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OPCML (opioid binding protein/cell adhesion molecule-like)

Written2009-01Artur Czekierdowski, Sylwia Czekierdowska
Ist Dept.of Gynecologic Oncology, Gynecology, Medical University in Lublin, Poland

(Note : for Links provided by Atlas : click)


HGNC Alias symbOPCM
HGNC Alias nameIgLON family member 1
LocusID (NCBI) 4978
Atlas_Id 44423
Location 11q25  [Link to chromosome band 11q25]
Location_base_pair Starts at 132414665 and ends at 132943637 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping OPCML.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)
GABPA (21q21.3) / OPCML (11q25)OPCML (11q25) / MIR5095 (1p32.3)OPCML (11q25) / NRDC (1p32.3)
OPCML (11q25) / SMARCD2 (17q23.3)SHANK2 (11q13.3) / OPCML (11q25)
Note OPCML belongs to the IgLON family of immunoglobulin domain containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, which includes OPCML, LSAMP, NEGR1 and HNT. The protein is localized in the plasma membrane and may have an accessory role in opioid receptor function.


Note OPCML comprises 7 exons, spans approximately 600 kb and is transcribed from telomere to centromere. Sequence analysis of the OPCML promoter revealed a GC-rich region spanning 900 bp approximate 500 bp upstream of the translational start site.


Description OPCML consisted of one half beta-sheets and one fourth alpha-helices. Hydropathy analysis suggested that hydrophobic and hydrophilic regions were evenly distributed along the sequence, but the NH2- and COOH-termini were hydrophobic. Hydrophobic moments and Fourier-transform amphipathic analyses further suggest that residues 23-30 and 83-93 were amphipathic beta-sheets. Structural elements include three, with the first and third being full C2 domains and the middle domain being a truncated C2 domain, and a GPI anchor. Protein is extensively glycosylated with six potential N-linked sites.
Expression OPCML is highly expressed in the nervous system and involved in cell adhesion and cell-cell recognition. During the first postnatal week, protein is prominent within cerebral cortex, developing hippocampus, pyriform cortex, and the mitral cell layer of the olfactory bulb. At later ages, OPCML is expressed prominently within all regions of Ammon's horn and in the mitral cell layer of the olfactory bulb and the pyriform cortex. OPCML is localized preferentially to dendrites compared with somata and terminals of hypothalamic vasopressin-secreting magnocellular neurons. This localization indicates that protein is one of the dendrite-associated cell adhesion molecules. It is synthesized within the somata, attached to vasopressin neurosecretory granules via the glycosylphosphatidylinositol anchor, and transported to the dendrites. Moreover, the subcellular localization of OPCML is changed in an activity-dependent manner.
Recently published data suggested that OPCML-v1 was widely expressed in all normal adult and fetal tissues except for placenta and peripheral blood mononuclear cells, though at varying levels (highly expressed in brain, kidney, spleen, stomach, trachea, testis, cervix, ovary and prostate, and weakly in lung, breast, and bone marrow). Compared to v1, OPCML-v2 displayed a more tissue-specific expression pattern in adult tissues, with expression absent or barely detectable in kidney, spleen, pancreas, breast, testis, lung, colon, liver, testis and bone marrow. In contrast to its expression in adult tissues, OPCML-v2 was expressed at moderate to high levels in all fetal tissues except for placenta.
