10.1038/ni.1763; RA Dong Z., Cruz-Munoz M.E., Zhong M.C., Chen R., Latour S., Veillette A.; RT "Essential function for SAP family adaptors in the surveillance of RT hematopoietic cells by natural killer cells."; RL Nat. Immunol. 10:973-980(2009). RN [15] RP FUNCTION. RX PubMed=20962259; DOI=10.4049/jimmunol.1001974; RA Wang N., Calpe S., Westcott J., Castro W., Ma C., Engel P., Schatzle J.D., RA Terhorst C.; RT "The adapters EAT-2A and -2B are positive regulators of CD244- and CD84- RT dependent NK cell functions in the C57BL/6 mouse."; RL J. Immunol. 185:5683-5687(2010). RN [16] RP FUNCTION. RX PubMed=22683124; DOI=10.1016/j.immuni.2012.03.023; RA Dong Z., Davidson D., Perez-Quintero L.A., Kurosaki T., Swat W., RA Veillette A.; RT "The adaptor SAP controls NK cell activation by regulating the enzymes Vav- RT 1 and SHIP-1 and by enhancing conjugates with target cells."; RL Immunity 36:974-985(2012). RN [17] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=25643613; DOI=10.1038/icb.2014.124; RA Georgoudaki A.M., Khodabandeh S., Puiac S., Persson C.M., Larsson M.K., RA Lind M., Hammarfjord O., Nabatti T.H., Wallin R.P., Yrlid U., Rhen M., RA Kumar V., Chambers B.J.; RT "CD244 is expressed on dendritic cells and regulates their functions."; RL Immunol. Cell Biol. 93:581-590(2015). RN [18] RP STRUCTURE BY NMR OF 21-129, AND DISULFIDE BOND. RX PubMed=15850375; DOI=10.1021/bi050139s; RA Ames J.B., Vyas V., Lusin J.D., Mariuzza R.; RT "NMR structure of the natural killer cell receptor 2B4 (CD244): RT implications for ligand recognition."; RL Biochemistry 44:6416-6423(2005). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 19-129 ALONE AND IN COMPLEX WITH RP CD48, AND DISULFIDE BOND. RX PubMed=17950006; DOI=10.1016/j.immuni.2007.08.019; RA Velikovsky C.A., Deng L., Chlewicki L.K., Fernandez M.M., Kumar V., RA Mariuzza R.A.; RT "Structure of natural killer receptor 2B4 bound to CD48 reveals basis for RT heterophilic recognition in signaling lymphocyte activation molecule RT family."; RL Immunity 27:572-584(2007). CC -!- FUNCTION: Heterophilic receptor of the signaling lymphocytic activation CC molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by CC homo- or heterotypic cell-cell interactions are modulating the CC activation and differentiation of a wide variety of immune cells and CC thus are involved in the regulation and interconnection of both innate CC and adaptive immune response. Activities are controlled by presence or CC absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or CC SH2D1B/EAT-2. Acts as activating natural killer (NK) cell receptor CC (PubMed:8326140, PubMed:12734329, PubMed:19648922, PubMed:20962259). CC Activating function implicates association with SH2D1A and FYN. CC Downstreaming signaling involves predominantly VAV1, and, to a lesser CC degree, INPP5D/SHIP1 and CBL. Signal attenuation in the absence of CC SH2D1A is proposed to be dependent on INPP5D and to a lesser extent CC PTPN6/SHP-1 and PTPN11/SHP-2. Stimulates NK cell cytotoxicity, CC production of IFN-gamma and granule exocytosis (PubMed:8326140, CC PubMed:15169881, PubMed:15998796, PubMed:22683124). Optimal expansion CC and activation of NK cells seems to be dependent on the engagement of CC CD244 with CD48 expressed on neighboring NK cells (PubMed:15905190). CC Regulation of NK cell activity by adapters Sh2d1b and Sh2d1b2 is CC reported conflictingly (PubMed:16127454, PubMed:16425036). Acts as CC costimulator in NK activation by enhancing signals by other NK CC receptors such as NCR3 and NCR1. At early stages of NK cell CC differentiation may function as an inhibitory receptor possibly CC ensuring the self-tolerance