Semaphorin-3A

Semaphorin-3A is a protein that in humans is encoded by the SEMA3A gene.^[5][6][7]

SEMA3A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Q47, 4GZ8, 4GZA
Identifiers
Aliases	SEMA3A, COLL1, HH16, Hsema-I, Hsema-III, SEMA1, SEMAD, SEMAIII, SEMAL, SemD, coll-1, semaphorin 3A
External IDs	OMIM: 603961; MGI: 107558; HomoloGene: 31358; GeneCards: SEMA3A; OMA:SEMA3A - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q21.11 Start 83,955,777 bp[1] End 84,492,724 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 A1 Start 13,175,381 bp[2] End 13,652,533 bp[2]
RNA expression pattern Bgee Human Mouse (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 chemorepellent activity semaphorin receptor binding neuropilin binding Cellular component extracellular region dendrite extracellular space axon integral component of plasma membrane Biological process sympathetic ganglion development negative regulation of axon extension cell differentiation ventral trunk neural crest cell migration regulation of axon extension involved in axon guidance semaphorin-plexin signaling pathway involved in neuron projection guidance negative chemotaxis neural crest cell migration involved in sympathetic nervous system development sympathetic nervous system development facioacoustic ganglion development dendrite morphogenesis trigeminal ganglion development neuron migration semaphorin-plexin signaling pathway involved in axon guidance regulation of heart rate nervous system development axon guidance multicellular organism development sympathetic neuron projection guidance neural crest cell migration involved in autonomic nervous system development branchiomotor neuron axon guidance gonadotrophin-releasing hormone neuronal migration to the hypothalamus axonogenesis involved in innervation dichotomous subdivision of terminal units involved in salivary gland branching facial nerve structural organization olfactory bulb development motor neuron axon guidance axonal fasciculation negative regulation of epithelial cell migration nerve development trigeminal nerve structural organization axon extension involved in axon guidance semaphorin-plexin signaling pathway sympathetic neuron projection extension positive regulation of male gonad development sensory system development apoptotic process negative regulation of neuron projection development negative regulation of axon extension involved in axon guidance positive regulation of neuron migration neural crest cell migration positive regulation of cell migration positive regulation of JNK cascade basal dendrite arborization Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 5: 13.18 – 13.65 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[7]

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, send 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 the 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.^[8][9][10] One of the first identified intracellular messengers 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.^[11]

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, contribute to the failure of neuronal regeneration after CNS injury by regulating axonal re-growth, re-myelination, re-vascularisation, and the immune response.^[12]

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.^[7][13]

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.^[14] This expression is greatest pre-symptomatically corresponding to ALS progression in which fast-fatigable fiber denervation precedes clinical symptoms.^[15] 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.^[14]