ID SIGL6_HUMAN Reviewed; 453 AA. AC O43699; A8MV71; B2RTS8; C9JBE5; F8WA78; O15388; O43700; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 13-FEB-2019, entry version 166. DE RecName: Full=Sialic acid-binding Ig-like lectin 6; DE Short=Siglec-6; DE AltName: Full=CD33 antigen-like 1; DE AltName: Full=CDw327; DE AltName: Full=Obesity-binding protein 1; DE Short=OB-BP1; DE AltName: CD_antigen=CD327; DE Flags: Precursor; GN Name=SIGLEC6; Synonyms=CD33L, CD33L1, OBBP1; 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] (ISOFORMS 1 AND 2). RC TISSUE=Placenta; RX PubMed=9465907; RA Takei Y., Sasaki S., Fujiwara T., Takahashi E., Muto T., Nakamura Y.; RT "Molecular cloning of a novel gene similar to myeloid antigen CD33 and RT its specific expression in placenta."; RL Cytogenet. Cell Genet. 78:295-300(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6), AND VARIANT RP VAL-57. RC TISSUE=Placenta; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-453 (ISOFORM 1), AND INTERACTION WITH RP LEP. RC TISSUE=Erythroleukemia; RX PubMed=10428856; DOI=10.1074/jbc.274.32.22729; RA Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C., RA Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F., RA Varki A., Kastelein R.A.; RT "OB-BP1/Siglec-6. A leptin- and sialic acid-binding protein of the RT immunoglobulin superfamily."; RL J. Biol. Chem. 274:22729-22738(1999). RN [6] RP ERRATUM. RA Patel N., Brinkman-Van der Linden E.C.M., Altmann S.W., Gish K.C., RA Balasubramanian S., Timans J.C., Peterson D., Bell M.P., Bazan J.F., RA Varki A., Kastelein R.A.; RL J. Biol. Chem. 274:28058-28058(1999). CC -!- FUNCTION: Putative adhesion molecule that mediates sialic-acid CC dependent binding to cells. Binds to alpha-2,6-linked sialic acid. CC The sialic acid recognition site may be masked by cis interactions CC with sialic acids on the same cell surface. CC -!- SUBUNIT: Interacts with LEP. {ECO:0000269|PubMed:10428856}. CC -!- INTERACTION: CC Q14192:FHL2; NbExp=3; IntAct=EBI-2814604, EBI-701903; CC P15884:TCF4; NbExp=3; IntAct=EBI-2814604, EBI-533224; CC O00206:TLR4; NbExp=2; IntAct=EBI-12161783, EBI-528701; CC -!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I CC membrane protein. CC -!- SUBCELLULAR LOCATION: Isoform 2: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=Membrane-bound, CD33L1; CC IsoId=O43699-1; Sequence=Displayed; CC Name=2; Synonyms=Secreted, CD33L2; CC IsoId=O43699-2; Sequence=VSP_002553, VSP_002554; CC Note=Should not be confused with SIGLEC5 which has been called CC CD33L2.; CC Name=3; CC IsoId=O43699-3; Sequence=VSP_035812; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=O43699-4; Sequence=VSP_035811, VSP_002553, VSP_002554; CC Note=No experimental confirmation available.; CC Name=5; CC IsoId=O43699-5; Sequence=VSP_045387, VSP_045388; CC Note=No experimental confirmation available. Ref.5 (AK300182) CC sequence is in conflict in position: 246:P->S. {ECO:0000305}; CC Name=6; CC IsoId=O43699-6; Sequence=VSP_046070, VSP_035812; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed at high levels in placenta CC (cyto- and syncytiotrophoblastic cells) and at lower levels in CC spleen, peripheral blood leukocytes (predominantly B-cells) and CC small intestine. CC -!- DOMAIN: Contains 1 copy of a cytoplasmic motif that is referred to CC as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This CC motif is involved in modulation of cellular responses. The CC phosphorylated ITIM motif can bind the SH2 domain of several SH2- CC containing phosphatases. CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. SIGLEC CC (sialic acid binding Ig-like lectin) family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB70702.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH35359.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAI40799.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA24983.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA24984.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding; CC Note=Siglec-6; CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Itlect_273"; 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; D86358; BAA24983.1; ALT_INIT; mRNA. DR EMBL; D86359; BAA24984.1; ALT_INIT; mRNA. DR EMBL; AK300170; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK300182; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC020914; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035359; AAH35359.2; ALT_INIT; mRNA. DR EMBL; BC140798; AAI40799.1; ALT_INIT; mRNA. DR EMBL; U71382; AAB70702.1; ALT_INIT; mRNA. DR CCDS; CCDS12834.3; -. [O43699-1] DR CCDS; CCDS12835.3; -. [O43699-3] DR CCDS; CCDS12836.3; -. [O43699-2] DR CCDS; CCDS54307.1; -. [O43699-6] DR CCDS; CCDS54308.1; -. [O43699-5] DR CCDS; CCDS59417.1; -. [O43699-4] DR RefSeq; NP_001171018.1; NM_001177547.2. [O43699-6] DR RefSeq; NP_001171019.1; NM_001177548.2. [O43699-5] DR RefSeq; NP_001171020.1; NM_001177549.2. [O43699-4] DR RefSeq; NP_001236.4; NM_001245.6. [O43699-1] DR RefSeq; NP_942142.3; NM_198845.5. [O43699-3] DR RefSeq; NP_942143.3; NM_198846.5. [O43699-2] DR UniGene; Hs.720304; -. DR ProteinModelPortal; O43699; -. DR SMR; O43699; -. DR BioGrid; 107384; 3. DR IntAct; O43699; 14. DR STRING; 9606.ENSP00000401502; -. DR iPTMnet; O43699; -. DR PhosphoSitePlus; O43699; -. DR BioMuta; SIGLEC6; -. DR jPOST; O43699; -. DR PaxDb; O43699; -. DR PeptideAtlas; O43699; -. DR PRIDE; O43699; -. DR ProteomicsDB; 49120; -. DR ProteomicsDB; 49121; -. [O43699-2] DR ProteomicsDB; 49122; -. [O43699-3] DR ProteomicsDB; 49123; -. [O43699-4] DR DNASU; 946; -. DR Ensembl; ENST00000343300; ENSP00000345907; ENSG00000105492. [O43699-2] DR Ensembl; ENST00000346477; ENSP00000344064; ENSG00000105492. [O43699-3] DR Ensembl; ENST00000359982; ENSP00000353071; ENSG00000105492. [O43699-5] DR Ensembl; ENST00000391797; ENSP00000375674; ENSG00000105492. [O43699-4] DR Ensembl; ENST00000425629; ENSP00000401502; ENSG00000105492. [O43699-1] DR Ensembl; ENST00000436458; ENSP00000410679; ENSG00000105492. [O43699-6] DR GeneID; 946; -. DR KEGG; hsa:946; -. DR UCSC; uc002pwy.4; human. [O43699-1] DR CTD; 946; -. DR DisGeNET; 946; -. DR EuPathDB; HostDB:ENSG00000105492.15; -. DR GeneCards; SIGLEC6; -. DR HGNC; HGNC:10875; SIGLEC6. DR HPA; HPA009084; -. DR HPA; HPA018198; -. DR MIM; 604405; gene. DR neXtProt; NX_O43699; -. DR OpenTargets; ENSG00000105492; -. DR PharmGKB; PA35776; -. DR eggNOG; ENOG410IJT6; Eukaryota. DR eggNOG; ENOG410YKZU; LUCA. DR GeneTree; ENSGT00940000153250; -. DR HOGENOM; HOG000236324; -. DR HOVERGEN; HBG036161; -. DR InParanoid; O43699; -. DR KO; K06738; -. DR OMA; ELHYAFL; -. DR OrthoDB; 416689at2759; -. DR PhylomeDB; O43699; -. DR TreeFam; TF332441; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR GenomeRNAi; 946; -. DR PRO; PR:O43699; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000105492; Expressed in 68 organ(s), highest expression level in placenta. DR ExpressionAtlas; O43699; baseline and differential. DR Genevisible; O43699; HS. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR Gene3D; 2.60.40.10; -; 3. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003006; Ig/MHC_CS. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR013106; Ig_V-set. DR InterPro; IPR013151; Immunoglobulin. DR Pfam; PF07679; I-set; 1. DR Pfam; PF00047; ig; 1. DR Pfam; PF07686; V-set; 1. DR SMART; SM00409; IG; 3. DR SMART; SM00408; IGc2; 1. DR SUPFAM; SSF48726; SSF48726; 3. DR PROSITE; PS50835; IG_LIKE; 2. DR PROSITE; PS00290; IG_MHC; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell adhesion; Cell membrane; Complete proteome; KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Lectin; Membrane; KW Polymorphism; Reference proteome; Repeat; Secreted; Signal; KW Transmembrane; Transmembrane helix. FT SIGNAL 1 26 {ECO:0000255}. FT CHAIN 27 453 Sialic acid-binding Ig-like lectin 6. FT /FTId=PRO_0000014946. FT TOPO_DOM 27 347 Extracellular. {ECO:0000255}. FT TRANSMEM 348 368 Helical. {ECO:0000255}. FT TOPO_DOM 369 453 Cytoplasmic. {ECO:0000255}. FT DOMAIN 28 123 Ig-like V-type. FT DOMAIN 148 231 Ig-like C2-type 1. FT DOMAIN 238 333 Ig-like C2-type 2. FT MOTIF 424 429 ITIM motif. FT MOTIF 444 449 SLAM-like motif. FT BINDING 122 122 Sialic acid. {ECO:0000250}. FT CARBOHYD 103 103 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 149 149 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 163 163 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 233 233 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 46 172 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 51 104 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 166 215 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT DISULFID 274 319 {ECO:0000255|PROSITE-ProRule:PRU00114}. FT VAR_SEQ 23 58 Missing (in isoform 6). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_046070. FT VAR_SEQ 143 153 Missing (in isoform 4). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_035811. FT VAR_SEQ 236 252 YAPQKVAISIFQGNSAA -> S (in isoform 3 and FT isoform 6). {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_035812. FT VAR_SEQ 236 236 Y -> WMLRRPPLSTPD (in isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045387. FT VAR_SEQ 339 391 KPEGRAGGVLGAVWGASITTLVFLCVCFIFRVKTRRKKAAQ FT PVQNTDDVNPVM -> SSAPVPDRHSFRPPC (in FT isoform 2 and isoform 4). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9465907}. FT /FTId=VSP_002553. FT VAR_SEQ 371 453 KTRRKKAAQPVQNTDDVNPVMVSGSRGHQHQFQTGIVSDHP FT AEAGPISEDEQELHYAVLHFHKVQPQEPKVTDTEYSEIKIH FT K -> ISTSSRQA (in isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045388. FT VAR_SEQ 392 453 Missing (in isoform 2 and isoform 4). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9465907}. FT /FTId=VSP_002554. FT VARIANT 57 57 L -> V (in dbSNP:rs2305773). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_014252. FT VARIANT 262 262 L -> F (in dbSNP:rs2005199). FT /FTId=VAR_014253. FT CONFLICT 6 6 E -> K (in Ref. 1; BAA24983/BAA24984). FT {ECO:0000305}. FT CONFLICT 137 138 LS -> IY (in Ref. 5; AAB70702). FT {ECO:0000305}. FT CONFLICT 155 161 TLESGHP -> PGVWPS (in Ref. 5; AAB70702). FT {ECO:0000305}. FT CONFLICT 183 183 M -> T (in Ref. 2; AK300170). FT {ECO:0000305}. FT CONFLICT 188 189 TS -> HL (in Ref. 5; AAB70702). FT {ECO:0000305}. FT CONFLICT 205 206 RP -> A (in Ref. 5; AAB70702). FT {ECO:0000305}. FT CONFLICT 389 389 P -> L (in Ref. 2; AK300170). FT {ECO:0000305}. SQ SEQUENCE 453 AA; 49913 MW; 9DD7FBD8F059E452 CRC64; MQGAQEASAS EMLPLLLPLL WAGALAQERR FQLEGPESLT VQEGLCVLVP CRLPTTLPAS YYGYGYWFLE GADVPVATND PDEEVQEETR GRFHLLWDPR RKNCSLSIRD ARRRDNAAYF FRLKSKWMKY GYTSSKLSVR VMALTHRPNI SIPGTLESGH PSNLTCSVPW VCEQGTPPIF SWMSAAPTSL GPRTTQSSVL TITPRPQDHS TNLTCQVTFP GAGVTMERTI QLNVSYAPQK VAISIFQGNS AAFKILQNTS SLPVLEGQAL RLLCDADGNP PAHLSWFQGF PALNATPISN TGVLELPQVG SAEEGDFTCR AQHPLGSLQI SLSLFVHWKP EGRAGGVLGA VWGASITTLV FLCVCFIFRV KTRRKKAAQP VQNTDDVNPV MVSGSRGHQH QFQTGIVSDH PAEAGPISED EQELHYAVLH FHKVQPQEPK VTDTEYSEIK IHK //