Atlas of Genetics and Cytogenetics in Oncology and Haematology

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GPA33 (glycoprotein A33 (transmembrane))

Written2008-06Tania Tabone, Joan K Heath
Ludwig Institute for Cancer Research, Melbourne Branch, PO Box 2008, Royal Melbourne Hospital, Parkville, VIC 3050, Australia

(Note : for Links provided by Atlas : click)


Alias (NCBI)A33
HGNC (Hugo) GPA33
HGNC Alias symbA33
HGNC Previous nameglycoprotein A33 (transmembrane)
LocusID (NCBI) 10223
Atlas_Id 40735
Location 1q24.1  [Link to chromosome band 1q24]
Location_base_pair Starts at 167052836 and ends at 167090377 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping GPA33.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DIAPH3 (13q21.2) / GPA33 (1q24.1)GPA33 (1q24.1) / SOD1 (21q22.11)
Note Location of GPA33 on human chromosome 1q24 showing flanking genes to demonstrate synteny to other vertebrates, such as mouse (chromosome 1) and zebrafish (chromosomes 1 and 9). Note that an evolutionary duplication event of the entire zebrafish genome has resulted in the two copies of gpa33 in zebrafish.


  Genomic organization of the GPA33 gene. Coding exonic sequences appear in red, non-coding exonic sequences are in blue and intronic sequence are in yellow, with the corresponding exon and intron sizes given below in base pairs (bp). The exon numbers are indicated above each exon. Note the GPA33 gene is in on the reverse strand.
Description The human GPA33 gene comprises 7 exons (all coding) spanning 37,787 bp of genomic DNA.
Transcription 2,793 bp mRNA; 960 bp open reading frame (Heath et al., 1997).


  Schematic representation of the GPA33 protein, indicating the position of the Ig-like V-type and Ig-like C2-type domain in the extracellular region and the polycysteine residue ('CCCC' motif).
Description 319 amino acids; 43 kDa protein. The A33 glycoprotein is a member of the immunoglobulin superfamily and contains three distinct structural domains: a 213 amino acid extracellular region containing two immunoglobulin-like domains (a C2-type domain and a v-type domain), a 23 amino acid hydrophobic transmembrane domain, and a 62 amino acid highly polar intracellular tail containing four consecutive cysteine residues (Heath et al., 1997). Post translational modification includes N-glycosylation (containing approximately 8 kDa of N-linked carbohydrate), and S-palmitoylation. The S-palmitoylation may be involved in regulating the internalization process initiated by binding of the monoclonal antibody A33 to the A33 antigen. There is no evidence of O-glycosylation, sialylation or glycophosphatidylinositol (Ritter et al., 1997).
Expression GPA33 demonstrates a rare tissue-specific expression pattern. GPA33 is a cell surface differentiation antigen that is constitutively expressed on the basolateral surfaces of normal human and mouse colon and small bowel epithelium. GPA33 is homogeneously expressed in over 95% of both human primary and metastatic colon cancers, and in 55% of gastric carcinomas, although absent in normal stomach epithelium (Welt et al., 1990).
Localisation Membrane; single-pass type 1 membrane protein.
Function Unknown; the protein structure is consistent with a putative role of GPA33 in cell-cell recognition and signaling (Heath et al., 1997). A33 may play a role in relaying information between intestinal epithelial cells and the gut immune system (Lee et al., 2007).
Homology The two Ig-like domains are well conserved between humans, chimpanzee, dog, mouse and rat, whereas chicken and zebrafish retain only the Ig-like V-like domain. The overall GPA33 protein similarity between humans and various species are: chimpanzee (Pan troglodytes) 97%, domestic dog (Canis lupus familiaris) 75%, mouse (Mus musculus) 66%, rat (Rattus norvegicus) 68%, domestic chicken (Gallus gallus) 44%, and zebrafish (Danio rerio) 35%.

