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Protein

ProSAAS

Gene

PCSK1N

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • receptor binding Source: ProtInc
  • serine-type endopeptidase inhibitor activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Neuropeptide

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102109-MONOMER.

Protein family/group databases

MEROPSiI49.001.

Names & Taxonomyi

Protein namesi
Recommended name:
ProSAAS
Alternative name(s):
Proprotein convertase subtilisin/kexin type 1 inhibitor
Short name:
Proprotein convertase 1 inhibitor
pro-SAAS
Cleaved into the following 7 chains:
Big SAAS
Short name:
b-SAAS
Little SAAS
Short name:
l-SAAS
Alternative name(s):
N-proSAAS
Big PEN-LEN
Short name:
b-PEN-LEN
Alternative name(s):
SAAS CT(1-49)
Little LEN
Short name:
l-LEN
Big LEN
Short name:
b-LEN
Alternative name(s):
SAAS CT(25-40)
Gene namesi
Name:PCSK1N
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:17301. PCSK1N.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular space Source: ProtInc
  • secretory granule Source: Ensembl
  • trans-Golgi network Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi235V → A: Reduces inhibition of PCSK1. 1 Publication1
Mutagenesisi236L → A: Greatly reduces inhibition of PCSK1. 1 Publication1
Mutagenesisi237G → A: Reduces inhibition of PCSK1. 1 Publication1
Mutagenesisi240L → A: Reduces inhibition of PCSK1. 1 Publication1
Mutagenesisi241R → A: Reduces inhibition of PCSK1. 1 Publication1
Mutagenesisi242V → A: Reduces inhibition of PCSK1. 1 Publication1
Mutagenesisi243K → A: Abolishes inhibition of PCSK1. 1 Publication1
Mutagenesisi244R → A: Abolishes inhibition of PCSK1. 1 Publication1
Mutagenesisi245L → A: Reduces inhibition of PCSK1. 1 Publication1
Mutagenesisi246E → A: Reduces inhibition of PCSK1. 1 Publication1

Organism-specific databases

DisGeNETi27344.
OpenTargetsiENSG00000102109.
PharmGKBiPA33090.

Polymorphism and mutation databases

DMDMi74735013.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33Sequence analysisAdd BLAST33
ChainiPRO_000025967334 – 260ProSAASAdd BLAST227
PeptideiPRO_000025967534 – 59Big SAASBy similarityAdd BLAST26
PeptideiPRO_000025967434 – 40KEPBy similarity7
PeptideiPRO_000025967642 – 59Little SAASBy similarityAdd BLAST18
PeptideiPRO_0000259677221 – 260Big PEN-LENBy similarityAdd BLAST40
PeptideiPRO_0000259678221 – 242PENBy similarityAdd BLAST22
PeptideiPRO_0000259679245 – 260Big LENBy similarityAdd BLAST16
PeptideiPRO_0000259680245 – 254Little LENBy similarity10

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi53O-linked (GalNAc...)2 Publications1
Glycosylationi228O-linked (GalNAc...)2 Publications1
Glycosylationi247O-linked (GalNAc...)2 Publications1

Post-translational modificationi

Proteolytically cleaved in the Golgi.1 Publication
O-glycosylated with a core 1 or possibly core 8 glycan.3 Publications

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein

Proteomic databases

MaxQBiQ9UHG2.
PaxDbiQ9UHG2.
PeptideAtlasiQ9UHG2.
PRIDEiQ9UHG2.

PTM databases

PhosphoSitePlusiQ9UHG2.
UniCarbKBiQ9UHG2.

Expressioni

Tissue specificityi

Expressed in brain and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000102109.
CleanExiHS_PCSK1N.
GenevisibleiQ9UHG2. HS.

Organism-specific databases

HPAiHPA003925.
HPA064734.

Interactioni

Subunit structurei

Interacts via the C-terminal inhibitory domain with PCSK1 66 kDa form.By similarity

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi118156. 7 interactors.
IntActiQ9UHG2. 1 interactor.
STRINGi9606.ENSP00000218230.

