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FLASH GENE

Symbol

AHSG

contributors: mct - updated : 15-12-2015

HGNC name	alpha-2-HS-glycoprotein
HGNC id	349

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Cardiovascular heart         Digestive liver         Lymphoid/Immune spleen         Nervous brain forebrain cerebral cortex     Homo sapiens Fetal   brain limbic system hippocampus     Homo sapiens Fetal Reproductive female system breast mammary gland     Urinary kidney tubule collecting duct     Homo sapiens   kidney tubule convoluted tubule     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Digestive hepatocyte Nervous ependymal cell Homo sapiens Fetal Skeleton osteoblast Homo sapiens

cell lineage
cell lines
fluid/secretion	serum

at STAGE

physiological period

embryo

Text	brain, bone marrow

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

GlycoP

isoforms

Precursor

HOMOLOGY

intraspecies	homolog to collagen
	paralog to fetuin b

Homologene

FAMILY

fetuin family

CATEGORY

regulatory , transport

SUBCELLULAR LOCALIZATION	extracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	FGF23 and AHSG proteins co-localized both in cytoplasm and nucleus, which suggests a possible reciprocal interactivity

basic FUNCTION	inhibitor of the insulin-receptor tyrosine kinase
	involved in skeletal development and chronic disorder such as vascular calcifications
	phosphate level is negatively correlated with AHSG level
	implicated in the regulation of body fat and insulin sensitivity
	negative acute phase protein involved in inflammatory diseases, thus being a potential physiological regulator of meprin (MEP1A, MEP1B) activity
	CST3 an AHSG are endogenous inhibitors of human meprin metalloproteases
	is a liver-derived blood protein that acts as a potent inhibitor of ectopic mineralization
	fulfills likely the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance
	regulates potentially endochondral ossification through mineralization inhibition and lipid (hormone) binding
	lipid-induced AHSG from adipocytes is an efficient chemokine for macrophage migration and polarization
	acts as an inhibitor of systemic and local ectopic calcification and inflammatory response
	mediator of inflammatory response that might also be involved in the pathogenesis of inflammatory bowel disease (IBD)
	AHSG and/or palmitate influence the expression of proinflammatory and angiogenic proteins only partially via TLR4 signalling
	contributes to the prevention of soft tissue calcification, modulates inflammation, reduces insulin sensitivity and fosters weight gain following high fat diet or ageing
	liver-derived plasma protein with multiple functions, which is proteolytically processed to yield a disulfide-linked two-chain form
	role in iron homeostasis
	liver protein known to inhibit insulin actions
	serum glycoprotein with recognized anti-calcification activity, also been suggested to modulate both bone formation and resorption

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development , endocytosis transport

text	brain,bone mineralization

PATHWAY

metabolism

signaling

a component

two polypeptide chains cleaved from the precursor and linked by a disulfide bond

INTERACTION

DNA

RNA

small molecule

protein	type II transmembrane serine protease controlling the expression of hepcidin, the key regulator of iron homeostasis
	testosterone participates in the regulation of hepatic AHSG expression, an effect mediated, at least partially, by androgen receptor activation
	substrate of TMPRSS6
	AHSG is produced in bone, mainly in osteocytes, and its production is modulated by FGF23

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   is correlated with the development of cardiovascular diseases (CVD) constitutional     --low   decreased serum AHSG levels were independently associated with disease activity in patients with Crohn disease and ulcerative colitis constitutional     --low   in patients with Alzheimer, disease in proportion to the severity of cognitive impairment constitutional     --low   nephrolithiasis patients had lower AHSG protein level in urine and renal tissue constitutional     --low   AHSG, MMP9, and MMP3 levels were significantly lower in migraine than controls constitutional     --over   in diabetes patients with nonalcoholic fatty liver disease (NAFLD) constitutional     --low   serum AHSG concentration is decreased and reflects-at least partly-systemic inflammation in preeclampsia

Susceptibility

to low body mass index

Variant & Polymorphism SNP	SNP associated to low body mass index
	variant Thr230Met associated with a marked increase in beta2-adrenoceptor sensitivity in subcutaneous fat cells, which may be of importance in body weight regulation

Candidate gene
Marker	may serve as a biological link between vascular disease and normal age-related cognitive decline
	biomarker reported to be important in many metabolic disorders, including obesity, diabetes, and hepatic steatosis
Therapy target

ANIMAL & CELL MODELS

Fetuin-A deficiency in mice resulted in decreased hepcidin mRNA levels