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FLASH GENE

Symbol

ADCYAP1

contributors: mct/npt - updated : 29-12-2020

HGNC name	adenylate cyclase activating polypeptide 1 (pituitary)
HGNC id	241

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001117 6 - 3089 NP_001108 - 176 - 2020 32651949 NM_001099733 5 - 3259 NP_001093203 27 176 - 2020 32651949 ACAP27 cross the BBB by diffusion over the membrane, but after crossing the endothelial membrane both isoforms (ACAP27 and ACAP38) are either rapidly degraded or efflux back from brain to blood PACAP38 - - - - - - 2018 29785578 ACAP38 is transported over the BBB actively, while PACAP27 cross the BBB by diffusion over the membrane, but after crossing the endothelial membrane both isoforms are either rapidly degraded or efflux back from brain to blood

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   brain diencephalon pituitary   highly Homo sapiens Endocrine pancreas       highly Nervous brain diencephalon hypothalamus   highly Homo sapiens   brain limbic system hippocampus   highly Homo sapiens   nerve spinal nerve hypoglossal nerve   predominantly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central     highly Homo sapiens Nervous peripherous     highly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	pituitary placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

isoforms

Precursor

for PACAP27 (N terminal 27 AA of PACAP38) and PACAP38 (N terminal, 38 residues)

HOMOLOGY

Homologene

FAMILY	glucagon VIP family
	vasoactive intestinal peptide (VIP)/secretin/glucagon family of peptides

CATEGORY

enzyme , regulatory

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,mitochondria

basic FUNCTION	pituitary adenylyl cyclase activating polypeptide, acting as a pivotal modulator of glutamatergic regulation of the suprachiasmatic circadian clock
	regulator of insulin genes of glucose sensing system (GLTI) and hexokinase
	auto and paracrine function in the peri and post ovulatory events involving acute progesterone production and subsequent luteinization in periovulatory granulosa/lutein cells
	decreasing neuronal cell death after ischemia by suppressing cytochrome C release by means of BCL2 regulation
	participates in the processes forming the neuronal laminas in the developing cortex via the intracellular PKA pathway
	inhibits proliferation of cortical progenitors and promotes neurogenesis
	affects two different processes of cortical progenitors via the PKA/CREB signaling pathway acting at different times of the cell cycle, providing a novel cue for unveiling the molecular mechanisms underlying the effects of environmental factors on laminar formation during corticogenesis
	participates in the processes forming the neuronal laminas in the developing cortex via the intracellular PKA pathway
	is a key player in reproduction through its actions as a pituitary autocrine/paracrine hormone
	acting at several levels, influences the balance between pro- and anti-apoptotic factors in favor of anti-apoptosis, thereby providing protection in oxidative stress-induced injury of human retinal pigment epithelial cells
	may play a significant role in the complex interactions of gonadotropin and growth factors during ovulation and fertilisation
	ADCYAP1 is a positive regulator of chondrogenesis, while VIP has been reported playing an important role in the inflammatory reactions of surrounding joint tissues
	is a neuromodulator implicated in anxiety, metabolism and reproductive behavior
	act as a hormone, a neuromodulator, a neurotransmitter and a trophic factor, and has been implicated in a variety of developmental and regenerative processes

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with IL6 (prevents neuronal cell death after ischemia via a signaling mechanism involving IL6)
	GNRH1 augments the ability of ADCYAP1 to regulate gonadotrope function by increasing pituitary ADCYAP1 and PACAP receptor expression
	ADCYAP1/ADCYAP1R1 internalization and recruitment of endosomal signaling regulate cardiac neuron excitability

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function following nerve decompression, and its and its expression was associated with recovery of intraepidermal nerve fibres constitutional       loss of function are associated with clinical severity in the mild cognitive impairment (MCI), and dementia stages of Alzheimer disease (AD)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 2   may serve as a potential target for the treatment of Gestational diabetes mellitus (GDM) miscelleaneous pain   ADCYAP1 and its receptors may be promising targets for migraine therapeutics

ANIMAL & CELL MODELS

	Pacap global knockout mice have decreased fertility and Pacap modulates LH release
	Pacap Knockout (KO) mice exhibit a Sudden Infant Death Syndrome (SIDS)-like phenotype, with an inability to overcome noxious insults, compression of baseline ventilation, and death in the early post-neonatal period (