CD109 (CD109 molecule)

2011-08-01 Shinji Mii , Yoshiki Murakumo , Masahide Takahashi Affiliation

Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan

Identity

HGNC

CD109

LOCATION

6q13

LOCUSID

135228

ALIAS

CPAMD7,p180,r150

FUSION GENES

Show Gene Fusions

DNA/RNA

Exon-intron structure of CD109 gene. The vertical bars correspond to exons.

Description

CD109 is a gene of 132.53 kb comprising 33 exons and 32 introns. The 5 part of exon 1 and the 3 part of exon 33 are non-coding.

Transcription

Three splice variants are known. The length of the longest variant is 9464 bp (CDS: 426-4763). mRNA is mainly expressed in skin and testis.

Pseudogene

Not known.

Proteins

Representation of the CD109 protein with localization of recognized domains. CD109 protein is a GPI-anchored protein having signal peptide, Gov antigen, thioester region, and furinase cleavage site.

Description

CD109 is a GPI-anchored cell-surface glycoprotein and is a member of the alpha-2-macroglobulin/C3,C4,C5 family of thioester-containing proteins (Sutherland et al., 1991; Haregewoin et al., 1994; Smith et al., 1995; Lin et al., 2002). The CD109 protein was first identified as a cell-surface antigen detected by a monoclonal antibody raised against the primitive lymphoid/myeloid cell line KG1a (Sutherland et al., 1991). It was also shown that CD109 carries the biallelic platelet-specific alloantigen Gov (Kelton et al., 1990; Smith et al., 1995).

Expression

CD109 is expressed on a subset of fetal and adult CD34⁺ bone marrow mononuclear cells, mesenchymal stem cell subsets, phytohemagglutinin (PHA)-activated T lymphoblasts, thrombin-activated platelets, leukemic megakaryoblasts, endothelial cells, and some human tumor cell lines, but not on fresh peripheral leukocytes and normal bone marrow leukocytes (Kelton et al., 1990; Murray et al., 1999; Giesert et al., 2003).
In normal human tissues other than hematopoietic cells, CD109 is expressed in limited cells including the myoepithelial cells of the mammary, lacrimal, salivary and bronchial glands and the basal cells of the prostate and the bronchial epithelia (Hashimoto et al., 2004; Zhang et al., 2005; Sato et al., 2007; Hasegawa et al., 2007; Hasegawa et al., 2008).
Recently, it has been reported that CD109 is highly expressed in several types of human cancer tissues, in particular squamous cell carcinomas (Hashimoto et al., 2004; Zhang et al., 2005; Sato et al., 2007; Hasegawa et al., 2007; Hasegawa et al., 2008; Järvinen et al., 2008; Hagiwara et al., 2008; Ohshima et al., 2010; Hagikura et al., 2010).

Localisation

Plasma membrane.

Function

CD109 negatively regulates TGF-beta signaling in keratinocytes by directly modulating TGF-beta receptor activity in vitro (Finnson et al., 2006).

Homology

Orthologs: mouse CD109, rat CD109, cow CD109, dog CD109, chicken CD109, hagfish CD109, nematode CD109.
Paralogs: alpha-2-macroglobulin, alpha-2-macroglobulin-like-1, C3, C4, C5, PZP, CPAMD8.

Mutations

Note

A Tyr703Ser polymorphism of CD109 is associated with Gov^a and Gov^b alloantigenic determination (Schuh et al., 2002).

Implicated in

Entity name

Various cancer

Note

CD109 is upregulated in squamous cell carcinomas (SCCs) of lung, esophagus, uterus and oral cavity, malignant melanoma of skin, and urothelial carcinoma of urinary bladder (Hashimoto et al., 2004; Zhang et al., 2005; Sato et al., 2007; Hasegawa et al., 2007; Hasegawa et al., 2008; Järvinen et al., 2008; Hagiwara et al., 2008; Ohshima et al., 2010; Hagikura et al., 2010).

Prognosis

The CD109 expression is significantly higher in well-differentiated SCCs of the oral cavity and in low-grade urothelial carcinomas of the urinary bladder than in moderately- or poorly-differentiated SCCs and in high-grade urothelial carcinomas, respectively (Hagiwara et al., 2008; Hagikura et al., 2010).

