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Protein

Myeloid cell surface antigen CD33

Gene

CD33

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei119Sialic acidBy similarity1

GO - Molecular functioni

  • carbohydrate binding Source: UniProtKB-KW
  • receptor activity Source: ProtInc

GO - Biological processi

  • cell adhesion Source: ProtInc
  • cell-cell signaling Source: ProtInc
  • negative regulation of cell proliferation Source: ProtInc
  • regulation of immune response Source: Reactome
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Lectin

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105383-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-6798695. Neutrophil degranulation.
SIGNORiP20138.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CD33
Synonyms:SIGLEC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:1659. CD33.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini18 – 259ExtracellularSequence analysisAdd BLAST242
Transmembranei260 – 282HelicalSequence analysisAdd BLAST23
Topological domaini283 – 364CytoplasmicSequence analysisAdd BLAST82

GO - Cellular componenti

  • external side of plasma membrane Source: MGI
  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi340Y → A: Abolishes binding to PTPN6 and PTPN11. Increases binding of red blood cells. 1 Publication1
Mutagenesisi358Y → A or F: Reduces binding to PTPN6. 1 Publication1

Organism-specific databases

DisGeNETi945.
OpenTargetsiENSG00000105383.
PharmGKBiPA26210.

Chemistry databases

ChEMBLiCHEMBL1842.
DrugBankiDB00056. Gemtuzumab ozogamicin.
GuidetoPHARMACOLOGYi2601.

Polymorphism and mutation databases

BioMutaiCD33.
DMDMi116241290.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000001487818 – 364Myeloid cell surface antigen CD33Add BLAST347

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi36 ↔ 169PROSITE-ProRule annotation
Disulfide bondi41 ↔ 101PROSITE-ProRule annotation
Glycosylationi100N-linked (GlcNAc...)Sequence analysis1
Glycosylationi113N-linked (GlcNAc...)Sequence analysis1
Glycosylationi160N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi163 ↔ 212PROSITE-ProRule annotation
Glycosylationi209N-linked (GlcNAc...)Sequence analysis1
Glycosylationi230N-linked (GlcNAc...)Sequence analysis1
Modified residuei340Phosphotyrosine2 Publications1
Modified residuei358Phosphotyrosine2 Publications1

Post-translational modificationi

Phosphorylation of Tyr-340 is involved in binding to PTPN6 and PTPN11. Phosphorylation of Tyr-358 is involved in binding to PTPN6.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP20138.
PaxDbiP20138.
PeptideAtlasiP20138.
PRIDEiP20138.

PTM databases

iPTMnetiP20138.
PhosphoSitePlusiP20138.

Expressioni

Tissue specificityi

Monocytic/myeloid lineage cells.

Gene expression databases

BgeeiENSG00000105383.
CleanExiHS_CD33.
ExpressionAtlasiP20138. baseline and differential.
GenevisibleiP20138. HS.

Organism-specific databases

HPAiCAB011442.
HPA035832.
HPA064807.

Interactioni

Subunit structurei

Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KRT31Q153235EBI-3906571,EBI-948001
KRT40Q6A1623EBI-3906571,EBI-10171697
PTPN11Q061245EBI-3906571,EBI-297779
PTPN6P293508EBI-3906571,EBI-78260

Protein-protein interaction databases

BioGridi107383. 11 interactors.
IntActiP20138. 6 interactors.
MINTiMINT-8020077.
STRINGi9606.ENSP00000262262.

Structurei

3D structure databases

ProteinModelPortaliP20138.
SMRiP20138.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 135Ig-like V-typeAdd BLAST117
Domaini145 – 228Ig-like C2-typeAdd BLAST84

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi338 – 343ITIM motif 16
Motifi356 – 361ITIM motif 26

Domaini

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IJT6. Eukaryota.
ENOG410YKZU. LUCA.
GeneTreeiENSGT00760000119139.
HOGENOMiHOG000169138.
HOVERGENiHBG036161.
InParanoidiP20138.
KOiK06473.
OMAiDEELHYA.
OrthoDBiEOG091G0M13.
PhylomeDBiP20138.
TreeFamiTF332441.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamiPF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P20138-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPLLLLLPLL WAGALAMDPN FWLQVQESVT VQEGLCVLVP CTFFHPIPYY
60 70 80 90 100
DKNSPVHGYW FREGAIISRD SPVATNKLDQ EVQEETQGRF RLLGDPSRNN
110 120 130 140 150
CSLSIVDARR RDNGSYFFRM ERGSTKYSYK SPQLSVHVTD LTHRPKILIP
160 170 180 190 200
GTLEPGHSKN LTCSVSWACE QGTPPIFSWL SAAPTSLGPR TTHSSVLIIT
210 220 230 240 250
PRPQDHGTNL TCQVKFAGAG VTTERTIQLN VTYVPQNPTT GIFPGDGSGK
260 270 280 290 300
QETRAGVVHG AIGGAGVTAL LALCLCLIFF IVKTHRRKAA RTAVGRNDTH
310 320 330 340 350
PTTGSASPKH QKKSKLHGPT ETSSCSGAAP TVEMDEELHY ASLNFHGMNP
360
SKDTSTEYSE VRTQ
Length:364
Mass (Da):39,825
Last modified:October 17, 2006 - v2
Checksum:i1C73E588240FBAD8
GO
Isoform 2 (identifier: P20138-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:310
Mass (Da):33,890
Checksum:iF3618D0661DBE51E
GO
Isoform 3 (identifier: P20138-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:237
Mass (Da):25,293
Checksum:i52C8CF965ACC740C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04990414A → V.1 PublicationCorresponds to variant rs12459419dbSNPEnsembl.1
Natural variantiVAR_04990522W → R.Corresponds to variant rs35814802dbSNPEnsembl.1
Natural variantiVAR_02826069R → G.2 PublicationsCorresponds to variant rs2455069dbSNPEnsembl.1
Natural variantiVAR_049906128S → N.Corresponds to variant rs34919259dbSNPEnsembl.1
Natural variantiVAR_028261202R → W.Corresponds to variant rs4082929dbSNPEnsembl.1
Natural variantiVAR_028262242I → L.Corresponds to variant rs988337dbSNPEnsembl.1
Natural variantiVAR_028263243F → L.Corresponds to variant rs11882250dbSNPEnsembl.1
Natural variantiVAR_061319267V → I.Corresponds to variant rs58981829dbSNPEnsembl.1
Natural variantiVAR_028264294V → L.Corresponds to variant rs2271652dbSNPEnsembl.1
Natural variantiVAR_049907304G → R.1 PublicationCorresponds to variant rs35112940dbSNPEnsembl.1
Natural variantiVAR_049908331T → A.Corresponds to variant rs35632246dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04617213 – 139Missing in isoform 3. 1 PublicationAdd BLAST127
Alternative sequenceiVSP_045364309 – 364KHQKK…EVRTQ → VR in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS33084.1. [P20138-1]
CCDS46157.1. [P20138-3]
CCDS54299.1. [P20138-2]
PIRiA30521.
RefSeqiNP_001076087.1. NM_001082618.1. [P20138-3]
NP_001171079.1. NM_001177608.1. [P20138-2]
NP_001763.3. NM_001772.3. [P20138-1]
XP_011525834.1. XM_011527532.2. [P20138-1]
UniGeneiHs.83731.

Genome annotation databases

EnsembliENST00000262262; ENSP00000262262; ENSG00000105383. [P20138-1]
ENST00000391796; ENSP00000375673; ENSG00000105383. [P20138-2]
ENST00000421133; ENSP00000410126; ENSG00000105383. [P20138-3]
GeneIDi945.
KEGGihsa:945.
UCSCiuc010eos.2. human. [P20138-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Functional Glycomics Gateway - Glycan Binding

Siglec-3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS33084.1. [P20138-1]
CCDS46157.1. [P20138-3]
CCDS54299.1. [P20138-2]
PIRiA30521.
RefSeqiNP_001076087.1. NM_001082618.1. [P20138-3]
NP_001171079.1. NM_001177608.1. [P20138-2]
NP_001763.3. NM_001772.3. [P20138-1]
XP_011525834.1. XM_011527532.2. [P20138-1]
UniGeneiHs.83731.

3D structure databases

ProteinModelPortaliP20138.
SMRiP20138.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107383. 11 interactors.
IntActiP20138. 6 interactors.
MINTiMINT-8020077.
STRINGi9606.ENSP00000262262.

Chemistry databases

ChEMBLiCHEMBL1842.
DrugBankiDB00056. Gemtuzumab ozogamicin.
GuidetoPHARMACOLOGYi2601.

PTM databases

iPTMnetiP20138.
PhosphoSitePlusiP20138.

Polymorphism and mutation databases

BioMutaiCD33.
DMDMi116241290.

Proteomic databases

EPDiP20138.
PaxDbiP20138.
PeptideAtlasiP20138.
PRIDEiP20138.

Protocols and materials databases

DNASUi945.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262262; ENSP00000262262; ENSG00000105383. [P20138-1]
ENST00000391796; ENSP00000375673; ENSG00000105383. [P20138-2]
ENST00000421133; ENSP00000410126; ENSG00000105383. [P20138-3]
GeneIDi945.
KEGGihsa:945.
UCSCiuc010eos.2. human. [P20138-1]

Organism-specific databases

CTDi945.
DisGeNETi945.
GeneCardsiCD33.
H-InvDBHIX0015379.
HGNCiHGNC:1659. CD33.
HPAiCAB011442.
HPA035832.
HPA064807.
MIMi159590. gene.
neXtProtiNX_P20138.
OpenTargetsiENSG00000105383.
PharmGKBiPA26210.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJT6. Eukaryota.
ENOG410YKZU. LUCA.
GeneTreeiENSGT00760000119139.
HOGENOMiHOG000169138.
HOVERGENiHBG036161.
InParanoidiP20138.
KOiK06473.
OMAiDEELHYA.
OrthoDBiEOG091G0M13.
PhylomeDBiP20138.
TreeFamiTF332441.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105383-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-6798695. Neutrophil degranulation.
SIGNORiP20138.

Miscellaneous databases

ChiTaRSiCD33. human.
GenomeRNAii945.
PROiP20138.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105383.
CleanExiHS_CD33.
ExpressionAtlasiP20138. baseline and differential.
GenevisibleiP20138. HS.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
PfamiPF00047. ig. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 2 hits.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 2 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCD33_HUMAN
AccessioniPrimary (citable) accession number: P20138
Secondary accession number(s): B4E3P8
, C9JEN7, F8WAL2, Q8TD24
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 175 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.