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P20138 (CD33_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

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) [Reference 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.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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PTPN11Q061245EBI-3906571,EBI-297779
PTPN6P293508EBI-3906571,EBI-78260

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 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 – 28223Helical; 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.9 Ref.10
Modified residue3581Phosphotyrosine Ref.9 Ref.10
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

Alternative sequence13 – 139127Missing in isoform 3.
VSP_046172
Alternative sequence309 – 36456KHQKK…EVRTQ → VR in isoform 2.
VSP_045364
Natural variant141A → V. Ref.4
Corresponds to variant rs12459419 [ dbSNP | Ensembl ].
VAR_049904
Natural variant221W → R.
Corresponds to variant rs35814802 [ dbSNP | Ensembl ].
VAR_049905
Natural variant691R → G. Ref.1 Ref.7
Corresponds to variant rs2455069 [ dbSNP | Ensembl ].
VAR_028260
Natural variant1281S → N.
Corresponds to variant rs34919259 [ dbSNP | Ensembl ].
VAR_049906
Natural variant2021R → W.
Corresponds to variant rs4082929 [ dbSNP | Ensembl ].
VAR_028261
Natural variant2421I → L.
Corresponds to variant rs988337 [ dbSNP | Ensembl ].
VAR_028262
Natural variant2431F → L.
Corresponds to variant rs11882250 [ dbSNP | Ensembl ].
VAR_028263
Natural variant2671V → I.
Corresponds to variant rs58981829 [ dbSNP | Ensembl ].
VAR_061319
Natural variant2941V → L.
Corresponds to variant rs2271652 [ dbSNP | Ensembl ].
VAR_028264
Natural variant3041G → R. Ref.4
Corresponds to variant rs35112940 [ dbSNP | Ensembl ].
VAR_049907
Natural variant3311T → A.
Corresponds to variant rs35632246 [ dbSNP | Ensembl ].
VAR_049908

Experimental info

Mutagenesis3401Y → A: Abolishes binding to PTPN6 and PTPN11. Increases binding of red blood cells. Ref.10
Mutagenesis3581Y → A or F: Reduces binding to PTPN6. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Isoform 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

Isoform 2 [UniParc].

Checksum: F3618D0661DBE51E
Show »

FASTA31033,890
Isoform 3 (CD33-m) [UniParc].

Checksum: 52C8CF965ACC740C
Show »

FASTA23725,293

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] [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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.

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.
CCDSCCDS33084.1. [P20138-1]
CCDS46157.1. [P20138-3]
CCDS54299.1. [P20138-2]
PIRA30521.
RefSeqNP_001076087.1. NM_001082618.1. [P20138-3]
NP_001171079.1. NM_001177608.1. [P20138-2]
NP_001763.3. NM_001772.3. [P20138-1]
UniGeneHs.83731.

3D structure databases

ProteinModelPortalP20138.
SMRP20138. Positions 20-232.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107383. 5 interactions.
IntActP20138. 3 interactions.
MINTMINT-8020077.
STRING9606.ENSP00000262262.

Chemistry

ChEMBLCHEMBL1842.
DrugBankDB00056. Gemtuzumab ozogamicin.
GuidetoPHARMACOLOGY2601.

PTM databases

PhosphoSiteP20138.

Polymorphism databases

DMDM116241290.

Proteomic databases

PaxDbP20138.
PRIDEP20138.

Protocols and materials databases

DNASU945.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262262; ENSP00000262262; ENSG00000105383. [P20138-1]
ENST00000391796; ENSP00000375673; ENSG00000105383. [P20138-2]
ENST00000421133; ENSP00000410126; ENSG00000105383. [P20138-3]
GeneID945.
KEGGhsa:945.
UCSCuc002pwa.2. human. [P20138-1]
uc010eot.1. human.

Organism-specific databases

CTD945.
GeneCardsGC19P051729.
H-InvDBHIX0015379.
HGNCHGNC:1659. CD33.
HPACAB011442.
HPA035832.
MIM159590. gene.
neXtProtNX_P20138.
PharmGKBPA26210.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG320441.
HOGENOMHOG000236324.
HOVERGENHBG036161.
InParanoidP20138.
KOK06473.
OMADEELHYA.
OrthoDBEOG73JKV5.
PhylomeDBP20138.
TreeFamTF332441.

Gene expression databases

ArrayExpressP20138.
BgeeP20138.
CleanExHS_CD33.
GenevestigatorP20138.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
[Graphical view]
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

ChiTaRSCD33. human.
GenomeRNAi945.
NextBio3918.
PROP20138.
SOURCESearch...

Entry information

Entry nameCD33_HUMAN
AccessionPrimary (citable) accession number: P20138
Secondary accession number(s): B4E3P8 expand/collapse secondary AC list , C9JEN7, F8WAL2, Q8TD24
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

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

Human cell differentiation molecules

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