Function OPCML was originally isolated as a potential micro-type opiate receptor. Subsequent studies have shown that the physiologic opiate receptors belong to the G-protein-coupled receptor family, however, they do not promote direct binding of opioids when transfected into heterologous cells. IgLONs have been suggested to play an important role in cell adhesion and cell-cell recognition, through both homo- and heterophilic interactions within the family. Recently, it has been proposed that IgLONs function mainly as heterodimers called Diglons. OPCML may contribute to the diversity at the surface of different populations of neurons during development. Some latest evidences also suggest that OPCML is a synaptic cell adhesion molecule concerning synaptogenesis and its surface localization is dynamically regulated in response to neuronal activity. Recently, it has been shown that IgLONs are expressed outside the nervous system, and OPCML might act as a tumor suppressor. As a cell adhesion molecule, OPCML comprises several protein-protein interaction domains, commonly found in cell surface- adhesion and receptor molecules. Through these domains, OPCML may bind directly to growth promoting or inhibitory molecules and modulate their functions in tumor cells.
New findings suggested that OPCML is an excellent candidate for tumor suppressor gene (TSG). OPCML is frequently somatically inactivated in cancer by allele loss and by CpG island methylation. OPCML has functional characteristics consistent with TSG properties both in vitro and in vivo. It has been found existence somatic missense mutation in individual with epithelial ovarian cancer and it shows clear evidence of loss of function. Another data showed that OPCML gene promoter methylation may play an important role in the carcinogenesis of cervical and lung carcinoma. OPCML probably functions as a tumor suppressor through interacting with other IgLONs to form heterodimeric complex involved in signal transduction. Among the IgLON family, OPCML was the first member reported to possess tumor suppressor functions in epithelial ovarian cancer, being frequently silenced genetically and epigenetically at the early step of ovarian carcinogenesis. This inactivation is due to its promoter methylation, which further impairs its response to environmental stresses. Loss of OPCML reduces the intercellular adhesion and heterodimeric complex formation and thus impairs the corresponding signaling pathways, thereby promoting the progress of carcinogenesis. Latest evidences of Cui et al (2008) suggested that OPCML is frequently inactivated epigenetically in multiple tumor cell line including nasopharyngeal, esophageal, lung, gastric, hepatocellular, colorectal, breast, cervical and prostate carcinomas. Authors showed that OPCML is a stress-responsive and p53-regulated gene, with the response abrogated when the promoter becomes methylated. Ectopic expression of OPCML in tumor cell lines with endogenous silencing led to strong inhibition of cell colony formation, dramatic anchorage-dependent and - independent growth inhibition demonstrating that OPCML acts as a broad tumor suppressor. The role of OPCML in DNA damage repair, apoptosis and cell cycle arrest with respect to stress response remains to be further investigated.
Homology Two alternative splice transcripts of OPCML, variant 1 (v1) and variant 2 (v2), were previously identified in human, which differ only in their 59 exons but encode an identical mature protein. Among the four IgLON family members, OPCML shares the highest homology to HNT that lies approximately 80 kb centromeric to OPCML in the opposite orientation. Notably, the coding region in exon 1 of OPCML-v1 and HNT is identical, and so is the exon 2 except for only several bases. The first Ig domains of these two proteins share 92% identity, while the second and third Ig domains share 70% and 66% identity, respectively. This raises the possibility that OPCML and HNT may originate from the same antecestor by gene conversion during evolution.

Implicated in

Entity Epithelial ovarian cancer (EOC)
Oncogenesis OPCML is frequently somatically inactivated in EOC by allele loss and by CpG island methylation (Sellar et al., 2003).
Hypermethylation of OPCML was not correlated to FIGO stage, however, in 80% of cases with methylated OPCML early clinical stage was also present. Tumor grading and histological type had no significant influence on the presence of hypermethylation of OPCML gene. In a group of OPCMLmRNA-negative tumors there were 75% of cases with hypermethylated exon of OPCML and the correlation between these variables was statistically significant. No promoter hypermethylation of the studied gene was found in normal ovaries (Czekierdowski et al., 2006).
Methylation-sensitive PCR analysis showed that the OPCML promoter was hypermethylated in RAS-transformed human ovarian epithelial cells (T29H) and that treatment with the DNA methyltransferase inhibitor 5'-aza-2'-deoxycytidine promoted demethylation of the OPCML promoter and restored OPCML expression in T29H cells. Suppression of oncogenic RAS activity by stable siRNA specific for HRAS(V12) led to the demethylation and re-expression of OPCML in T29H cells, demonstrating that oncogenic RAS activity is directly responsible for the observed OPCML promoter hypermethylation and epigenetic gene silencing of OPCML. RAS signaling pathway may play an important role in epigenetic inactivation of OPCML in human epithelial ovarian cancer (Mei et al., 2006).
Expression of OPCML mRNA in ovarian epithelial carcinoma was significantly lower than those of normal and benign tumors. Methylations were detected in 44.4% of cancer cells promoter, while 0% in normal ovarian tissue and benign ovarian tumors. The ratio of methylation of ovarian epithelial carcinoma was significantly higher than those of normal and benign tumors (Zhang et al., 2006).
The relationship between gene expression and promoter methylation was significantly correlated (OPCML expression in ovarian serous carcinomas was significantly higher than in ovarian adenomas and normal tissues. CpG island methylation and LOH are probably two mechanisms of OPCML inactivation. LOH at D11S4085 was also correlated with loss of OPCML expression. The LOH rate at D11S4085 in carcinomas was significantly higher than that for adenomas and normal tissues. Abnormal methylation of OPCML was found in 53.4% of the carcinomas, while in none of the adenomas or normal tissues (Chen et al., 2007).
Entity Invasive cervical carcinoma
Oncogenesis OPCML gene promoter methylation may play an important role in the carcinogenesis of cervical carcinoma and OPCML gene may be a cervical carcinoma-associated candidate tumor suppressor gene (Ye et al., 2008).
Entity Squamous cell lung carcinoma
Oncogenesis OPCML hypermethylation did not differ significantly based on gender, race, age or tumor stage, indicating their wide applicability as potential lung adenocarcinoma markers (Tsou et al., 2007).
Entity Gastric cancer
Oncogenesis OPCML could play a key role in the tumorigenesis and metastasis of gastric cancer. The expression level of these gene was the highest in normal gastric epithelium, which was decreased in primary carcinoma, and further decreased in metastatic lymph nodes (Wang et al., 2007).
Entity Hepatocellular carcinoma
Oncogenesis Hypermethylation rates of OPCML was higher in HCC than in pericancer tissues (70.0% vs. 64.6%). Promoter methylation of OPCML gene may play an important role in hepatocarcinogenesis (Liu et al., 2006).
Entity Gliomas
Oncogenesis OPCML was significantly reduced or absent in 83% of brain tumours and all cell lines compared with nonneoplastic whole brain. Two OPCML splice variants have been identified in humans, termed alpha1 and alpha2, but the latter has not been demonstrated in human neural tissues. Hypermethylation of the alpha1 OPCML promoter, associated did not correlate with expression levels in the subset of brain tumours tested, implying transcription of OPCML from an alternative promoter or a different mechanism of down-regulation (Reed et al., 2007).
Entity Phaeochromocytoma
Oncogenesis OPCML was methylated in 12% of phaeochromocytomas (Margetts et al., 2008).


