P20138 (CD33_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Myeloid cell surface antigen CD33

Alternative name(s):
Sialic acid-binding Ig-like lectin 3
Short name=Siglec-3
gp67
CD_antigen=CD33

Gene names

Name:	CD33
Synonyms:	SIGLEC3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	364 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Induces apoptosis in acute myeloid leukemia (in vitro). Ref.9 Ref.11
Subunit structure	Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation. Ref.9 Ref.10
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Tissue specificity	Monocytic/myeloid lineage cells.
Domain	Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.
Post-translational modification	Phosphorylation of Tyr-340 is involved in binding to PTPN6 and PTPN11. Phosphorylation of Tyr-358 is involved in binding to PTPN6.
Sequence similarities	Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	Lectin
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Non-traceable author statement PubMed 10611343. Source: ProtInc cell-cell signaling Traceable author statement PubMed 10611343. Source: ProtInc negative regulation of cell proliferation Traceable author statement PubMed 10611343. Source: ProtInc signal transduction Traceable author statement PubMed 10611343. Source: ProtInc
Cellular_component	external side of plasma membrane Inferred from direct assay PubMed 20660734. Source: MGI integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	receptor activity Traceable author statement PubMed 10611343. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P20138-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P20138-2)

The sequence of this isoform differs from the canonical sequence as follows:
     309-364: KHQKKSKLHGPTETSSCSGAAPTVEMDEELHYASLNFHGMNPSKDTSTEYSEVRTQ → VR

Note: No experimental confirmation available.

Isoform 3 (identifier: P20138-3)

Also known as: CD33-m;

The sequence of this isoform differs from the canonical sequence as follows:
     13-139: Missing.

Note: Mostly detected on NKL and myeloid cell lines but poorly expressed on B cell lines and T lymphocytes.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Chain	18 – 364	347	Myeloid cell surface antigen CD33		PRO_0000014878
Regions
	Topological domain	18 – 259	242	Extracellular Potential
	Transmembrane	260 – 282	23	Helical; Potential
	Topological domain	283 – 364	82	Cytoplasmic Potential
	Domain	19 – 135	117	Ig-like V-type
	Domain	145 – 228	84	Ig-like C2-type
	Motif	338 – 343	6	ITIM motif 1
	Motif	356 – 361	6	ITIM motif 2
Sites
	Binding site	119	1	Sialic acid By similarity
Amino acid modifications
	Modified residue	340	1	Phosphotyrosine Ref.9 Ref.10
	Modified residue	358	1	Phosphotyrosine Ref.9 Ref.10
	Glycosylation	100	1	N-linked (GlcNAc...) Potential
	Glycosylation	113	1	N-linked (GlcNAc...) Potential
	Glycosylation	160	1	N-linked (GlcNAc...) Potential
	Glycosylation	209	1	N-linked (GlcNAc...) Potential
	Glycosylation	230	1	N-linked (GlcNAc...) Potential
	Disulfide bond	36 ↔ 169		By similarity
	Disulfide bond	41 ↔ 101		By similarity
	Disulfide bond	163 ↔ 212		Potential
Natural variations
	Alternative sequence	13 – 139	127	Missing in isoform 3.		VSP_046172
	Alternative sequence	309 – 364	56	KHQKK…EVRTQ → VR in isoform 2.		VSP_045364
	Natural variant	14	1	A → V. Ref.4 Corresponds to variant rs12459419 [ dbSNP | Ensembl ].		VAR_049904
	Natural variant	22	1	W → R. Corresponds to variant rs35814802 [ dbSNP | Ensembl ].		VAR_049905
	Natural variant	69	1	R → G. Ref.1 Ref.7 Corresponds to variant rs2455069 [ dbSNP | Ensembl ].		VAR_028260
	Natural variant	128	1	S → N. Corresponds to variant rs34919259 [ dbSNP | Ensembl ].		VAR_049906
	Natural variant	202	1	R → W. Corresponds to variant rs4082929 [ dbSNP | Ensembl ].		VAR_028261
	Natural variant	242	1	I → L. Corresponds to variant rs988337 [ dbSNP | Ensembl ].		VAR_028262
	Natural variant	243	1	F → L. Corresponds to variant rs11882250 [ dbSNP | Ensembl ].		VAR_028263
	Natural variant	267	1	V → I. Corresponds to variant rs58981829 [ dbSNP | Ensembl ].		VAR_061319
	Natural variant	294	1	V → L. Corresponds to variant rs2271652 [ dbSNP | Ensembl ].		VAR_028264
	Natural variant	304	1	G → R. Ref.4 Corresponds to variant rs35112940 [ dbSNP | Ensembl ].		VAR_049907
	Natural variant	331	1	T → A. Corresponds to variant rs35632246 [ dbSNP | Ensembl ].		VAR_049908
Experimental info
	Mutagenesis	340	1	Y → A: Abolishes binding to PTPN6 and PTPN11. Increases binding of red blood cells. Ref.10
	Mutagenesis	358	1	Y → A or F: Reduces binding to PTPN6. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 1C73E588240FBAD8	FASTA	364	39,825
	10 20 30 40 50 60 MPLLLLLPLL WAGALAMDPN FWLQVQESVT VQEGLCVLVP CTFFHPIPYY DKNSPVHGYW 70 80 90 100 110 120 FREGAIISRD SPVATNKLDQ EVQEETQGRF RLLGDPSRNN CSLSIVDARR RDNGSYFFRM 130 140 150 160 170 180 ERGSTKYSYK SPQLSVHVTD LTHRPKILIP GTLEPGHSKN LTCSVSWACE QGTPPIFSWL 190 200 210 220 230 240 SAAPTSLGPR TTHSSVLIIT PRPQDHGTNL TCQVKFAGAG VTTERTIQLN VTYVPQNPTT 250 260 270 280 290 300 GIFPGDGSGK QETRAGVVHG AIGGAGVTAL LALCLCLIFF IVKTHRRKAA RTAVGRNDTH 310 320 330 340 350 360 PTTGSASPKH QKKSKLHGPT ETSSCSGAAP TVEMDEELHY ASLNFHGMNP SKDTSTEYSE VRTQ
	Isoform 2 [UniParc]. Checksum: F3618D0661DBE51E	FASTA	310	33,890
	10 20 30 40 50 60 MPLLLLLPLL WAGALAMDPN FWLQVQESVT VQEGLCVLVP CTFFHPIPYY DKNSPVHGYW 70 80 90 100 110 120 FREGAIISRD SPVATNKLDQ EVQEETQGRF RLLGDPSRNN CSLSIVDARR RDNGSYFFRM 130 140 150 160 170 180 ERGSTKYSYK SPQLSVHVTD LTHRPKILIP GTLEPGHSKN LTCSVSWACE QGTPPIFSWL 190 200 210 220 230 240 SAAPTSLGPR TTHSSVLIIT PRPQDHGTNL TCQVKFAGAG VTTERTIQLN VTYVPQNPTT 250 260 270 280 290 300 GIFPGDGSGK QETRAGVVHG AIGGAGVTAL LALCLCLIFF IVKTHRRKAA RTAVGRNDTH 310 PTTGSASPVR
	Isoform 3 (CD33-m) [UniParc]. Checksum: 52C8CF965ACC740C	FASTA	237	25,293
	10 20 30 40 50 60 MPLLLLLPLL WADLTHRPKI LIPGTLEPGH SKNLTCSVSW ACEQGTPPIF SWLSAAPTSL 70 80 90 100 110 120 GPRTTHSSVL IITPRPQDHG TNLTCQVKFA GAGVTTERTI QLNVTYVPQN PTTGIFPGDG 130 140 150 160 170 180 SGKQETRAGV VHGAIGGAGV TALLALCLCL IFFIVKTHRR KAARTAVGRN DTHPTTGSAS 190 200 210 220 230 PKHQKKSKLH GPTETSSCSG AAPTVEMDEE LHYASLNFHG MNPSKDTSTE YSEVRTQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells." Simmons D., Seed B. J. Immunol. 141:2797-2800(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-69. Tissue: Premonocytic lymphoma.
[2]	"Genomic organization of the siglec gene locus on chromosome 19q13.4 and cloning of two new siglec pseudogenes." Yousef G.M., Ordon M.H., Foussias G., Diamandis E.P. Gene 286:259-270(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: two isoforms of CD33 are generated by alternative splicing." Hernandez-Caselles T., Martinez-Esparza M., Perez-Oliva A.B., Quintanilla-Cecconi A.M., Garcia-Alonso A., Alvarez-Lopez D.M., Garcia-Penarrubia P. J. Leukoc. Biol. 79:46-58(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS VAL-14 AND ARG-304. Tissue: Uterus.
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLY-69. Tissue: Leukocyte.
[8]	"Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules." Freeman S.D., Kelm S., Barber E.K., Crocker P.R. Blood 85:2005-2012(1995) [PubMed] [Europe PMC] [Abstract] Cited for: SIALIC ACID-BINDING.
[9]	"The sialoadhesin CD33 is a myeloid-specific inhibitory receptor." Ulyanova T., Blasioli J., Woodford-Thomas T.A., Thomas M.L. Eur. J. Immunol. 29:3440-3449(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT TYR-340 AND TYR-358, MUTAGENESIS OF TYR-358, INTERACTION WITH PTPN6.
[10]	"The myeloid-specific sialic acid-binding receptor, CD33, associates with the protein-tyrosine phosphatases, SHP-1 and SHP-2." Taylor V.C., Buckley C.D., Douglas M., Cody A.J., Simmons D.L., Freeman S.D. J. Biol. Chem. 274:11505-11512(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-340 AND TYR-358, INTERACTION WITH PTPN6 AND PTPN11, MUTAGENESIS OF TYR-340.
[11]	"Surface expression and function of p75/AIRM-1 or CD33 in acute myeloid leukemias: engagement of CD33 induces apoptosis of leukemic cells." Vitale C., Romagnani C., Puccetti A., Olive D., Costello R., Chiossone L., Pitto A., Bacigalupo A., Moretta L., Mingari M.C. Proc. Natl. Acad. Sci. U.S.A. 98:5764-5769(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Siglec-3

Cross-references

Sequence databases
EMBL GenBank DDBJ	M23197 mRNA. Translation: AAA51948.1. Sequence problems. AY040541 Genomic DNA. Translation: AAK83654.1. AY162464 mRNA. No translation available. AK304810 mRNA. Translation: BAG65560.1. AC063977 Genomic DNA. No translation available. CH471135 Genomic DNA. Translation: EAW71996.1. BC028152 mRNA. Translation: AAH28152.1.
IPI	IPI00022203. IPI00844575. IPI00964702.
PIR	A30521.
RefSeq	NP_001076087.1. NM_001082618.1. NP_001171079.1. NM_001177608.1. NP_001763.3. NM_001772.3.
UniGene	Hs.83731.
3D structure databases
ProteinModelPortal	P20138.
ModBase	Search...
Protein-protein interaction databases
IntAct	P20138. 1 interaction.
MINT	MINT-8020077.
STRING	9606.ENSP00000262262.
PTM databases
PhosphoSite	P20138.
Polymorphism databases
DMDM	116241290.
Proteomic databases
PaxDb	P20138.
PRIDE	P20138.
Protocols and materials databases
DNASU	945.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262262; ENSP00000262262; ENSG00000105383. ENST00000391796; ENSP00000375673; ENSG00000105383. ENST00000421133; ENSP00000410126; ENSG00000105383.
GeneID	945.
KEGG	hsa:945.
UCSC	uc002pwa.2. human. uc010eos.1. human. uc010eot.1. human.
Organism-specific databases
CTD	945.
GeneCards	GC19P051729.
H-InvDB	HIX0015379.
HGNC	HGNC:1659. CD33.
HPA	CAB011442.
MIM	159590. gene.
neXtProt	NX_P20138.
PharmGKB	PA26210.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG320441.
HOGENOM	HOG000236324.
HOVERGEN	HBG036161.
InParanoid	P20138.
KO	K06473.
OMA	QKKSKLH.
OrthoDB	EOG43BMP7.
PhylomeDB	P20138.
Gene expression databases
ArrayExpress	P20138.
Bgee	P20138.
CleanEx	HS_CD33.
Genevestigator	P20138.
GermOnline	ENSG00000105383. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 2 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. IPR013151. Immunoglobulin. [Graphical view]
Pfam	PF00047. ig. 1 hit. PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 2 hits. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1842.
ChiTaRS	CD33. human.
DrugBank	DB00056. Gemtuzumab ozogamicin.
GenomeRNAi	945.
NextBio	3918.
SOURCE	Search...

Entry information

Entry name

CD33_HUMAN

Accession

Primary (citable) accession number: P20138
Secondary accession number(s): B4E3P8 , C9JEN7, F8WAL2, Q8TD24

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 17, 2006
Last modified:	May 29, 2013
This is version 143 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.