Browse SEMA4D

Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type I membrane protein
Domain PF00047 Immunoglobulin domain
PF01437 Plexin repeat
PF01403 Sema domain
Function

Cell surface receptor for PLXN1B and PLXNB2 that plays an important role in cell-cell signaling. Promotes reorganization of the actin cytoskeleton and plays a role in axonal growth cone guidance in the developing central nervous system. Regulates dendrite and axon branching and morphogenesis. Promotes the migration of cerebellar granule cells and of endothelial cells. Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro). Promotes signaling via SRC and PTK2B/PYK2, which then mediates activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Interaction with PLXNB1 mediates activation of RHOA.

> Gene Ontology
 
Biological Process GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001558 regulation of cell growth
GO:0001649 osteoblast differentiation
GO:0001667 ameboidal-type cell migration
GO:0001755 neural crest cell migration
GO:0001933 negative regulation of protein phosphorylation
GO:0007159 leukocyte cell-cell adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007409 axonogenesis
GO:0007411 axon guidance
GO:0008360 regulation of cell shape
GO:0008361 regulation of cell size
GO:0010692 regulation of alkaline phosphatase activity
GO:0010693 negative regulation of alkaline phosphatase activity
GO:0010720 positive regulation of cell development
GO:0010721 negative regulation of cell development
GO:0010769 regulation of cell morphogenesis involved in differentiation
GO:0010770 positive regulation of cell morphogenesis involved in differentiation
GO:0010771 negative regulation of cell morphogenesis involved in differentiation
GO:0010921 regulation of phosphatase activity
GO:0010923 negative regulation of phosphatase activity
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0010977 negative regulation of neuron projection development
GO:0014031 mesenchymal cell development
GO:0014032 neural crest cell development
GO:0014033 neural crest cell differentiation
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016049 cell growth
GO:0016311 dephosphorylation
GO:0016358 dendrite development
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0021700 developmental maturation
GO:0022604 regulation of cell morphogenesis
GO:0030278 regulation of ossification
GO:0030279 negative regulation of ossification
GO:0030307 positive regulation of cell growth
GO:0030308 negative regulation of cell growth
GO:0030335 positive regulation of cell migration
GO:0030516 regulation of axon extension
GO:0030517 negative regulation of axon extension
GO:0031345 negative regulation of cell projection organization
GO:0031346 positive regulation of cell projection organization
GO:0032102 negative regulation of response to external stimulus
GO:0032535 regulation of cellular component size
GO:0035303 regulation of dephosphorylation
GO:0035305 negative regulation of dephosphorylation
GO:0040013 negative regulation of locomotion
GO:0040017 positive regulation of locomotion
GO:0042326 negative regulation of phosphorylation
GO:0043931 ossification involved in bone maturation
GO:0045665 negative regulation of neuron differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045667 regulation of osteoblast differentiation
GO:0045668 negative regulation of osteoblast differentiation
GO:0045926 negative regulation of growth
GO:0045927 positive regulation of growth
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048588 developmental cell growth
GO:0048638 regulation of developmental growth
GO:0048639 positive regulation of developmental growth
GO:0048640 negative regulation of developmental growth
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048668 collateral sprouting
GO:0048670 regulation of collateral sprouting
GO:0048672 positive regulation of collateral sprouting
GO:0048675 axon extension
GO:0048762 mesenchymal cell differentiation
GO:0048799 animal organ maturation
GO:0048813 dendrite morphogenesis
GO:0048814 regulation of dendrite morphogenesis
GO:0048841 regulation of axon extension involved in axon guidance
GO:0048843 negative regulation of axon extension involved in axon guidance
GO:0048846 axon extension involved in axon guidance
GO:0048863 stem cell differentiation
GO:0048864 stem cell development
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050732 negative regulation of peptidyl-tyrosine phosphorylation
GO:0050768 negative regulation of neurogenesis
GO:0050769 positive regulation of neurogenesis
GO:0050770 regulation of axonogenesis
GO:0050771 negative regulation of axonogenesis
GO:0050772 positive regulation of axonogenesis
GO:0050773 regulation of dendrite development
GO:0050919 negative chemotaxis
GO:0050920 regulation of chemotaxis
GO:0050922 negative regulation of chemotaxis
GO:0051271 negative regulation of cellular component movement
GO:0051272 positive regulation of cellular component movement
GO:0051346 negative regulation of hydrolase activity
GO:0051961 negative regulation of nervous system development
GO:0051962 positive regulation of nervous system development
GO:0060348 bone development
GO:0060485 mesenchyme development
GO:0060560 developmental growth involved in morphogenesis
GO:0061383 trabecula morphogenesis
GO:0061387 regulation of extent of cell growth
GO:0061430 bone trabecula morphogenesis
GO:0061564 axon development
GO:0070486 leukocyte aggregation
GO:0070977 bone maturation
GO:0071526 semaphorin-plexin signaling pathway
GO:0071695 anatomical structure maturation
GO:0090066 regulation of anatomical structure size
GO:0097485 neuron projection guidance
GO:1900220 semaphorin-plexin signaling pathway involved in bone trabecula morphogenesis
GO:1902284 neuron projection extension involved in neuron projection guidance
GO:1902667 regulation of axon guidance
GO:1902668 negative regulation of axon guidance
GO:1990138 neuron projection extension
GO:2000147 positive regulation of cell motility
Molecular Function GO:0030215 semaphorin receptor binding
GO:0045499 chemorepellent activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04360 Axon guidance
Reactome R-HSA-422475: Axon guidance
R-HSA-1266738: Developmental Biology
R-HSA-416700: Other semaphorin interactions
R-HSA-400685: Sema4D in semaphorin signaling
R-HSA-416572: Sema4D induced cell migration and growth-cone collapse
R-HSA-416550: Sema4D mediated inhibition of cell attachment and migration
R-HSA-373755: Semaphorin interactions
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SEMA4D and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between SEMA4D and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26740106Head and Neck Squamous Cell CarcinomaInhibit immunity (T cell function)Human Head and Neck Squamous Cell Carcinoma-Associated Semaphorin 4D Induces Expansion of Myeloid-Derived Suppressor Cells.
25614511Colon CarcinomaInhibit immunity (infiltration)Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies.
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SEMA4D in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SEMA4D in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0030.993
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2740.817
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.2040.827
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.8320.0374
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.5920.773
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.1440.689
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4520.246
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.8310.52
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0510.972
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2180.872
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.3140.872
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0070.939
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SEMA4D in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277302.7-2.71
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91633.3033.30.0365
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47500500.109
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.907.90.26
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161412.5012.50.485
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SEMA4D. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SEMA4D. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SEMA4D.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SEMA4D. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SEMA4D expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SEMA4D and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSEMA4D
Namesema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D
Aliases CD100; coll-4; FLJ39737; M-sema G; SEMAJ; C9orf164; chromosome 9 open reading frame 164; M-sema-G; BB18; sem ......
Chromosomal Location9q22-q31
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SEMA4D collected from DrugBank database.
> Drugs from DrugBank database
 

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