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SEMA3B (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3B)

Written2009-08Munmi Bhattacharyya, Ranjan Tamuli
Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSEMAA
sema domain
Alias_symbol (synonym)SemA
semaV
LUCA-1
sema5
Other aliasFLJ34863
SEMA5
HGNC (Hugo) SEMA3B
LocusID (NCBI) 7869
Atlas_Id 42252
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 50267558 and ends at 50277171 bp from pter ( according to hg19-Feb_2009)  [Mapping SEMA3B.png]
Fusion genes
(updated 2016)
ATP5G1 (17q21.32) / SEMA3B (3p21.31)PCOLCE (7q22.1) / SEMA3B (3p21.31)

DNA/RNA

Note SEMA3B was first discovered as a secreted member of the semaphorin/collapsing family (contains a highly conserved semaphorin domain) and it has a role in axonal guidance.
 
Description DNA size 11.53kb; mRNA size 9534 bp 18 exons.

Protein

 
Description 749 amino acids; region 1-24 (24) is a signal peptide, 30-513 (484) is the sema domain and 573-659 (87) is the Ig-like C2-type domain.
Isoforms: two isoforms have been identified.
- Isoform 1 (identifier: Q13214-1): this isoform has been chosen as the 'canonical' sequence.
- Isoform 2 (identifier: Q13214-2): the sequence of this isoform differs from the 'canonical' sequence, amino acid residues from 332-332 are missing.
Expression It is expressed abundantly, but expressed differentially in neural and non-neural tissues.
Localisation Secreted.
Function SEMA3B belongs to the semaphorin/collapsing group of family (contains a highly conserved 749 amino acid semaphoring domain at NH2-terminal). SEMA3B involves in diverse processes such as immune modulation, organogenesis, neuronal apoptosis and drug resistance. SEM3B also plays a critical role in axonal guidance during neuronal development. SEMA3B can act as a tumour suppressor by inducing apoptosis either by its expression in tumour cells or when applied as a soluble ligand. SEM3B induced apoptosis is associated with increase in cytochrome c release and caspase-3 cleavage, as well as increased phosphorylation of several proapoptotic proteins, including glycogen synthase kinase-3beta, FKHR and MDM-2. The common method of inactivation of SEMA3B is by allelic loss and gene inactivation via promoter methylation and consequently, expression level of SEM3B is reduced in tumor cells.
Homology The percent identity below represents identity of SEMA3B over an aligned region in UniGene.
Pan troglodytes 98.54%, Bos taurus 90.24%, Rattus norvegicus 89.19%, Canis lupus familiaris 88.72%, Mus musculus 88.65%.

Mutations

Note A missense mutation in SEMA3B is reported in African-American and Latino-American population.

Implicated in

Note
  
Entity Gallbladder carcinoma (GBC)
Note SEMA3B believes to play a role in gallbladder carcinoma (GBC), which is a highly malignant neoplasm in the Chilean females. A very high frequency (46/50, 92%) of abnormal promoter methylation that causes epigenetic inactivation of SEMA3B and the loss of heterozygosity at 3p21.3 (14/32, 44%) region (that contains SEMA3B gene) was detected among the Chilean females with GBC. Therefore, SEMA3B gene alterations may play a role in GBC pathogenesis via a two-hit mechanism, including allelic loss and abnormal promoter methylation.
  
  
Entity Nasopharyngeal carcinoma
Note SEMA3B is associated with nasopharyngeal carcinoma (NPC), as evident from both loss of heterozygosity analysis and functional studies. 21 primary NPC tumors and 2 NPC cell lines (CNE2 and SUNE1) screened for mutations by PCR-sequencing and two missense polymorphisms including Thr415Ile and lle242Met were found in SEMA3B. For the Thr415Ile polymorphism, the Ile allele type which leads to SEMA3B function defects was predominant in NPC with the allele frequency of 64% (27/42). SEMA3B mRNA is expressed in non-neoplastic nasopharyngeal epithelia, but found absent or down-regulated in 76% (16/21) of primary NPC tumors. Thus, high frequency of SEMA3B expression alterations suggests that the inactivation of this gene was strongly associated with NPC.
  
