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Protein

Myeloid cell surface antigen CD33

Gene

CD33

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • signaling receptor activity Source: ProtInc

GO - Biological processi

  • cell adhesion Source: ProtInc
  • cell-cell signaling Source: ProtInc
  • negative regulation of cell proliferation Source: ProtInc
  • neutrophil degranulation Source: Reactome
  • regulation of immune response Source: Reactome
  • signal transduction Source: ProtInc

Keywordsi

Biological processCell adhesion
LigandLectin

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000105383.14
HGNCiHGNC:1659 CD33
MIMi159590 gene
neXtProtiNX_P20138

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Glycosylationi113N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi160N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi163 ↔ 212PROSITE-ProRule annotation
Glycosylationi209N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi230N-linked (GlcNAc...) asparagineSequence 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

Show more details

Protein-protein interaction databases

BioGridi107383, 12 interactors
IntActiP20138, 13 interactors
MINTiP20138
STRINGi9606.ENSP00000262262

Structurei

Secondary structure

1364
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 25Combined sources4
Beta strandi27 – 32Combined sources6
Beta strandi37 – 39Combined sources3
Beta strandi41 – 44Combined sources4
Helixi49 – 51Combined sources3
Beta strandi56 – 62Combined sources7
Helixi65 – 68Combined sources4
Beta strandi73 – 76Combined sources4
Turni84 – 89Combined sources6
Beta strandi90 – 92Combined sources3
Helixi96 – 98Combined sources3
Beta strandi103 – 105Combined sources3
Helixi110 – 112Combined sources3
Beta strandi114 – 122Combined sources9
Beta strandi125 – 128Combined sources4
Beta strandi134 – 139Combined sources6
Beta strandi146 – 148Combined sources3
Beta strandi159 – 164Combined sources6
Beta strandi176 – 191Combined sources16
Beta strandi194 – 199Combined sources6
Helixi203 – 205Combined sources3
Beta strandi209 – 215Combined sources7
Beta strandi217 – 220Combined sources4
Beta strandi222 – 228Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IHBX-ray2.24A/B/C/D21-232[»]
5J06X-ray2.66A/B/C/D21-232[»]
5J0BX-ray2.48A/B/C/D21-232[»]
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
OMAiASLNFHG
OrthoDBiEOG091G0M13
PhylomeDBiP20138
TreeFamiTF332441

Family and domain databases

Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR013106 Ig_V-set
IPR013151 Immunoglobulin
PfamiView protein in Pfam
PF00047 ig, 1 hit
PF07686 V-set, 1 hit
SMARTiView protein in SMART
SM00409 IG, 2 hits
SUPFAMiSSF48726 SSF48726, 2 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 2 hits

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 → V1 PublicationCorresponds to variant dbSNP:rs12459419Ensembl.1
Natural variantiVAR_04990522W → R. Corresponds to variant dbSNP:rs35814802Ensembl.1
Natural variantiVAR_02826069R → G2 PublicationsCorresponds to variant dbSNP:rs2455069Ensembl.1
Natural variantiVAR_049906128S → N. Corresponds to variant dbSNP:rs34919259Ensembl.1
Natural variantiVAR_028261202R → W. Corresponds to variant dbSNP:rs4082929Ensembl.1
Natural variantiVAR_028262242I → L. Corresponds to variant dbSNP:rs988337Ensembl.1
Natural variantiVAR_028263243F → L. Corresponds to variant dbSNP:rs11882250Ensembl.1
Natural variantiVAR_061319267V → I. Corresponds to variant dbSNP:rs58981829Ensembl.1
Natural variantiVAR_028264294V → L. Corresponds to variant dbSNP:rs2271652Ensembl.1
Natural variantiVAR_049907304G → R1 PublicationCorresponds to variant dbSNP:rs35112940Ensembl.1
Natural variantiVAR_049908331T → A. Corresponds to variant dbSNP:rs35632246Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiCD33_HUMAN
AccessioniPrimary (citable) accession number: P20138
Secondary accession number(s): B4E3P8
, C9JEN7, F8WAL2, Q8TD24
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: October 17, 2006
Last modified: May 23, 2018
This is version 184 of the entry and version 2 of the sequence. See 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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