Details for: SEMA3F

Gene ID: 6405

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SEMA3F

Ensembl ID: ENSG00000001617

Description: semaphorin 3F

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • secretory cell CL0000151
    CSI 6.22
    rCSI 6.49%
    PRS 87.51
  • pulmonary capillary endothelial cell CL4028001
    CSI 4.26
    rCSI 8.13%
    PRS 94.62
  • respiratory suprabasal cell CL4033048
    CSI 3.44
    rCSI 4.41%
    PRS 90.64
  • ciliated cell CL0000064
    CSI 3.23
    rCSI 5.23%
    PRS 83.05
  • lung endothelial cell CL1001567
    CSI 3.16
    rCSI 7.36%
    PRS 94.88
  • cardiac endothelial cell CL0010008
    CSI 3.13
    rCSI 12.65%
    PRS 89.24
  • stem cell CL0000034
    CSI 3.12
    rCSI 3%
    PRS 84.12
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.9
    rCSI 4.64%
    PRS 91.34
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.45
    rCSI 3.48%
    PRS 86.05
  • blood vessel endothelial cell CL0000071
    CSI 2.33
    rCSI 4.83%
    PRS 86.71
  • Mueller cell CL0000636
    CSI 2.19
    rCSI 5%
    PRS 81.54
  • cerebral cortex endothelial cell CL1001602
    CSI 2.01
    rCSI 3.47%
    PRS 82.62
  • retinal cone cell CL0000573
    CSI 2
    rCSI 3.21%
    PRS 80.42
  • retinal bipolar neuron CL0000748
    CSI 1.95
    rCSI 3.65%
    PRS 79.4
  • rod bipolar cell CL0000751
    CSI 1.95
    rCSI 3.5%
    PRS 83.23
  • pulmonary artery endothelial cell CL1001568
    CSI 1.9
    rCSI 2.58%
    PRS 93.63
  • club cell CL0000158
    CSI 1.88
    rCSI 2.76%
    PRS 83.88
  • conjunctival epithelial cell CL1000432
    CSI 1.85
    rCSI 2.82%
    PRS 88.02
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.77
    rCSI 2.97%
    PRS 74.37
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 1.7
    rCSI 5.24%
    PRS 91.03
  • parietal epithelial cell CL1000452
    CSI 1.64
    rCSI 4.37%
    PRS 82.52
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.59
    rCSI 4.03%
    PRS 81.62
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.58
    rCSI 4.09%
    PRS 85.29
  • basal cell of epidermis CL0002187
    CSI 1.45
    rCSI 2.57%
    PRS 59.26
  • placental villous trophoblast CL2000060
    CSI 1.32
    rCSI 2.05%
    PRS 87.13
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 0.93
    rCSI 1.13%
    PRS 69.31
  • suprabasal keratinocyte CL4033013
    CSI 0.88
    rCSI 1.43%
    PRS 58.75
  • melanocyte of skin CL1000458
    CSI 0.83
    rCSI 1.13%
    PRS 58.52
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.44
    rCSI 3.03%
    PRS 92.28

