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

 PCSK1_HUMAN             Reviewed;         260 AA.
Q9UHG2; Q4VC04;
31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
23-MAY-2018, entry version 127.
RecName: Full=ProSAAS;
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;
AltName: Full=N-proSAAS;
Contains:
RecName: Full=Big PEN-LEN;
Short=b-PEN-LEN;
AltName: Full=SAAS CT(1-49);
Contains:
RecName: Full=PEN;
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;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
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], AND VARIANT THR-31.
TISSUE=Brain, and Uterus;
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]
MUTAGENESIS OF VAL-235; LEU-236; GLY-237; LEU-240; ARG-241; VAL-242;
LYS-243; ARG-244; LEU-245 AND GLU-246.
PubMed=11435430; DOI=10.1074/jbc.M104064200;
Basak A., Koch P., Dupelle M., Fricker L.D., Devi L.A., Chretien M.,
Seidah N.G.;
"Inhibitory specificity and potency of proSAAS-derived peptides toward
proprotein convertase 1.";
J. Biol. Chem. 276:32720-32728(2001).
[4]
SUBCELLULAR LOCATION (PROTEIN TAU DEPOSITS), AND PROTEOLYTIC
PROCESSING.
PubMed=12914799; DOI=10.1016/S0006-291X(03)01391-3;
Kikuchi K., Arawaka S., Koyama S., Kimura H., Ren C.H., Wada M.,
Kawanami T., Kurita K., Daimon M., Kawakatsu S., Kadoya T., Goto K.,
Kato T.;
"An N-terminal fragment of ProSAAS (a granin-like neuroendocrine
peptide precursor) is associated with tau inclusions in Pick's
disease.";
Biochem. Biophys. Res. Commun. 308:646-654(2003).
[5]
SUBCELLULAR LOCATION (PROTEIN TAU DEPOSITS).
PubMed=14746899; DOI=10.1016/j.neulet.2003.11.028;
Wada M., Ren C.H., Koyama S., Arawaka S., Kawakatsu S., Kimura H.,
Nagasawa H., Kawanami T., Kurita K., Daimon M., Hirano A., Kato T.;
"A human granin-like neuroendocrine peptide precursor (proSAAS)
immunoreactivity in tau inclusions of Alzheimer's disease and
parkinsonism-dementia complex on Guam.";
Neurosci. Lett. 356:49-52(2004).
[6]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-53 AND THR-247, AND
STRUCTURE OF CARBOHYDRATES.
TISSUE=Cerebrospinal fluid;
PubMed=19838169; DOI=10.1038/nmeth.1392;
Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E.,
Brinkmalm G., Larson G.;
"Enrichment of glycopeptides for glycan structure and attachment site
identification.";
Nat. Methods 6:809-811(2009).
[7]
GLYCOSYLATION AT THR-53; SER-228 AND THR-247, STRUCTURE OF
CARBOHYDRATES, AND IDENTIFICATION BY MASS SPECTROMETRY.
PubMed=22171320; DOI=10.1074/mcp.M111.013649;
Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
"Human urinary glycoproteomics; attachment site specific analysis of
N-and O-linked glycosylations by CID and ECD.";
Mol. Cell. Proteomics 11:1-17(2012).
[8]
GLYCOSYLATION AT SER-228, AND IDENTIFICATION BY MASS SPECTROMETRY.
PubMed=23234360; DOI=10.1021/pr300963h;
Halim A., Ruetschi U., Larson G., Nilsson J.;
"LC-MS/MS characterization of O-glycosylation sites and glycan
structures of human cerebrospinal fluid glycoproteins.";
J. Proteome Res. 12:573-584(2013).
-!- 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 further processed peptides reduce
PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces
the activity of the 84 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 (By similarity). {ECO:0000250}.
-!- SUBUNIT: Interacts via the C-terminal inhibitory domain with PCSK1
66 kDa form. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9QXV0}.
Golgi apparatus, trans-Golgi network
{ECO:0000250|UniProtKB:Q9QXV0}. Note=A N-terminal processed
peptide, probably Big SAAS or Little SAAS, is accumulated in
cytoplasmic protein tau deposits in frontotemporal dementia and
parkinsonism linked to chromosome 17 (Pick disease), Alzheimer
disease and amyotrophic lateral sclerosis-parkinsonism/dementia
complex 1 (Guam disease). {ECO:0000269|PubMed:12914799,
ECO:0000269|PubMed:14746899}.
-!- TISSUE SPECIFICITY: Expressed in brain and pancreas.
{ECO:0000269|PubMed:10632593}.
-!- DOMAIN: ProSAAS(1-180) increases secretion of enzymatically
inactive PCSK1. {ECO:0000250}.
-!- 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 (By similarity). {ECO:0000250}.
-!- PTM: Proteolytically cleaved in the Golgi.
{ECO:0000269|PubMed:12914799}.
-!- PTM: O-glycosylated with a core 1 or possibly core 8 glycan.
{ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320,
ECO:0000269|PubMed:23234360}.
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EMBL; AF181562; AAF22643.1; -; mRNA.
EMBL; BC002851; AAH02851.1; -; mRNA.
CCDS; CCDS14307.1; -.
RefSeq; NP_037403.1; NM_013271.4.
UniGene; Hs.522640; -.
ProteinModelPortal; Q9UHG2; -.
SMR; Q9UHG2; -.
BioGrid; 118156; 10.
IntAct; Q9UHG2; 1.
MINT; Q9UHG2; -.
STRING; 9606.ENSP00000218230; -.
MEROPS; I49.001; -.
GlyConnect; 743; -.
iPTMnet; Q9UHG2; -.
PhosphoSitePlus; Q9UHG2; -.
UniCarbKB; Q9UHG2; -.
DMDM; 74735013; -.
MaxQB; Q9UHG2; -.
PaxDb; Q9UHG2; -.
PeptideAtlas; Q9UHG2; -.
PRIDE; Q9UHG2; -.
DNASU; 27344; -.
Ensembl; ENST00000218230; ENSP00000218230; ENSG00000102109.
GeneID; 27344; -.
KEGG; hsa:27344; -.
UCSC; uc004dkz.6; human.
CTD; 27344; -.
DisGeNET; 27344; -.
EuPathDB; HostDB:ENSG00000102109.8; -.
GeneCards; PCSK1N; -.
HGNC; HGNC:17301; PCSK1N.
HPA; HPA003925; -.
HPA; HPA064734; -.
MIM; 300399; gene.
neXtProt; NX_Q9UHG2; -.
OpenTargets; ENSG00000102109; -.
PharmGKB; PA33090; -.
eggNOG; ENOG410IWT4; Eukaryota.
eggNOG; ENOG4111DVB; LUCA.
GeneTree; ENSGT00390000013488; -.
HOGENOM; HOG000261638; -.
HOVERGEN; HBG080210; -.
InParanoid; Q9UHG2; -.
OMA; RPVKEPR; -.
OrthoDB; EOG091G0R4Z; -.
PhylomeDB; Q9UHG2; -.
TreeFam; TF338201; -.
GenomeRNAi; 27344; -.
PRO; PR:Q9UHG2; -.
Proteomes; UP000005640; Chromosome X.
Bgee; ENSG00000102109; -.
CleanEx; HS_PCSK1N; -.
Genevisible; Q9UHG2; HS.
GO; GO:0005615; C:extracellular space; IBA:GO_Central.
GO; GO:0030141; C:secretory granule; IEA:Ensembl.
GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:Ensembl.
GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
GO; GO:0016486; P:peptide hormone processing; IEA:Ensembl.
GO; GO:0009409; P:response to cold; IEA:Ensembl.
GO; GO:0002021; P:response to dietary excess; IEA:Ensembl.
InterPro; IPR010832; ProSAAS.
PANTHER; PTHR15531; PTHR15531; 1.
Pfam; PF07259; ProSAAS; 1.
1: Evidence at protein level;
Cleavage on pair of basic residues; Complete proteome; Glycoprotein;
Golgi apparatus; Neuropeptide; Polymorphism; Reference proteome;
Secreted; Signal.
SIGNAL 1 33 {ECO:0000255}.
CHAIN 34 260 ProSAAS.
/FTId=PRO_0000259673.
PEPTIDE 34 59 Big SAAS. {ECO:0000250}.
/FTId=PRO_0000259675.
PEPTIDE 34 40 KEP. {ECO:0000250}.
/FTId=PRO_0000259674.
PEPTIDE 42 59 Little SAAS. {ECO:0000250}.
/FTId=PRO_0000259676.
PEPTIDE 221 260 Big PEN-LEN. {ECO:0000250}.
/FTId=PRO_0000259677.
PEPTIDE 221 242 PEN. {ECO:0000250}.
/FTId=PRO_0000259678.
PEPTIDE 245 260 Big LEN. {ECO:0000250}.
/FTId=PRO_0000259679.
PEPTIDE 245 254 Little LEN. {ECO:0000250}.
/FTId=PRO_0000259680.
REGION 34 215 ProSAAS(1-180). {ECO:0000250}.
REGION 221 260 C-terminal inhibitory domain; interacts
with PCSK1. {ECO:0000250}.
MOTIF 239 244 Sufficient for inhibition of PCSK1.
CARBOHYD 53 53 O-linked (GalNAc...) threonine.
{ECO:0000269|PubMed:19838169,
ECO:0000269|PubMed:22171320}.
CARBOHYD 228 228 O-linked (GalNAc...) serine.
{ECO:0000269|PubMed:22171320,
ECO:0000269|PubMed:23234360}.
CARBOHYD 247 247 O-linked (GalNAc...) threonine.
{ECO:0000269|PubMed:19838169,
ECO:0000269|PubMed:22171320}.
VARIANT 31 31 A -> T (in dbSNP:rs11538176).
{ECO:0000269|PubMed:15489334}.
/FTId=VAR_028971.
MUTAGEN 235 235 V->A: Reduces inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 236 236 L->A: Greatly reduces inhibition of
PCSK1. {ECO:0000269|PubMed:11435430}.
MUTAGEN 237 237 G->A: Reduces inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 240 240 L->A: Reduces inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 241 241 R->A: Reduces inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 242 242 V->A: Reduces inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 243 243 K->A: Abolishes inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 244 244 R->A: Abolishes inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 245 245 L->A: Reduces inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
MUTAGEN 246 246 E->A: Reduces inhibition of PCSK1.
{ECO:0000269|PubMed:11435430}.
SEQUENCE 260 AA; 27372 MW; FF8E2722784B7A5C CRC64;
MAGSPLLWGP RAGGVGLLVL LLLGLFRPPP ALCARPVKEP RGLSAASPPL AETGAPRRFR
RSVPRGEAAG AVQELARALA HLLEAERQER ARAEAQEAED QQARVLAQLL RVWGAPRNSD
PALGLDDDPD APAAQLARAL LRARLDPAAL AAQLVPAPVP AAALRPRPPV YDDGPAGPDA
EEAGDETPDV DPELLRYLLG RILAGSADSE GVAAPRRLRR AADHDVGSEL PPEGVLGALL
RVKRLETPAP QVPARRLLPP


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Catalog number Product name Quantity
EIAAB30199 Homo sapiens,Human,PCSK1N,Proprotein convertase 1 inhibitor,Proprotein convertase subtilisin_kexin type 1 inhibitor,ProSAAS,pro-SAAS
EIAAB30198 IA-4,Mouse,Mus musculus,Pcsk1n,Proprotein convertase 1 inhibitor,Proprotein convertase subtilisin_kexin type 1 inhibitor,ProSAAS,pro-SAAS
EIAAB30200 Pcsk1n,Proprotein convertase 1 inhibitor,Proprotein convertase subtilisin_kexin type 1 inhibitor,ProSAAS,pro-SAAS,Rat,Rattus norvegicus
004-64 SAAS (62_89)_Pro _ 100ug 100 µg
004-54 SAAS (42_59) _Pro (little PEN)(Rat) _ 200ug 200 µg
004-56 SAAS (245_260) _Pro (big 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
004-63 SAAS (68_89)_Pro _ 100ug 100 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
004-59 SAAS (243_258) _Pro (big PEN)(Mouse) _ 200ug 200 µg
004-57 SAAS (42_59) _Pro (little PEN)(Mouse) _ 200ug 200 µg
004-51 SAAS (42_59) _Pro (Human) _ 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
004-60 SAAS (235_246) _Pro (Human, Rat) _ 200ug 200 µg
004-58 SAAS (219_240) _Pro (PEN)(Mouse) _ 200ug 200 µg
FG-004-52A SAAS (221_242) _Pro (PEN)(Human) _ FAM Labeled _ 1 nmol 1 nmol
WBK-004-52 SAAS (221_242) _Pro (PEN)(Human) _ Western Blot Kit Kit
B-004-56 SAAS (245_260) _Pro (big PEN)(Rat) _ Biotin Labeled _ 20ug 20 µg
B-004-54 SAAS (42_59) _Pro (little PEN)(Rat) _ Biotin Labeled _ 20ug 20 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
H-004-52 SAAS (221_242) _Pro (PEN)(Human) _ Antibody for Immunohistochemistry _ 100ul 100 µl


 

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