ID CD33_HUMAN Reviewed; 364 AA. AC P20138; B4E3P8; C9JEN7; F8WAL2; Q8TD24; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 04-NOV-2026, entry version 234. DE RecName: Full=Myeloid cell surface antigen CD33; DE AltName: Full=Sialic acid-binding Ig-like lectin 3; DE Short=Siglec-3; DE AltName: Full=gp67; DE AltName: CD_antigen=CD33; DE Flags: Precursor; GN Name=CD33; Synonyms=SIGLEC3; 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 CD33M), AND VARIANT GLY-69. RC TISSUE=Premonocytic lymphoma; RX PubMed=3139766; DOI=10.4049/jimmunol.141.8.2797; RA Simmons D., Seed B.; RT "Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid RT progenitor cells."; RL J. Immunol. 141:2797-2800(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11943481; DOI=10.1016/s0378-1119(02)00432-8; RA Yousef G.M., Ordon M.H., Foussias G., Diamandis E.P.; RT "Genomic organization of the siglec gene locus on chromosome 19q13.4 and RT cloning of two new siglec pseudogenes."; RL Gene 286:259-270(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CD33M), AND ALTERNATIVE SPLICING. RX PubMed=16380601; DOI=10.1189/jlb.0205096; RA Hernandez-Caselles T., Martinez-Esparza M., Perez-Oliva A.B., RA Quintanilla-Cecconi A.M., Garcia-Alonso A., Alvarez-Lopez D.M., RA Garcia-Penarrubia P.; RT "A study of CD33 (SIGLEC-3) antigen expression and function on activated RT human T and NK cells: two isoforms of CD33 are generated by alternative RT splicing."; RL J. Leukoc. Biol. 79:46-58(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS VAL-14 AND RP ARG-304. RC TISSUE=Uterus; 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 GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CD33M), AND VARIANT GLY-69. RC TISSUE=Leukocyte; 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 [8] RP FUNCTION, AND SIALIC ACID-BINDING. RX PubMed=7718872; DOI=10.1182/blood.v85.8.2005.bloodjournal8582005; RA Freeman S.D., Kelm S., Barber E.K., Crocker P.R.; RT "Characterization of CD33 as a new member of the sialoadhesin family of RT cellular interaction molecules."; RL Blood 85:2005-2012(1995). RN [9] RP GLYCOSYLATION AT ASN-100, AND MUTAGENESIS OF ASN-100. RX PubMed=8702538; DOI=10.1074/jbc.271.31.18803; RA Sgroi D., Nocks A., Stamenkovic I.; RT "A single N-linked glycosylation site is implicated in the regulation of RT ligand recognition by the I-type lectins CD22 and CD33."; RL J. Biol. Chem. 271:18803-18809(1996). RN [10] RP FUNCTION, PHOSPHORYLATION AT TYR-340 AND TYR-358, MUTAGENESIS OF TYR-358, RP AND INTERACTION WITH PTPN6. RX PubMed=10556798; RX DOI=10.1002/(sici)1521-4141(199911)29:11<3440::aid-immu3440>3.0.co;2-c; RA Ulyanova T., Blasioli J., Woodford-Thomas T.A., Thomas M.L.; RT "The sialoadhesin CD33 is a myeloid-specific inhibitory receptor."; RL Eur. J. Immunol. 29:3440-3449(1999). RN [11] RP PHOSPHORYLATION AT TYR-340 AND TYR-358, INTERACTION WITH PTPN6 AND PTPN11, RP AND MUTAGENESIS OF TYR-340. RX PubMed=10206955; DOI=10.1074/jbc.274.17.11505; RA Taylor V.C., Buckley C.D., Douglas M., Cody A.J., Simmons D.L., RA Freeman S.D.; RT "The myeloid-specific sialic acid-binding receptor, CD33, associates with RT the protein-tyrosine phosphatases, SHP-1 and SHP-2."; RL J. Biol. Chem. 274:11505-11512(1999). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10611343; DOI=10.1073/pnas.96.26.15091; RA Vitale C., Romagnani C., Falco M., Ponte M., Vitale M., Moretta A., RA Bacigalupo A., Moretta L., Mingari M.C.; RT "Engagement of p75/AIRM1 or CD33 inhibits the proliferation of normal or RT leukemic myeloid cells."; RL Proc. Natl. Acad. Sci. U.S.A. 96:15091-15096(1999). RN [13] RP FUNCTION, PHOSPHORYLATION AT TYR-340 AND TYR-358, MUTAGENESIS OF TYR-340 RP AND TYR-358, AND SUBUNIT. RX PubMed=10887109; DOI=10.1182/blood.v96.2.483; RA Paul S.P., Taylor L.S., Stansbury E.K., McVicar D.W.; RT "Myeloid specific human CD33 is an inhibitory receptor with differential RT ITIM function in recruiting the phosphatases SHP-1 and SHP-2."; RL Blood 96:483-490(2000). RN [14] RP FUNCTION. RX PubMed=11320212; DOI=10.1073/pnas.091097198; RA Vitale C., Romagnani C., Puccetti A., Olive D., Costello R., Chiossone L., RA Pitto A., Bacigalupo A., Moretta L., Mingari M.C.; RT "Surface expression and function of p75/AIRM-1 or CD33 in acute myeloid RT leukemias: engagement of CD33 induces apoptosis of leukemic cells."; RL Proc. Natl. Acad. Sci. U.S.A. 98:5764-5769(2001). RN [15] RP FUNCTION. RX PubMed=15597323; DOI=10.1002/eji.200425273; RA Lajaunias F., Dayer J.M., Chizzolini C.; RT "Constitutive repressor activity of CD33 on human monocytes requires sialic RT acid recognition and phosphoinositide 3-kinase-mediated intracellular RT signaling."; RL Eur. J. Immunol. 35:243-251(2005). RN [16] RP FUNCTION, AND INTERACTION WITH C1QA. RX PubMed=28325905; DOI=10.1038/s41598-017-00290-w; RA Son M., Diamond B., Volpe B.T., Aranow C.B., Mackay M.C., RA Santiago-Schwarz F.; RT "Evidence for C1q-mediated crosslinking of CD33/LAIR-1 inhibitory RT immunoreceptors and biological control of CD33/LAIR-1 expression."; RL Sci. Rep. 7:270-270(2017). RN [17] RP SUBCELLULAR LOCATION. RX PubMed=28747436; DOI=10.1074/jbc.m117.799346; RA Siddiqui S.S., Springer S.A., Verhagen A., Sundaramurthy V., RA Alisson-Silva F., Jiang W., Ghosh P., Varki A.; RT "The Alzheimer's disease-protective CD33 splice variant mediates adaptive RT loss of function via diversion to an intracellular pool."; RL J. Biol. Chem. 292:15312-15320(2017). RN [18] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH GALACTOSE, GLYCOSYLATION AT ASN-100; RP ASN-160; ASN-209 AND ASN-230, AND DISULFIDE BONDS. RA Dodd R.B., Meadows W., Qamar S., Johnson C.M., Kronenberg-Versteeg D., RA St George-Hyslop P.; RT "Structure of ligand bound CD33 receptor associated with Alzheimer's RT disease."; RL Submitted (MAR-2016) to the PDB data bank. CC -!- FUNCTION: Sialic-acid-binding immunoglobulin-like lectin (Siglec) that CC plays a role in mediating cell-cell interactions and in maintaining CC immune cells in a resting state (PubMed:10611343, PubMed:11320212, CC PubMed:15597323). Preferentially recognizes and binds alpha-2,3- and CC more avidly alpha-2,6-linked sialic acid-bearing glycans CC (PubMed:7718872). Upon engagement of ligands such as C1q or syalylated CC glycoproteins, two immunoreceptor tyrosine-based inhibitory motifs CC (ITIMs) located in CD33 cytoplasmic tail are phosphorylated by Src-like CC kinases such as LCK (PubMed:10887109, PubMed:28325905). These