Maspin

SERPINB5
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1WZ9, 1XQG, 1XQJ, 1XU8
Identifiers
Aliases	SERPINB5, PI5, maspin, serpin family B member 5
External IDs	OMIM: 154790; MGI: 109579; HomoloGene: 20580; GeneCards: SERPINB5; OMA:SERPINB5 - orthologs
Gene location (Human)
Chr.	Chromosome 18 (human)
End	63,505,085 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	106,811,078 bp
RNA expression pattern
	Top expressed in
	skin of abdomen; ; skin of leg; ; olfactory zone of nasal mucosa; ; skin of thigh; ; testicle; ; minor salivary glands; ; vagina; ; tonsil; ; human penis; ; appendix;
	Top expressed in
	skin of external ear; ; hair follicle; ; esophagus; ; skin of back; ; corneal stroma; ; lip; ; conjunctival fornix; ; skin of abdomen; ; Eustachian tube; ; lumbar spinal ganglion;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding; serine-type endopeptidase inhibitor activity;
Cellular component	cytoplasm; extracellular region; extracellular space;
Biological process	morphogenesis of an epithelium; extracellular matrix organization; regulation of epithelial cell proliferation; prostate gland morphogenesis; negative regulation of endopeptidase activity;
	Sources:Amigo / QuickGO
Orthologs
	5268
	20724
	ENSG00000206075
	ENSMUSG00000067006
	P36952
	P70124
	NM_002639
	NM_009257; NM_001360853; NM_001360854
	NP_002630
	NP_033283; NP_001347782; NP_001347783
	Wikidata
View/Edit Human	View/Edit Mouse

Maspin (mammary serine protease inhibitor) is a protein that in humans is encoded by the SERPINB5 gene.^[5] This protein belongs to the serpin (serine protease inhibitor) superfamily.^[5] SERPINB5 was originally reported to function as a tumor suppressor gene in epithelial cells, suppressing the ability of cancer cells to invade and metastasize to other tissues.^[6] Furthermore, and consistent with an important biological function, Maspin knockout mice were reported to be non-viable, dying in early embryogenesis.^[7] However, a subsequent study using viral transduction as a method of gene transfer (rather than single cell cloning) was not able to reproduce the original findings and found no role for maspin in tumour biology.^[8] Furthermore, the latter study demonstrated that maspin knockout mice are viable and display no obvious phenotype.^[8] These data are consistent with the observation that maspin is not expressed in early embryogenesis.^[8] The precise molecular function of maspin is thus currently unknown.

Tissue distribution

Maspin is expressed in the skin, prostate, testis, intestine, tongue, lung, and the thymus.^[5]

Serpin superfamily

Maspin is a member of the serpin superfamily of serine protease inhibitors.^[5] The primary function of most members of this family is to regulate the breakdown of proteins by inhibiting the catalytic activity of proteinases. Through this mechanism of action, serpins regulate a number of cellular processes including phagocytosis, coagulation, and fibrinolysis.^[9]

Serpins have a complex structure, a key component of which is the reactive site loop, RSL.^[10] Inhibitory serpins transition between a stress and relaxed stage. The catalytic serine residue in the protease target attacks the stressed conformation of the RSL loop to form an acyl intermediate. The loop then undergoes a conformational change to the relaxed state irreversibly trapping the protease in an inactive state. Hence the serpin functions as a suicide inhibitor of the protease.^[11] This transition does not occur in serpins that lack inhibitory activity.^[10]

Function

Given its original reported role in cancer biology,^[6] numerous studies have investigated a role for maspin in tumour metastasis.^[12] However, to date no detailed molecular mechanism for maspin function in cell proliferation or tumour biology has been comprehensively described. Further, it is suggested that original reports of maspin as a tumor suppressor may reflect clonal artefacts rather than true maspin function.^[8] Importantly, and in contrast to original reports, maspin knockout mice are viable, displaying no overt phenotype in the absence of suitable biological or environmental challenge.^[8] Accordingly, the molecular function of maspin remains unclear.

From a structural perspective, maspin is a non-inhibitory and obligate intracellular member of the serpin superfamily.^[13] Specifically, its RSL does not transition between a stressed and relaxed state following proteolytic cleavage.^[14] This region is also shorter than the RSL loop in other serpins. Accordingly, in the absence of an obvious protease-related function, other targets of maspin have been suggested. For example, rather than being a protease inhibitor, maspin is proposed to function as an inhibitor of histone deacetylase 1 (HDAC1).^[10]^[15]

Clinical significance

A comprehensive analysis of maspin expression in breast cancer revealed no significant correlation between maspin expression and overall survival, distant metastasis-free survival or recurrence-free survival.^[8] Changes in maspin expression may, however, reflect the expression status of the known tumour suppressor PHLPP1.^[8]