PCS1N_RAT
ID PCS1N_RAT Reviewed; 260 AA.
AC Q9QXU9;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 94.
DE RecName: Full=ProSAAS;
DE AltName: Full=Proprotein convertase subtilisin/kexin type 1 inhibitor;
DE Short=Proprotein convertase 1 inhibitor;
DE AltName: Full=pro-SAAS;
DE Contains:
DE RecName: Full=KEP;
DE Contains:
DE RecName: Full=Big SAAS;
DE Short=b-SAAS;
DE Contains:
DE RecName: Full=Little SAAS;
DE Short=l-SAAS;
DE Contains:
DE RecName: Full=Big PEN-LEN;
DE Short=b-PEN-LEN;
DE AltName: Full=SAAS CT(1-49);
DE Contains:
DE RecName: Full=PEN;
DE Contains:
DE RecName: Full=PEN-20;
DE Contains:
DE RecName: Full=Little LEN;
DE Short=l-LEN;
DE Contains:
DE RecName: Full=Big LEN;
DE Short=b-LEN;
DE AltName: Full=SAAS CT(25-40);
DE Flags: Precursor;
GN Name=Pcsk1n;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10632593; DOI=10.1523/jneurosci.20-02-00639.2000;
RA Fricker L., McKinzie A.A., Sun J., Curran E., Qian Y., Yan L.,
RA Patterson S.D., Courchesne P.L., Richards B., Levin N., Mzhavia N.,
RA Devi L.A., Douglass J.;
RT "Identification and characterization of proSAAS, a granin-like
RT neuroendocrine peptide precursor that inhibits prohormone processing.";
RL J. Neurosci. 20:639-648(2000).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=9630436; DOI=10.1159/000054314;
RA Donadel G., Marinos N., DeSilva M.G., Lu J., Notkins A.L., Lan M.S.;
RT "Molecular cloning and characterization of a highly basic protein, IA-4,
RT expressed in pancreatic islets and brain.";
RL Neuroendocrinology 67:190-196(1998).
RN [3]
RP FUNCTION, AND INTERACTION WITH PCSK1.
RX PubMed=10816562; DOI=10.1074/jbc.m001583200;
RA Qian Y., Devi L.A., Mzhavia N., Munzer S., Seidah N.G., Fricker L.D.;
RT "The C-terminal region of proSAAS is a potent inhibitor of prohormone
RT convertase 1.";
RL J. Biol. Chem. 275:23596-23601(2000).
RN [4]
RP PROTEOLYTIC PROCESSING (BIG SAAS; LITTLE SAAS; BIG PEN-LEN; PEN; PEN-20 AND
RP BIG LEN).
RX PubMed=11742530; DOI=10.1042/0264-6021:3610067;
RA Mzhavia N., Qian Y., Feng Y., Che F.-Y., Devi L.A., Fricker L.D.;
RT "Processing of proSAAS in neuroendocrine cell lines.";
RL Biochem. J. 361:67-76(2002).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=15935061; DOI=10.1111/j.1471-4159.2005.03138.x;
RA Morgan D.J., Mzhavia N., Peng B., Pan H., Devi L.A., Pintar J.E.;
RT "Embryonic gene expression and pro-protein processing of proSAAS during
RT rodent development.";
RL J. Neurochem. 93:1454-1462(2005).
CC -!- FUNCTION: May function in the control of the neuroendocrine secretory
CC pathway. Proposed be a specific endogenous inhibitor of PCSK1
CC (PubMed:10632593, PubMed:10816562). ProSAAS and Big PEN-LEN, both
CC containing the C-terminal inhibitory domain, but not the processed
CC peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi.
CC It reduces the activity of the 87 kDa form but not the
CC autocatalytically derived 65 kDa form of PCSK1. Subsequent processing
CC of proSAAS may eliminate the inhibition. Slows down convertase-mediated
CC processing of proopiomelanocortin and proenkephalin. May control the
CC intracellular timing of PCSK1 rather than its total level of activity
CC (By similarity). {ECO:0000250|UniProtKB:Q9QXV0,
CC ECO:0000269|PubMed:10632593, ECO:0000269|PubMed:10816562}.
CC -!- FUNCTION: [Big LEN]: Endogenous ligand for GPR171. Neuropeptide
CC involved in the regulation of feeding. {ECO:0000250|UniProtKB:Q9QXV0}.
CC -!- FUNCTION: [PEN]: Endogenous ligand for GPR171. Neuropeptide involved in
CC the regulation of feeding. {ECO:0000250|UniProtKB:Q9QXV0}.
CC -!- SUBUNIT: Interacts via the C-terminal inhibitory domain with PCSK1 65
CC kDa form. {ECO:0000269|PubMed:10816562}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9QXV0}. Golgi
CC apparatus, trans-Golgi network {ECO:0000250|UniProtKB:Q9QXV0}.
CC -!- TISSUE SPECIFICITY: Expressed in adult brain (all major structural
CC regions), adrenal gland (medulla) and spinal cord (dorsal and ventral
CC horn). Expressed in pancreatic islands. {ECO:0000269|PubMed:10632593,
CC ECO:0000269|PubMed:9630436}.
CC -!- DEVELOPMENTAL STAGE: Expressed by E12.5 in essentially all
CC differentiating neurons in the mantle layer of the myelencephalon,
CC metencephalon, diencephalon, spinal cord and several sympathetic
CC ganglia. During later stages of prenatal development, widespread
CC expression continues in post-mitotic neurons of both the CNS and PNS
CC and begins in endocrine cells of the anterior and intermediate
CC pituitary. {ECO:0000269|PubMed:15935061}.
CC -!- DOMAIN: ProSAAS(1-180) increases secretion of enzymatically inactive
CC PCSK1. {ECO:0000250}.
CC -!- DOMAIN: The C-terminal inhibitory domain is involved in inhibition of
CC PCSK1. It corresponds to the probable processing intermediate Big PEN-
CC LEN, binds to PCSK1 in vitro and contains the hexapeptide L-L-R-V-K-R,
CC which, as a synthetic peptide, is sufficient for PCSK1 inhibition.
CC -!- DOMAIN: [Big LEN]: The four C-terminal amino acids of Big LEN are
CC sufficient to bind and activate GPR171. {ECO:0000250|UniProtKB:Q9QXV0}.
CC -!- PTM: Proteolytically cleaved in the Golgi. Big SAAS, Little SAAS, PEN
CC and Big LEN are the major processed peptides in proSAAS-overexpressing
CC PC-12 phaeochromocytoma cells (lacking PCSK1 and PCSK2 endopeptidases).
CC Peptides corresponding to PEN and a proSAAS aa 40-59 have been detected
CC in wild-type PC-12 cells. {ECO:0000269|PubMed:11742530}.
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DR EMBL; AF181561; AAF22642.1; -; mRNA.
DR RefSeq; NP_062152.1; NM_019279.1.
DR AlphaFoldDB; Q9QXU9; -.
DR SMR; Q9QXU9; -.
DR BioGRID; 251598; 1.
DR IntAct; Q9QXU9; 1.
DR MEROPS; I49.001; -.
DR iPTMnet; Q9QXU9; -.
DR PhosphoSitePlus; Q9QXU9; -.
DR jPOST; Q9QXU9; -.
DR PaxDb; Q9QXU9; -.
DR PRIDE; Q9QXU9; -.
DR GeneID; 246333; -.
DR KEGG; rno:246333; -.
DR UCSC; RGD:3617; rat.
DR CTD; 27344; -.
DR RGD; 3617; Pcsk1n.
DR eggNOG; ENOG502RYS0; Eukaryota.
DR InParanoid; Q9QXU9; -.
DR OrthoDB; 1511698at2759; -.
DR PhylomeDB; Q9QXU9; -.
DR PRO; PR:Q9QXU9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0030141; C:secretory granule; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; ISO:RGD.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:RGD.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0016486; P:peptide hormone processing; ISO:RGD.
DR GO; GO:0009409; P:response to cold; ISO:RGD.
DR GO; GO:0002021; P:response to dietary excess; ISO:RGD.
DR InterPro; IPR010832; ProSAAS.
DR PANTHER; PTHR15531; PTHR15531; 1.
DR Pfam; PF07259; ProSAAS; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Golgi apparatus; Neuropeptide;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..260
FT /note="ProSAAS"
FT /id="PRO_0000259691"
FT PEPTIDE 34..59
FT /note="Big SAAS"
FT /id="PRO_0000259693"
FT PEPTIDE 34..40
FT /note="KEP"
FT /evidence="ECO:0000250"
FT /id="PRO_0000259692"
FT PEPTIDE 42..59
FT /note="Little SAAS"
FT /id="PRO_0000259694"
FT PEPTIDE 221..260
FT /note="Big PEN-LEN"
FT /evidence="ECO:0000250"
FT /id="PRO_0000259695"
FT PEPTIDE 221..242
FT /note="PEN"
FT /id="PRO_0000259696"
FT PEPTIDE 221..240
FT /note="PEN-20"
FT /id="PRO_0000259697"
FT PEPTIDE 245..260
FT /note="Big LEN"
FT /id="PRO_0000259698"
FT PEPTIDE 245..254
FT /note="Little LEN"
FT /evidence="ECO:0000250"
FT /id="PRO_0000259699"
FT REGION 34..215
FT /note="ProSAAS(1-180)"
FT REGION 162..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 206..234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..260
FT /note="C-terminal inhibitory domain; interacts with PCSK1"
FT MOTIF 239..244
FT /note="Sufficient for inhibition of PCSK1"
FT /evidence="ECO:0000250"
SQ SEQUENCE 260 AA; 27414 MW; C84F688BDEB5313E CRC64;
MAGSPLLCGP RAGGVGLLVL LLLGLLRLPP TLSARPVKEP RSLSAASAPL AETSTPLRLR
RAVPRGEAAG AVQELARALA HLLEAERQER ARAEAQEAED QQARVLAQLL RAWGSPRASD
PPLAPDDDPD APAAQLARAL LRARLDPAAL AAQLVPAPAP AAALRPRPPV YDDGPTGPDV
EDAADETPDV DPELLRYLLG RILTGSSEPE AAPAPRRLRR AVDQDLGPEV PPENVLGALL
RVKRLENSSP QAPARRLLPP