CC phosphorylations provide docking sites for the recruitment and CC activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP- CC 2 (PubMed:10206955, PubMed:10556798, PubMed:10887109). In turn, these CC phosphatases regulate downstream pathways through dephosphorylation of CC signaling molecules (PubMed:10206955, PubMed:10887109). One of the CC repressive effect of CD33 on monocyte activation requires CC phosphoinositide 3-kinase/PI3K (PubMed:15597323). CC {ECO:0000269|PubMed:10206955, ECO:0000269|PubMed:10556798, CC ECO:0000269|PubMed:10611343, ECO:0000269|PubMed:10887109, CC ECO:0000269|PubMed:11320212, ECO:0000269|PubMed:15597323, CC ECO:0000269|PubMed:28325905, ECO:0000269|PubMed:7718872}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:10887109). Interacts with CC PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation (PubMed:10206955, CC PubMed:10556798). Interacts with C1QA (via C-terminus); this CC interaction activates CD33 inhibitory motifs (PubMed:28325905). CC {ECO:0000269|PubMed:10206955, ECO:0000269|PubMed:10556798, CC ECO:0000269|PubMed:10887109, ECO:0000269|PubMed:28325905}. CC -!- INTERACTION: CC P20138; O95393: BMP10; NbExp=3; IntAct=EBI-3906571, EBI-3922513; CC P20138; Q07325: CXCL9; NbExp=3; IntAct=EBI-3906571, EBI-3911467; CC P20138; O43169: CYB5B; NbExp=3; IntAct=EBI-3906571, EBI-1058710; CC P20138; P50402: EMD; NbExp=3; IntAct=EBI-3906571, EBI-489887; CC P20138; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-3906571, EBI-6166686; CC P20138; Q15323: KRT31; NbExp=6; IntAct=EBI-3906571, EBI-948001; CC P20138; Q92764: KRT35; NbExp=3; IntAct=EBI-3906571, EBI-1058674; CC P20138; Q6A162: KRT40; NbExp=3; IntAct=EBI-3906571, EBI-10171697; CC P20138; Q06124: PTPN11; NbExp=5; IntAct=EBI-3906571, EBI-297779; CC P20138; P29350: PTPN6; NbExp=10; IntAct=EBI-3906571, EBI-78260; CC P20138; Q9NS64: RPRM; NbExp=3; IntAct=EBI-3906571, EBI-1052363; CC P20138; P06702: S100A9; NbExp=5; IntAct=EBI-3906571, EBI-1055001; CC P20138; O00767: SCD; NbExp=3; IntAct=EBI-3906571, EBI-2684237; CC P20138; Q08ET2: SIGLEC14; NbExp=2; IntAct=EBI-3906571, EBI-2214818; CC P20138; Q6ZMC9: SIGLEC15; NbExp=2; IntAct=EBI-3906571, EBI-64049832; CC P20138; O15389: SIGLEC5; NbExp=2; IntAct=EBI-3906571, EBI-750381; CC P20138; Q9NYZ4: SIGLEC8; NbExp=2; IntAct=EBI-3906571, EBI-4314991; CC P20138; Q9Y336: SIGLEC9; NbExp=2; IntAct=EBI-3906571, EBI-12857926; CC P20138; Q9UPZ6: THSD7A; NbExp=3; IntAct=EBI-3906571, EBI-310962; CC P20138; Q969X1: TMBIM1; NbExp=3; IntAct=EBI-3906571, EBI-2820569; CC P20138; Q9NV29: TMEM100; NbExp=3; IntAct=EBI-3906571, EBI-8644968; CC P20138; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-3906571, EBI-12887458; CC P20138; Q9H2S6-2: TNMD; NbExp=3; IntAct=EBI-3906571, EBI-12003398; CC P20138; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-3906571, EBI-10243654; CC P20138; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-3906571, EBI-2819725; CC -!- SUBCELLULAR LOCATION: [Isoform CD33M]: Cell membrane CC {ECO:0000269|PubMed:10611343, ECO:0000269|PubMed:28747436}; Single-pass CC type I membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform CD33m]: Peroxisome CC {ECO:0000269|PubMed:28747436}. Note=CD33m isoform does not localize to CC cell surfaces but instead accumulates in peroxisomes. CC {ECO:0000269|PubMed:28747436}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=CD33M; CC IsoId=P20138-1; Sequence=Displayed; CC Name=3; CC IsoId=P20138-2; Sequence=VSP_045364; CC Name=CD33m; CC IsoId=P20138-3; Sequence=VSP_046172; CC -!- TISSUE SPECIFICITY: Monocytic/myeloid lineage cells. In the brain, CD33 CC is mainly expressed on microglial cells. CC -!- DOMAIN: Contains 2 copies of a cytoplasmic motif that is referred to as CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is CC involved in modulation of cellular responses. The phosphorylated ITIM CC motif can bind the SH2 domain of several SH2-containing phosphatases. CC -!- PTM: Glycosylated. Glycosylation at Asn-100 is critical for regulating CC ligand recognition. {ECO:0000269|PubMed:8702538}. CC -!- PTM: Phosphorylation of Tyr-340 is involved in binding to PTPN6 and CC PTPN11. Phosphorylation of Tyr-358 is involved in binding to PTPN6. LCK CC phosphorylates Tyr-340 efficiently and Tyr-358 to a lesser extent. CC {ECO:0000269|PubMed:10206955, ECO:0000269|PubMed:10556798, CC ECO:0000269|PubMed:10887109}. CC -!- MISCELLANEOUS: [Isoform CD33m]: Mostly detected on NKL and myeloid cell CC lines but poorly expressed on B-cell lines and T-lymphocytes. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. SIGLEC (sialic CC acid binding Ig-like lectin) family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding; CC Note=Siglec-3; CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Itlect_270"; 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; M23197; AAA51948.1; ALT_SEQ; mRNA. DR EMBL; AY040541; AAK83654.1; -; Genomic_DNA. DR EMBL; AY162464; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK304810; BAG65560.1; -; mRNA. DR EMBL; AC063977; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471135; EAW71996.1; -; Genomic_DNA. DR EMBL; BC028152; AAH28152.1; -; mRNA. DR CCDS; CCDS33084.1; -. [P20138-1] DR CCDS; CCDS46157.1; -. [P20138-3] DR CCDS; CCDS54299.1; -. [P20138-2] DR PIR; A30521; A30521. DR RefSeq; NP_001076087.1; NM_001082618.2. [P20138-3] DR RefSeq; NP_001171079.1; NM_001177608.2. [P20138-2] DR RefSeq; NP_001763.3; NM_001772.4. [P20138-1] DR RefSeq; XP_011525834.1; XM_011527532.3. [P20138-1] DR PDB; 5IHB; X-ray; 2.24 A; A/B/C/D=21-232. DR PDB; 5J06; X-ray; 2.66 A; A/B/C/D=21-232. DR PDB; 5J0B; X-ray; 2.48 A; A/B/C/D=21-232. DR PDB; 6D48; X-ray; 1.78 A; E/F/G/H=18-143. DR PDB; 6D49; X-ray; 1.80 A; A/B=18-143. DR PDB; 6D4A; X-ray; 1.75 A; A/B=18-143. DR PDB; 6TL8; X-ray; 2.80 A; A/B/C/D=1-16. DR PDB; 7AW6; X-ray; 1.95 A; A/B=21-232. DR PDB; 9BET; NMR; -; A=251-291. DR PDB; 9MKG; EM; 3.45 A; C=18-260. DR PDB; 9VL2; X-ray; 3.18 A; A/D=18-231. DR AlphaFoldDB; P20138; -. DR EMDB; EMD-48326; -. DR MDRepo; P20138; -. DR SMR; P20138; -. DR BioGRID; 107383; 48. DR FunCoup; P20138; 411. DR IntAct; P20138; 62. DR STRING; 9606.ENSP00000262262; -. DR BindingDB; P20138; -. DR ChEMBL; CHEMBL1842; -. DR DrugBank; DB12860; Actinium. DR DrugBank; DB06318; AVE9633. DR DrugBank; DB00056; Gemtuzumab ozogamicin. DR DrugBank; DB11884; Vadastuximab talirine. DR DrugCentral; P20138; -. DR GuidetoPHARMACOLOGY; 2601; -. DR UniLectin; P20138; -. DR