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

2009-08-01   Munmi Bhattacharyya , Ranjan Tamuli 

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India

Identity

HGNC
LOCATION
3p21.31
LOCUSID
ALIAS
LUCA-1,SEMA5,SEMAA,SemA,semaV
FUSION GENES

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.
Atlas Image

Description

DNA size 11.53kb; mRNA size 9534 bp 18 exons.

Proteins

Atlas Image

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

Entity name
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 name
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 name
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 name
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 name
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 name
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 name
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

Pubmed IDLast YearTitleAuthors
189229012008Semaphorin 3B inhibits the phosphatidylinositol 3-kinase/Akt pathway through neuropilin-1 in lung and breast cancer cells.Castro-Rivera E et al
128106702003Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B in non-small cell lung cancer.Kuroki T et al
110855362000The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium.Lerman MI et al
125614292003[Mutation and expression of SEMA3B and SEMA3F gene in nasopharyngeal carcinoma].Liu XQ et al
158315292005The race associated allele of Semaphorin 3B (SEMA3B) T415I and its role in lung cancer in African-Americans and Latino-Americans.Marsit CJ et al
174522502007High-resolution analysis of 3p deletion in neuroblastoma and differential methylation of the SEMA3B tumor suppressor gene.Nair PN et al
170104102006Expression 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 et al
195485302009[Alteration of SEMA3B gene expression levels in epithelial tumors].Pronina IV et al
77485611995Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension.Püschel AW et al
170849652007Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma.Riquelme E et al
184581152008The tumor suppressor semaphorin 3B triggers a prometastatic program mediated by interleukin 8 and the tumor microenvironment.Rolny C et al
86330261996Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.Sekido Y et al
118097072002Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line.Tse C et al

Other Information

Locus ID:

NCBI: 7869
MIM: 601281
HGNC: 10724
Ensembl: ENSG00000012171

Variants:

dbSNP: 7869
ClinVar: 7869
TCGA: ENSG00000012171
COSMIC: SEMA3B

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000012171ENST00000418576B4DEK9
ENSG00000012171ENST00000433753Q13214
ENSG00000012171ENST00000456560B4DEK9
ENSG00000012171ENST00000611067A0A0C4DGV8
ENSG00000012171ENST00000616701Q13214
ENSG00000012171ENST00000618865Q13214
ENSG00000012171ENST00000621029A0A087WZE0

Expression (GTEx)

0
100
200
300
400
500
600
700

Pathways

PathwaySourceExternal ID
Axon guidanceKEGGko04360
Axon guidanceKEGGhsa04360

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
152732882004Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect.59
187574062008Semaphorin-3B is an angiogenesis inhibitor that is inactivated by furin-like pro-protein convertases.45
118097072002Human Semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line.34
184581152008The tumor suppressor semaphorin 3B triggers a prometastatic program mediated by interleukin 8 and the tumor microenvironment.32
189229012008Semaphorin 3B inhibits the phosphatidylinositol 3-kinase/Akt pathway through neuropilin-1 in lung and breast cancer cells.29
128106702003Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B in non-small cell lung cancer.21
183562902008Semaphorin 3B is a 1,25-Dihydroxyvitamin D3-induced gene in osteoblasts that promotes osteoclastogenesis and induces osteopenia in mice.20
119223942002Identification of semaphorin3B as a direct target of p53.15
201244442010Hormonal regulation and distinct functions of semaphorin-3B and semaphorin-3F in ovarian cancer.15
174522502007High-resolution analysis of 3p deletion in neuroblastoma and differential methylation of the SEMA3B tumor suppressor gene.13

Citation

Munmi Bhattacharyya ; Ranjan Tamuli

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

Atlas Genet Cytogenet Oncol Haematol. 2009-08-01

Online version: http://atlasgeneticsoncology.org/gene/42252/sema3b