  
Entity Neuroblastoma
Note In neuroblastoma, significantly higher percentage of methylated CpG sites in the SEMA3B promoter was detected in tumors exhibiting 3p loss (95%), relative to tumors without loss (52%), suggesting a two-hit mechanism of allele inactivation. Additionally, low levels of SEMA3B expression were also seen in tumors with unmethylated SEMA3B promoters (n = 4). However, SEMA3B was upregulated in the SK-N-BE neuroblastoma cell line following induction of differentiation with retinoic acid and interestingly, higher levels of SEMA3B expression was found in differentiated tumors with favorable histopathology (n = 19) than in tumors with unfavorable histology (n = 22). The association of SEMA3B expression with neuroblastoma differentiation suggests that this TSG may play a role in neuroblastoma pathobiology and SEMA3B expression profile suggests that transcriptional regulation of this locus is complex.
  
  
Entity Colorectal carcinoma
Disease SEMA3B was also found frequently downregulated in colorectal cancer, which suggests that SEMA3B is involved in the suppression of colon tumor growth. However, the molecular mechanism through which SEM3B suppresses colorectal cancer is not clear.
  
  
Entity Breast cancer
Disease Expression of SEMA3B induces apoptosis in breast cancer cells. SEMA3B induces apoptosis through the neuropilin-1 (Np-1) receptor by inactivating the Akt signaling pathway.
  
  
Entity Ovarian cancer
Note Decreased expression of SEMA3B and loss of heterozygosity (LOH) at SEMA gene loci also account for ovarian cancer progression. Patients with a high vascular endothelial growth factor/SEMA (VEGF/SEMA) ratio showed poor survival than those with a low VEGF/SEMA ratio.
  
  
Entity Lung cancer
Note A single nucleotide alteration in the SEMA3B leads to amino acid substitution T415I and this variant protein has a reduced ability to act as a tumour suppressor. Thr to Ile substitution alters the structure of protein by altering its conformation and affects binding of SEMA3B with neuropilin receptors-1 (NRP-1) and NRP-2. The variant Ile allele occurs at an allele frequency of 0.18 in African-American and 0.39 in Latino-American population.
  

Bibliography

Semaphorin 3B inhibits the phosphatidylinositol 3-kinase/Akt pathway through neuropilin-1 in lung and breast cancer cells.
Castro-Rivera E, Ran S, Brekken RA, Minna JD.
Cancer Res. 2008 Oct 15;68(20):8295-303.
PMID 18922901
 
Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B in non-small cell lung cancer.
Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Williams NN, Kaiser LR, Croce CM.
Cancer Res. 2003 Jun 15;63(12):3352-5.
PMID 12810670
 
The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes.
Lerman MI, Minna JD.
Cancer Res. 2000 Nov 1;60(21):6116-33.
PMID 11085536
 
Mutation and expression of SEMA3B and SEMA3F gene in nasopharyngeal carcinoma.
Liu XQ, Sun M, Chen HK, Li JX, Pan ZG, Long QX, Wang XZ, Zeng YX.
Ai Zheng. 2003 Jan;22(1):16-20.
PMID 12561429
 
The race associated allele of Semaphorin 3B (SEMA3B) T415I and its role in lung cancer in African-Americans and Latino-Americans.
Marsit CJ, Wiencke JK, Liu M, Kelsey KT.
Carcinogenesis. 2005 Aug;26(8):1446-9.
PMID 15831529
 
High-resolution analysis of 3p deletion in neuroblastoma and differential methylation of the SEMA3B tumor suppressor gene.
Nair PN, McArdle L, Cornell J, Cohn SL, Stallings RL.
Cancer Genet Cytogenet. 2007 Apr 15;174(2):100-10.
PMID 17452250
 