GlyCosmos; P20138; 9 sites, 3 glycans. DR GlyGen; P20138; 10 sites, 1 N-linked glycan (1 site), 3 O-linked glycans (3 sites). DR iPTMnet; P20138; -. DR PhosphoSitePlus; P20138; -. DR BioMuta; CD33; -. DR DMDM; 116241290; -. DR CPTAC; CPTAC-5951; -. DR jPOST; P20138; -. DR MassIVE; P20138; -. DR PaxDb; 9606-ENSP00000262262; -. DR PeptideAtlas; P20138; -. DR ProteomicsDB; 30518; -. DR ProteomicsDB; 53725; -. [P20138-1] DR ProteomicsDB; 9878; -. DR ABCD; P20138; 5 sequenced antibodies. DR Antibodypedia; 4419; 3614 antibodies from 56 providers. DR CPTC; P20138; 5 antibodies. DR DNASU; 945; -. DR Ensembl; ENST00000262262.5; ENSP00000262262.3; ENSG00000105383.17. [P20138-1] DR Ensembl; ENST00000391796.7; ENSP00000375673.2; ENSG00000105383.17. [P20138-2] DR Ensembl; ENST00000421133.6; ENSP00000410126.1; ENSG00000105383.17. [P20138-3] DR Ensembl; ENST00000945453.1; ENSP00000615512.1; ENSG00000105383.17. [P20138-1] DR GeneID; 945; -. DR KEGG; hsa:945; -. DR MANE-Select; ENST00000262262.5; ENSP00000262262.3; NM_001772.4; NP_001763.3. DR UCSC; uc010eos.2; human. [P20138-1] DR AGR; HGNC:1659; -. DR ClinPGx; PA26210; -. DR CTD; 945; -. DR DisGeNET; 945; -. DR GeneCards; CD33; -. DR HGNC; HGNC:1659; CD33. DR HPA; ENSG00000105383; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; CD33; -. DR MIM; 159590; gene. DR OpenTargets; ENSG00000105383; -. DR VEuPathDB; HostDB:ENSG00000105383; -. DR eggNOG; ENOG502S41V; Eukaryota. DR GeneTree; ENSGT01150000286907; -. DR HOGENOM; CLU_102212_0_0_1; -. DR InParanoid; P20138; -. DR OMA; AADHKRN; -. DR OrthoDB; 5843397at2759; -. DR PAN-GO; P20138; 3 GO annotations based on evolutionary models. DR PhylomeDB; P20138; -. DR PathwayCommons; P20138; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9918485; Dengue Virus Attachment and Entry. DR SignaLink; P20138; -. DR SIGNOR; P20138; -. DR Agora; ENSG00000105383; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 945; 10 hits in 1163 CRISPR screens. DR ChiTaRS; CD33; human. DR GenomeRNAi; 945; -. DR Pharos; P20138; Tclin. DR PRO; PR:P20138; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P20138; protein. DR Bgee; ENSG00000105383; Expressed in monocyte and 116 other cell types or tissues. DR ExpressionAtlas; P20138; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI. DR GO; GO:0005794; C:Golgi apparatus; IDA:ARUK-UCL. DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0008160; F:protein tyrosine phosphatase activator activity; IMP:ARUK-UCL. DR GO; GO:0033691; F:sialic acid binding; IMP:ARUK-UCL. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0098609; P:cell-cell adhesion; IMP:ARUK-UCL. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0038094; P:Fc-gamma receptor signaling pathway; IDA:ARUK-UCL. DR GO; GO:0002765; P:immune response-inhibiting signal transduction; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:ARUK-UCL. DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IMP:ARUK-UCL. DR GO; GO:0150102; P:negative regulation of monocyte activation; IDA:ARUK-UCL. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:ARUK-UCL. DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd20987; IgC2_CD33_d2_like; 1. DR CDD; cd05712; IgV_CD33; 1. DR FunFam; 2.60.40.10:FF:000912; Myeloid cell surface antigen CD33; 1. DR FunFam; 2.60.40.10:FF:000829; Sialic acid-binding Ig-like lectin 8; 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 InterPro; IPR013151; Immunoglobulin_dom. DR InterPro; IPR051036; SIGLEC. DR InterPro; IPR061941; SIGLECL1_C. DR PANTHER; PTHR12035:SF132; MYELOID CELL SURFACE ANTIGEN CD33; 1. DR PANTHER; PTHR12035; SIALIC ACID BINDING IMMUNOGLOBULIN-LIKE LECTIN; 1. DR Pfam; PF00047; ig; 1. DR Pfam; PF27822; SIGLECL1_C; 1. DR Pfam; PF07686; V-set; 1. DR SMART; SM00409; IG; 2. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR PROSITE; PS50835; IG_LIKE; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell adhesion; Cell membrane; KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Lectin; Membrane; KW Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome; KW Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..17 FT /evidence="ECO:0000255" FT CHAIN 18..364 FT /note="Myeloid cell surface antigen CD33" FT /id="PRO_0000014878" FT TOPO_DOM 18..259 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 260..282 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 283..364 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 19..135 FT /note="Ig-like V-type" FT DOMAIN 145..228 FT /note="Ig-like C2-type" FT REGION 290..364 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 338..343 FT /note="ITIM motif 1" FT MOTIF 356..361 FT /note="ITIM motif 2" FT BINDING 119 FT /ligand="N-acetylneuraminate" FT /ligand_id="ChEBI:CHEBI:35418" FT /evidence="ECO:0000250" FT BINDING 154 FT /ligand="D-galactose" FT /ligand_id="ChEBI:CHEBI:4139" FT /evidence="ECO:0007744|PDB:5J0B" FT MOD_RES 340 FT /note="Phosphotyrosine; by LCK" FT /evidence="ECO:0000269|PubMed:10206955, FT ECO:0000269|PubMed:10556798, ECO:0000269|PubMed:10887109" FT MOD_RES 358 FT /note="Phosphotyrosine; by LCK" FT /evidence="ECO:0000269|PubMed:10206955, FT ECO:0000269|PubMed:10556798, ECO:0000269|PubMed:10887109" FT CARBOHYD 100 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:8702538, FT ECO:0007744|PDB:5IHB, ECO:0007744|PDB:5J06, FT ECO:0007744|PDB:5J0B" FT CARBOHYD 113 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0007744|PDB:5IHB, ECO:0007744|PDB:5J06, FT ECO:0007744|PDB:5J0B" FT CARBOHYD 209 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0007744|PDB:5IHB, ECO:0007744|PDB:5J06, FT ECO:0007744|PDB:5J0B" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0007744|PDB:5J06" FT DISULFID 36..169 FT /evidence="ECO:0000269|Ref.18" FT DISULFID 41..101 FT /evidence="ECO:0000269|Ref.18" FT DISULFID 163..212 FT /evidence="ECO:0000269|Ref.18" FT VAR_SEQ 13..139 FT /note="Missing (in isoform CD33m)" FT /evidence="ECO:0000303|PubMed:16380601" FT /id="VSP_046172" FT VAR_SEQ 309..364 FT /note="KHQKKSKLHGPTETSSCSGAAPTVEMDEELHYASLNFHGMNPSKDTSTEYSE FT VRTQ -> VR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045364" FT VARIANT 14 FT /note="A -> V (in dbSNP:rs12459419)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_049904" FT VARIANT 22 FT /note="W -> R (in dbSNP:rs35814802)" FT /id="VAR_049905" FT VARIANT 69 FT /note="R -> G (in dbSNP:rs2455069)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:3139766" FT /id="VAR_028260" FT VARIANT 128 FT /note="S -> N (in dbSNP:rs34919259)" FT /id="VAR_049906" FT VARIANT 202 FT /note="R -> W (in dbSNP:rs4082929)" FT /id="VAR_028261" FT VARIANT 242 FT /note="I -> L (in dbSNP:rs988337)" FT /id="VAR_028262" FT VARIANT 243 FT /note="F -> L (in dbSNP:rs11882250)" FT /id="VAR_028263" FT VARIANT 267 FT /note="V -> I (in dbSNP:rs58981829)" FT /id="VAR_061319" FT VARIANT 294 FT /note="V -> L (in dbSNP:rs2271652)" FT /id="VAR_028264" FT VARIANT 304 FT /note="G -> R (in dbSNP:rs35112940)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_049907" FT VARIANT 331 FT /note="T -> A (in dbSNP:rs35632246)" FT /id="VAR_049908" FT MUTAGEN 100 FT /note="N->A: Significant loss of binding to peripheral FT blood granulocytes." FT /evidence="ECO:0000269|PubMed:8702538" FT MUTAGEN 340 FT /note="Y->A: Abolishes binding to PTPN6 and PTPN11. FT Increases binding of red blood cells." FT /evidence="ECO:0000269|PubMed:10206955" FT MUTAGEN 340 FT /note="Y->F: Complete loss of phosphorylation by LCK." FT /evidence="ECO:0000269|PubMed:10887109" FT MUTAGEN 358 FT /note="Y->A,F: Reduces binding to PTPN6." FT /evidence="ECO:0000269|PubMed:10556798" FT MUTAGEN 358 FT /note="Y->F: More than 50% loss of phosphorylation by LCK." FT /evidence="ECO:0000269|PubMed:10887109" FT STRAND 22..25 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 27..32 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 37..39 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 41..44 FT /evidence="ECO:0007829|PDB:6D4A" FT HELIX 49..51 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 56..62 FT /evidence="ECO:0007829|PDB:6D4A" FT TURN 67..69 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 73..76 FT /evidence="ECO:0007829|PDB:6D4A" FT TURN 84..89 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 90..92 FT /evidence="ECO:0007829|PDB:6D4A" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 103..105 FT /evidence="ECO:0007829|PDB:6D4A" FT HELIX 110..112 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 114..122 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 125..128 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 134..139 FT /evidence="ECO:0007829|PDB:6D4A" FT STRAND 146..148 FT /evidence="ECO:0007829|PDB:7AW6" FT STRAND 159..164 FT /evidence="ECO:0007829|PDB:7AW6" FT STRAND 176..191 FT /evidence="ECO:0007829|PDB:7AW6" FT STRAND 194..199 FT /evidence="ECO:0007829|PDB:7AW6" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:7AW6" FT STRAND 209..215 FT /evidence="ECO:0007829|PDB:7AW6" FT STRAND 217..220 FT /evidence="ECO:0007829|PDB:5IHB" FT STRAND 222..228 FT /evidence="ECO:0007829|PDB:7AW6" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:9BET" FT STRAND 259..262 FT /evidence="ECO:0007829|PDB:9BET" FT HELIX 265..285 FT /evidence="ECO:0007829|PDB:9BET" SQ SEQUENCE 364 AA; 39825 MW; 1C73E588240FBAD8 CRC64; MPLLLLLPLL WAGALAMDPN FWLQVQESVT VQEGLCVLVP CTFFHPIPYY DKNSPVHGYW FREGAIISRD SPVATNKLDQ EVQEETQGRF RLLGDPSRNN CSLSIVDARR RDNGSYFFRM ERGSTKYSYK SPQLSVHVTD LTHRPKILIP GTLEPGHSKN LTCSVSWACE QGTPPIFSWL SAAPTSLGPR TTHSSVLIIT PRPQDHGTNL TCQVKFAGAG VTTERTIQLN VTYVPQNPTT GIFPGDGSGK QETRAGVVHG AIGGAGVTAL LALCLCLIFF IVKTHRRKAA RTAVGRNDTH PTTGSASPKH QKKSKLHGPT ETSSCSGAAP TVEMDEELHY ASLNFHGMNP SKDTSTEYSE VRTQ //