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FLASH GENE

Symbol

SERPINA12

contributors: sge/npt/pgu - updated : 24-02-2015

HGNC name	serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 12
HGNC id	18359

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	14q32.13      Physical location : 94.953.620 - 94.984.181
Synonym name	vaspin
	visceral adipose-specific SERPIN
	visceral adipose tissue-derived serine protease inhibitor
	serpin A12
	serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 12
Synonym symbol(s)	OL-64, Vaspin

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
text	serine protease inhibitor (serpin) gene cluster
STRUCTURE	30.56 kb     6 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_173850 6 - 2087 NP_776249 - 414 - 2004 15014966

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue       Reproductive female system placenta       Homo sapiens Skin/Tegument skin

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol not specific adipocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

GlycoP

HOMOLOGY

Homologene

FAMILY

serine protease inhibitor (serpin) family

CATEGORY

signaling cytokine

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in diabetes
	exerting an insulin-sensitizing effect targeted toward visceral white adipose tissues in states of obesity
	IAPP and SERPINA12 are modulated by energy status in the placenta, which suggests that these proteins may be involved in the regulation of placental metabolic functions (pMID: 19554505)
	acting as regulator of insulin sensitivity but also as mediators of the inflammatory process
	adipocytokine with insulin-sensitizing effects
	protects vascular endothelial cells from free fatty acid-induced apoptosis through upregulation of the PI3-kinase/Akt signaling pathway
	activates the PI3-kinase/Akt signaling cascade in aortic endothelial cells
	is a novel adipocytokine with anti-inflammatory property in vascular SMCs
	is a novel ligand for cell-surface HSPA5/DNAJC1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions
	protects osteoblasts (hOBs) from serum deprivation-induced apoptosis, which may be mediated by activating the MAPK/ERK signaling pathway
	might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NFKB1 following AMPK activation
	role of vaspin in atherosclerosis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	SERPINA12 significantly inhibited PDGFB-induced smooth muscle cells (SMCs) migration
	PDGFB-induced activation of MAPK14 was significantly suppressed by SERPINA12
	binds to cell-surface HSPA5, which is recruited from ER to plasma membrane under ER stress
	likely downregulates osteoclastogenesis in part by inhibiting expression of the transcription factor NFATC1
	KLK7 inhibition by SERPINA12 is an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance
	KLK14 is a second KLK protease to be inhibited by SERPINA12

cell & other

REGULATION

Other

expression in adipose tissue is regulated in a fat depot-specific manner and could be associated with parameters of obesity, insulin resistance, and glucose metabolism

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   only expressed in patients with type 2 diabetes constitutional     --over   associated with obesity and impaired insulin sensitivity constitutional     --over   serum vaspin concentrations were significantly higher in patients with ulcerative colitis (UC) than in patients with Crohn disease (CD) and controls constitutional     --over   Vaspin levels have been shown to increase in acute ischemic stroke patients constitutional     --over   SERPINA12 and ITLN1 are up-regulated in large for gestational age infants at term

Susceptibility

to carotid atherosclerosis to Chronic Obstructive Pulmonary Disease

Variant & Polymorphism SNP	SNP rs2236242 associated with type 2 diabete mellitus with the AA genotype bearing an increased risk
	serum vaspin level was positively associated with carotid intima-media thickness (c-IMT) and carotid atherosclerosis
	SNP (rs140198372), in SERPINA12, increase the risk of Chronic Obstructive Pulmonary Disease (COPD)

Candidate gene	serum SERPINA12 is one of the predictors for insulin-resistance in obese children
	serum concentration is altered in patients with non-alcoholic fatty liver disease
Marker	may aid the auxiliary diagnosis of UC and may be useful for assessing disease activity in patients
Therapy target
	System Type Disorder Pubmed obesity     promising candidate for drug development for the treatment of obesity-related insulin resistance and inflammation diabete type 2   promising candidate for drug development for the treatment of obesity-related insulin resistance and inflammation

ANIMAL & CELL MODELS

vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers