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SEMA7A
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3NVQ
Identifiers
Aliases	SEMA7A, CD108, CDw108, H-SEMA-K1, H-Sema-L, JMH, SEMAK1, SEMAL, semaphorin 7A (John Milton Hagen blood group), PFIC11
External IDs	OMIM: 607961; MGI: 1306826; HomoloGene: 2678; GeneCards: SEMA7A; OMA:SEMA7A - orthologs
Gene location (Human)
Chr.	Chromosome 15 (human)
End	74,433,958 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	57,870,148 bp
RNA expression pattern
	Top expressed in
	spleen; ; C1 segment; ; primary visual cortex; ; placenta; ; right hemisphere of cerebellum; ; prefrontal cortex; ; stromal cell of endometrium; ; superior frontal gyrus; ; Brodmann area 9; ; right frontal lobe;
	Top expressed in
	cumulus cell; ; cerebellar cortex; ; primary visual cortex; ; superior frontal gyrus; ; lumbar subsegment of spinal cord; ; anterior horn of spinal cord; ; dentate gyrus of hippocampal formation granule cell; ; primary motor cortex; ; lateral geniculate nucleus; ; lobe of cerebellum;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding; integrin binding; neuropilin binding; semaphorin receptor binding; chemorepellent activity;
Cellular component	membrane; plasma membrane; anchored component of membrane; extracellular space; external side of plasma membrane; integral component of plasma membrane; collagen-containing extracellular matrix;
Biological process	cell differentiation; positive regulation of protein phosphorylation; nervous system development; multicellular organism development; osteoblast differentiation; immune response; positive regulation of ERK1 and ERK2 cascade; axon extension; olfactory lobe development; integrin-mediated signaling pathway; positive regulation of axon extension; inflammatory response; neuron projection development; regulation of inflammatory response; negative chemotaxis; positive regulation of macrophage cytokine production; neural crest cell migration; positive regulation of cell migration; negative regulation of axon extension involved in axon guidance; semaphorin-plexin signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	8482
	20361
	ENSG00000138623; ENSG00000288455
	ENSMUSG00000038264
	O75326
	Q9QUR8
	NM_003612; NM_001146029; NM_001146030
	NM_011352
	NP_001139501; NP_001139502; NP_003603
	NP_035482
	Wikidata
View/Edit Human	View/Edit Mouse

Semaphorin 7A, GPI membrane anchor (John Milton Hagen blood group) (SEMA7A) also known as CD108 (Cluster of Differentiation 108), is a human gene.^[5]

SEMA7A is a membrane-bound semaphorin that associates with cell surfaces via a glycosylphosphatidylinositol (GPI) linkage. SEMA7A is also known as the John-Milton-Hagen (JMH) blood group antigen, an 80-kD glycoprotein expressed on activated lymphocytes and erythrocytes.[supplied by OMIM]^[5] SEMA7A is expressed in various adult tissues such as adipose, colon, esophagus, heart, brain, spleen, testis, lung, ovary, and uterus.^[6]

Development

SEMA7A promotes axonal growth and is involved in mesoderm derived somite formation. Murine embryonic Sema7A expression is highest on day 7, which is indicative of its role on the differentiation of germ layer structure.^[7] Embryonic Sema7A expression is noticeable at all developmental stages as well as in the newborn and adult thymus, indicative of a development T-cell role.^[7] In wild type neurons, addition of Sema7A under in vitro conditions promotes elongation and branching in a dose dependent manner.^[8] Unlike the majority of semaphorins, SEMA7A enhances axonal growth and is imperative for proper embryonic axonal tract formation.^[9] Limited expression of SEMA7A is found in the hindbrain as opposed to an abundance of SEMA7A expression found in both the cranial and trunk neural crest cells, which indicates an involvement in migration and differentiation.^[10] Sema7A -/- mice show defects in olfactory tract development.^[11]

Tumorigenesis

In normal breast tissue, mRNA expression of SEMA7A is low or not expressed, but activation to re-express SEMA7A occurs in these adult tissues to cause pleiotropic effects which increase tumorigenesis.^[12]^[13] Tumor cell growth, EMT, lung metastasis and angiogenesis have been linked to increased Sema7a expression in murine models.^[14]^[15]^[16] Increased SEMA7A expression correlates with poor prognosis in breast cancer patients.^[13] Tumors increase SEMA7A expression in an involuting environment, but knockout of SEMA7a in mouse models undergoing involution decreases lymphangiogenesis.^[17]

Genetics

This protein is known to have eight variants in the extracellular region: seven lie within the Sema domain and one within the PSI domain.^{[citation needed]}

Molecular biology

This protein forms dimers.^{[citation needed]}

Notes

This protein acts as a receptor for the malaria parasite Plasmodium falciparum.

References

^ ^a ^b ^c ENSG00000288455 GRCh38: Ensembl release 89: ENSG00000138623, ENSG00000288455 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000038264 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: SEMA7A semaphorin 7A, GPI membrane anchor (John Milton Hagen blood group)".
^ "Tissue expression of SEMA7A - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2020-04-14.
^ ^a ^b Mine T, Harada K, Matsumoto T, Yamana H, Shirouzu K, Itoh K, et al. (May 2000). "CDw108 expression during T-cell development". Tissue Antigens. 55 (5): 429–436. doi:10.1034/j.1399-0039.2000.550505.x. PMID 10885563.
^ Moresco EM, Donaldson S, Williamson A, Koleske AJ (June 2005). "Integrin-mediated dendrite branch maintenance requires Abelson (Abl) family kinases". The Journal of Neuroscience. 25 (26): 6105–6118. doi:10.1523/JNEUROSCI.1432-05.2005. PMC 6725048. PMID 15987940.
^ Scott GA, McClelland LA, Fricke AF (January 2008). "Semaphorin 7a promotes spreading and dendricity in human melanocytes through beta1-integrins". The Journal of Investigative Dermatology. 128 (1): 151–161. doi:10.1038/sj.jid.5700974. PMID 17671519.
^ Bao ZZ, Jin Z (August 2006). "Sema3D and Sema7A have distinct expression patterns in chick embryonic development". Developmental Dynamics. 235 (8): 2282–2289. doi:10.1002/dvdy.20882. PMC 1564195. PMID 16804892.
^ Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL (July 2003). "Semaphorin 7A promotes axon outgrowth through integrins and MAPKs". Nature. 424 (6947): 398–405. Bibcode:2003Natur.424..398J. doi:10.1038/nature01790. PMID 12879062. S2CID 12690989.
^ Moserle L, Casanovas O (March 2012). "Exploiting pleiotropic activities of semaphorins as multi-target therapies for cancer". EMBO Molecular Medicine. 4 (3): 168–170. doi:10.1002/emmm.201200206. PMC 3376851. PMID 22323445.
^ ^a ^b Black SA, Nelson AC, Gurule NJ, Futscher BW, Lyons TR (September 2016). "Semaphorin 7a exerts pleiotropic effects to promote breast tumor progression". Oncogene. 35 (39): 5170–5178. doi:10.1038/onc.2016.49. PMC 5720143. PMID 27065336.
^ Garcia-Areas R, Libreros S, Amat S, Keating P, Carrio R, Robinson P, et al. (2014). "Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice". Frontiers in Physiology. 5: 17. doi:10.3389/fphys.2014.00017. PMC 3914020. PMID 24550834.
^ Allegra M, Zaragkoulias A, Vorgia E, Ioannou M, Litos G, Beug H, et al. (October 2012). Chernoff J (ed.). "Semaphorin-7a reverses the ERF-induced inhibition of EMT in Ras-dependent mouse mammary epithelial cells". Molecular Biology of the Cell. 23 (19): 3873–3881. doi:10.1091/mbc.e12-04-0276. PMC 3459863. PMID 22875994.
^ Ringnér M, Fredlund E, Häkkinen J, Borg Å, Staaf J (March 2011). Creighton C (ed.). "GOBO: gene expression-based outcome for breast cancer online". PLOS ONE. 6 (3): e17911. Bibcode:2011PLoSO...617911R. doi:10.1371/journal.pone.0017911. PMC 3061871. PMID 21445301.
^ Elder AM, Tamburini BA, Crump LS, Black SA, Wessells VM, Schedin PJ, et al. (November 2018). "Semaphorin 7A Promotes Macrophage-Mediated Lymphatic Remodeling during Postpartum Mammary Gland Involution and in Breast Cancer". Cancer Research. 78 (22): 6473–6485. doi:10.1158/0008-5472.CAN-18-1642. PMC 6239927. PMID 30254150.

External links

SEMA7A+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
John Milton Hagen blood group system in the BGMUT blood group antigen gene mutation database
PDBe-KB provides an overview of all the structure information available in the PDB for Human Semaphorin-7A

This article incorporates text from the United States National Library of Medicine, which is in the public domain.