Implicated in

Entity Colorectal cancer
Note Colorectal cancer marker.
Although the biochemical, immunological and molecular biology of the A33 antigen has been extensively characterized, the function of the molecule remains unknown. The antigen has several identified properties that contribute to a potential therapeutic target for colon cancer. The A33 antigen is expressed homogenously and at high levels in colorectal carcinomas, there are a high number of A33 binding sites per cell and it is not shed or secreted into the blood stream (Welt et al., 1990). In addition, upon mAB binding to the A33 antigen, the antibody-antigen complex is internalized and sequestered in vesicles (Daghighian et al., 1996).
Selective immunological targeting of tumors with monoclonal antibodies (mAb) is an important therapeutic approach in cancer therapy. Clinical imaging and biopsy-based biodistribution studies using radiolabeled murine mAb A33 demonstrated specific targeting to antigen-positive tumor tissues in 95% of colorectal patients with tumor retention for up to six weeks (Welt et al., 1990; Welt et al., 1994). The only normal tissue reported to accumulate the radioisotope was the bowel, with clearance from the normal gastrointestinal tract within one week. Phase I and II therapy trials using 125I- and 131I-labeled murine A33 mAb were shown to have antitumor effects without bowel toxicity, however human anti-mouse antibody development in all patients prevented repeated dosing and led to the development of humanized mAb A33 (huA33). Phase I clinical trials using multiple dose schedules of 125I- and 131I-labled huA33 mAb in patients with colorectal carcinoma have been conducted and have shown safety and possible efficacy, with future trials proposed (Chong et al., 2005; Scott et al., 2005).


Phase I trial of 131I-huA33 in patients with advanced colorectal carcinoma.
Chong G, Lee FT, Hopkins W, Tebbutt N, Cebon JS, Mountain AJ, Chappell B, Papenfuss A, Schleyer P, U P, Murphy R, Wirth V, Smyth FE, Potasz N, Poon A, Davis ID, Saunder T, O'keefe GJ, Burgess AW, Hoffman EW, Old LJ, Scott AM.
Clin Cancer Res. 2005; 11(13): 4818-4826.
PMID 16000579
Enhancement of radiation dose to the nucleus by vesicular internalization of iodine-125-labeled A33 monoclonal antibody.
Daghighian F, Barendswaard E, Welt S, Humm J, Scott A, Willingham MC, McGuffie E, Old LJ, Larson SM.
J Nucl Med. 1996; 37(6): 1052-1057.
PMID 8683300
The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily.
Heath JK, White SJ, Johnstone CN, Catimel B, Simpson RJ, Moritz RL, Tu GF, Ji H, Whitehead RH, Groenen LC, Scott AM, Ritter G, Cohen L, Welt S, Old LJ, Nice EC, Burgess AW.
Proc Natl Acad Sci USA 1997; 94(2): 469-474.
PMID 9012807
Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self.
Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura AR, Heath JK, Turley SJ.
Nat Immunol. 2007; 8(2): 181-190.
PMID 17195844
Characterization of posttranslational modifications of human A33 antigen, a novel palmitoylated surface glycoprotein of human gastrointestinal epithelium.
Ritter G, Cohen LS, Nice EC, Catimel B, Burgess AW, Moritz RL, Ji H, Heath JK, White SJ, Welt S, Old LJ, Simpson RJ.
Biochem Biophys Res Commun. 1997; 236(3): 682-686.
PMID 9245713
A phase I trial of humanized monoclonal antibody A33 in patients with colorectal carcinoma: biodistribution, pharmacokinetics, and quantitative tumor uptake.
Scott AM, Lee FT, Jones R, Hopkins W, MacGregor D, Cebon JS, Hannah A, Chong G, U P, Papenfuss A, Rigopoulos A, Sturrock S, Murphy R, Wirth V, Murone C, Smyth FE, Knight S, Welt S, Ritter G, Richards E, Nice EC, Burgess AW, Old LJ.
Clin Cancer Res. 2005; 11(13): 4810-4817.
PMID 16000578
Phase I/II study of iodine 131-labeled monoclonal antibody A33 in patients with advanced colon cancer.
Welt S, Divgi CR, Kemeny N, Finn RD, Scott AM, Graham M, Germain JS, Richards EC, Larson SM, Oettgen HF, Old LJ.
J Clin Oncol 1994; 12(8): 1561-1571.
PMID 8040668
Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33.
Welt S, Divigi CR, Real FX, Yeh SD, Garin-Chesa P, Finstad CL, Sakamoto J, Choen A, Sigurdson ER, Kemeny N, Carswell EA, Oettgen HF, Old LJ.
J Clin Oncol 1990; 8(11): 1894-1906.
PMID 2230877


