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FLASH GENE

Symbol

ADM

contributors: mct - updated : 12-06-2016

HGNC name	adrenomedullin
HGNC id	259

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	11p15.4      Physical location : 10.326.641 - 10.328.923
Synonym name	preproadrenomedullin
Synonym symbol(s)	AM

DNA

TYPE	functioning gene
STRUCTURE	2.28 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site   enhancer
text structure	AP2
	cAMP regulated enhancer element
	KLF15 binding site (Nagare 2009)

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001124 4 - 1449 NP_001115 20.3 185 - 2001 11310580

EXPRESSION

Type	ubiquitous

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         Reproductive female system oviduct     highly Mus musculus   female system ovary     highly Homo sapiens Respiratory lung         Homo sapiens Fetal Visual eye retina       Mus musculus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Nervous autonomous       Nervous peripherous

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a intramolecular disulfide bond

HOMOLOGY

Homologene

FAMILY	calcitonin peptide family
	adrenomedullin family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm

basic FUNCTION	playing a role in the physiologic control of fluid and electrolyte homeostasis
	acting in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in blood vessels
	potent hypotensive and vasodilatator agent
	acting as a survival factor in osteoblastic cells via a CALCA receptor-MEK-ERK pathway, which provides further understanding on the physiological function of ADM in osteoblasts
	required for the normal development of the lymphatic vascular system and having role in controlling lymphatic endothelial permeability and lymphatic flow through reorganization of junctional proteins
	stimulates ciliary motility of the human oviduct (
	plays an important role in the regulation of osteoblastic cells through both a proliferative and an anti-apoptotic effects
	could also exert its survival effect in osteoblast via components of the Wnt pathway
	is indeed a factor that can possibi1ity affect cumulus cells and oocytes and involve meiotic arrest during oocyte maturation
	regulates the proliferation rate and the differentiation into neurons, astrocytes, and oligodendrocytes of stem/progenitor cells, probably through the PI3K/Akt pathway
	may contribute to neural stem cell growth regulation by allowing cells to pass through mitosis
	promotes osteoblast growth and proliferation, inducing an increase in bone mass
	facilitates voltage-dependent Ca(2+) channels in osteoblasts
	expression of the pregnancy-related peptide adrenomedullin by fetal trophoblast cells is necessary and sufficient to promote appropriate recruitment and activation of maternal uterine NK (uNK) cells to the placenta and ultimately facilitate remodeling of maternal
	exerts anti-inflammatory and antibacterial effects and stimulates mucosal regeneration for the maintenance of the colonic epithelial barrier
	acts as an autocrine and/or paracrine factor to play a key role in the regulation of cardiovascular function
	can act as a GVBD (germinal vesicle breakdown) regulator
	major regulators of vascular tone and cardiovascular development
	ADM-RAMP2 system suppresses ER stress-induced tubule cell death, thereby exerting a protective effect on kidney

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

ADM-RAMP2 system is a key determinant of vascular integrity and homeostasis from prenatal stages through adulthood

INTERACTION

DNA

RNA

small molecule

protein	binding to calcitonin receptor and calcitonin receptor-like receptor
	RAMP2 is a key determinant of the effects of ADM on the vasculature and is essential for angiogenesis and vascular integrity
	up-regulated the mRNA and protein expressions of HIF1A- and HIF1-targeted genes, and ADM up-regulated the protein expressions of HIF1A through down-regulation of PH4TM mRNA expression and PH4TM activity
	reciprocal synergistic effects of ADM and CFH (
	correlation between ADM and TNF that could hypothesise the existence of a complex interaction between ADM and this inflammatory cytokine

cell & other

REGULATION

inhibited by

KLF15 (inhibits transcription of the adrenomedullin gene in adipocytes)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   aberrantly expressed in multiple myeloma and promotes angiogenesis constitutional     --over   significant increase of ADM, and TNF in the idiopathic IUGR tumoral     --over   in patients with pancreatic cancer and causes insulin resistance in beta cells constitutional     --over   in eyes with ocular pathologies such as diabetic retinopathy, glaucoma, retinitis pigmentosa, and uveitis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	proADM appears to have the advantage of predicting localized bacterial infection and differentiating sepsis from systemic inflammatory response syndrome, in febrile patients with hematologic malignancies
	dysregulated levels of ADM may be involved in sepsis pathophysiology and may be utilized as potential diagnostic biomarkers
Therapy target
	System Type Disorder Pubmed immunology inflammatory   has potential as a new therapeutic agent for the treatment of refractory ulcerative colitis immunology infectious   ADM/CFH is a novel therapy target for safe and effective therapy of patients with hemorrhagic shock, sepsis, and ischemic injury cancer angiogenesis   new potential therapy in cancer, complementary to other existing treatments

ANIMAL & CELL MODELS