of developing NK cells (By similarity). CC Involved in the regulation of CD8(+) T-cell proliferation; expression CC on activated T-cells and binding to CD48 provides costimulatory-like CC function for neighboring T-cells (PubMed:11739483). Inhibits CC inflammatory responses in dendritic cells (DCs) (PubMed:25643613). CC {ECO:0000250|UniProtKB:Q9BZW8, ECO:0000269|PubMed:11739483, CC ECO:0000269|PubMed:12734329, ECO:0000269|PubMed:15169881, CC ECO:0000269|PubMed:15998796, ECO:0000269|PubMed:19648922, CC ECO:0000269|PubMed:20962259, ECO:0000269|PubMed:22683124, CC ECO:0000269|PubMed:8326140, ECO:0000305|PubMed:16127454, CC ECO:0000305|PubMed:16425036}. CC -!- SUBUNIT: Interacts with CD48 (PubMed:9841922, PubMed:15905190). CC Interacts (via phosphorylated ITSM 1-4) with SH2D1A/SAP (via SH2 CC domain); SH2D1A probably mediates association with FYN. Interacts (via CC phosphorylated ITSM 3) with PTPN11/SHP-2, INPP5D/SHIP1, PTPN6/SHP-1 and CC CSK; binding of SH2D1A prevents association with PTPN11, PTPN6 and CSK. CC Interacts weakly (via phosphorylated ITSM 2) with PTPN11 and CSK. CC Interacts with SH2D1B and SH2D1B2. Interacts with MHC class I proteins; CC the interaction is proposed to prevent self-killing of NK cells (By CC similarity). {ECO:0000250|UniProtKB:Q9BZW8, CC ECO:0000269|PubMed:15905190, ECO:0000269|PubMed:16127454, CC ECO:0000269|PubMed:9841922}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I CC membrane protein {ECO:0000305}. Cell membrane {ECO:0000305}. CC Note=Receptor engagement results in a recruitment to lipid drafts CC essential for the subsequent tyrosine phosphorylation of the ITSMs. CC {ECO:0000250|UniProtKB:Q9BZW8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=m2B4L; CC IsoId=Q07763-1; Sequence=Displayed; CC Name=2; Synonyms=m2B4S; CC IsoId=Q07763-2; Sequence=VSP_010401, VSP_010402; CC -!- TISSUE SPECIFICITY: Expressed in natural killer (NK) cells, T cells and CC dendritic cells. {ECO:0000269|PubMed:25643613, CC ECO:0000269|PubMed:8326140}. CC -!- DOMAIN: The ITSMs (immunoreceptor tyrosine-based switch motifs) with CC the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors CC have overlapping specificity for activating and inhibitory SH2 domain- CC containing binding partners. Especially they mediate the interaction CC with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism CC is proposed involving threonine (position -2), phosphorylated tyrosine CC (position 0) and valine/isoleucine (position +3). CC {ECO:0000250|UniProtKB:Q13291, ECO:0000305|PubMed:15169881}. CC -!- PTM: N-linked glycosylation is essential for the binding to its ligand CC CD48. Also O-glycosylated, in contrast, O-linked sialylation has a CC negative impact on ligand binding (By similarity). {ECO:0000250}. CC -!- PTM: Phosphorylated by FYN and CSK at tyrosine residues following CC activation. Coligation with inhibitory receptors such as KIR2DL1 CC inhibits phosphorylation upon contact of NK cells with sensitive target CC cells. {ECO:0000250|UniProtKB:Q9BZW8}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L19057; AAA16353.1; -; mRNA. DR EMBL; AF234831; AAF91290.1; -; mRNA. DR EMBL; AF082803; AAC34859.1; -; mRNA. DR EMBL; AK137505; BAE23386.1; -; mRNA. DR CCDS; CCDS35778.1; -. [Q07763-1] DR PIR; I49443; I49443. DR RefSeq; NP_061199.2; NM_018729.2. [Q07763-1] DR PDB; 1Z2K; NMR; -; A=21-129. DR PDB; 2PTT; X-ray; 1.63 A; B=19-129. DR PDB; 2PTU; X-ray; 2.38 A; A/B/C/D=19-129. DR PDBsum; 1Z2K; -. DR PDBsum; 2PTT; -. DR PDBsum; 2PTU; -. DR AlphaFoldDB; Q07763; -. DR SMR; Q07763; -. DR BioGRID; 201792; 2. DR STRING; 10090.ENSMUSP00000004829; -. DR GlyCosmos; Q07763; 7 sites, No reported glycans. DR GlyGen; Q07763; 7 sites. DR iPTMnet; Q07763; -. DR PhosphoSitePlus; Q07763; -. DR EPD; Q07763; -. DR PaxDb; 10090-ENSMUSP00000004829; -. DR ProteomicsDB; 283743; -. [Q07763-1] DR ProteomicsDB; 283744; -. [Q07763-2] DR Antibodypedia; 2392; 914 antibodies from 43 providers. DR DNASU; 18106; -. DR Ensembl; ENSMUST00000004829.13; ENSMUSP00000004829.8; ENSMUSG00000004709.15. [Q07763-1] DR GeneID; 18106; -. DR KEGG; mmu:18106; -. DR UCSC; uc007dor.1; mouse. [Q07763-2] DR UCSC; uc007dos.1; mouse. [Q07763-1] DR AGR; MGI:109294; -. DR CTD; 18106; -. DR MGI; MGI:109294; Cd244. DR VEuPathDB; HostDB:ENSMUSG00000004709; -. DR eggNOG; ENOG502S7N7; Eukaryota. DR GeneTree; ENSGT01030000234540; -. DR HOGENOM; CLU_065827_0_0_1; -. DR InParanoid; Q07763; -. DR OMA; VDIHGTH; -. DR OrthoDB; 5363071at2759; -. DR PhylomeDB; Q07763; -. DR TreeFam; TF334964; -. DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall. DR BioGRID-ORCS; 18106; 4 hits in 77 CRISPR screens. DR EvolutionaryTrace; Q07763; -. DR PRO; PR:Q07763; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; Q07763; Protein. DR Bgee; ENSMUSG00000004709; Expressed in granulocyte and 49 other cell types or tissues. DR ExpressionAtlas; Q07763; baseline and differential. DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI. DR GO; GO:0042288; F:MHC class I protein binding; ISO:MGI. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0001773; P:myeloid dendritic cell activation; IMP:UniProtKB. DR GO; GO:0002323; P:natural killer cell activation involved in immune response; IMP:UniProtKB. DR GO; GO:2000566; P:positive regulation of CD8-positive, alpha-beta T cell proliferation; IMP:UniProtKB. DR GO; GO:0071663; P:positive regulation of granzyme B production; ISO:MGI. DR GO; GO:0060732; P:positive regulation of inositol phosphate biosynthetic process; ISO:MGI. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI. DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IMP:UniProtKB. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISO:MGI. DR CDD; cd05741; IgV_CEACAM_like; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR024303; NK_rcpt_2B4_Ig_dom. DR PANTHER; PTHR12080:SF56; NATURAL KILLER CELL RECEPTOR 2B4; 1. DR PANTHER; PTHR12080; SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE; 1. DR Pfam; PF11465; Receptor_2B4; 1. DR SUPFAM; SSF48726; Immunoglobulin; 1. DR Genevisible; Q07763; MM. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; KW Innate immunity; Membrane; Phosphoprotein; Receptor; Reference proteome; KW Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..397 FT /note="Natural killer cell receptor 2B4" FT /id="PRO_0000014669" FT TOPO_DOM 20..226 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 227..247 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 248..397 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 22..129 FT /note="Ig-like 1" FT DOMAIN 131..215 FT /note="Ig-like 2" FT REGION 277..300 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 264..269 FT /note="ITSM 1" FT /evidence="ECO:0000250|UniProtKB:Q13291" FT MOTIF 323..328 FT /note="ITSM 2" FT /evidence="ECO:0000250|UniProtKB:Q13291" FT MOTIF 342..347 FT /note="ITSM 3" FT /evidence="ECO:0000250|UniProtKB:Q13291" FT MOTIF 367..372 FT /note="ITSM 4" FT /evidence="ECO:0000250|UniProtKB:Q13291" FT COMPBIAS 278..292 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 266 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:15169881" FT MOD_RES 325 FT /note="Phosphotyrosine; by FYN" FT /evidence="ECO:0000305|PubMed:15169881" FT MOD_RES 344 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:15169881" FT MOD_RES 369 FT /note="Phosphotyrosine; by FYN" FT /evidence="ECO:0000305|PubMed:15169881" FT CARBOHYD 78 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 145 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 161 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 178 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 197 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 206 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 210 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 22..119 FT /evidence="ECO:0000269|PubMed:15850375, FT ECO:0000269|PubMed:17950006" FT DISULFID 154..196 FT /evidence="ECO:0000250" FT VAR_SEQ 309..340 FT /note="LEQLPQQTFPGDRGTMYSMIQCKPSDSTSQEK -> MFSSLLAFLLHQFPGS FT TQRGKEKRERAEKNGK (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_010401" FT VAR_SEQ 341..397 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_010402" FT MUTAGEN 266 FT /note="Y->F: Abolishes downstream phosphorylation of CBL FT and VAV1; when associated with F-325, F-344 and F-369." FT /evidence="ECO:0000269|PubMed:15169881" FT MUTAGEN 266 FT /note="Y->F: Decreases downstream phosphorylation of CBL FT and VAV1." FT /evidence="ECO:0000269|PubMed:15169881" FT MUTAGEN 325 FT /note="Y->F: Abolishes downstream phosphorylation of CBL FT and VAV1; when associated with F-266, F-344 and F-369." FT /evidence="ECO:0000269|PubMed:15169881" FT MUTAGEN 325 FT /note="Y->F: Weakly decreases downstream phosphorylation of FT CBL and VAV1; when associated with F-344 and F-369." FT /evidence="ECO:0000269|PubMed:15169881" FT MUTAGEN 344 FT /note="Y->F: Abolishes downstream phosphorylation of CBL FT and VAV1; when associated with F-266, F-325 and F-369." FT /evidence="ECO:0000269|PubMed:15169881" FT MUTAGEN 344 FT /note="Y->F: Weakly decreases downstream phosphorylation of FT CBL and VAV1; when associated with F-325 and F-369." FT /evidence="ECO:0000269|PubMed:15169881" FT MUTAGEN 369 FT /note="Y->F: Abolishes downstream phosphorylation of CBL FT and VAV1; when associated with F-266, F-325 and F-344." FT /evidence="ECO:0000269|PubMed:15169881" FT MUTAGEN 369 FT /note="Y->F: Weakly decreases downstream phosphorylation of FT CBL and VAV1; when associated with F-325 and F-344." FT /evidence="ECO:0000269|PubMed:15169881" FT CONFLICT 38 FT /note="Q -> P (in Ref. 2; AAF91290)" FT /evidence="ECO:0000305" FT CONFLICT 156 FT /note="V -> A (in Ref. 2; AAF91290)" FT /evidence="ECO:0000305" FT CONFLICT 166 FT /note="L -> FW (in Ref. 1; AAA16353)" FT /evidence="ECO:0000305" FT CONFLICT 362 FT /note="S -> Y (in Ref. 1; AAA16353)" FT /evidence="ECO:0000305" FT STRAND 25..31 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 37..39 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 50..56 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:2PTU" FT STRAND 63..73 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 76..78 FT /evidence="ECO:0007829|PDB:2PTT" FT HELIX 79..83 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:2PTT" FT TURN 89..91 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 94..98 FT /evidence="ECO:0007829|PDB:2PTT" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 105..112 FT /evidence="ECO:0007829|PDB:2PTT" FT STRAND 117..127 FT /evidence="ECO:0007829|PDB:2PTT" SQ SEQUENCE 397 AA; 44836 MW; 0E2F0D946F7B63A7 CRC64; MLGQAVLFTT FLLLRAHQGQ DCPDSSEEVV GVSGKPVQLR PSNIQTKDVS VQWKKTEQGS HRKIEILNWY NDGPSWSNVS FSDIYGFDYG DFALSIKSAK LQDSGHYLLE ITNTGGKVCN KNFQLLILDH VETPNLKAQW KPWTNGTCQL FLSCLVTKDD NVSYALYRGS TLISNQRNST HWENQIDASS LHTYTCNVSN RASWANHTLN FTHGCQSVPS NFRFLPFGVI IVILVTLFLG AIICFCVWTK KRKQLQFSPK EPLTIYEYVK DSRASRDQQG CSRASGSPSA VQEDGRGQRE LDRRVSEVLE QLPQQTFPGD RGTMYSMIQC KPSDSTSQEK CTVYSVVQPS RKSGSKKRNQ NSSLSCTVYE EVGNPWLKAH NPARLSRREL ENFDVYS //