Expression of semaphorins, vascular endothelial growth factor, and their common receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is a poor prognostic factor in ovarian carcinomas.
Osada R, Horiuchi A, Kikuchi N, Ohira S, Ota M, Katsuyama Y, Konishi I.
Hum Pathol. 2006 Nov;37(11):1414-25.
PMID 17010410
 
Altered Expression of the SEMA3Bgene in Epithelial Tumors.
Pronina IV, Loginov VI, Prasolov VS, Klimov EA, Khodyrev DS, Kazubskaia TP, Gar'kavtseva RF, Sulimova GE, Braga EA.
Mol Biol (Mosk). 2009 May-Jun;43(3):439-45.
PMID 19548530
 
Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension.
Puschel AW, Adams RH, Betz H.
Neuron. 1995 May;14(5):941-8.
PMID 7748561
 
Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma.
Riquelme E, Tang M, Baez S, Diaz A, Pruyas M, Wistuba II, Corvalan A.
Cancer Lett. 2007 May 18;250(1):100-6.
PMID 17084965
 
The tumor suppressor semaphorin 3B triggers a prometastatic program mediated by interleukin 8 and the tumor microenvironment.
Rolny C, Capparuccia L, Casazza A, Mazzone M, Vallario A, Cignetti A, Medico E, Carmeliet P, Comoglio PM, Tamagnone L.
J Exp Med. 2008 May 12;205(5):1155-71.
PMID 18458115
 
Human semaphorins A (V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.
Sekido Y, Bader S, Latif F, Chen JY, Duh FM, Wei MH, Albanesi JP, Lee CC, Lerman MI, Minna JD.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4120-5.
PMID 8633026
 
Human semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line.
Tse C, Xiang RH, Bracht T, Naylor SL.
Cancer Res. 2002 Jan 15;62(2):542-6.
PMID 11809707
 

Citation

This paper should be referenced as such :
Bhattacharyya, M ; Tamuli, R
SEMA3B (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3B)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):662-664.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SEMA3BID42252ch3p21.html


External links

Nomenclature
HGNC (Hugo)SEMA3B   10724
Cards
AtlasSEMA3BID42252ch3p21
Entrez_Gene (NCBI)SEMA3B  7869  semaphorin 3B
AliasesLUCA-1; SEMA5; SEMAA; SemA; 
semaV
GeneCards (Weizmann)SEMA3B
Ensembl hg19 (Hinxton)ENSG00000012171 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000012171 [Gene_View]  chr3:50267558-50277171 [Contig_View]  SEMA3B [Vega]
ICGC DataPortalENSG00000012171
TCGA cBioPortalSEMA3B
AceView (NCBI)SEMA3B
Genatlas (Paris)SEMA3B
WikiGenes7869
SOURCE (Princeton)SEMA3B
Genetics Home Reference (NIH)SEMA3B
Genomic and cartography
GoldenPath hg38 (UCSC)SEMA3B  -     chr3:50267558-50277171 +  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SEMA3B  -     3p21.31   [Description]    (hg19-Feb_2009)
EnsemblSEMA3B - 3p21.31 [CytoView hg19]  SEMA3B - 3p21.31 [CytoView hg38]
Mapping of homologs : NCBISEMA3B [Mapview hg19]  SEMA3B [Mapview hg38]
OMIM601281   
Gene and transcription
Genbank (Entrez)AB083186 AB209322 AF217991 AI309508 AK092182
RefSeq transcript (Entrez)NM_001005914 NM_001290060 NM_001290061 NM_001290062 NM_001290063 NM_004636
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SEMA3B
Cluster EST : UnigeneHs.82222 [ NCBI ]
CGAP (NCI)Hs.82222
Alternative Splicing GalleryENSG00000012171
Gene ExpressionSEMA3B [ NCBI-GEO ]   SEMA3B [ EBI - ARRAY_EXPRESS ]   SEMA3B [ SEEK ]   SEMA3B [ MEM ]
Gene Expression Viewer (FireBrowse)SEMA3B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7869
GTEX Portal (Tissue expression)SEMA3B
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13214   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13214  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13214
Splice isoforms : SwissVarQ13214
PhosPhoSitePlusQ13214
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)    SEMA (PS51004)   
Domains : Interpro (EBI)Ig-like_dom    Ig-like_fold    Ig_sub    Immunoglobulin    PSI    Semap_dom    Semaphorin    WD40/YVTN_repeat-like_dom   
Domain families : Pfam (Sanger)ig (PF00047)    Sema (PF01403)   
Domain families : Pfam (NCBI)pfam00047    pfam01403   
Domain families : Smart (EMBL)IG (SM00409)  PSI (SM00423)  Sema (SM00630)  
Conserved Domain (NCBI)SEMA3B
DMDM Disease mutations7869
Blocks (Seattle)SEMA3B
SuperfamilyQ13214
Human Protein AtlasENSG00000012171
Peptide AtlasQ13214
HPRD03179
IPIIPI00012283   IPI00556335   IPI00448569   IPI00168096   IPI00030027   
Protein Interaction databases
DIP (DOE-UCLA)Q13214
IntAct (EBI)Q13214
FunCoupENSG00000012171
BioGRIDSEMA3B
STRING (EMBL)SEMA3B
ZODIACSEMA3B
Ontologies - Pathways
QuickGOQ13214
Ontology : AmiGOendoplasmic reticulum  cell-cell signaling  axon guidance  extracellular exosome  
Ontology : EGO-EBIendoplasmic reticulum  cell-cell signaling  axon guidance  extracellular exosome  
Pathways : KEGGAxon guidance   
NDEx NetworkSEMA3B
Atlas of Cancer Signalling NetworkSEMA3B
Wikipedia pathwaysSEMA3B
Orthology - Evolution
OrthoDB7869
GeneTree (enSembl)ENSG00000012171
Phylogenetic Trees/Animal Genes : TreeFamSEMA3B
HOVERGENQ13214
HOGENOMQ13214
Homologs : HomoloGeneSEMA3B
Homology/Alignments : Family Browser (UCSC)SEMA3B
Gene fusions - Rearrangements
Fusion Cancer (Beijing)ATP5G1 [17q21.32]  -  SEMA3B [3p21.31]  [FUSC000151]  [FUSC000151]  [FUSC000151]  [FUSC000151]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSEMA3B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SEMA3B
dbVarSEMA3B
ClinVarSEMA3B
1000_GenomesSEMA3B 
Exome Variant ServerSEMA3B
ExAC (Exome Aggregation Consortium)SEMA3B (select the gene name)
Genetic variants : HAPMAP7869
Genomic Variants (DGV)SEMA3B [DGVbeta]
DECIPHERSEMA3B [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSEMA3B 
Mutations
ICGC Data PortalSEMA3B 
TCGA Data PortalSEMA3B 
Broad Tumor PortalSEMA3B
OASIS PortalSEMA3B [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSEMA3B  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSEMA3B
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 SEMA3B
DgiDB (Drug Gene Interaction Database)SEMA3B
DoCM (Curated mutations)SEMA3B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SEMA3B (select a term)
intoGenSEMA3B
NCG5 (London)SEMA3B
Cancer3DSEMA3B(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601281   
Orphanet
MedgenSEMA3B
Genetic Testing Registry SEMA3B
NextProtQ13214 [Medical]
TSGene7869
GENETestsSEMA3B
Target ValidationSEMA3B
Huge Navigator SEMA3B [HugePedia]
snp3D : Map Gene to Disease7869
BioCentury BCIQSEMA3B
ClinGenSEMA3B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7869
Chemical/Pharm GKB GenePA35646
Clinical trialSEMA3B
Miscellaneous
canSAR (ICR)SEMA3B (select the gene name)
Probes
Litterature
PubMed38 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSEMA3B
EVEXSEMA3B
GoPubMedSEMA3B
iHOPSEMA3B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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