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OLFM4 (olfactomedin 4)

Identity

Other namesbA209J19.1
GC1
GW112
hGC-1
hOLfD
KIAA4294
OlfD
OLM4
UNQ362
HGNC (Hugo) OLFM4
LocusID (NCBI) 10562
Location 13q14.3
Location_base_pair Starts at 53602876 and ends at 53626196 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
Note OLFM4 is a member of olfactomedin-related protein family. This gene was originally cloned from human myeloblasts and constitutively expressed in normal bone marrow, stomach, small intestine, colon, prostate and pancreas.

DNA/RNA

 
Description OLFM4 gene locus was mapped to chromosome 13q14.3 with five exons spanning 23220 bp.
Transcription OLFM4 is transcribed to 2861 bp mRNA with an open reading frame of 1530 nucleotides. There is no alternative mRNA splicing.
mRNA expression: highly in bone marrow and small intestine; lowly expressed in stomach, colon, pancreas and prostate; no expression is detected in other tissues determined by Northern blot. OLFM4 transcription is regulated by transcription factors, PU1 and NF-kB.

Protein

Description OLFM4 encodes a 510 amino acid protein with a molecular weight of 55 kD. OLFM4 has a signal peptide and six N-linked glycosylation motifs and forms disulfide-bonded multimers. It has a N-terminal coil-coil domain and C-terminal olfactomedin domain.
Expression OLFM4 protein is endogenously expressed in mature neutrophils and gastric and intestinal epithelial cells. Its expression in bone marrow neutrophils is significantly higher than peripheral blood neutrophils. OLFM4 is more abundantly expressed in intestinal crypts than in surface epithelial cells.
Localisation OLFM4 is localized in multiple subcellular compartments including cytoplasm, mitochondria and membrane. It is also secreted extracellularly.
Function OLFM4 binds to cadherins and lectins and mediates cell adhesion. OLFM4 is a robust marker for stem cells in human intestine.
Homology Human OLFM4 is highly homologous to its mouse homologue (pDP4) with 93% amino acid identity. OLFM4 C-terminal olfactomedin domain has significant homology with other olfactomedin-related proteins including olfactomedin, TIGR, Noelin-1, Noeline-2 and latrophilin-1, etc.

Mutations

Note No known genetic mutation in normal or cancer tissues.

Implicated in

Entity Stomach cancer
Note OLFM4 mRNA expression is upregulated in gastric cancer patients. OLFM4 protein staining by immunohistochemistry was observed more frequently in well-differentiated cancer tissues and more frequently in stage I/II cases than in stage III/IV cases. Serum OLFM4 is a useful marker for gastric cancer patients.
  
Entity Colon cancer
Note OLFM4 mRNA is upregulated in colon cancer patients. OLFM4 protein expression is correlated with prognosis for colon cancer patients. Lower or lost OLFM4 protein expression is correlated with more malignancy and poor survival.
  
Entity Prostate cancer
Note OLFM4 mRNA expression is upregulated in prostate cancer patients. OLFM4 interacts with GRIM-19, a mitochondria pro-apoptosis protein and has an anti-apoptotic function in prostate cancer cells when it is overexpressed.
  
Entity Pancreatic cancer
Note OLFM4 mRNA is upregulated in pancreatic cancer patients. OLFM4 promotes S-phase transition in proliferation of pancreatic cancer cells.
  
Entity Breast cancer
Note OLFM4 mRNA is upregulated in breast cancer patients.
  
Entity Chronic bowel disease (Crohn's disease and ulcerative colitis)
Note OLFM4 mRNA expression is upregulated in the intestines of chronic bowel disease patients including Crohn's disease and ulcerative colitis.
  
Entity H. pylori gastritis
Note OLFM4 mRNA expression is upregulated in the gastric mucosa of H. pylori infected patients than normal individuals.
  

External links

Nomenclature
HGNC (Hugo)OLFM4   17190
Cards
AtlasOLFM4ID49730ch13q14
Entrez_Gene (NCBI)OLFM4  10562  olfactomedin 4
GeneCards (Weizmann)OLFM4
Ensembl (Hinxton)ENSG00000102837 [Gene_View]  chr13:53602876-53626196 [Contig_View]  OLFM4 [Vega]
ICGC DataPortalENSG00000102837
cBioPortalOLFM4
AceView (NCBI)OLFM4
Genatlas (Paris)OLFM4
WikiGenes10562
SOURCE (Princeton)NM_006418
Genomic and cartography
GoldenPath (UCSC)OLFM4  -  13q14.3   chr13:53602876-53626196 +  13q14   [Description]    (hg19-Feb_2009)
EnsemblOLFM4 - 13q14 [CytoView]
Mapping of homologs : NCBIOLFM4 [Mapview]
OMIM614061   
Gene and transcription
Genbank (Entrez)AF097021 AI560739 AK000683 AK300947 AY358567
RefSeq transcript (Entrez)NM_006418
RefSeq genomic (Entrez)AC_000145 NC_000013 NC_018924 NT_024524 NW_001838080 NW_004929388
Consensus coding sequences : CCDS (NCBI)OLFM4
Cluster EST : UnigeneHs.508113 [ NCBI ]
CGAP (NCI)Hs.508113
Alternative Splicing : Fast-db (Paris)GSHG0008146
Alternative Splicing GalleryENSG00000102837
Gene ExpressionOLFM4 [ NCBI-GEO ]     OLFM4 [ SEEK ]   OLFM4 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ6UX06 (Uniprot)
NextProtQ6UX06  [Medical]
With graphics : InterProQ6UX06
Splice isoforms : SwissVarQ6UX06 (Swissvar)
Domaine pattern : Prosite (Expaxy)OLF (PS51132)   
Domains : Interpro (EBI)Olfac-like [organisation]   Quinoprot_gluc/sorb_DH [organisation]  
Related proteins : CluSTrQ6UX06
Domain families : Pfam (Sanger)OLF (PF02191)   
Domain families : Pfam (NCBI)pfam02191   
Domain families : Smart (EMBL)OLF (SM00284)  
DMDM Disease mutations10562
Blocks (Seattle)Q6UX06
Human Protein AtlasENSG00000102837 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ6UX06
HPRD06580
IPIIPI00022255   
Protein Interaction databases
DIP (DOE-UCLA)Q6UX06
IntAct (EBI)Q6UX06
FunCoupENSG00000102837
BioGRIDOLFM4
InParanoidQ6UX06
Interologous Interaction database Q6UX06
IntegromeDBOLFM4
STRING (EMBL)OLFM4
Ontologies - Pathways
Ontology : AmiGOcatalytic activity  extracellular space  extracellular space  mitochondrion  plasma membrane  cell adhesion  metabolic process  regulation of necrotic cell death  secretory granule  specific granule  azurophil granule  protein homodimerization activity  regulation of apoptotic process  negative regulation of I-kappaB kinase/NF-kappaB signaling  cadherin binding  perinuclear region of cytoplasm  regulation of phagocytosis  negative regulation of immune response  protein homooligomerization  extracellular vesicular exosome  positive regulation of substrate adhesion-dependent cell spreading  regulation of neutrophil extravasation  
Ontology : EGO-EBIcatalytic activity  extracellular space  extracellular space  mitochondrion  plasma membrane  cell adhesion  metabolic process  regulation of necrotic cell death  secretory granule  specific granule  azurophil granule  protein homodimerization activity  regulation of apoptotic process  negative regulation of I-kappaB kinase/NF-kappaB signaling  cadherin binding  perinuclear region of cytoplasm  regulation of phagocytosis  negative regulation of immune response  protein homooligomerization  extracellular vesicular exosome  positive regulation of substrate adhesion-dependent cell spreading  regulation of neutrophil extravasation  
Protein Interaction DatabaseOLFM4
Wikipedia pathwaysOLFM4
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)OLFM4
snp3D : Map Gene to Disease10562
SNP (GeneSNP Utah)OLFM4
SNP : HGBaseOLFM4
Genetic variants : HAPMAPOLFM4
Exome VariantOLFM4
1000_GenomesOLFM4 
ICGC programENSG00000102837 
Somatic Mutations in Cancer : COSMICOLFM4 
CONAN: Copy Number AnalysisOLFM4 
Mutations and Diseases : HGMDOLFM4
Mutations and Diseases : intOGenOLFM4
Genomic VariantsOLFM4  OLFM4 [DGVbeta]
dbVarOLFM4
ClinVarOLFM4
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM614061   
MedgenOLFM4
GENETestsOLFM4
Disease Genetic AssociationOLFM4
Huge Navigator OLFM4 [HugePedia]  OLFM4 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneOLFM4
Homology/Alignments : Family Browser (UCSC)OLFM4
Phylogenetic Trees/Animal Genes : TreeFamOLFM4
Chemical/Protein Interactions : CTD10562
Chemical/Pharm GKB GenePA134984745
Clinical trialOLFM4
Cancer Resource (Charite)ENSG00000102837
Other databases
Probes
Litterature
PubMed34 Pubmed reference(s) in Entrez
CoreMineOLFM4
iHOPOLFM4
OncoSearchOLFM4

Bibliography

Upregulation of Reg 1alpha and GW112 in the epithelium of inflamed colonic mucosa.
Shinozaki S, Nakamura T, Iimura M, Kato Y, Iizuka B, Kobayashi M, Hayashi N.
Gut. 2001 May;48(5):623-9.
PMID 11302958
 
Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development.
Zhang J, Liu WL, Tang DC, Chen L, Wang M, Pack SD, Zhuang Z, Rodgers GP.
Gene. 2002 Jan 23;283(1-2):83-93.
PMID 11867215
 
pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by transcription factor PU.1.
Rosenbauer F, Wagner K, Zhang P, Knobeloch KP, Iwama A, Tenen DG.
Blood. 2004 Jun 1;103(11):4294-301. Epub 2004 Feb 12.
PMID 14962908
 
GW112, a novel antiapoptotic protein that promotes tumor growth.
Zhang X, Huang Q, Yang Z, Li Y, Li CY.
Cancer Res. 2004 Apr 1;64(7):2474-81.
PMID 15059901
 
Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression.
Oue N, Aung PP, Mitani Y, Kuniyasu H, Nakayama H, Yasui W.
Oncology. 2005;69 Suppl 1:17-22. (REVIEW)
PMID 16210872
 
Molecular-pathological prognostic factors of gastric cancer.
Yasui W, Oue N, Aung PP, Matsumura S, Shutoh M, Nakayama H.
Gastric Cancer. 2005;8(2):86-94. (REVIEW)
PMID 15864715
 
Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer.
Aung PP, Oue N, Mitani Y, Nakayama H, Yoshida K, Noguchi T, Bosserhoff AK, Yasui W.
Oncogene. 2006 Apr 20;25(17):2546-57.
PMID 16331256
 
The glycoprotein hGC-1 binds to cadherin and lectins.
Liu W, Chen L, Zhu J, Rodgers GP.
Exp Cell Res. 2006 Jun 10;312(10):1785-97. Epub 2006 Mar 29.
PMID 16566923
 
Olfactomedin 4 promotes S-phase transition in proliferation of pancreatic cancer cells.
Kobayashi D, Koshida S, Moriai R, Tsuji N, Watanabe N.
Cancer Sci. 2007 Mar;98(3):334-40.
PMID 17270022
 
Specific overexpression of OLFM4(GW112/HGC-1) mRNA in colon, breast and lung cancer tissues detected using quantitative analysis.
Koshida S, Kobayashi D, Moriai R, Tsuji N, Watanabe N.
Cancer Sci. 2007 Mar;98(3):315-20.
PMID 17270020
 
Expression of hGC-1 is correlated with differentiation of gastric carcinoma.
Liu W, Zhu J, Cao L, Rodgers GP.
Histopathology. 2007 Aug;51(2):157-65.
PMID 17650212
 
The regulation of OLFM4 expression in myeloid precursor cells relies on NF-kappaB transcription factor.
Chin KL, Aerbajinai W, Zhu J, Drew L, Chen L, Liu W, Rodgers GP.
Br J Haematol. 2008 Nov;143(3):421-32. Epub 2008 Sep 1.
PMID 18764868
 
Identification of new accessible tumor antigens in human colon cancer by ex vivo protein biotinylation and comparative mass spectrometry analysis.
Conrotto P, Roesli C, Rybak J, Kischel P, Waltregny D, Neri D, Castronovo V.
Int J Cancer. 2008 Dec 15;123(12):2856-64.
PMID 18798264
 
Reduced hGC-1 protein expression is associated with malignant progression of colon carcinoma.
Liu W, Liu Y, Zhu J, Wright E, Ding I, Rodgers GP.
Clin Cancer Res. 2008 Feb 15;14(4):1041-9.
PMID 18281536
 
Serum olfactomedin 4 (GW112, hGC-1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients.
Oue N, Sentani K, Noguchi T, Ohara S, Sakamoto N, Hayashi T, Anami K, Motoshita J, Ito M, Tanaka S, Yoshida K, Yasui W.
Int J Cancer. 2009 Nov 15;125(10):2383-92.
PMID 19670418
 
OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells.
van der Flier LG, Haegebarth A, Stange DE, van de Wetering M, Clevers H.
Gastroenterology. 2009 Jul;137(1):15-7. Epub 2009 May 18.
PMID 19450592
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written01-2010Wenli Liu, Griffin P Rodgers
Molecular and Clinical Hematology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9N115, 10 Center Drive, Bethesda, MD 20892, USA

Citation

This paper should be referenced as such :
Liu, W ; Rodgers, GP
OLFM4 (olfactomedin 4)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(11):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/OLFM4ID49730ch13q14.html

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indexed on : Sat Oct 4 13:07:01 CEST 2014

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