Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q04592 (PCSK5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proprotein convertase subtilisin/kexin type 5

EC=3.4.21.-
Alternative name(s):
Proprotein convertase 5
Short name=PC5
Proprotein convertase 6
Short name=PC6
Subtilisin-like proprotein convertase 6
Short name=SPC6
Subtilisin/kexin-like protease PC5
Gene names
Name:Pcsk5
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1877 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays an essential role in pregnancy establishment by proteolytic activation of a number of important factors such as BMP2, CALD1 and alpha-integrins. Likely to represent a widespread endoprotease activity within the constitutive and regulated secretory pathway. Capable of cleavage at the RX(K/R)R consensus motif. May be responsible for the maturation of gastrointestinal peptides. May be involved in the cellular proliferation of adrenal cortex via the activation of growth factors By similarity.

Catalytic activity

Release of mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-|-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys.

Subcellular location

Isoform PC5A: Secreted. Note: Secreted through the regulated secretory pathway. Ref.5

Isoform PC5B: Endomembrane system; Single-pass type I membrane protein. Note: Type I membrane protein localized to a paranuclear post-Golgi network compartment in communication with early endosomes. Ref.5

Tissue specificity

PC5A is expressed in most tissues but is most abundant in the intestine and adrenals. PC5B is expressed in the intestine, adrenals and lung but not in the brain.

Developmental stage

Weakly expressed throughout the embryo, except in the developing nervous system, the ribs and the liver, but markedly up-regulated at discrete sites during development. At E6.5, prominent expression observed in differentiated decidua. At E7.5, intense expression in extraembryonic endoderm, amnion and nascent mesoderm. At E8.5, abundant expression in somites and yolk sac followed by a confinement to dermamyotome compartment. Between E9.5 and E11.5, abundant expression in AER (thickened ectodermal cells of limb buds). At E12.5, expression in the limbs is confined to the condensing mesenchyme surrounding the cartilage. At this stage, strong expression also detected in vertebral and facial cartilage primordia and in the muscle of the tongue. At E16.5, abundant expression in epithelial cells of the intestinal villi. Isoform Ais most abundant at all stages but significant levels of isoform Boccur at E12.5. Ref.6 Ref.7

Domain

The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum.

AC 1 and AC 2 (clusters of acidic amino acids) contain sorting information. AC 1 directs TGN localization and interacts with the TGN sorting protein PACS-1.

Sequence similarities

Belongs to the peptidase S8 family.

Contains 1 homo B/P domain.

Ontologies

Keywords
   Biological processPregnancy
   Cellular componentMembrane
Secreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionHydrolase
Protease
Serine protease
   PTMCleavage on pair of basic residues
Glycoprotein
Zymogen
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processanterior/posterior pattern specification

Inferred from mutant phenotype PubMed 18519639. Source: BHF-UCL

cytokine biosynthetic process

Inferred from direct assay PubMed 18519639. Source: BHF-UCL

embryo implantation

Inferred from mutant phenotype PubMed 15601911. Source: BHF-UCL

embryonic digestive tract development

Inferred from mutant phenotype PubMed 18519639. Source: BHF-UCL

embryonic skeletal system development

Inferred from mutant phenotype PubMed 18519639. Source: BHF-UCL

heart development

Inferred from mutant phenotype PubMed 18519639. Source: BHF-UCL

kidney development

Inferred from mutant phenotype PubMed 18519639. Source: BHF-UCL

limb morphogenesis

Inferred from mutant phenotype PubMed 18519639. Source: BHF-UCL

peptide biosynthetic process

Inferred from direct assay PubMed 18519639Ref.2. Source: BHF-UCL

peptide hormone processing

Inferred from direct assay PubMed 18519639Ref.2PubMed 9242664. Source: BHF-UCL

protein processing

Inferred from direct assay PubMed 18519639Ref.2PubMed 9242664. Source: BHF-UCL

renin secretion into blood stream

Inferred from electronic annotation. Source: Ensembl

respiratory tube development

Inferred from mutant phenotype PubMed 18519639. Source: BHF-UCL

signal peptide processing

Inferred from electronic annotation. Source: Ensembl

viral life cycle

Inferred from direct assay PubMed 8940009. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.5. Source: MGI

