GPA33 (glycoprotein A33 (transmembrane))

2008-06-01   Tania Tabone , Joan K Heath 

Ludwig Institute for Cancer Research, Melbourne Branch, PO Box 2008, Royal Melbourne Hospital, Parkville, VIC 3050, Australia


Atlas Image


Atlas Image
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.


The human GPA33 gene comprises 7 exons (all coding) spanning 37,787 bp of genomic DNA.


2,793 bp mRNA; 960 bp open reading frame (Heath et al., 1997).


Atlas Image
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).


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).


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).


Membrane; single-pass type 1 membrane protein.


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).


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 name
Colorectal cancer
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).


Pubmed IDLast YearTitleAuthors
160005792005Phase I trial of 131I-huA33 in patients with advanced colorectal carcinoma.Chong G et al
86833001996Enhancement of radiation dose to the nucleus by vesicular internalization of iodine-125-labeled A33 monoclonal antibody.Daghighian F et al
90128071997The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily.Heath JK et al
171958442007Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self.Lee JW et al
92457131997Characterization of posttranslational modifications of human A33 antigen, a novel palmitoylated surface glycoprotein of human gastrointestinal epithelium.Ritter G et al
160005782005A phase I trial of humanized monoclonal antibody A33 in patients with colorectal carcinoma: biodistribution, pharmacokinetics, and quantitative tumor uptake.Scott AM et al
80406681994Phase I/II study of iodine 131-labeled monoclonal antibody A33 in patients with advanced colon cancer.Welt S et al
22308771990Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33.Welt S et al

Other Information

Locus ID:

NCBI: 10223
MIM: 602171
HGNC: 4445
Ensembl: ENSG00000143167


dbSNP: 10223
ClinVar: 10223
TCGA: ENSG00000143167


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
232302782013Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids.125
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
195361752009Follow-up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study.30
182360422008A33 antigen displays persistent surface expression.25
190646102009Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation.16
121145232002Analysis of the regulation of the A33 antigen gene reveals intestine-specific mechanisms of gene expression.14
226237772012The A33-dependent incorporation of B5 into extracellular enveloped vaccinia virions is mediated through an interaction between their lumenal domains.6
226237822012Increased interaction between vaccinia virus proteins A33 and B5 is detrimental to infectious extracellular enveloped virion production.5
232946082013Safety, pharmacokinetics and pharmacodynamics of the anti-A33 fully-human monoclonal antibody, KRN330, in patients with advanced colorectal cancer.5
128539802003Transcriptional regulation of A33 antigen expression by gut-enriched Krüppel-like factor.4


Tania Tabone ; Joan K Heath

GPA33 (glycoprotein A33 (transmembrane))

Atlas Genet Cytogenet Oncol Haematol. 2008-06-01

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