Structurei

3D structure databases

ProteinModelPortaliQ9UHG2.
SMRiQ9UHG2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni34 – 215ProSAAS(1-180)By similarityAdd BLAST182
Regioni221 – 260C-terminal inhibitory domain; interacts with PCSK1By similarityAdd BLAST40

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi239 – 244Sufficient for inhibition of PCSK16

Domaini

ProSAAS(1-180) increases secretion of enzymatically inactive PCSK1.By similarity
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).By similarity

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IWT4. Eukaryota.
ENOG4111DVB. LUCA.
GeneTreeiENSGT00390000013488.
HOGENOMiHOG000261638.
HOVERGENiHBG080210.
InParanoidiQ9UHG2.
OMAiRPVKEPR.
OrthoDBiEOG091G0R4Z.
PhylomeDBiQ9UHG2.
TreeFamiTF338201.

Family and domain databases

InterProiIPR010832. ProSAAS.
[Graphical view]
PANTHERiPTHR15531. PTHR15531. 1 hit.
PfamiPF07259. ProSAAS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UHG2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGSPLLWGP RAGGVGLLVL LLLGLFRPPP ALCARPVKEP RGLSAASPPL
60 70 80 90 100
AETGAPRRFR RSVPRGEAAG AVQELARALA HLLEAERQER ARAEAQEAED
110 120 130 140 150
QQARVLAQLL RVWGAPRNSD PALGLDDDPD APAAQLARAL LRARLDPAAL
160 170 180 190 200
AAQLVPAPVP AAALRPRPPV YDDGPAGPDA EEAGDETPDV DPELLRYLLG
210 220 230 240 250
RILAGSADSE GVAAPRRLRR AADHDVGSEL PPEGVLGALL RVKRLETPAP
260
QVPARRLLPP
Length:260
Mass (Da):27,372
Last modified:May 1, 2000 - v1
Checksum:iFF8E2722784B7A5C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02897131A → T.1 PublicationCorresponds to variant rs11538176dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF181562 mRNA. Translation: AAF22643.1.
BC002851 mRNA. Translation: AAH02851.1.
CCDSiCCDS14307.1.
RefSeqiNP_037403.1. NM_013271.4.
UniGeneiHs.522640.

Genome annotation databases

EnsembliENST00000218230; ENSP00000218230; ENSG00000102109.
GeneIDi27344.
KEGGihsa:27344.
UCSCiuc004dkz.6. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF181562 mRNA. Translation: AAF22643.1.
BC002851 mRNA. Translation: AAH02851.1.
CCDSiCCDS14307.1.
RefSeqiNP_037403.1. NM_013271.4.
UniGeneiHs.522640.

3D structure databases

ProteinModelPortaliQ9UHG2.
SMRiQ9UHG2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118156. 7 interactors.
IntActiQ9UHG2. 1 interactor.
STRINGi9606.ENSP00000218230.

Protein family/group databases

MEROPSiI49.001.

PTM databases

PhosphoSitePlusiQ9UHG2.
UniCarbKBiQ9UHG2.

Polymorphism and mutation databases

DMDMi74735013.

Proteomic databases

MaxQBiQ9UHG2.
PaxDbiQ9UHG2.
PeptideAtlasiQ9UHG2.
PRIDEiQ9UHG2.

Protocols and materials databases

DNASUi27344.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000218230; ENSP00000218230; ENSG00000102109.
GeneIDi27344.
KEGGihsa:27344.
UCSCiuc004dkz.6. human.

Organism-specific databases

CTDi27344.
DisGeNETi27344.
GeneCardsiPCSK1N.
HGNCiHGNC:17301. PCSK1N.
HPAiHPA003925.
HPA064734.
MIMi300399. gene.
neXtProtiNX_Q9UHG2.
OpenTargetsiENSG00000102109.
PharmGKBiPA33090.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWT4. Eukaryota.
ENOG4111DVB. LUCA.
GeneTreeiENSGT00390000013488.
HOGENOMiHOG000261638.
HOVERGENiHBG080210.
InParanoidiQ9UHG2.
OMAiRPVKEPR.
OrthoDBiEOG091G0R4Z.
PhylomeDBiQ9UHG2.
TreeFamiTF338201.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102109-MONOMER.

Miscellaneous databases

GenomeRNAii27344.
PROiQ9UHG2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102109.
CleanExiHS_PCSK1N.
GenevisibleiQ9UHG2. HS.

Family and domain databases

InterProiIPR010832. ProSAAS.
[Graphical view]
PANTHERiPTHR15531. PTHR15531. 1 hit.
PfamiPF07259. ProSAAS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPCSK1_HUMAN
AccessioniPrimary (citable) accession number: Q9UHG2
Secondary accession number(s): Q4VC04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.