OPCML Is a Broad Tumor Suppressor for Multiple Carcinomas and Lymphomas with Frequently Epigenetic Inactivation.
Cui Y, Ying Y, van Hasselt A, Ng KM, Yu J, Zhang Q, Jin J, Liu D, Rhim JS, Rha SY, Loyo M, Chan AT, Srivastava G, Tsao GS, Sellar GC, Sung JJ, Sidransky D, Tao Q.
PLoS ONE. 2008 Aug 20;3(8):e2990.
PMID 18714356
Opioid-binding protein/cell adhesion molecule-like (OPCML) gene and promoter methylation status in women with ovarian cancer.
Czekierdowski A, Czekierdowska S, Szymanski M, Wielgos M, Kaminski P, Kotarski J.
Neuro Endocrinol Lett. 2006 Oct;27(5):609-13.
PMID 17159813
Characterization and tissue distribution of opioid-binding cell adhesion molecule (OBCAM) using monoclonal antibodies.
Hachisuka A, Yamazaki T, Sawada J, Terao T.
Neurochem Int. 1996 Apr;28(4):373-9.
PMID 8740443
Regulation of an opioid-binding protein in NG108-15 cells parallels regulation of delta-opioid receptors.
Lane CM, Elde R, Loh HH, Lee NM.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11234-8.
PMID 1333602
Postnatal expression profile of OBCAM implies its involvement in visual cortex development and plasticity.
Li P, Prasad SS, Mitchell DE, Hachisuka A, Sawada JI, Al-Housseini AM, Gu Q.
Cereb Cortex. 2006 Feb;16(2):291-9. Epub 2005 May 18.
PMID 15901654
Correlations of CpG island methylator phenotype and OPCML gene methylation to carcinogenesis of hepatocellular carcinoma.
Liu WJ, Wang L, Wang JP, Li JQ, Zhang CQ, Zheng L, Yuan YF.
Ai Zheng. 2006 Jun;25(6):696-700.
PMID 16764763
Evaluation of a functional epigenetic approach to identify promoter region methylation in phaeochromocytoma and neuroblastoma.
Margetts CD, Morris M, Astuti D, Gentle DC, Cascon A, McRonald FE, Catchpoole D, Robledo M, Neumann HP, Latif F, Maher ER.
Endocr Relat Cancer. 2008 Sep;15(3):777-86. Epub 2008 May 22.
PMID 18499731
RAS-mediated epigenetic inactivation of OPCML in oncogenic transformation of human ovarian surface epithelial cells.
Mei FC, Young TW, Liu J, Cheng X.
FASEB J. 2006 Mar;20(3):497-9. Epub 2005 Dec 29.
PMID 16384911
Biochemical and ultrastructural analyses of IgLON cell adhesion molecules, Kilon and OBCAM in the rat brain.
Miyata S, Matsumoto N, Taguchi K, Akagi A, Iino T, Funatsu N, Maekawa S.
Neuroscience. 2003;117(3):645-58.
PMID 12617969
Dendrite-associated opioid-binding cell adhesion molecule localizes at neurosecretory granules in the hypothalamic magnocellular neurons.
Miyata S, Taguchi K, Maekawa S.
Neuroscience. 2003;122(1):169-81.
PMID 14596858
Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO inhibits neurite outgrowth from cerebellar granule cells.
Reed J, McNamee C, Rackstraw S, Jenkins J, Moss D.
J Cell Sci. 2004 Aug 1;117(Pt 17):3961-73. Epub 2004 Jul 20.
PMID 15265982
Expression of cellular adhesion molecule 'OPCML' is down-regulated in gliomas and other brain tumours.
Reed JE, Dunn JR, du Plessis DG, Shaw EJ, Reeves P, Gee AL, Warnke PC, Sellar GC, Moss DJ, Walker C.
Neuropathol Appl Neurobiol. 2007 Feb;33(1):77-85.
PMID 17239010
OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer.
Sellar GC, Watt KP, Rabiasz GJ, Stronach EA, Li L, Miller EP, Massie CE, Miller J, Contreras-Moreira B, Scott D, Brown I, Williams AR, Bates PA, Smyth JF, Gabra H.
Nat Genet. 2003 Jul;34(3):337-43.
PMID 12819783
Cloning, sequencing and localization to chromosome 11 of a cDNA encoding a human opioid-binding cell adhesion molecule (OBCAM).
Shark KB, Lee NM.
Gene. 1995 Apr 3;155(2):213-7.
PMID 7721093
Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma.
Tsou JA, Galler JS, Siegmund KD, Laird PW, Turla S, Cozen W, Hagen JA, Koss MN, Laird-Offringa IA.
Mol Cancer. 2007 Oct 29;6:70.
PMID 17967182
Comparison of gene expression profiles between primary tumor and metastatic lesions in gastric cancer patients using laser microdissection and cDNA microarray.
Wang L, Zhu JS, Song MQ, Chen GQ, Chen JL.
World J Gastroenterol. 2006 Nov 21;12(43):6949-54.
PMID 17109515
Opioid-binding protein (OBCAM) is rich in beta-sheets.
Wu CS, Hasegawa J, Smith AP, Loh HH, Lee NM, Yang JT.
J Protein Chem. 1990 Feb;9(1):3-7.
PMID 2340074
Synaptic adhesion molecule OBCAM; synaptogenesis and dynamic internalization.
Yamada M, Hashimoto T, Hayashi N, Higuchi M, Murakami A, Nakashima T, Maekawa S, Miyata S.
Brain Res. 2007 Aug 24;1165:5-14. Epub 2007 Apr 27.
PMID 17658490
OPCML gene promoter methylation and gene expression in tumor and stroma cells of invasive cervical carcinoma.
Ye F, Zhang SF, Xie X, Lu WG.
Cancer Invest. 2008 Jul;26(6):569-74.
PMID 18584347
Deletion of OPCML gene and promoter methylation in ovarian epithelial carcinoma.
Zhang J, Ye F, Chen HZ, Ye DF, Lu WG, Xie X.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2006 Apr;28(2):173-7.
PMID 16733898