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 8940009. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

secretory granule

Inferred from direct assay Ref.5. Source: MGI

   Molecular_functionendopeptidase activity

Inferred from direct assay PubMed 18519639PubMed 9242664. Source: BHF-UCL

peptidase activity

Inferred from sequence orthology PubMed 15606899. Source: MGI

peptide binding

Inferred from direct assay PubMed 8940009. Source: BHF-UCL

serine-type endopeptidase activity

Inferred from direct assay Ref.2. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform PC5B (identifier: Q04592-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform PC5A (identifier: Q04592-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     878-915: GEYIDDQGHC...ISCPVTRVLD → ATEESWAEGG...LCCKTCTFQG
     916-1877: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434
Propeptide35 – 11682
PRO_0000027104
Chain117 – 18771761Proprotein convertase subtilisin/kexin type 5
PRO_0000027105

Regions

Topological domain117 – 17681652Extracellular Potential
Transmembrane1769 – 178921Helical; Potential
Topological domain1790 – 187788Cytoplasmic Potential
Domain464 – 602139Homo B/P
Region117 – 452336Catalytic
Region638 – 17531116CRM (Cys-rich motif)
Region1825 – 184420AC 1
Region1856 – 187722AC 2
Motif521 – 5233Cell attachment site Potential

Sites

Active site1731Charge relay system By similarity
Active site2141Charge relay system By similarity
Active site3881Charge relay system By similarity
Site116 – 1172Cleavage; by autolysis By similarity

Amino acid modifications

Glycosylation2271N-linked (GlcNAc...) Potential
Glycosylation3831N-linked (GlcNAc...) Potential
Glycosylation6671N-linked (GlcNAc...) Potential
Glycosylation7541N-linked (GlcNAc...) Potential
Glycosylation8041N-linked (GlcNAc...) Potential
Glycosylation8541N-linked (GlcNAc...) Potential
Glycosylation9511N-linked (GlcNAc...) Potential
Glycosylation10161N-linked (GlcNAc...) Potential
Glycosylation12201N-linked (GlcNAc...) Potential
Glycosylation13171N-linked (GlcNAc...) Potential
Glycosylation15231N-linked (GlcNAc...) Potential
Glycosylation17111N-linked (GlcNAc...) Potential
Glycosylation17331N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence878 – 91538GEYID…TRVLD → ATEESWAEGGFCMLVKKNNL CQRKVLQQLCCKTCTFQG in isoform PC5A.
VSP_005438
Alternative sequence916 – 1877962Missing in isoform PC5A.
VSP_005439

Experimental info

Sequence conflict7041N → D in BAA04507. Ref.1
Sequence conflict7041N → D in BAA02143. Ref.2
Sequence conflict7041N → D in AAA74636. Ref.3
Sequence conflict9861A → T in BAA04507. Ref.1
Sequence conflict10021V → I in BAA04507. Ref.1
Sequence conflict11391N → T in BAA04507. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform PC5B (Long) [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 68F7B768E063872B

FASTA1,877209,257
        10         20         30         40         50         60 
MDWDWGNRCS RPGRRDLLCV LALLAGCLLP VCRTRVYTNH WAVKIAGGFA EADRIASKYG 

        70         80         90        100        110        120 
FINVGQIGAL KDYYHFYHSR TIKRSVLSSR GTHSFISMEP KVEWIQQQVV KKRTKRDYDL 

       130        140        150        160        170        180 
SHAQSTYFND PKWPSMWYMH CSDNTHPCQS DMNIEGAWKR GYTGKNIVVT ILDDGIERTH 

       190        200        210        220        230        240 
PDLMQNYDAL ASCDVNGNDL DPMPRYDASN ENKHGTRCAG EVAATANNSH CTVGIAFNAK 

       250        260        270        280        290        300 
IGGVRMLDGD VTDMVEAKSV SYNPQHVHIY SASWGPDDDG KTVDGPAPLT RQAFENGVRM 

       310        320        330        340        350        360 
GRRGLGSVFV WASGNGGRSK DHCSCDGYTN SIYTISISST AESGKKPWYL EECSSTLATT 

       370        380        390        400        410        420 
YSSGESYDKK IITTDLRQRC TDNHTGTSAS APMAAGIIAL ALEANPFLTW RDVQHVIVRT 

       430        440        450        460        470        480 
SRAGHLNAND WKTNAAGFKV SHLYGFGLMD AEAMVMEAEK WTTVPQQHVC VESTDRQIKT 

       490        500        510        520        530        540 
IRPNSAVRSI YKASGCSDNP NHHVNYLEHV VVRITITHPR RGDLAIYLTS PSGTRSQLLA 