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SEMA3F](/details-gene/6405) (semaphorin 3F) is a protein-coding gene located on chromosome 3p21.31, a region frequently deleted in lung cancer ([Link](https://pubmed.ncbi.nlm.nih.gov/8649831/)). As a member of the semaphorin family, [SEMA3F](/details-gene/6405) is a secreted protein that functions primarily as a chemorepellent guidance cue in the nervous system, playing a critical role in processes such as axon guidance and neural crest cell migration. Beyond its well-established neurodevelopmental functions, expression data suggests a significant role in non-neuronal tissues. **Overall**, it is a highly significant marker in [secretory cells](/details-cell/CL0000151) and various types of endothelial cells, including those of the lung and heart, indicating broader functions in vascular biology, tissue architecture, and potentially tumor suppression. ## Cellular Roles and Expression Landscape The expression profile of [SEMA3F](/details-gene/6405) highlights its importance in both epithelial/secretory and endothelial cell populations, extending its functional context beyond the nervous system. **Overall**, the gene shows its highest significance in [secretory cells](/details-cell/CL0000151) (CSI: 6.22), suggesting a primary role in cellular secretion and communication within glandular or mucosal tissues. This is complemented by high significance in other respiratory tract cells, such as [respiratory suprabasal cells](/details-cell/CL4033048) and [ciliated cells](/details-cell/CL0000064). A second major functional axis is its prominent role in the vasculature. [SEMA3F](/details-gene/6405) is a significant marker for a diverse array of endothelial cells, including [pulmonary capillary endothelial cells](/details-cell/CL4028001), [lung endothelial cells](/details-cell/CL1001567), [cardiac endothelial cells](/details-cell/CL0010008), and [cerebral cortex endothelial cells](/details-cell/CL1001602). This widespread expression across different vascular beds suggests a conserved role in maintaining vascular integrity, regulating angiogenesis, or guiding vessel patterning. Finally, consistent with its canonical function, [SEMA3F](/details-gene/6405) is also significantly expressed in specialized cells of the nervous system, particularly the retina, including [Mueller cells](/details-cell/CL0000636), [retinal cone cells](/details-cell/CL0000573), and [retinal bipolar neurons](/details-cell/CL0000748). ## Pathways and Molecular Function The functional annotations for [SEMA3F](/details-gene/6405) are predominantly centered on its role as an extracellular signaling molecule in neuronal development. * **Biological Processes:** [SEMA3F](/details-gene/6405) is a key participant in the [semaphorin-plexin signaling pathway](/details-ontology/GO:0071526), which governs [axon guidance](/details-ontology/GO:0007411) and [nerve development](/details-ontology/GO:0021675). It is specifically implicated in the negative regulation of axon extension ([GO:0048843](/details-ontology/GO:0048843)) and acts as a guidance cue for various neuronal projections, including those of branchiomotor, sympathetic, and trigeminal nerves. It also regulates [neural crest cell migration](/details-ontology/GO:0001755), a fundamental process in embryonic development. Its described function in the [positive regulation of cell migration](/details-ontology/GO:0030335) in some contexts may appear contradictory but could reflect cell-type specific responses to semaphorin signaling. * **Molecular Function:** At the molecular level, [SEMA3F](/details-gene/6405) exerts its effects through [semaphorin receptor binding](/details-ontology/GO:0030215) and [neuropilin binding](/details-ontology/GO:0038191). This interaction typically results in [chemorepellent activity](/details-ontology/GO:0045499), driving cells away from the source of the SEMA3F signal. * **Cellular Component:** As a secreted protein, [SEMA3F](/details-gene/6405) is found in the [extracellular space](/details-ontology/GO:0005615), where it can diffuse to form signaling gradients. It is also associated with the [plasma membrane](/details-ontology/GO:0005886) and is a component of the [glutamatergic synapse](/details-ontology/GO:0098978). ## Research Directions The established role of [SEMA3F](/details-gene/6405) as a chemorepulsive guidance cue, combined with its expression in endothelial cells and its location in a tumor suppressor locus, generates several compelling avenues for future research. **Proposed Hypotheses:** 1. Given its location in a chromosomal region (3p21.3) deleted in lung cancer ([Link](https://doi.org/10.1073/pnas.93.9.4120/)) and its chemorepulsive properties, loss of [SEMA3F](/details-gene/6405) expression in the lung tumor microenvironment may remove an inhibitory barrier, thereby promoting tumor angiogenesis and metastatic invasion. 2. Based on its high expression in diverse endothelial populations and its function as a guidance molecule, [SEMA3F](/details-gene/6405) may function as a key regulator of vascular patterning, preventing aberrant vessel growth in healthy tissues and guiding endothelial cell migration during wound healing or development. **Experimental Approach:** To test the hypothesis that [SEMA3F](/details-gene/6405) acts as a tumor suppressor by inhibiting angiogenesis, a co-culture angiogenesis assay could be performed. Human umbilical vein endothelial cells (HUVECs) could be cultured on a Matrigel matrix to form capillary-like tubes. These cultures could then be treated with conditioned media from lung cancer cell lines with and without [SEMA3F](/details-gene/6405) expression (e.g., using CRISPR-Cas9 knockout or shRNA knockdown). A significant increase in tube formation, branching, and length in the presence of media from [SEMA3F](/details-gene/6405)-deficient cancer cells would support its role as an anti-angiogenic factor. **Therapeutic Potential:** As [SEMA3F](/details-gene/6405) is a secreted protein and its loss is associated with cancer progression ([OMIM: [601124](https://omim.org/entry/601124)]), it represents a candidate for **restoration** or **activation** therapy rather than inhibition. The administration of a recombinant SEMA3F protein or a peptide mimetic could potentially restore its chemorepulsive and anti-angiogenic signals in the tumor microenvironment. This approach could serve as a novel anti-metastatic and anti-angiogenic treatment, particularly for non-small cell lung cancer where its loss of function is well-documented.

Genular Protein ID: 854203885

Symbol: SEM3F_HUMAN

Name: Semaphorin-3F

UniProtKB Accession Codes:

Q13275 C9JQ85 Q13274 Q13372 Q15704 Q6GTR4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 22 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 5 SIGNOR 1 SMART 4 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8649831

Title: Distinct 3p21.3 deletions in lung cancer and identification of a new human semaphorin.

PubMed ID: 8649831

PubMed ID: 8786119

Title: Isolation of the human semaphorin III/F gene (SEMA3F) at chromosome 3p21, a region deleted in lung cancer.

PubMed ID: 8786119

DOI: 10.1006/geno.1996.0074

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8633026

Title: Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns.

PubMed ID: 8633026

DOI: 10.1073/pnas.93.9.4120

Sequence Information:

  • Length: 785
  • Mass: 88381
  • Checksum: FE3FC796EEC1608E
  • Sequence:
    • MLVAGLLLWA SLLTGAWPSF PTQDHLPATP RVRLSFKELK ATGTAHFFNF LLNTTDYRIL 
LKDEDHDRMY VGSKDYVLSL DLHDINREPL IIHWAASPQR IEECVLSGKD VNGECGNFVR 
LIQPWNRTHL YVCGTGAYNP MCTYVNRGRR AQATPWTQTQ AVRGRGSRAT DGALRPMPTA 
PRQDYIFYLE PERLESGKGK CPYDPKLDTA SALINEELYA GVYIDFMGTD AAIFRTLGKQ 
TAMRTDQYNS RWLNDPSFIH AELIPDSAER NDDKLYFFFR ERSAEAPQSP AVYARIGRIC 
LNDDGGHCCL VNKWSTFLKA RLVCSVPGED GIETHFDELQ DVFVQQTQDV RNPVIYAVFT 
SSGSVFRGSA VCVYSMADIR MVFNGPFAHK EGPNYQWMPF SGKMPYPRPG TCPGGTFTPS 
MKSTKDYPDE VINFMRSHPL MYQAVYPLQR RPLVVRTGAP YRLTTIAVDQ VDAADGRYEV 
LFLGTDRGTV QKVIVLPKDD QELEELMLEE VEVFKDPAPV KTMTISSKRQ QLYVASAVGV 
THLSLHRCQA YGAACADCCL ARDPYCAWDG QACSRYTASS KRRSRRQDVR HGNPIRQCRG 
FNSNANKNAV ESVQYGVAGS AAFLECQPRS PQATVKWLFQ RDPGDRRREI RAEDRFLRTE 
QGLLLRALQL SDRGLYSCTA TENNFKHVVT RVQLHVLGRD AVHAALFPPL SMSAPPPPGA 
GPPTPPYQEL AQLLAQPEVG LIHQYCQGYW RHVPPSPREA PGAPRSPEPQ DQKKPRNRRH 
HPPDT

Genular Protein ID: 4027682705

Symbol: Q59G50_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q59G50

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 8 Gene3D 3 InterPro 10 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 4 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 1 RefSeq 2 SAM 1 SMART 4 SUPFAM 3

Sequence Information:

  • Length: 750
  • Mass: 84961
  • Checksum: 2DA6A703B764FC98
  • Sequence:
    • ERANEPRRSG EPRAQRRTWD HLPATPRVRL SFKELKATGT AHFFNFLLNT TDYRILLKDE 
DHDRMYVGSK DYVLSLDLHD INREPLIIHW AASPQRIEEC VLSGKDVNGE CGNFVRLIQP 
WNRTHLYVCG TGAYNPMCTY VNRGRRAQDY IFYLEPERLE SGKGKCPYDP KLDTASALIN 
EELYAGVYID FMGTDAAIFR TLGKQTAMRT DQYNSRWLND PSFIHAELIP DSAERNDDKL 
YFFFRERSAE APQSPAVYAR IGRICLNDDG GHCCLVNKWS TFLKARLVCS VPGEDGIETH 
FDELQDVFVQ QTQDVRNPVI YAVFTSSGSV FRGSAVCVYS MADIRMVFNG PFAHKEGPNY 
QWMPFSGKMP YPRPGTCPGG TFTPSMKSTK DYPDEVINFM RSHPLMYQAV YPLQRRPLVV 
RTGAPYRLTT IAVDQVDAAD GRYEVLFLGT DRGTVQKVIV LPKDDQEMEE LMLEEVEVFK 
DPAPVKTMTI SSKRQQLYVA SAVGVTHLSL HRCQAYGAAC ADCCLARDPY CAWDGQACSR 
YTASSKRRSR RQDVRHGNPI RQCRGFNSNA NKNAVESVQY GVAGSAAFLE CQPRSPQATV 
KWLFQRDPGD RRREIRAEDR FLRTEQGLLL RALQLSDRGL YSCTATENNF KHVVTRVQLH 
VLGRDAVHAA LFPPLSMSAP PPPGAGPPTP PYQELAQLLA QPEVGLIHQY CQGYWRHVPP 
SPREAPGAPR SPEPQDQKKP RNRRHHPPDT

Genular Protein ID: 1155240077

Symbol: C9JPG5_HUMAN

Name: N/A

UniProtKB Accession Codes:

C9JPG5

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 3 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 10 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 4 PROSITE-ProRule 1 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SMART 4 SMR 1 SUPFAM 3 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

Sequence Information:

  • Length: 686
  • Mass: 77313
  • Checksum: 914C25054DA56BC8
  • Sequence:
    • MYVGSKDYVL SLDLHDINRE PLIIHWAASP QRIEECVLSG KDVNGECGNF VRLIQPWNRT 
HLYVCGTGAY NPMCTYVNRG RRAQDYIFYL EPERLESGKG KCPYDPKLDT ASALINEELY 
AGVYIDFMGT DAAIFRTLGK QTAMRTDQYN SRWLNDPSFI HAELIPDSAE RNDDKLYFFF 
RERSAEAPQS PAVYARIGRI CLNDDGGHCC LVNKWSTFLK ARLVCSVPGE DGIETHFDEL 
QDVFVQQTQD VRNPVIYAVF TSSGSVFRGS AVCVYSMADI RMVFNGPFAH KEGPNYQWMP 
FSGKMPYPRP GTCPGGTFTP SMKSTKDYPD EVINFMRSHP LMYQAVYPLQ RRPLVVRTGA 
PYRLTTIAVD QVDAADGRYE VLFLGTDRGT VQKVIVLPKD DQELEELMLE EVEVFKDPAP 
VKTMTISSKR QQLYVASAVG VTHLSLHRCQ AYGAACADCC LARDPYCAWD GQACSRYTAS 
SKRRSRRQDV RHGNPIRQCR GFNSNANKNA VESVQYGVAG SAAFLECQPR SPQATVKWLF 
QRDPGDRRRE IRAEDRFLRT EQGLLLRALQ LSDRGLYSCT ATENNFKHVV TRVQLHVLGR 
DAVHAALFPP LSMSAPPPPG AGPPTPPYQE LAQLLAQPEV GLIHQYCQGY WRHVPPSPRE 
APGAPRSPEP QDQKKPRNRR HHPPDT