Entity name

Alloimmune thrombocytopenic syndromes

Note

Refractoriness to platelet transfusion, post-transfusion purpura, and neonatal alloimmune thrombocytopenia (Smith et al., 1995).

Disease

These diseases are included in alloimmune thrombocytopenic syndromes. Gov^a/b platelet alloantigens, which reside in the CD109 protein, are the cause of these 3 diseases.

Bibliography

Pubmed ID	Last Year	Title	Authors
16754747	2006	Identification of CD109 as part of the TGF-beta receptor system in human keratinocytes.	Finnson KW et al
12799300	2003	Antibody W7C5 defines a CD109 epitope expressed on CD34+ and CD34- hematopoietic and mesenchymal stem cell subsets.	Giesert C et al
20946523	2010	Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression.	Hagikura M et al
19016750	2008	Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity.	Hagiwara S et al
8025953	1994	Cellular expression of a GPI-linked T cell activation protein.	Haregewoin A et al
18429827	2008	CD109 expression in basal-like breast carcinoma.	Hasegawa M et al
15116102	2004	Expression of CD109 in human cancer.	Hashimoto M et al
18314910	2008	High-resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx.	Järvinen AK et al
2346781	1990	Gova/b alloantigen system on human platelets.	Kelton JG et al
11861284	2002	Cell surface antigen CD109 is a novel member of the alpha(2) macroglobulin/C3, C4, C5 family of thioester-containing proteins.	Lin M et al
10428505	1999	CD109 is expressed on a subpopulation of CD34+ cells enriched in hematopoietic stem and progenitor cells.	Murray LJ et al
20034764	2010	CD109 expression levels in malignant melanoma.	Ohshima Y et al
17922683	2007	High-level expression of CD109 is frequently detected in lung squamous cell carcinomas.	Sato T et al
11861285	2002	A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens.	Schuh AC et al
7670116	1995	Characterization and localization of the Gova/b alloantigens to the glycosylphosphatidylinositol-anchored protein CDw109 on human platelets.	Smith JW et al
1984805	1991	Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets.	Sutherland DR et al
15826242	2005	CD109 expression in squamous cell carcinoma of the uterine cervix.	Zhang JM et al

Other Information

Locus ID:

NCBI: 135228
MIM: 608859
HGNC: 21685
Ensembl: ENSG00000156535

Variants:

dbSNP: 135228
ClinVar: 135228
TCGA: ENSG00000156535
COSMIC: CD109

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000156535	ENST00000287097	Q6YHK3
ENSG00000156535	ENST00000422508	Q6YHK3
ENSG00000156535	ENST00000437994	Q6YHK3

Expression (GTEx)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Metabolism of proteins	REACTOME	R-HSA-392499
Post-translational protein modification	REACTOME	R-HSA-597592
Post-translational modification: synthesis of GPI-anchored proteins	REACTOME	R-HSA-163125
Hemostasis	REACTOME	R-HSA-109582
Platelet activation, signaling and aggregation	REACTOME	R-HSA-76002
Response to elevated platelet cytosolic Ca2+	REACTOME	R-HSA-76005
Platelet degranulation	REACTOME	R-HSA-114608

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
16959974	2006	The consensus coding sequences of human breast and colorectal cancers.	1360
19898481	2009	Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk.	131
18519826	2008	Molecular genetics of successful smoking cessation: convergent genome-wide association study results.	130
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
21295082	2011	The TGF-β co-receptor, CD109, promotes internalization and degradation of TGF-β receptors.	46
11861284	2002	Cell surface antigen CD109 is a novel member of the alpha(2) macroglobulin/C3, C4, C5 family of thioester-containing proteins.	39
16754747	2006	Identification of CD109 as part of the TGF-beta receptor system in human keratinocytes.	39
21898545	2012	CD109-mediated degradation of TGF-β receptors and inhibition of TGF-β responses involve regulation of SMAD7 and Smurf2 localization and function.	34
20035377	2010	Mesotrypsin promotes malignant growth of breast cancer cells through shedding of CD109.	23
19016750	2008	Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity.	22

Citation

Shinji Mii ; Yoshiki Murakumo ; Masahide Takahashi

CD109 (CD109 molecule)

Atlas Genet Cytogenet Oncol Haematol. 2011-08-01

Online version: http://atlasgeneticsoncology.org/gene/42925/cd109