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Semaphorin-3A

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Protein-coding gene in the species Homo sapiens
SEMA3A
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1Q47, 4GZ8, 4GZA

Identifiers
AliasesSEMA3A, COLL1, HH16, Hsema-I, Hsema-III, SEMA1, SEMAD, SEMAIII, SEMAL, SemD, coll-1, semaphorin 3A
External IDsOMIM: 603961; MGI: 107558; HomoloGene: 31358; GeneCards: SEMA3A; OMA:SEMA3A - orthologs
Gene location (Human)
Chromosome 7 (human)
Chr.Chromosome 7 (human)
Chromosome 7 (human)Genomic location for SEMA3AGenomic location for SEMA3A
Band7q21.11Start83,955,777 bp
End84,492,724 bp
Gene location (Mouse)
Chromosome 5 (mouse)
Chr.Chromosome 5 (mouse)
Chromosome 5 (mouse)Genomic location for SEMA3AGenomic location for SEMA3A
Band5|5 A1Start13,175,381 bp
End13,652,533 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • stromal cell of endometrium

  • epithelium of colon

  • cartilage tissue

  • ventricular zone

  • ganglionic eminence

  • muscle layer of sigmoid colon

  • gonad

  • testicle

  • sural nerve

  • gastric mucosa
Top expressed in
  • outer enamel epithelium

  • medial vestibular nucleus

  • cervical loop

  • genital tubercle

  • lumbar subsegment of spinal cord

  • fossa

  • left lung lobe

  • epithelium of lens

  • tail of embryo

  • olfactory tubercle
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

10371

20346

Ensembl

ENSG00000075213

ENSMUSG00000028883

UniProt

Q14563

O08665

RefSeq (mRNA)

NM_006080

NM_001243072
NM_001243073
NM_009152

RefSeq (protein)

NP_006071

NP_001230001
NP_001230002
NP_033178

Location (UCSC)Chr 7: 83.96 – 84.49 MbChr 5: 13.18 – 13.65 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Semaphorin-3A is a protein that in humans is encoded by the SEMA3A gene.

Function

The SEMA3A gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted Semaphorin-3A protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development.

Semaphorin-3A is secreted by neurons and surrounding tissue to guide migrating cells and axons in the developing nervous system. Axon pathfinding is the process by which neurons follow very precise paths, sends out axons, and react to specific chemical environments to reach the correct endpoint. The guidance is critical for the precise formation of neurons and the surrounding vasculature. Guidance cues, such as Sema3A, induce the collapse and paralysis of neuronal growth cones during development of the nervous system.

This guidance cue for axons of neurons is signaled through receptor complexes containing Neuropilin-1 (NRP1) and a co-receptor. One of the first identified intracellular messenger required for the growth cone-collapse induced by Sema3A is the CRMP protein called CRMP2.

In addition to its role in the nervous system, Sema3A also acts as an inhibitor of angiogenesis, the process by which new blood vessels develop.

Clinical significance

The protein semaphorin-3A is highly expressed in scar tissue after traumatic central nervous system injuries, such as spinal cord injury. Semaphorin-3A, and the other class 3 semaphorins, contributes to the failure of neuronal regeneration after CNS injury by regulating axonal re-growth, re-myelination, re-vascularisation, and the immune response.

Increased expression of semaphorin-3A is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease.

Additionally, the terminal Schwann cells of amyotrophic lateral sclerosis (ALS) mice (SOD1 mutant) express semaphorin-3A at fast-fatigable fiber neuromuscular junctions greater than wild-type mice. This expression is greatest pre-symptomatically corresponding to ALS progression in which fast-fatigable fiber denervation precedes clinical symptoms. Because semaphorin-3A is involved in growth cone collapse, axon pruning, and repulsion, it potentially holds a causal relationship to synaptic weakening and denervation that precedes motor neuron apoptosis in ALS.

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000075213Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000028883Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Kolodkin AL, Matthes DJ, Goodman CS (Jan 1994). "The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules". Cell. 75 (7): 1389–99. doi:10.1016/0092-8674(93)90625-Z. PMID 8269517. S2CID 21047504.
  6. Püschel AW, Adams RH, Betz H (Jun 1995). "Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension". Neuron. 14 (5): 941–8. doi:10.1016/0896-6273(95)90332-1. PMID 7748561.
  7. ^ "Entrez Gene: SEMA3A sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A".
  8. Moret F, Renaudot C, Bozon M, Castellani V (December 2007). "Semaphorin and neuropilin co-expression in motoneurons sets axon sensitivity to environmental semaphorin sources during motor axon pathfinding". Development. 134 (24): 4491–501. doi:10.1242/dev.011452. PMID 18039974.
  9. Vieira JM, Schwarz Q, Ruhrberg C (May 2007). "Selective requirements for NRP1 ligands during neurovascular patterning". Development. 134 (10): 1833–43. doi:10.1242/dev.002402. PMC 2702678. PMID 17428830.
  10. Sharma A, Verhaagen J, Harvey AR (2012). "Receptor complexes for each of the Class 3 Semaphorins". Frontiers in Cellular Neuroscience. 6: 28. doi:10.3389/fncel.2012.00028. PMC 3389612. PMID 22783168.
  11. Maione F, Molla F, Meda C, Latini R, Zentilin L, Giacca M, Seano G, Serini G, Bussolino F, Giraudo E (2009). "Semaphorin 3A is an endogenous angiogenesis inhibitor that blocks tumor growth and normalizes tumor vasculature in transgenic mouse models". The Journal of Clinical Investigation. 119 (11): 3356–72. doi:10.1172/JCI36308. PMC 2769187. PMID 19809158.
  12. Mecollari V, Nieuwenhuis B, Verhaagen J (2014). "A perspective on the role of class III semaphorin signaling in central nervous system trauma". Frontiers in Cellular Neuroscience. 8: 328. doi:10.3389/fncel.2014.00328. PMC 4209881. PMID 25386118.
  13. Good PF, Alapat D, Hsu A, Chu C, Perl D, Wen X, Burstein DE, Kohtz DS (November 2004). "A role for semaphorin 3A signaling in degeneration of hippocampal neurons during Alzheimer's disease". J. Neurochem. 91 (3): 716–36. doi:10.1111/j.1471-4159.2004.02766.x. PMID 15485501. S2CID 25337688.
  14. ^ De Winter F, Vo T, Stam FJ, Wisman LA, Bär PR, Niclou SP, van Muiswinkel FL, Verhaagen J (2006). "The expression of the chemorepellent Semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease". Mol. Cell. Neurosci. 32 (1–2): 102–17. doi:10.1016/j.mcn.2006.03.002. PMID 16677822. S2CID 466902.
  15. Frey D, Schneider C, Xu L, Borg J, Spooren W, Caroni P (April 2000). "Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases". J. Neurosci. 20 (7): 2534–42. doi:10.1523/JNEUROSCI.20-07-02534.2000. PMC 6772256. PMID 10729333.

Further reading

External links

PDB gallery
  • 1q47: Structure of the Semaphorin 3A Receptor-Binding Module 1q47: Structure of the Semaphorin 3A Receptor-Binding Module
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