This paper should be referenced as such :
Tabone, T ; Heath, JK
GPA33 (glycoprotein A33 (transmembrane))
Atlas Genet Cytogenet Oncol Haematol. 2009;13(5):354-356.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)GPA33   4445
Entrez_Gene (NCBI)GPA33    glycoprotein A33
GeneCards (Weizmann)GPA33
Ensembl hg19 (Hinxton)ENSG00000143167 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000143167 [Gene_View]  ENSG00000143167 [Sequence]  chr1:167052836-167090377 [Contig_View]  GPA33 [Vega]
ICGC DataPortalENSG00000143167
TCGA cBioPortalGPA33
AceView (NCBI)GPA33
Genatlas (Paris)GPA33
SOURCE (Princeton)GPA33
Genetics Home Reference (NIH)GPA33
Genomic and cartography
GoldenPath hg38 (UCSC)GPA33  -     chr1:167052836-167090377 -  1q24.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GPA33  -     1q24.1   [Description]    (hg19-Feb_2009)
GoldenPathGPA33 - 1q24.1 [CytoView hg19]  GPA33 - 1q24.1 [CytoView hg38]
genome Data Viewer NCBIGPA33 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AK312833 BC069705 BC069723 BC069745 BC069761
RefSeq transcript (Entrez)NM_005814
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)GPA33
Alternative Splicing GalleryENSG00000143167
Gene ExpressionGPA33 [ NCBI-GEO ]   GPA33 [ EBI - ARRAY_EXPRESS ]   GPA33 [ SEEK ]   GPA33 [ MEM ]
Gene Expression Viewer (FireBrowse)GPA33 [ Firebrowse - Broad ]
GenevisibleExpression of GPA33 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10223
GTEX Portal (Tissue expression)GPA33
Human Protein AtlasENSG00000143167-GPA33 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99795   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ99795  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ99795
Splice isoforms : SwissVarQ99795
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)   
Domains : Interpro (EBI)A33    Ig-like_dom    Ig-like_dom_sf    Ig-like_fold    Ig_sub    Ig_sub2    Ig_V-set   
Domain families : Pfam (Sanger)V-set (PF07686)   
Domain families : Pfam (NCBI)pfam07686   
Domain families : Smart (EMBL)IG (SM00409)  IGc2 (SM00408)  IGv (SM00406)  
Conserved Domain (NCBI)GPA33
Blocks (Seattle)GPA33
Human Protein Atlas [tissue]ENSG00000143167-GPA33 [tissue]
Peptide AtlasQ99795
IPIIPI00293853   IPI00984027   
Protein Interaction databases
IntAct (EBI)Q99795
Ontologies - Pathways
Ontology : AmiGOprotein binding  plasma membrane  integral component of plasma membrane  signaling receptor activity  extracellular exosome  
Ontology : EGO-EBIprotein binding  plasma membrane  integral component of plasma membrane  signaling receptor activity  extracellular exosome  
NDEx NetworkGPA33
Atlas of Cancer Signalling NetworkGPA33
Wikipedia pathwaysGPA33
Orthology - Evolution
GeneTree (enSembl)ENSG00000143167
Phylogenetic Trees/Animal Genes : TreeFamGPA33
Homologs : HomoloGeneGPA33
Homology/Alignments : Family Browser (UCSC)GPA33
Gene fusions - Rearrangements
Fusion : Fusion_HubDIAPH3--GPA33    GPA33--SOD1    HSA-MIR-6723--GPA33   
Fusion : QuiverGPA33
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGPA33 [hg38]
Exome Variant ServerGPA33
GNOMAD BrowserENSG00000143167
Varsome BrowserGPA33
Genomic Variants (DGV)GPA33 [DGVbeta]
DECIPHERGPA33 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGPA33 
ICGC Data PortalGPA33 
TCGA Data PortalGPA33 
Broad Tumor PortalGPA33
OASIS PortalGPA33 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGPA33  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DGPA33
Mutations and Diseases : HGMDGPA33
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GPA33
DgiDB (Drug Gene Interaction Database)GPA33
DoCM (Curated mutations)GPA33 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GPA33 (select a term)
NCG6 (London) select GPA33
Cancer3DGPA33(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry GPA33
NextProtQ99795 [Medical]
Target ValidationGPA33
Huge Navigator GPA33 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA28826
Clinical trialGPA33
canSAR (ICR)GPA33 (select the gene name)
DataMed IndexGPA33
PubMed29 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Feb 19 17:51:41 CET 2021

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