This paper should be referenced as such :
Czekierdowski, A ; Czekierdowska, S
OPCML (opioid binding protein/cell adhesion molecule-like)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(12):956-959.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)OPCML   8143
Entrez_Gene (NCBI)OPCML    opioid binding protein/cell adhesion molecule like
GeneCards (Weizmann)OPCML
Ensembl hg19 (Hinxton)ENSG00000183715 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000183715 [Gene_View]  ENSG00000183715 [Sequence]  chr11:132414665-132943637 [Contig_View]  OPCML [Vega]
ICGC DataPortalENSG00000183715
Genatlas (Paris)OPCML
Genetics Home Reference (NIH)OPCML
Genomic and cartography
GoldenPath hg38 (UCSC)OPCML  -     chr11:132414665-132943637 -  11q25   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)OPCML  -     11q25   [Description]    (hg19-Feb_2009)
GoldenPathOPCML - 11q25 [CytoView hg19]  OPCML - 11q25 [CytoView hg38]
genome Data Viewer NCBIOPCML [Mapview hg19]  
OMIM167000   600632   
Gene and transcription
Genbank (Entrez)AF070577 AK125185 AK289695 AK299528 AK299908
RefSeq transcript (Entrez)NM_001012393 NM_001319103 NM_001319104 NM_001319105 NM_001319106 NM_002545
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)OPCML
Alternative Splicing GalleryENSG00000183715
Gene Expression Viewer (FireBrowse)OPCML [ Firebrowse - Broad ]
GenevisibleExpression of OPCML in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4978
GTEX Portal (Tissue expression)OPCML
Human Protein AtlasENSG00000183715-OPCML [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ14982   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ14982  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ14982
Splice isoforms : SwissVarQ14982
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)   
Domains : Interpro (EBI)Ig-like_dom    Ig-like_dom_sf    Ig-like_fold    Ig_I-set    Ig_sub    Ig_sub2   
Domain families : Pfam (Sanger)I-set (PF07679)   
Domain families : Pfam (NCBI)pfam07679   
Domain families : Smart (EMBL)IG (SM00409)  IGc2 (SM00408)  
Conserved Domain (NCBI)OPCML
Blocks (Seattle)OPCML
PDB Europe5UV6   
PDB (PDBSum)5UV6   
PDB (IMB)5UV6   
Structural Biology KnowledgeBase5UV6   
SCOP (Structural Classification of Proteins)5UV6   
CATH (Classification of proteins structures)5UV6   
Human Protein Atlas [tissue]ENSG00000183715-OPCML [tissue]
Peptide AtlasQ14982
IPIIPI01014255   IPI00001662   IPI00977567   IPI00552450   
Protein Interaction databases
IntAct (EBI)Q14982
Ontologies - Pathways
Ontology : AmiGOprotein binding  extracellular region  plasma membrane  cell adhesion  neuron recognition  anchored component of membrane  
Ontology : EGO-EBIprotein binding  extracellular region  plasma membrane  cell adhesion  neuron recognition  anchored component of membrane  
REACTOMEQ14982 [protein]
REACTOME PathwaysR-HSA-163125 [pathway]   
Atlas of Cancer Signalling NetworkOPCML
Wikipedia pathwaysOPCML
Orthology - Evolution
GeneTree (enSembl)ENSG00000183715
Phylogenetic Trees/Animal Genes : TreeFamOPCML
Homologs : HomoloGeneOPCML
Homology/Alignments : Family Browser (UCSC)OPCML
Gene fusions - Rearrangements
Fusion : MitelmanSHANK2/OPCML [11q13.3/11q25]  
Fusion PortalSHANK2 11q13.3 OPCML 11q25 BRCA
Fusion : QuiverOPCML
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerOPCML [hg38]
Exome Variant ServerOPCML
GNOMAD BrowserENSG00000183715
Varsome BrowserOPCML
Genomic Variants (DGV)OPCML [DGVbeta]
DECIPHEROPCML [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisOPCML 
ICGC Data PortalOPCML 
TCGA Data PortalOPCML 
Broad Tumor PortalOPCML
OASIS PortalOPCML [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICOPCML  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DOPCML
Mutations and Diseases : HGMDOPCML
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 OPCML
DgiDB (Drug Gene Interaction Database)OPCML
DoCM (Curated mutations)OPCML (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)OPCML (select a term)
NCG6 (London) select OPCML
Cancer3DOPCML(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM167000    600632   
Genetic Testing Registry OPCML
NextProtQ14982 [Medical]
Target ValidationOPCML
Huge Navigator OPCML [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA31930
Clinical trialOPCML
canSAR (ICR)OPCML (select the gene name)
DataMed IndexOPCML
PubMed56 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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