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Reviewed, UniProtKB/Swiss-Prot P20138 (CD33_HUMAN)

Last modified November 24, 2009. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length364 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 364347Myeloid cell surface antigen CD33
PRO_0000014878

Regions

Topological domain18 – 259242Extracellular Potential
Transmembrane260 – 28223 Potential
Topological domain283 – 36482Cytoplasmic Potential
Domain19 – 135117Ig-like V-type
Domain145 – 22884Ig-like C2-type
Motif338 – 3436ITIM motif 1
Motif356 – 3616ITIM motif 2

Sites

Binding site1191Sialic acid By similarity

Amino acid modifications

Modified residue3401Phosphotyrosine Ref.5 Ref.6
Modified residue3581Phosphotyrosine Ref.5 Ref.6
Glycosylation1001N-linked (GlcNAc...) Potential
Glycosylation1131N-linked (GlcNAc...) Potential
Glycosylation1601N-linked (GlcNAc...) Potential
Glycosylation2091N-linked (GlcNAc...) Potential
Glycosylation2301N-linked (GlcNAc...) Potential
Disulfide bond36 ↔ 169 By similarity
Disulfide bond41 ↔ 101 By similarity
Disulfide bond163 ↔ 212 Potential

Natural variations

Natural variant141A → V: dbSNP rs12459419.
VAR_049904
Natural variant221W → R: dbSNP rs35814802.
VAR_049905
Natural variant691R → G: dbSNP rs2455069. Ref.1 Ref.3
VAR_028260
Natural variant1281S → N: dbSNP rs34919259.
VAR_049906
Natural variant2021R → W: dbSNP rs4082929.
VAR_028261
Natural variant2421I → L: dbSNP rs988337.
VAR_028262
Natural variant2431F → L: dbSNP rs11882250.
VAR_028263
Natural variant2941V → L: dbSNP rs2271652.
VAR_028264
Natural variant3041G → R: dbSNP rs35112940.
VAR_049907
Natural variant3311T → A: dbSNP rs35632246.
VAR_049908

Experimental info

Mutagenesis3401Y → A: Abolishes binding to PTPN6 and PTPN11. Increases binding of red blood cells. Ref.6
Mutagenesis3581Y → A or F: Reduces binding to PTPN6. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P20138-1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 1C73E588240FBAD8

FASTA36439,825
        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 

« Hide

References

« Hide '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.

Cross-references

Sequence databases

M23197 mRNA. Translation: AAA51948.1. Sequence problems.
AY040541 Genomic DNA. Translation: AAK83654.1.
BC028152 mRNA. Translation: AAH28152.1.
IPIIPI00022203.
PIRA30521.
RefSeqNP_001763.3.
UniGeneHs.83731

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

STRINGP20138.

PTM databases

PhosphoSiteP20138.

Proteomic databases

PRIDEP20138.

Genome annotation databases

EnsemblENST00000262262; ENSP00000262262; ENSG00000105383; Homo sapiens. [Genome view]
GeneID945.
UCSCuc002pwa.2. human.

Organism-specific databases

CTD945.
GeneCardsGC19P056420.
H-InvDBHIX0015379.
HGNCHGNC:1659. CD33.
HPACAB011442.
MIM159590. gene.
PharmGKBPA26210.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP20138.
HOVERGENP20138.
OMAEMDEELH
OrthoDBEOG9P5NVG

Gene expression databases

ArrayExpressP20138.
BgeeP20138.
CleanExHS_CD33.
GenevestigatorP20138.
GermOnlineENSG00000105383. Homo sapiens.

Family and domain databases

InterProIPR013151. Ig.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 1 hit.
PfamPF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 2 hits.
[Graphical view]
PROSITEPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00056. Gemtuzumab ozogamicin.
NextBio3918.
SOURCESearch...

Entry information

Entry nameCD33_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny 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.

Relevant documents

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents