CD33_HUMAN
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 03-AUG-2022, entry version 214.
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;
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;
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;
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 (2.48 ANGSTROMS) OF 21-232 IN COMPLEX WITH GALACTOSE,
RP GLYCOSYLATION AT ASN-100; ASN-160; ASN-209 AND ASN-230, AND DISULFIDE
RP 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:15597323,
CC PubMed:11320212). 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:28325905, PubMed:10887109). 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:10556798, PubMed:10206955, 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:10556798,
CC PubMed:10206955). 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; 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";
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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_001082618.1. [P20138-3]
DR RefSeq; NP_001171079.1; NM_001177608.1. [P20138-2]
DR RefSeq; NP_001763.3; NM_001772.3. [P20138-1]
DR RefSeq; XP_011525834.1; XM_011527532.2. [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 PDBsum; 5IHB; -.
DR PDBsum; 5J06; -.
DR PDBsum; 5J0B; -.
DR PDBsum; 6D48; -.
DR PDBsum; 6D49; -.
DR PDBsum; 6D4A; -.
DR PDBsum; 6TL8; -.
DR PDBsum; 7AW6; -.
DR AlphaFoldDB; P20138; -.
DR SMR; P20138; -.
DR BioGRID; 107383; 48.
DR IntAct; P20138; 33.
DR MINT; P20138; -.
DR STRING; 9606.ENSP00000262262; -.
DR ChEMBL; CHEMBL1842; -.
DR DrugBank; DB06318; AVE9633.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugCentral; P20138; -.
DR GuidetoPHARMACOLOGY; 2601; -.
DR UniLectin; P20138; -.
DR GlyGen; P20138; 8 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P20138; -.
DR PhosphoSitePlus; P20138; -.
DR BioMuta; CD33; -.
DR DMDM; 116241290; -.
DR EPD; P20138; -.
DR jPOST; P20138; -.
DR MassIVE; P20138; -.
DR PaxDb; P20138; -.
DR PeptideAtlas; P20138; -.
DR PRIDE; P20138; -.
DR ProteomicsDB; 30518; -.
DR ProteomicsDB; 53725; -. [P20138-1]
DR ProteomicsDB; 9878; -.
DR ABCD; P20138; 5 sequenced antibodies.
DR Antibodypedia; 4419; 2695 antibodies from 51 providers.
DR CPTC; P20138; 5 antibodies.
DR DNASU; 945; -.
DR Ensembl; ENST00000262262.5; ENSP00000262262.3; ENSG00000105383.15. [P20138-1]
DR Ensembl; ENST00000391796.7; ENSP00000375673.2; ENSG00000105383.15. [P20138-2]
DR Ensembl; ENST00000421133.6; ENSP00000410126.1; ENSG00000105383.15. [P20138-3]
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 CTD; 945; -.
DR DisGeNET; 945; -.
DR GeneCards; CD33; -.
DR HGNC; HGNC:1659; CD33.
DR HPA; ENSG00000105383; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 159590; gene.
DR neXtProt; NX_P20138; -.
DR OpenTargets; ENSG00000105383; -.
DR PharmGKB; PA26210; -.
DR VEuPathDB; HostDB:ENSG00000105383; -.
DR eggNOG; ENOG502S41V; Eukaryota.
DR GeneTree; ENSGT01040000240469; -.
DR HOGENOM; CLU_102212_0_0_1; -.
DR InParanoid; P20138; -.
DR OMA; EGAIVSW; -.
DR PhylomeDB; P20138; -.
DR TreeFam; TF332441; -.
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 SignaLink; P20138; -.
DR SIGNOR; P20138; -.
DR BioGRID-ORCS; 945; 10 hits in 1077 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 115 other tissues.
DR ExpressionAtlas; P20138; baseline and differential.
DR Genevisible; P20138; HS.
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:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
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:0002765; P:immune response-inhibiting signal transduction; IDA:UniProtKB.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IMP:ARUK-UCL.
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:1903615; P:positive regulation of protein tyrosine phosphatase activity; IMP:ARUK-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 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.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 2.
DR SUPFAM; SSF48726; SSF48726; 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; Reference proteome; Repeat; Signal;
KW 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 COMPBIAS 347..364
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 (GalNAc...) 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"
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
