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ProSAAS (IA-4) (Proprotein convertase subtilisin/kexin type 1 inhibitor) (Proprotein convertase 1 inhibitor) (pro-SAAS) [Cleaved into: KEP; Big SAAS (b-SAAS); Little SAAS (l-SAAS); Big PEN-LEN (b-PEN-LEN) (SAAS CT(1-49)); PEN; PEN-20; PEN-19; Little LEN (l-LEN); Big LEN (b-LEN) (SAAS CT(25-40))]

 PCSK1_MOUSE             Reviewed;         258 AA.
Q9QXV0; Q91W26;
31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
31-OCT-2006, sequence version 2.
10-MAY-2017, entry version 100.
RecName: Full=ProSAAS;
AltName: Full=IA-4;
AltName: Full=Proprotein convertase subtilisin/kexin type 1 inhibitor;
Short=Proprotein convertase 1 inhibitor;
AltName: Full=pro-SAAS;
Contains:
RecName: Full=KEP;
Contains:
RecName: Full=Big SAAS;
Short=b-SAAS;
Contains:
RecName: Full=Little SAAS;
Short=l-SAAS;
Contains:
RecName: Full=Big PEN-LEN;
Short=b-PEN-LEN;
AltName: Full=SAAS CT(1-49);
Contains:
RecName: Full=PEN;
Contains:
RecName: Full=PEN-20;
Contains:
RecName: Full=PEN-19;
Contains:
RecName: Full=Little LEN;
Short=l-LEN;
Contains:
RecName: Full=Big LEN;
Short=b-LEN;
AltName: Full=SAAS CT(25-40);
Flags: Precursor;
Name=Pcsk1n;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, PROTEOLYTIC PROCESSING (KEP; BIG
SAAS; LITTLE SAAS; PEN AND LITTLE LEN), TISSUE SPECIFICITY,
SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
PubMed=10632593;
Fricker L., McKinzie A.A., Sun J., Curran E., Qian Y., Yan L.,
Patterson S.D., Courchesne P.L., Richards B., Levin N., Mzhavia N.,
Devi L.A., Douglass J.;
"Identification and characterization of proSAAS, a granin-like
neuroendocrine peptide precursor that inhibits prohormone
processing.";
J. Neurosci. 20:639-648(2000).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=FVB/N; TISSUE=Colon;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
IDENTIFICATION OF PCSK1-INHIBITING HEXAPEPTIDE.
PubMed=9756897; DOI=10.1074/jbc.273.41.26589;
Apletalina E., Appel J., Lamango N.S., Houghten R.A., Lindberg I.;
"Identification of inhibitors of prohormone convertases 1 and 2 using
a peptide combinatorial library.";
J. Biol. Chem. 273:26589-26595(1998).
[4]
TISSUE SPECIFICITY.
PubMed=9630436; DOI=10.1159/000054314;
Donadel G., Marinos N., DeSilva M.G., Lu J., Notkins A.L., Lan M.S.;
"Molecular cloning and characterization of a highly basic protein, IA-
4, expressed in pancreatic islets and brain.";
Neuroendocrinology 67:190-196(1998).
[5]
PROTEOLYTIC PROCESSING (LITTLE SAAS; PEN AND BIG LEN).
PubMed=11094058; DOI=10.1074/jbc.M009067200;
Mzhavia N., Berman Y., Che F.-Y., Fricker L.D., Devi L.A.;
"ProSAAS processing in mouse brain and pituitary.";
J. Biol. Chem. 276:6207-6213(2001).
[6]
TISSUE SPECIFICITY, AND PROTEOLYTIC PROCESSING.
PubMed=11259501; DOI=10.1046/j.1471-4159.2001.00165.x;
Sayah M., Fortenberry Y., Cameron A., Lindberg I.;
"Tissue distribution and processing of proSAAS by proprotein
convertases.";
J. Neurochem. 76:1833-1841(2001).
[7]
FUNCTION, PROTEOLYTIC PROCESSING (BIG SAAS; LITTLE SAAS; BIG PEN-LEN;
PEN; PEN-20; PEN-19 AND BIG LEN), AND SUBCELLULAR LOCATION.
PubMed=11742530; DOI=10.1042/0264-6021:3610067;
Mzhavia N., Qian Y., Feng Y., Che F.-Y., Devi L.A., Fricker L.D.;
"Processing of proSAAS in neuroendocrine cell lines.";
Biochem. J. 361:67-76(2002).
[8]
DEVELOPMENTAL STAGE.
PubMed=15018810; DOI=10.1016/S1567-133X(02)00002-9;
Feng Y., Reznik S.E., Fricker L.D.;
"ProSAAS and prohormone convertase 1 are broadly expressed during
mouse development.";
Gene Expr. Patterns 1:135-140(2002).
[9]
FUNCTION, PROTEOLYTIC PROCESSING (BIG PEN-LEN AND BIG LEN), AND
MUTAGENESIS OF 241-LYS-ARG-242.
PubMed=11719503; DOI=10.1074/jbc.M104531200;
Fortenberry Y., Hwang J.R., Apletalina E.V., Lindberg I.;
"Functional characterization of ProSAAS: similarities and differences
with 7B2.";
J. Biol. Chem. 277:5175-5186(2002).
[10]
TISSUE SPECIFICITY (PEN).
PubMed=16631141; DOI=10.1016/j.brainres.2006.02.124;
Chakraborty T.R., Tkalych O., Nanno D., Garcia A.L., Devi L.A.,
Salton S.R.;
"Quantification of VGF- and pro-SAAS-derived peptides in endocrine
tissues and the brain, and their regulation by diet and cold stress.";
Brain Res. 1089:21-32(2006).
[11]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: May function in the control of the neuroendocrine
secretory pathway. Proposed be a specific endogenous inhibitor of
PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal
inhibitory domain, but not the processed peptides reduce PCSK1
activity in the endoplasmic reticulum and Golgi. It reduces the
activity of the 87 kDa form but not the autocatalytically derived
66 kDa form of PCSK1. Subsequent processing of proSAAS may
eliminate the inhibition. Slows down convertase-mediated
processing of proopiomelanocortin and proenkephalin. May control
the intracellular timing of PCSK1 rather than its total level of
activity. The function of the processed secreted peptides is not
known. {ECO:0000269|PubMed:10632593, ECO:0000269|PubMed:11719503,
ECO:0000269|PubMed:11742530}.
-!- SUBUNIT: Interacts via the C-terminal inhibitory domain with PCSK1
66 kDa form. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10632593,
ECO:0000269|PubMed:11742530}. Golgi apparatus, trans-Golgi network
{ECO:0000269|PubMed:11742530}.
-!- TISSUE SPECIFICITY: Expressed in brain (mostly hypothalamus and
pituitary) and gut. Expressed in trigeminal ganglia and
neuroendocrine cell lines. PEN is expressed in pancreas, spinal
cord and brain (most abundant in striatum, hippocampus, pons and
medulla, and cortex) (at protein level).
{ECO:0000269|PubMed:10632593, ECO:0000269|PubMed:11259501,
ECO:0000269|PubMed:16631141, ECO:0000269|PubMed:9630436}.
-!- DEVELOPMENTAL STAGE: Broadly expressed from E9 to E11, with some
enrichment in neural tube-derived tissues. By E15, the expression
is largely restricted to neuroendocrine tissues.
{ECO:0000269|PubMed:15018810}.
-!- DOMAIN: ProSAAS(1-180) increases secretion of enzymatically
inactive PCSK1.
-!- DOMAIN: The C-terminal inhibitory domain is involved in inhibition
of PCSK1. It corresponds to the probable processing intermediate
Big PEN-LEN, binds to PCSK1 in vitro and contains the hexapeptide
L-L-R-V-K-R, which, as a synthetic peptide, is sufficient for
PCSK1 inhibition.
-!- PTM: Proteolytically cleaved in the Golgi. Little SAAS, PEN, PEN-
20 and Big LEN are the major processed peptides in proSAAS-
overexpressing AtT-20 pituitary corticotropic cell line.
{ECO:0000269|PubMed:10632593, ECO:0000269|PubMed:11094058,
ECO:0000269|PubMed:11259501, ECO:0000269|PubMed:11719503,
ECO:0000269|PubMed:11742530}.
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EMBL; AF181560; AAF22641.1; -; mRNA.
EMBL; BC012263; AAH12263.1; -; mRNA.
CCDS; CCDS29979.1; -.
RefSeq; NP_038920.2; NM_013892.3.
UniGene; Mm.4881; -.
ProteinModelPortal; Q9QXV0; -.
SMR; Q9QXV0; -.
BioGrid; 205954; 1.
IntAct; Q9QXV0; 2.
MINT; MINT-4130541; -.
STRING; 10090.ENSMUSP00000040342; -.
MEROPS; I49.001; -.
iPTMnet; Q9QXV0; -.
PhosphoSitePlus; Q9QXV0; -.
MaxQB; Q9QXV0; -.
PaxDb; Q9QXV0; -.
PeptideAtlas; Q9QXV0; -.
PRIDE; Q9QXV0; -.
Ensembl; ENSMUST00000041096; ENSMUSP00000040342; ENSMUSG00000039278.
GeneID; 30052; -.
KEGG; mmu:30052; -.
UCSC; uc009snf.2; mouse.
CTD; 27344; -.
MGI; MGI:1353431; Pcsk1n.
eggNOG; ENOG410IWT4; Eukaryota.
eggNOG; ENOG4111DVB; LUCA.
GeneTree; ENSGT00390000013488; -.
HOGENOM; HOG000261638; -.
HOVERGEN; HBG080210; -.
InParanoid; Q9QXV0; -.
OMA; RPVKEPR; -.
OrthoDB; EOG091G0R4Z; -.
PhylomeDB; Q9QXV0; -.
TreeFam; TF338201; -.
PRO; PR:Q9QXV0; -.
Proteomes; UP000000589; Chromosome X.
Bgee; ENSMUSG00000039278; -.
Genevisible; Q9QXV0; MM.
GO; GO:0070062; C:extracellular exosome; ISO:MGI.
GO; GO:0005615; C:extracellular space; IDA:MGI.
GO; GO:0030141; C:secretory granule; IDA:MGI.
GO; GO:0005802; C:trans-Golgi network; IDA:MGI.
GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:MGI.
GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
GO; GO:0016486; P:peptide hormone processing; IDA:MGI.
GO; GO:0009409; P:response to cold; IDA:MGI.
GO; GO:0002021; P:response to dietary excess; IDA:MGI.
InterPro; IPR010832; ProSAAS.
PANTHER; PTHR15531; PTHR15531; 1.
Pfam; PF07259; ProSAAS; 1.
1: Evidence at protein level;
Cleavage on pair of basic residues; Complete proteome;
Golgi apparatus; Neuropeptide; Reference proteome; Secreted; Signal.
SIGNAL 1 33 {ECO:0000255}.
CHAIN 34 258 ProSAAS.
/FTId=PRO_0000259681.
PEPTIDE 34 59 Big SAAS.
/FTId=PRO_0000259683.
PEPTIDE 34 40 KEP.
/FTId=PRO_0000259682.
PEPTIDE 42 59 Little SAAS.
/FTId=PRO_0000259684.
PEPTIDE 219 258 Big PEN-LEN.
/FTId=PRO_0000259685.
PEPTIDE 219 240 PEN.
/FTId=PRO_0000259686.
PEPTIDE 219 238 PEN-20.
/FTId=PRO_0000259687.
PEPTIDE 219 237 PEN-19.
/FTId=PRO_0000259688.
PEPTIDE 243 258 Big LEN.
/FTId=PRO_0000259690.
PEPTIDE 243 252 Little LEN.
/FTId=PRO_0000259689.
REGION 34 213 ProSAAS(1-180).
REGION 219 258 C-terminal inhibitory domain; interacts
with PCSK1.
MOTIF 237 242 Sufficient for inhibition of PCSK1.
MUTAGEN 241 242 KR->SS: Abolishes inhibition of PCSK1.
{ECO:0000269|PubMed:11719503}.
CONFLICT 83 83 L -> Q (in Ref. 1; AAF22641).
{ECO:0000305}.
SEQUENCE 258 AA; 27270 MW; 4197C8B077A20A22 CRC64;
MAGSPLLCGP RAGGVGILVL LLLGLLRLPP TLSARPVKEP RSLSAASAPL VETSTPLRLR
RAVPRGEAAG AVQELARALA HLLEAERQER ARAEAQEAED QQARVLAQLL RAWGSPRASD
PPLAPDDDPD APAAQLARAL LRARLDPAAL AAQLVPAPAA APRPRPPVYD DGPTGPDVED
AGDETPDVDP ELLRYLLGRI LTGSSEPEAA PAPRRLRRSV DQDLGPEVPP ENVLGALLRV
KRLENPSPQA PARRLLPP


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Catalog number Product name Quantity
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004-63 SAAS (68_89)_Pro _ 100ug 100 µg
004-54 SAAS (42_59) _Pro (little PEN)(Rat) _ 200ug 200 µg
004-55 SAAS (221_242) _Pro (PEN)(Rat) _ 200ug 200 µg
004-62 SAAS (221_254) _Pro (Rat) _ 100ug 100 µg
004-64 SAAS (62_89)_Pro _ 100ug 100 µg
004-56 SAAS (245_260) _Pro (big PEN)(Rat) _ 200ug 200 µg
004-57 SAAS (42_59) _Pro (little PEN)(Mouse) _ 200ug 200 µg
004-58 SAAS (219_240) _Pro (PEN)(Mouse) _ 200ug 200 µg
004-53 SAAS (245_260) _Pro (big PEN)(Human) _ 200ug 200 µg
004-61 SAAS (235_244) _Pro (Human, Rat) _ 200ug 200 µg
004-59 SAAS (243_258) _Pro (big PEN)(Mouse) _ 200ug 200 µg
004-51 SAAS (42_59) _Pro (Human) _ 200ug 200 µg
004-60 SAAS (235_246) _Pro (Human, Rat) _ 200ug 200 µg
004-52 SAAS (221_242) _Pro (PEN)(Human) _ 200ug 200 µg
DBK-004-52 SAAS (221_242) _Pro (PEN)(Human) _ Dot Blot Kit Kit
FG-004-52A SAAS (221_242) _Pro (PEN)(Human) _ FAM Labeled _ 1 nmol 1 nmol
B-004-54 SAAS (42_59) _Pro (little PEN)(Rat) _ Biotin Labeled _ 20ug 20 µg
B-004-56 SAAS (245_260) _Pro (big PEN)(Rat) _ Biotin Labeled _ 20ug 20 µg
WBK-004-52 SAAS (221_242) _Pro (PEN)(Human) _ Western Blot Kit Kit
G-004-52 SAAS (221_242) _Pro (PEN)(Human) _ Purified IgG Antibody _ 200ug 200 µg
FG-G-004-52A SAAS (221_242) _Pro (PEN)(Human) _ FAM Labeled Purified IgG _ 100ul 100 µl
FR-004-52 SAAS (221_242) _Pro (PEN)(Human) _ Rhodamine Labeled _ 1 nmol 1 nmol


 

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