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Protein

Proprotein convertase subtilisin/kexin type 5

Gene

Pcsk5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive and regulated secretory pathways. Plays an essential role in pregnancy establishment by proteolytic activation of a number of important factors such as BMP2, CALD1 and alpha-integrins. 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei173Charge relay systemBy similarity1
Active sitei214Charge relay systemBy similarity1
Active sitei388Charge relay systemBy similarity1

GO - Molecular functioni

  • endopeptidase activity Source: BHF-UCL
  • peptidase activity Source: MGI
  • peptide binding Source: BHF-UCL
  • serine-type endopeptidase activity Source: BHF-UCL

GO - Biological processi

  • anterior/posterior pattern specification Source: BHF-UCL
  • cardiac septum development Source: MGI
  • coronary vasculature development Source: MGI
  • cytokine biosynthetic process Source: BHF-UCL
  • determination of left/right symmetry Source: MGI
  • embryo implantation Source: BHF-UCL
  • embryonic digestive tract development Source: BHF-UCL
  • embryonic skeletal system development Source: BHF-UCL
  • heart development Source: BHF-UCL
  • kidney development Source: BHF-UCL
  • limb morphogenesis Source: BHF-UCL
  • peptide biosynthetic process Source: BHF-UCL
  • peptide hormone processing Source: BHF-UCL
  • protein processing Source: BHF-UCL
  • renin secretion into blood stream Source: Ensembl
  • respiratory tube development Source: BHF-UCL
  • signal peptide processing Source: MGI
  • viral life cycle Source: BHF-UCL

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processPregnancy

Enzyme and pathway databases

BRENDAi3.4.21.B26 3474
ReactomeiR-MMU-167060 NGF processing
R-MMU-8963889 Assembly of active LPL and LIPC lipase complexes

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Pcsk5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:97515 Pcsk5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini117 – 1768ExtracellularSequence analysisAdd BLAST1652
Transmembranei1769 – 1789HelicalSequence analysisAdd BLAST21
Topological domaini1790 – 1877CytoplasmicSequence analysisAdd BLAST88

Keywords - Cellular componenti

Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Add BLAST34
PropeptideiPRO_000002710435 – 116Add BLAST82
ChainiPRO_0000027105117 – 1877Proprotein convertase subtilisin/kexin type 5Add BLAST1761

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi227N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi383N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi667N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi754N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi804N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi854N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi951N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1016N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1220N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1317N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1523N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1711N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1733N-linked (GlcNAc...) asparagineSequence analysis1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei116 – 117Cleavage; by autolysisBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

MaxQBiQ04592
PaxDbiQ04592
PeptideAtlasiQ04592
PRIDEiQ04592

PTM databases

iPTMnetiQ04592
PhosphoSitePlusiQ04592

Expressioni

Tissue specificityi

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 stagei

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 A is most abundant at all stages but significant levels of isoform B occur at E12.5.2 Publications

Gene expression databases

BgeeiENSMUSG00000024713
CleanExiMM_PCSK5
ExpressionAtlasiQ04592 baseline and differential
GenevisibleiQ04592 MM

Interactioni

Protein-protein interaction databases

BioGridi202061, 4 interactors
IntActiQ04592, 1 interactor
MINTiQ04592
STRINGi10090.ENSMUSP00000025618

Structurei

3D structure databases

ProteinModelPortaliQ04592
SMRiQ04592
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini168 – 455Peptidase S8Add BLAST288
Domaini463 – 603P/Homo BPROSITE-ProRule annotationAdd BLAST141
Repeati632 – 682FU 1Add BLAST51
Repeati685 – 732FU 2Add BLAST48
Repeati736 – 779FU 3Add BLAST44
Repeati781 – 826FU 4Add BLAST46
Repeati834 – 881FU 5Add BLAST48
Repeati884 – 929FU 6Add BLAST46
Repeati931 – 981FU 7Add BLAST51
Repeati984 – 1030FU 8Add BLAST47
Repeati1034 – 1079FU 9Add BLAST46
Repeati1081 – 1123FU 10Add BLAST43
Repeati1127 – 1168FU 11Add BLAST42
Repeati1206 – 1248FU 12Add BLAST43
Repeati1252 – 1299FU 13Add BLAST48
Repeati1301 – 1345FU 14Add BLAST45
Repeati1347 – 1390FU 15Add BLAST44
Repeati1392 – 1438FU 16Add BLAST47
Repeati1442 – 1487FU 17Add BLAST46
Repeati1491 – 1536FU 18Add BLAST46
Repeati1540 – 1585FU 19Add BLAST46
Repeati1589 – 1636FU 20Add BLAST48
Repeati1640 – 1685FU 21Add BLAST46
Repeati1691 – 1738FU 22Add BLAST48

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni638 – 1753CRM (Cys-rich motif)Add BLAST1116
Regioni1825 – 1844AC 1Add BLAST20
Regioni1856 – 1877AC 2Add BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi521 – 523Cell attachment siteSequence analysis3

Domaini

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 similaritiesi

Belongs to the peptidase S8 family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
COG1404 LUCA
COG4935 LUCA
GeneTreeiENSGT00750000117358
HOGENOMiHOG000192536
HOVERGENiHBG008705
InParanoidiQ04592
KOiK08654
OMAiSSCRTCE
OrthoDBiEOG091G05HI
TreeFamiTF314277

Family and domain databases

CDDicd04059 Peptidases_S8_Protein_converta, 1 hit
Gene3Di2.60.120.260, 1 hit
3.30.70.850, 1 hit
3.40.50.200, 1 hit
InterProiView protein in InterPro
IPR000742 EGF-like_dom
IPR006212 Furin_repeat
IPR008979 Galactose-bd-like_sf
IPR032778 GF_recep_IV
IPR009030 Growth_fac_rcpt_cys_sf
IPR034182 Kexin/furin
IPR002884 P_dom
IPR000209 Peptidase_S8/S53_dom
IPR036852 Peptidase_S8/S53_dom_sf
IPR023827 Peptidase_S8_Asp-AS
IPR022398 Peptidase_S8_His-AS
IPR023828 Peptidase_S8_Ser-AS
IPR015500 Peptidase_S8_subtilisin-rel
IPR032815 S8_pro-domain
IPR038466 S8_pro-domain_sf
PfamiView protein in Pfam
PF15913 Furin-like_2, 1 hit
PF14843 GF_recep_IV, 2 hits
PF01483 P_proprotein, 1 hit
PF00082 Peptidase_S8, 1 hit
PF16470 S8_pro-domain, 1 hit
PRINTSiPR00723 SUBTILISIN
SMARTiView protein in SMART
SM00181 EGF, 18 hits
SM00261 FU, 22 hits
SUPFAMiSSF49785 SSF49785, 1 hit
SSF52743 SSF52743, 1 hit
SSF57184 SSF57184, 8 hits
PROSITEiView protein in PROSITE
PS51829 P_HOMO_B, 1 hit
PS00136 SUBTILASE_ASP, 1 hit
PS00137 SUBTILASE_HIS, 1 hit
PS00138 SUBTILASE_SER, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform PC5B (identifier: Q04592-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MDWDWGNRCS RPGRRDLLCV LALLAGCLLP VCRTRVYTNH WAVKIAGGFA
60 70 80 90 100
EADRIASKYG FINVGQIGAL KDYYHFYHSR TIKRSVLSSR GTHSFISMEP
110 120 130 140 150
KVEWIQQQVV KKRTKRDYDL SHAQSTYFND PKWPSMWYMH CSDNTHPCQS
160 170 180 190 200
DMNIEGAWKR GYTGKNIVVT ILDDGIERTH PDLMQNYDAL ASCDVNGNDL
210 220 230 240 250
DPMPRYDASN ENKHGTRCAG EVAATANNSH CTVGIAFNAK IGGVRMLDGD
260 270 280 290 300
VTDMVEAKSV SYNPQHVHIY SASWGPDDDG KTVDGPAPLT RQAFENGVRM
310 320 330 340 350
GRRGLGSVFV WASGNGGRSK DHCSCDGYTN SIYTISISST AESGKKPWYL
360 370 380 390 400
EECSSTLATT YSSGESYDKK IITTDLRQRC TDNHTGTSAS APMAAGIIAL
410 420 430 440 450
ALEANPFLTW RDVQHVIVRT SRAGHLNAND WKTNAAGFKV SHLYGFGLMD
460 470 480 490 500
AEAMVMEAEK WTTVPQQHVC VESTDRQIKT IRPNSAVRSI YKASGCSDNP
510 520 530 540 550
NHHVNYLEHV VVRITITHPR RGDLAIYLTS PSGTRSQLLA NRLFDHSMEG
560 570 580 590 600
FKNWEFMTIH CWGERAAGDW VLEVYDTPSQ LRNFKTPGKL KEWSLVLYGT
610 620 630 640 650
SVQPYSPTNE FPKVERFRYS RVEDPTDDYG AEDYAGPCDP ECSEVGCDGP
660 670 680 690 700
GPDHCSDCLH YYYKLKNNTR ICVSSCPPGH YHADKKRCRK CAPNCESCFG
710 720 730 740 750
SHGNQCLSCK YGYFLNEETS SCVTQCPDGS YEDIKKNVCG KCSENCKACI
760 770 780 790 800
GFHNCTECKG GLSLQGSRCS VTCEDGQFFN GHDCQPCHRF CATCSGAGAD
810 820 830 840 850
GCINCTEGYV MEEGRCVQSC SVSYYLDHSS EGGYKSCKRC DNSCLTCNGP
860 870 880 890 900
GFKNCSSCPS GYLLDLGTCQ MGAICKDGEY IDDQGHCQTC EASCAKCWGP
910 920 930 940 950
TQEDCISCPV TRVLDDGRCV MNCPSWKFEF KKQCHPCHYT CQGCQGSGPS
960 970 980 990 1000
NCTSCRADKH GQERFLYHGE CLENCPVGHY PAKGHACLPC PDNCELCYNP
1010 1020 1030 1040 1050
HVCSRCMSGY VIIPPNHTCQ KLECRQGEFQ DSEYEECMPC EEGCLGCTED
1060 1070 1080 1090 1100
DPGACTSCAT GYYMFERHCY KACPEKTFGV KWECRACGTN CGSCDQHECY
1110 1120 1130 1140 1150
WCEEGFFLSG GSCVQDCGPG FHGDQELGEC KPCHRACENC TGSGYNQCSS
1160 1170 1180 1190 1200
CQEGLQLWHG TCLWSTWPQV EGKDWNEAVP TEKPSLVRSL LQDRRKWKVQ
1210 1220 1230 1240 1250
IKRDATSQNQ PCHSSCKTCN GSLCASCPTG MYLWLQACVP SCPQGTWPSV
1260 1270 1280 1290 1300
TSGSCEKCSE DCVSCSGADL CQQCLSQPDN TLLLHEGRCY HSCPEGFYAK
1310 1320 1330 1340 1350
DGVCEHCSSP CKTCEGNATS CNSCEGDFVL DHGVCWKTCP EKHVAVEGVC
1360 1370 1380 1390 1400
KHCPERCQDC IHEKTCKECM PDFFLYNDMC HRSCPKSFYP DMRQCVPCHK
1410 1420 1430 1440 1450
NCLECNGPKE DDCKVCADTS KALHNGLCLD ECPEGTYKEE ENDECRDCPE
1460 1470 1480 1490 1500
SCLICSSAWT CLACREGFTV VHDVCTAPKE CAAVEYWDEG SHRCQPCHKK
1510 1520 1530 1540 1550
CSRCSGPSED QCYTCPRETF LLNTTCVKEC PEGYHTDKDS QQCVLCHSSC
1560 1570 1580 1590 1600
RTCEGPHSMQ CLSCRPGWFQ LGKECLLQCR DGYYGESTSG RCEKCDKSCK
1610 1620 1630 1640 1650
SCRGPRPTDC QSCDTFFFLL RSKGQCHRAC PEHYYADQHA QTCERCHPTC
1660 1670 1680 1690 1700
DKCSGKEAWS CLSCVWSYHL LKGICIPECI VGEYREGKGE NFNCKKCHES
1710 1720 1730 1740 1750
CMECKGPGSK NCTGCSAGLL LDMDDNRCLH CCNASHSRRS QDCCDCQSST
1760 1770 1780 1790 1800
DECILPAREA EFYEHTKTAL LVTSGAMLLL LLGAAAVVWR KSRSRPVAKG
1810 1820 1830 1840 1850
RYEKLAEPTV SYSSYRSSYL DEDQVIEYRD RDYDEDDEDD IVYMGQDGTV
1860 1870
YRKFKYGLLD ETEDDELEYD DESYSYQ
Length:1,877
Mass (Da):209,257
Last modified:July 27, 2011 - v3
Checksum:i68F7B768E063872B
GO
Isoform PC5A (identifier: Q04592-2) [UniParc]FASTAAdd to basket
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.

Show »
Length:915
Mass (Da):101,489
Checksum:iEE13FF8F7AFC78EE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti704N → D in BAA04507 (PubMed:8335106).Curated1
Sequence conflicti704N → D in BAA02143 (PubMed:8468318).Curated1
Sequence conflicti704N → D in AAA74636 (PubMed:8341687).Curated1
Sequence conflicti986A → T in BAA04507 (PubMed:8335106).Curated1
Sequence conflicti1002V → I in BAA04507 (PubMed:8335106).Curated1
Sequence conflicti1139N → T in BAA04507 (PubMed:8335106).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005438878 – 915GEYID…TRVLD → ATEESWAEGGFCMLVKKNNL CQRKVLQQLCCKTCTFQG in isoform PC5A. 2 PublicationsAdd BLAST38
Alternative sequenceiVSP_005439916 – 1877Missing in isoform PC5A. 2 PublicationsAdd BLAST962

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS50401.1 [Q04592-1]
CCDS50402.1 [Q04592-2]
PIRiA48225
S34583
RefSeqiNP_001177412.1, NM_001190483.2 [Q04592-1]
UniGeneiMm.3401

Genome annotation databases

EnsembliENSMUST00000025618; ENSMUSP00000025618; ENSMUSG00000024713 [Q04592-1]
ENSMUST00000050715; ENSMUSP00000050272; ENSMUSG00000024713 [Q04592-2]
GeneIDi18552
KEGGimmu:18552
UCSCiuc008gxp.2 mouse [Q04592-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPCSK5_MOUSE
AccessioniPrimary (citable) accession number: Q04592
Secondary accession number(s): E9QPB7, Q62040
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 27, 2011
Last modified: March 28, 2018
This is version 169 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

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