PACA_RAT
ID PACA_RAT Reviewed; 175 AA.
AC P13589;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Pituitary adenylate cyclase-activating polypeptide;
DE Short=PACAP;
DE Contains:
DE RecName: Full=PACAP-related peptide;
DE AltName: Full=PRP-48;
DE Contains:
DE RecName: Full=Pituitary adenylate cyclase-activating polypeptide 27;
DE Short=PACAP-27;
DE Short=PACAP27;
DE Contains:
DE RecName: Full=Pituitary adenylate cyclase-activating polypeptide 38;
DE Short=PACAP-38;
DE Short=PACAP38;
DE Flags: Precursor;
GN Name=Adcyap1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=2268329; DOI=10.1016/s0006-291x(05)80924-6;
RA Ogi K., Kimura C., Onda H., Arimura A., Fujino M.;
RT "Molecular cloning and characterization of cDNA for the precursor of rat
RT pituitary adenylate cyclase activating polypeptide (PACAP).";
RL Biochem. Biophys. Res. Commun. 173:1271-1279(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Testis;
RX PubMed=7835287; DOI=10.1210/endo.136.2.7835287;
RA Hurley J.D., Gardiner J.V., Jones P.M., Bloom S.R.;
RT "Cloning and molecular characterization of complementary deoxyribonucleic
RT acid corresponding to a novel form of pituitary adenylate cyclase-
RT activating polypeptide messenger ribonucleic acid in the rat testis.";
RL Endocrinology 136:550-557(1995).
RN [3]
RP PROTEIN SEQUENCE OF 131-168, AND AMIDATION AT LYS-168.
RX PubMed=2803320; DOI=10.1016/0006-291x(89)91757-9;
RA Miyata A., Arimura A., Dahl R.R., Minamino N., Uehara A., Jiang A.,
RA Culler M.D., Coy D.H.;
RT "Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates
RT adenylate cyclase in pituitary cells.";
RL Biochem. Biophys. Res. Commun. 164:567-574(1989).
RN [4]
RP FUNCTION.
RX PubMed=18198219; DOI=10.1096/fj.06-075820;
RA Grumolato L., Ghzili H., Montero-Hadjadje M., Gasman S., Lesage J.,
RA Tanguy Y., Galas L., Ait-Ali D., Leprince J., Guerineau N.C.,
RA Elkahloun A.G., Fournier A., Vieau D., Vaudry H., Anouar Y.;
RT "Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca2+
RT mobilization and neuroendocrine secretion.";
RL FASEB J. 22:1756-1768(2008).
RN [5]
RP FUNCTION.
RX PubMed=23800469; DOI=10.1126/scisignal.2003993;
RA Emery A.C., Eiden M.V., Mustafa T., Eiden L.E.;
RT "Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal
RT and Endocrine Cells.";
RL Sci. Signal. 6:RA51-RA51(2013).
CC -!- FUNCTION: Binding to its receptor activates G proteins and stimulates
CC adenylate cyclase in pituitary cells (By similarity). Promotes neuron
CC projection development through the RAPGEF2/Rap1/B-Raf/ERK pathway. In
CC chromaffin cells, induces long-lasting increase of intracellular
CC calcium concentrations and neuroendocrine secretion (PubMed:18198219).
CC Involved in the control of glucose homeostasis, induces insulin
CC secretion by pancreatic beta cells (By similarity).
CC {ECO:0000250|UniProtKB:O70176, ECO:0000250|UniProtKB:P18509,
CC ECO:0000250|UniProtKB:Q29W19, ECO:0000269|PubMed:18198219,
CC ECO:0000269|PubMed:23800469}.
CC -!- SUBUNIT: Interacts with ADCYAP1R1 (via N-terminal extracellular
CC domain). {ECO:0000250|UniProtKB:P18509}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR EMBL; M63006; AAA41791.1; -; mRNA.
DR EMBL; X80290; CAA56564.1; -; mRNA.
DR PIR; A37786; A37786.
DR RefSeq; NP_058685.1; NM_016989.2.
DR RefSeq; XP_006245734.1; XM_006245672.3.
DR RefSeq; XP_006245735.1; XM_006245673.3.
DR RefSeq; XP_006245736.1; XM_006245674.3.
DR RefSeq; XP_008765640.1; XM_008767418.2.
DR AlphaFoldDB; P13589; -.
DR BMRB; P13589; -.
DR SMR; P13589; -.
DR STRING; 10116.ENSRNOP00000063920; -.
DR BindingDB; P13589; -.
DR PaxDb; P13589; -.
DR Ensembl; ENSRNOT00000073432; ENSRNOP00000063920; ENSRNOG00000049882.
DR GeneID; 24166; -.
DR KEGG; rno:24166; -.
DR CTD; 116; -.
