ID SLAF6_HUMAN Reviewed; 332 AA. AC Q96DU3; A6NMW2; B2R8X8; Q14CF0; Q5TAS4; Q5TAS6; Q5TAT3; Q96DV0; DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 3. DT 29-MAY-2024, entry version 186. DE RecName: Full=SLAM family member 6; DE AltName: Full=Activating NK receptor; DE AltName: Full=NK-T-B-antigen; DE Short=NTB-A; DE AltName: CD_antigen=CD352; DE Flags: Precursor; GN Name=SLAMF6; Synonyms=KALI; ORFNames=UNQ6123/PRO20080; 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] (ISOFORMS 1 AND 2), FUNCTION, PHOSPHORYLATION, RP TISSUE SPECIFICITY, AND INTERACTION WITH SH2D1A; PTN6 AND PTN11. RC TISSUE=Lymphoid tissue; RX PubMed=11489943; DOI=10.1084/jem.194.3.235; RA Bottino C., Falco M., Parolini S., Marcenaro E., Augugliaro R., Sivori S., RA Landi E., Biassoni R., Notarangelo L.D., Moretta L., Moretta A.; RT "NTB-A, a novel SH2D1A-associated surface molecule contributing to the RT inability of natural killer cells to kill Epstein-Barr virus-infected B RT cells in X-linked Lymphoproliferative disease."; RL J. Exp. Med. 194:235-246(2001). RN [2] RP ERRATUM OF PUBMED:11489943. RA Bottino C., Falco M., Parolini S., Marcenaro E., Augugliaro R., Sivori S., RA Landi E., Biassoni R., Notarangelo L.D., Moretta L., Moretta A.; RL J. Exp. Med. 194:705-705(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Spleen; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph node; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] 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 [7] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [9] RP PROTEIN SEQUENCE OF 22-36. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [10] RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH SH2D1A AND SH2D1B, AND RP MUTAGENESIS OF TYR-274; TYR-285 AND TYR-309. RX PubMed=16920955; DOI=10.4049/jimmunol.177.5.3170; RA Eissmann P., Watzl C.; RT "Molecular analysis of NTB-A signaling: a role for EAT-2 in NTB-A-mediated RT activation of human NK cells."; RL J. Immunol. 177:3170-3177(2006). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-178. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-274; SER-278 AND TYR-309, 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). RN [13] RP FUNCTION. RX PubMed=22989874; DOI=10.1074/jbc.m112.415067; RA Chatterjee M., Hedrich C.M., Rauen T., Ioannidis C., Terhorst C., RA Tsokos G.C.; RT "CD3-T cell receptor co-stimulation through SLAMF3 and SLAMF6 receptors RT enhances RORgammat recruitment to the IL17A promoter in human T RT lymphocytes."; RL J. Biol. Chem. 287:38168-38177(2012). RN [14] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=22184727; DOI=10.4049/jimmunol.1102773; RA Chatterjee M., Rauen T., Kis-Toth K., Kyttaris V.C., Hedrich C.M., RA Terhorst C., Tsokos G.C.; RT "Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus RT erythematosus T lymphocytes promotes Th17 differentiation."; RL J. Immunol. 188:1206-1212(2012). RN [15] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 24-215, SUBUNIT, DISULFIDE BONDS, RP AND MUTAGENESIS OF ARG-108; GLN-110 AND SER-112. RX PubMed=17045824; DOI=10.1016/j.immuni.2006.06.020; RA Cao E., Ramagopal U.A., Fedorov A., Fedorov E., Yan Q., Lary J.W., RA Cole J.L., Nathenson S.G., Almo S.C.; RT "NTB-A receptor crystal structure: insights into homophilic interactions in RT the signaling lymphocytic activation molecule receptor family."; RL Immunity 25:559-570(2006). CC -!- FUNCTION: Self-ligand receptor of the signaling lymphocytic activation CC molecule (SLAM) family. SLAM receptors triggered by homo- or CC heterotypic cell-cell interactions are modulating the activation and CC differentiation of a wide variety of immune cells and thus are involved CC in the regulation and interconnection of both innate and adaptive CC immune response. Activities are controlled by presence or absence of CC small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. CC Triggers cytolytic activity only in natural killer cells (NK) CC expressing high surface densities of natural cytotoxicity receptors CC (PubMed:11489943, PubMed:16920955). Positive signaling in NK cells CC implicates phosphorylation of VAV1. NK cell activation seems to depend CC on SH2D1B and not on SH2D1A (PubMed:16920955). In conjunction with CC SLAMF1 controls the transition between positive selection and the CC subsequent expansion and differentiation of the thymocytic natural CC killer T (NKT) cell lineage (By similarity). Promotes T-cell CC differentiation into a helper T-cell Th17 phenotype leading to CC increased IL-17 secretion; the costimulatory activity requires SH2D1A CC (PubMed:16920955, PubMed:22184727). Promotes recruitment of RORC to the CC IL-17 promoter (PubMed:22989874). In conjunction with SLAMF1 and CC CD84/SLAMF5 may be a negative regulator of the humoral immune response. CC In the absence of SH2D1A/SAP can transmit negative signals to CD4(+) T- CC cells and NKT cells. Negatively regulates germinal center formation by CC inhibiting T-cell:B-cell adhesion; the function probably implicates CC increased association with PTPN6/SHP-1 via ITSMs in absence of CC SH2D1A/SAP. However, reported to be involved in maintaining B-cell CC tolerance in germinal centers and in preventing autoimmunity (By CC similarity). {ECO:0000250|UniProtKB:Q9ET39, CC ECO:0000269|PubMed:11489943, ECO:0000269|PubMed:16920955, CC ECO:0000269|PubMed:22184727, ECO:0000269|PubMed:22989874}. CC -!- SUBUNIT: Homodimer. Interacts with PTN6. Interacts (phosphorylated) CC with PTN11. Interacts (phosphorylated on tyrosine residues) with CC SH2D1A/SAP and SH2D1B/EAT2; SH2D1A and SH2D1B can associate with the CC same SLAMF6 molecule; interaction with SH2D1B is mediated by ITSM 2. CC {ECO:0000269|PubMed:11489943, ECO:0000269|PubMed:16920955, CC ECO:0000269|PubMed:17045824}. CC -!- INTERACTION: CC Q96DU3; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-14058448, EBI-12244618; CC Q96DU3; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-14058448, EBI-12256978; CC Q96DU3; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-14058448, EBI-10266796; CC Q96DU3; Q9UI14: RABAC1; NbExp=3; IntAct=EBI-14058448, EBI-712367; CC Q96DU3; O60880: SH2D1A; NbExp=12; IntAct=EBI-14058448, EBI-6983382; CC Q96DU3; O14796: SH2D1B; NbExp=4; IntAct=EBI-14058448, EBI-3923013; CC Q96DU3; P55061: TMBIM6; NbExp=3; IntAct=EBI-14058448, EBI-1045825; CC Q96DU3; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-14058448, EBI-11724433; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I CC membrane protein {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96DU3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96DU3-2; Sequence=VSP_034620; CC Name=3; CC IsoId=Q96DU3-3; Sequence=VSP_043230; CC -!- TISSUE SPECIFICITY: Expressed by all (resting and activated) natural CC killer cells (NK), T- and B-lymphocytes (PubMed:11489943). Increased CC surface expression on T-cells of systemic lupus erythematosus (SLE) CC patients (PubMed:22184727). {ECO:0000269|PubMed:11489943, CC ECO:0000269|PubMed:22184727}. 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 containingbinding partners. Especially they mediate the with the SH2 CC domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is CC proposed involving threonine (position -2), phosphorylated tyrosine CC (position 0) and valine/isoleucine (position +3). CC {ECO:0000250|UniProtKB:Q13291}. CC -!- PTM: Phosphorylation in NK cells upon engagment by SLAMF6-expressing CC target cells is leading to receptor activation. CC {ECO:0000269|PubMed:16920955}. 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; AJ277141; CAC59749.1; -; mRNA. DR EMBL; AJ306388; CAC59750.1; -; mRNA. DR EMBL; AY358159; AAQ88526.1; -; mRNA. DR EMBL; AL832854; CAI46161.1; -; mRNA. DR EMBL; AK125624; BAG54223.1; -; mRNA. DR EMBL; AK301026; BAG62642.1; -; mRNA. DR EMBL; AK313549; BAG36325.1; -; mRNA. DR EMBL; AL138930; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW52713.1; -; Genomic_DNA. DR EMBL; CH471121; EAW52715.1; -; Genomic_DNA. DR EMBL; BC113893; AAI13894.1; -; mRNA. DR EMBL; BC114495; AAI14496.1; -; mRNA. DR CCDS; CCDS1205.1; -. [Q96DU3-2] DR CCDS; CCDS53393.1; -. [Q96DU3-3] DR CCDS; CCDS53394.1; -. [Q96DU3-1] DR RefSeq; NP_001171643.1; NM_001184714.1. [Q96DU3-1] DR RefSeq; NP_001171644.1; NM_001184715.1. DR RefSeq; NP_001171645.1; NM_001184716.1. [Q96DU3-3] DR RefSeq; NP_443163.1; NM_052931.4. [Q96DU3-2] DR PDB; 2IF7; X-ray; 3.00 A; A/B/C/D=24-215. DR PDBsum; 2IF7; -. DR AlphaFoldDB; Q96DU3; -. DR SMR; Q96DU3; -. DR BioGRID; 125378; 15. DR IntAct; Q96DU3; 14. DR STRING; 9606.ENSP00000357036; -. DR GlyCosmos; Q96DU3; 8 sites, 1 glycan. DR GlyGen; Q96DU3; 8 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q96DU3; -. DR PhosphoSitePlus; Q96DU3; -. DR BioMuta; SLAMF6; -. DR DMDM; 205830927; -. DR jPOST; Q96DU3; -. DR MassIVE; Q96DU3; -. DR MaxQB; Q96DU3; -. DR PaxDb; 9606-ENSP00000357036; -. DR PeptideAtlas; Q96DU3; -. DR ProteomicsDB; 76325; -. [Q96DU3-1] DR ProteomicsDB; 76326; -. [Q96DU3-2] DR ProteomicsDB; 76327; -. [Q96DU3-3] DR Antibodypedia; 34279; 517 antibodies from 34 providers. DR DNASU; 114836; -. DR Ensembl; ENST00000368055.1; ENSP00000357034.1; ENSG00000162739.14. [Q96DU3-3] DR Ensembl; ENST00000368057.8; ENSP00000357036.3; ENSG00000162739.14. [Q96DU3-1] DR Ensembl; ENST00000368059.7; ENSP00000357038.3; ENSG00000162739.14. [Q96DU3-2] DR GeneID; 114836; -. DR KEGG; hsa:114836; -. DR MANE-Select; ENST00000368057.8; ENSP00000357036.3; NM_001184714.2; NP_001171643.1. DR UCSC; uc001fwd.2; human. [Q96DU3-1] DR AGR; HGNC:21392; -. DR CTD; 114836; -. DR DisGeNET; 114836; -. DR GeneCards; SLAMF6; -. DR HGNC; HGNC:21392; SLAMF6. DR HPA; ENSG00000162739; Tissue enriched (lymphoid). DR MIM; 606446; gene. DR neXtProt; NX_Q96DU3; -. DR OpenTargets; ENSG00000162739; -. DR PharmGKB; PA134959277; -. DR VEuPathDB; HostDB:ENSG00000162739; -. DR eggNOG; ENOG502SSRG; Eukaryota. DR GeneTree; ENSGT01030000234540; -. DR HOGENOM; CLU_069386_2_0_1; -. DR InParanoid; Q96DU3; -. DR OMA; DIRWIII; -. DR OrthoDB; 5362625at2759; -. DR PhylomeDB; Q96DU3; -. DR TreeFam; TF334964; -. DR PathwayCommons; Q96DU3; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR SignaLink; Q96DU3; -. DR BioGRID-ORCS; 114836; 15 hits in 1158 CRISPR screens. DR EvolutionaryTrace; Q96DU3; -. DR GeneWiki; SLAMF6; -. DR GenomeRNAi; 114836; -. DR Pharos; Q96DU3; Tbio. DR PRO; PR:Q96DU3; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q96DU3; Protein. DR Bgee; ENSG00000162739; Expressed in granulocyte and 96 other cell types or tissues. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:UniProtKB. DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB. DR GO; GO:0032729; P:positive regulation of type II interferon production; IMP:UniProtKB. DR GO; GO:0042110; P:T cell activation; IBA:GO_Central. DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; IDA:UniProtKB. DR CDD; cd16842; Ig_SLAM-like_N; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR013106; Ig_V-set. DR PANTHER; PTHR12080; SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE; 1. DR PANTHER; PTHR12080:SF16; SLAM FAMILY MEMBER 6; 1. DR Pfam; PF07686; V-set; 1. DR SMART; SM00409; IG; 1. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR PROSITE; PS50835; IG_LIKE; 1. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity; KW Immunoglobulin domain; Innate immunity; Membrane; Phosphoprotein; Receptor; KW Reference proteome; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 22..332 FT /note="SLAM family member 6" FT /id="PRO_0000014961" FT TOPO_DOM 22..226 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 227..247 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 248..331 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 35..120 FT /note="Ig-like V-type" FT DOMAIN 132..209 FT /note="Ig-like C2-type" FT MOTIF 283..288 FT /note="ITSM 1" FT /evidence="ECO:0000250|UniProtKB:Q13291" FT MOTIF 307..312 FT /note="ITSM 2" FT /evidence="ECO:0000250|UniProtKB:Q13291" FT MOD_RES 274 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 278 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 309 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT CARBOHYD 58 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 87 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 137 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 144 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:0000269|PubMed:19349973" FT CARBOHYD 203 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 147..214 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17045824" FT DISULFID 153..195 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:17045824" FT VAR_SEQ 18..128 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043230" FT VAR_SEQ 266 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11489943, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_034620" FT MUTAGEN 108 FT /note="R->A: Inhibits dimerization." FT /evidence="ECO:0000269|PubMed:17045824" FT MUTAGEN 110 FT /note="Q->A: Inhibits dimerization." FT /evidence="ECO:0000269|PubMed:17045824" FT MUTAGEN 112 FT /note="S->A: Inhibits dimerization." FT /evidence="ECO:0000269|PubMed:17045824" FT MUTAGEN 274 FT /note="Y->F: Retains reduced SLAMF6-mediated cytotoxity, FT disrupts interaction with SH2D1A and retains interaction FT with SH2D1B; when associated with F-309." FT /evidence="ECO:0000269|PubMed:16920955" FT MUTAGEN 285 FT /note="Y->F: Abolishes SLAMF6-mediated cytotoxity, disrupts FT interaction with SH2D1B and retains interaction with FT SH2D1A." FT /evidence="ECO:0000269|PubMed:16920955" FT MUTAGEN 309 FT /note="Y->F: Reduced SLAMF6-mediated cytotoxity." FT /evidence="ECO:0000269|PubMed:16920955" FT MUTAGEN 309 FT /note="Y->F: Retains reduced SLAMF6-mediated cytotoxity, FT disrupts interaction with SH2D1A and retains interaction FT with SH2D1B; when associated with F-273." FT /evidence="ECO:0000269|PubMed:16920955" FT STRAND 28..33 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 52..57 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 60..66 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 74..77 FT /evidence="ECO:0007829|PDB:2IF7" FT HELIX 80..83 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:2IF7" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 105..112 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 117..127 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 131..137 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 145..157 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 163..168 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 171..183 FT /evidence="ECO:0007829|PDB:2IF7" FT TURN 185..187 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 192..199 FT /evidence="ECO:0007829|PDB:2IF7" FT STRAND 202..209 FT /evidence="ECO:0007829|PDB:2IF7" FT HELIX 210..213 FT /evidence="ECO:0007829|PDB:2IF7" SQ SEQUENCE 332 AA; 37345 MW; 46D8141A0D198091 CRC64; MLWLFQSLLF VFCFGPGNVV SQSSLTPLMV NGILGESVTL PLEFPAGEKV NFITWLFNET SLAFIVPHET KSPEIHVTNP KQGKRLNFTQ SYSLQLSNLK MEDTGSYRAQ ISTKTSAKLS SYTLRILRQL RNIQVTNHSQ LFQNMTCELH LTCSVEDADD NVSFRWEALG NTLSSQPNLT VSWDPRISSE QDYTCIAENA VSNLSFSVSA QKLCEDVKIQ YTDTKMILFM VSGICIVFGF IILLLLVLRK RRDSLSLSTQ RTQGPAESAR NLEYVSVSPT NNTVYASVTH SNRETEIWTP RENDTITIYS TINHSKESKP TFSRATALDN VV //