Reviewed, UniProtKB/Swiss-Prot P20138 (CD33_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.5 Ref.7
Subunit structure	Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation. Ref.5 Ref.6
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	Polymorphism
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	Lectin
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cell adhesion Non-traceable author statement. Source: ProtInc cell-cell signaling Traceable author statement. Source: ProtInc negative regulation of cell proliferation Traceable author statement. Source: ProtInc signal transduction Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from electronic annotation. Source: UniProtKB-KW receptor activity Traceable author statement. Source: ProtInc sugar binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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	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.5 Ref.6
	Modified residue	358	1	Phosphotyrosine Ref.5 Ref.6
	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
	Natural variant	14	1	A → V: dbSNP rs12459419.		VAR_049904
	Natural variant	22	1	W → R: dbSNP rs35814802.		VAR_049905
	Natural variant	69	1	R → G: dbSNP rs2455069. Ref.1 Ref.3		VAR_028260
	Natural variant	128	1	S → N: dbSNP rs34919259.		VAR_049906
	Natural variant	202	1	R → W: dbSNP rs4082929.		VAR_028261
	Natural variant	242	1	I → L: dbSNP rs988337.		VAR_028262
	Natural variant	243	1	F → L: dbSNP rs11882250.		VAR_028263
	Natural variant	294	1	V → L: dbSNP rs2271652.		VAR_028264
	Natural variant	304	1	G → R: dbSNP rs35112940.		VAR_049907
	Natural variant	331	1	T → A: dbSNP rs35632246.		VAR_049908
Experimental info
	Mutagenesis	340	1	Y → A: Abolishes binding to PTPN6 and PTPN11. Increases binding of red blood cells. Ref.6
	Mutagenesis	358	1	Y → A or F: Reduces binding to PTPN6. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P20138-1 [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

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: 3139766] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 11943481] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLY-69. Tissue: Leukocyte.
[4]	"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: 7718872] [Abstract] Cited for: SIALIC ACID-BINDING.
[5]	"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: 10556798] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT TYR-340 AND TYR-358, MUTAGENESIS OF TYR-358, INTERACTION WITH PTPN6.
[6]	"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: 10206955] [Abstract] Cited for: PHOSPHORYLATION AT TYR-340 AND TYR-358, INTERACTION WITH PTPN6 AND PTPN11, MUTAGENESIS OF TYR-340.
[7]	"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: 11320212] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

Siglec-3

Cross-references

Sequence databases
EMBLGenBankDDBJ	M23197 mRNA. Translation: AAA51948.1. Sequence problems. AY040541 Genomic DNA. Translation: AAK83654.1. BC028152 mRNA. Translation: AAH28152.1.
IPI	IPI00022203.
PIR	A30521.
RefSeq	NP_001763.3.
UniGene	Hs.83731
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P20138.
PTM databases
PhosphoSite	P20138.
Proteomic databases
PRIDE	P20138.
Genome annotation databases
Ensembl	ENST00000262262; ENSP00000262262; ENSG00000105383; Homo sapiens. [Genome view]
GeneID	945.
UCSC	uc002pwa.2. human.
Organism-specific databases
CTD	945.
GeneCards	GC19P056420.
H-InvDB	HIX0015379.
HGNC	HGNC:1659. CD33.
HPA	CAB011442.
MIM	159590. gene.
PharmGKB	PA26210.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P20138.
HOVERGEN	P20138.
OMA	EMDEELH
OrthoDB	EOG9P5NVG
Gene expression databases
ArrayExpress	P20138.
Bgee	P20138.
CleanEx	HS_CD33.
Genevestigator	P20138.
GermOnline	ENSG00000105383. Homo sapiens.
Family and domain databases
InterPro	IPR013151. Ig. IPR007110. Ig-like. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Gene3D	G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
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 Resources
DrugBank	DB00056. Gemtuzumab ozogamicin.
NextBio	3918.
SOURCE	Search...

Entry information

Entry name

CD33_HUMAN

Accession

Primary (citable) accession number: P20138
Secondary accession number(s): Q8TD24

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 17, 2006
Last modified:	November 24, 2009
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.