DR RGD; 2037; Adcyap1.
DR eggNOG; ENOG502QSGB; Eukaryota.
DR GeneTree; ENSGT00950000183154; -.
DR InParanoid; P13589; -.
DR OMA; QDFAYDQ; -.
DR OrthoDB; 1415722at2759; -.
DR PhylomeDB; P13589; -.
DR Reactome; R-RNO-420092; Glucagon-type ligand receptors.
DR PRO; PR:P13589; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000049882; Expressed in testis and 8 other tissues.
DR ExpressionAtlas; P13589; baseline and differential.
DR Genevisible; P13589; RN.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0005184; F:neuropeptide hormone activity; IDA:UniProtKB.
DR GO; GO:0051428; F:peptide hormone receptor binding; ISS:UniProtKB.
DR GO; GO:0016521; F:pituitary adenylate cyclase activating polypeptide activity; IDA:BHF-UCL.
DR GO; GO:0031858; F:pituitary adenylate cyclase-activating polypeptide receptor binding; IDA:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0046034; P:ATP metabolic process; IDA:RGD.
DR GO; GO:0001662; P:behavioral fear response; IDA:RGD.
DR GO; GO:0019933; P:cAMP-mediated signaling; IMP:UniProtKB.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD.
DR GO; GO:0001821; P:histamine secretion; IDA:RGD.
DR GO; GO:0030073; P:insulin secretion; ISS:UniProtKB.
DR GO; GO:0002865; P:negative regulation of acute inflammatory response to antigenic stimulus; IDA:RGD.
DR GO; GO:0002878; P:negative regulation of acute inflammatory response to non-antigenic stimulus; IDA:RGD.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:RGD.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IDA:RGD.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:RGD.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IDA:RGD.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IDA:RGD.
DR GO; GO:0031175; P:neuron projection development; IDA:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; IDA:RGD.
DR GO; GO:0021983; P:pituitary gland development; IEP:RGD.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0071651; P:positive regulation of chemokine (C-C motif) ligand 5 production; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0060124; P:positive regulation of growth hormone secretion; IDA:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0090274; P:positive regulation of somatostatin secretion; IDA:RGD.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IDA:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0070445; P:regulation of oligodendrocyte progenitor proliferation; IDA:RGD.
DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IDA:RGD.
DR GO; GO:0032880; P:regulation of protein localization; IDA:BHF-UCL.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IGI:ParkinsonsUK-UCL.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0019233; P:sensory perception of pain; IDA:RGD.
DR GO; GO:0042311; P:vasodilation; IDA:RGD.
DR InterPro; IPR015550; Glucagon.
DR InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR InterPro; IPR039080; PACAP.
DR PANTHER; PTHR11213; PTHR11213; 1.
DR PANTHER; PTHR11213:SF1; PTHR11213:SF1; 1.
DR Pfam; PF00123; Hormone_2; 2.
DR PRINTS; PR00275; GLUCAGON.
DR SMART; SM00070; GLUCA; 2.
DR PROSITE; PS00260; GLUCAGON; 1.
PE 1: Evidence at protein level;
KW Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW Hormone; Neurogenesis; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..78
FT /id="PRO_0000011501"
FT PEPTIDE 81..128
FT /note="PACAP-related peptide"
FT /id="PRO_0000011502"
FT PEPTIDE 131..168
FT /note="Pituitary adenylate cyclase-activating polypeptide
FT 38"
FT /id="PRO_0000011503"
FT PEPTIDE 131..157
FT /note="Pituitary adenylate cyclase-activating polypeptide
FT 27"
FT /id="PRO_0000011504"
FT PROPEP 172..175
FT /id="PRO_0000011505"
FT REGION 149..157
FT /note="Important for receptor binding"
FT /evidence="ECO:0000250"
FT MOD_RES 157
FT /note="Leucine amide"
FT /evidence="ECO:0000250|UniProtKB:P18509"
FT MOD_RES 168
FT /note="Lysine amide"
FT /evidence="ECO:0000269|PubMed:2803320"
FT CONFLICT 7
FT /note="A -> R (in Ref. 2; CAA56564)"
FT /evidence="ECO:0000305"
FT CONFLICT 26
FT /note="P -> L (in Ref. 2; CAA56564)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 175 AA; 19557 MW; 0398946896602B04 CRC64;
MTMCSGARLA LLVYGIIMHN SVSCSPAAGL SFPGIRPEEE AYDQDGNPLQ DFYDWDPPGA
GSPASALRDA YALYYPADRR DVAHEILNEA YRKVLDQLSA RKYLQSMVAR GMGENLAAAA
VDDRAPLTKR HSDGIFTDSY SRYRKQMAVK KYLAAVLGKR YKQRVKNKGR RIAYL