       550        560        570        580        590        600 
NRLFDHSMEG FKNWEFMTIH CWGERAAGDW VLEVYDTPSQ LRNFKTPGKL KEWSLVLYGT 

       610        620        630        640        650        660 
SVQPYSPTNE FPKVERFRYS RVEDPTDDYG AEDYAGPCDP ECSEVGCDGP GPDHCSDCLH 

       670        680        690        700        710        720 
YYYKLKNNTR ICVSSCPPGH YHADKKRCRK CAPNCESCFG SHGNQCLSCK YGYFLNEETS 

       730        740        750        760        770        780 
SCVTQCPDGS YEDIKKNVCG KCSENCKACI GFHNCTECKG GLSLQGSRCS VTCEDGQFFN 

       790        800        810        820        830        840 
GHDCQPCHRF CATCSGAGAD GCINCTEGYV MEEGRCVQSC SVSYYLDHSS EGGYKSCKRC 

       850        860        870        880        890        900 
DNSCLTCNGP GFKNCSSCPS GYLLDLGTCQ MGAICKDGEY IDDQGHCQTC EASCAKCWGP 

       910        920        930        940        950        960 
TQEDCISCPV TRVLDDGRCV MNCPSWKFEF KKQCHPCHYT CQGCQGSGPS NCTSCRADKH 

       970        980        990       1000       1010       1020 
GQERFLYHGE CLENCPVGHY PAKGHACLPC PDNCELCYNP HVCSRCMSGY VIIPPNHTCQ 

      1030       1040       1050       1060       1070       1080 
KLECRQGEFQ DSEYEECMPC EEGCLGCTED DPGACTSCAT GYYMFERHCY KACPEKTFGV 

      1090       1100       1110       1120       1130       1140 
KWECRACGTN CGSCDQHECY WCEEGFFLSG GSCVQDCGPG FHGDQELGEC KPCHRACENC 

      1150       1160       1170       1180       1190       1200 
TGSGYNQCSS CQEGLQLWHG TCLWSTWPQV EGKDWNEAVP TEKPSLVRSL LQDRRKWKVQ 

      1210       1220       1230       1240       1250       1260 
IKRDATSQNQ PCHSSCKTCN GSLCASCPTG MYLWLQACVP SCPQGTWPSV TSGSCEKCSE 

      1270       1280       1290       1300       1310       1320 
DCVSCSGADL CQQCLSQPDN TLLLHEGRCY HSCPEGFYAK DGVCEHCSSP CKTCEGNATS 

      1330       1340       1350       1360       1370       1380 
CNSCEGDFVL DHGVCWKTCP EKHVAVEGVC KHCPERCQDC IHEKTCKECM PDFFLYNDMC 

      1390       1400       1410       1420       1430       1440 
HRSCPKSFYP DMRQCVPCHK NCLECNGPKE DDCKVCADTS KALHNGLCLD ECPEGTYKEE 

      1450       1460       1470       1480       1490       1500 
ENDECRDCPE SCLICSSAWT CLACREGFTV VHDVCTAPKE CAAVEYWDEG SHRCQPCHKK 

      1510       1520       1530       1540       1550       1560 
CSRCSGPSED QCYTCPRETF LLNTTCVKEC PEGYHTDKDS QQCVLCHSSC RTCEGPHSMQ 

      1570       1580       1590       1600       1610       1620 
CLSCRPGWFQ LGKECLLQCR DGYYGESTSG RCEKCDKSCK SCRGPRPTDC QSCDTFFFLL 

      1630       1640       1650       1660       1670       1680 
RSKGQCHRAC PEHYYADQHA QTCERCHPTC DKCSGKEAWS CLSCVWSYHL LKGICIPECI 

      1690       1700       1710       1720       1730       1740 
VGEYREGKGE NFNCKKCHES CMECKGPGSK NCTGCSAGLL LDMDDNRCLH CCNASHSRRS 

      1750       1760       1770       1780       1790       1800 
QDCCDCQSST DECILPAREA EFYEHTKTAL LVTSGAMLLL LLGAAAVVWR KSRSRPVAKG 

      1810       1820       1830       1840       1850       1860 
RYEKLAEPTV SYSSYRSSYL DEDQVIEYRD RDYDEDDEDD IVYMGQDGTV YRKFKYGLLD 

      1870 
ETEDDELEYD DESYSYQ 

« Hide

Isoform PC5A (Short) [UniParc].

Checksum: EE13FF8F7AFC78EE
Show »

FASTA915101,489

References

« Hide 'large scale' references
[1]"Identification of an isoform with an extremely large Cys-rich region of PC6, a Kex2-like processing endoprotease."
Nakagawa T., Murakami K., Nakayama K.
FEBS Lett. 327:165-171(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 330-1877 (ISOFORM PC5B).
Strain: ICR.
Tissue: Intestine.
[2]"Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4."
Nakagawa T., Hosaka M., Torii S., Watanabe T., Murakami K., Nakayama K.
J. Biochem. 113:132-135(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PC5A).
Tissue: Brain and Intestine.
[3]"cDNA structure of the mouse and rat subtilisin/kexin-like PC5: a candidate proprotein convertase expressed in endocrine and nonendocrine cells."
Lusson J., Vieau D., Hamelin J., Day R., Chretien M., Seidah N.G.
Proc. Natl. Acad. Sci. U.S.A. 90:6691-6695(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PC5A).
Tissue: Adrenal cortex.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"The isoforms of proprotein convertase PC5 are sorted to different subcellular compartments."
De Bie I., Marcinkiewicz M., Malide D., Lazure C., Nakayama K., Bendayan M., Seidah N.G.
J. Cell Biol. 135:1261-1275(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION.
[6]"SPC4, SPC6, and the novel protease SPC7 are coexpressed with bone morphogenetic proteins at distinct sites during embryogenesis."
Constam D.B., Calfon M., Robertson E.J.
J. Cell Biol. 134:181-191(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[7]"Murine subtilisin-like proteinase SPC6 is expressed during embryonic implantation, somitogenesis, and skeletal formation."
Rancourt S.L., Rancourt D.E.
Dev. Genet. 21:75-81(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D17583 mRNA. Translation: BAA04507.1.
D12619 mRNA. Translation: BAA02143.1.
L14932 mRNA. Translation: AAA74636.1.
AC125203 Genomic DNA. No translation available.
AC126940 Genomic DNA. No translation available.
AC133509 Genomic DNA. No translation available.
AC147369 Genomic DNA. No translation available.
CCDSCCDS50401.1. [Q04592-1]
CCDS50402.1. [Q04592-2]
PIRA48225.
S34583.
RefSeqNP_001177412.1. NM_001190483.1. [Q04592-1]
UniGeneMm.3401.

3D structure databases

ProteinModelPortalQ04592.
SMRQ04592. Positions 130-601.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ04592. 1 interaction.
MINTMINT-5314211.

Protein family/group databases

MEROPSS08.076.

PTM databases

PhosphoSiteQ04592.

Proteomic databases

PRIDEQ04592.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025618; ENSMUSP00000025618; ENSMUSG00000024713. [Q04592-1]
ENSMUST00000050715; ENSMUSP00000050272; ENSMUSG00000024713. [Q04592-2]
GeneID18552.
KEGGmmu:18552.
UCSCuc008gxp.2. mouse. [Q04592-1]

Organism-specific databases

CTD5125.
MGIMGI:97515. Pcsk5.

Phylogenomic databases

eggNOGCOG4935.
GeneTreeENSGT00750000117358.
HOGENOMHOG000192536.
HOVERGENHBG008705.
InParanoidQ04592.
KOK08654.
OMALHEGRCY.
OrthoDBEOG7BW0JD.
TreeFamTF314277.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.

Gene expression databases

ArrayExpressQ04592.
BgeeQ04592.
CleanExMM_PCSK5.
GenevestigatorQ04592.

Family and domain databases

Gene3D2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProIPR000742. EG-like_dom.
IPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000209. Peptidase_S8/S53_dom.
IPR023827. Peptidase_S8_Asp-AS.
IPR022398. Peptidase_S8_His-AS.
IPR023828. Peptidase_S8_Ser-AS.
IPR015500. Peptidase_S8_subtilisin-rel.
IPR009020. Prot_inh_propept.
IPR002884. PrprotnconvertsP.
[Graphical view]
PANTHERPTHR10795. PTHR10795. 1 hit.
PfamPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
[Graphical view]
PRINTSPR00723. SUBTILISIN.
SMARTSM00181. EGF. 2 hits.
SM00261. FU. 22 hits.
[Graphical view]
SUPFAMSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 8 hits.
PROSITEPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294356.
PROQ04592.
SOURCESearch...

Entry information

Entry namePCSK5_MOUSE
AccessionPrimary (citable) accession number: Q04592
Secondary accession number(s): E9QPB7, Q62040
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 139 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot