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Protein

Proprotein convertase subtilisin/kexin type 5

Gene

PCSK5

Organism
Homo sapiens (Human)
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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei171Charge relay systemBy similarity1
Active sitei212Charge relay systemBy similarity1
Active sitei386Charge relay systemBy similarity1

GO - Molecular functioni

  • endopeptidase activity Source: Reactome
  • 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: Ensembl
  • cell-cell signaling Source: ProtInc
  • coronary vasculature development Source: Ensembl
  • cytokine biosynthetic process Source: BHF-UCL
  • determination of left/right symmetry Source: Ensembl
  • 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
  • regulation of lipoprotein lipase activity Source: Reactome
  • renin secretion into blood stream Source: BHF-UCL
  • respiratory tube development Source: BHF-UCL
  • signal peptide processing Source: HGNC
  • viral life cycle Source: BHF-UCL

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processPregnancy

Enzyme and pathway databases

BRENDAi3.4.21.B26 2681
ReactomeiR-HSA-167060 NGF processing
R-HSA-8963889 Assembly of active LPL and LIPC lipase complexes
SignaLinkiQ92824

Protein family/group databases

MEROPSiS08.076

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
Short name:
hPC6
Subtilisin/kexin-like protease PC5
Gene namesi
Name:PCSK5
Synonyms:PC5, PC6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000099139.13
HGNCiHGNC:8747 PCSK5
MIMi600488 gene
neXtProtiNX_Q92824

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 domaini115 – 1743ExtracellularSequence analysisAdd BLAST1629
Transmembranei1744 – 1764HelicalSequence analysisAdd BLAST21
Topological domaini1765 – 1860CytoplasmicSequence analysisAdd BLAST96

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi5125
OpenTargetsiENSG00000099139
PharmGKBiPA33093

Chemistry databases

ChEMBLiCHEMBL2826
GuidetoPHARMACOLOGYi2385

Polymorphism and mutation databases

BioMutaiPCSK5
DMDMi357529585

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32By similarityAdd BLAST32
PropeptideiPRO_000002710233 – 114By similarityAdd BLAST82
ChainiPRO_0000027103115 – 1860Proprotein convertase subtilisin/kexin type 5Add BLAST1746

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi225N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi381N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi665N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi752N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi802N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi852N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1014N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1191N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1290N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1497N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1685N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1707N-linked (GlcNAc...) asparagineSequence analysis1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei114 – 115Cleavage; by autolysisBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ92824
PeptideAtlasiQ92824
PRIDEiQ92824

PTM databases

iPTMnetiQ92824
PhosphoSitePlusiQ92824

Miscellaneous databases

PMAP-CutDBiQ92824

Expressioni

Tissue specificityi

Expressed in T-lymphocytes.

Gene expression databases

BgeeiENSG00000099139
CleanExiHS_PCSK5
ExpressionAtlasiQ92824 baseline and differential
GenevisibleiQ92824 HS

Organism-specific databases

HPAiHPA031072

Interactioni

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111152, 32 interactors
IntActiQ92824, 53 interactors
STRINGi9606.ENSP00000446280

Chemistry databases

BindingDBiQ92824

Structurei

3D structure databases

ProteinModelPortaliQ92824
SMRiQ92824
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini166 – 453Peptidase S8Add BLAST288
Domaini461 – 601P/Homo BPROSITE-ProRule annotationAdd BLAST141
Repeati630 – 680FU 1Add BLAST51
Repeati683 – 730FU 2Add BLAST48
Repeati734 – 777FU 3Add BLAST44
Repeati779 – 824FU 4Add BLAST46
Repeati832 – 879FU 5Add BLAST48
Domaini869 – 913PLACAdd BLAST45
Repeati882 – 927FU 6Add BLAST46
Repeati929 – 979FU 7Add BLAST51
Repeati982 – 1028FU 8Add BLAST47
Repeati1032 – 1077FU 9Add BLAST46
Repeati1079 – 1121FU 10Add BLAST43
Repeati1125 – 1168FU 11Add BLAST44
Repeati1177 – 1221FU 12Add BLAST45
Repeati1225 – 1272FU 13Add BLAST48
Repeati1274 – 1318FU 14Add BLAST45
Repeati1320 – 1363FU 15Add BLAST44
Repeati1365 – 1411FU 16Add BLAST47
Repeati1415 – 1461FU 17Add BLAST47
Repeati1465 – 1510FU 18Add BLAST46
Repeati1514 – 1559FU 19Add BLAST46
Repeati1563 – 1610FU 20Add BLAST48
Repeati1614 – 1659FU 21Add BLAST46
Repeati1665 – 1712FU 22Add BLAST48

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni636 – 1727CRM (Cys-rich motif)Add BLAST1092
Regioni1807 – 1826AC 1By similarityAdd BLAST20
Regioni1838 – 1860AC 2By similarityAdd BLAST23

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi519 – 521Cell attachment siteSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1812 – 1853Asp-richAdd BLAST42

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 (By similarity).By similarity

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
InParanoidiQ92824
KOiK08654
OMAiSSCRTCE
OrthoDBiEOG091G05HI
PhylomeDBiQ92824
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
IPR011641 Tyr-kin_ephrin_A/B_rcpt-like
PfamiView protein in Pfam
PF14843 GF_recep_IV, 1 hit
PF01483 P_proprotein, 1 hit
PF00082 Peptidase_S8, 1 hit
PF16470 S8_pro-domain, 1 hit
PRINTSiPR00723 SUBTILISIN
SMARTiView protein in SMART
SM00181 EGF, 16 hits
SM01411 Ephrin_rec_like, 8 hits
SM00261 FU, 22 hits
SUPFAMiSSF49785 SSF49785, 1 hit
SSF52743 SSF52743, 1 hit
SSF57184 SSF57184, 7 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

Isoform PC6B (identifier: Q92824-1) [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
MGWGSRCCCP GRLDLLCVLA LLGGCLLPVC RTRVYTNHWA VKIAGGFPEA
60 70 80 90 100
NRIASKYGFI NIGQIGALKD YYHFYHSRTI KRSVISSRGT HSFISMEPKV
110 120 130 140 150
EWIQQQVVKK RTKRDYDFSR AQSTYFNDPK WPSMWYMHCS DNTHPCQSDM
160 170 180 190 200
NIEGAWKRGY TGKNIVVTIL DDGIERTHPD LMQNYDALAS CDVNGNDLDP
210 220 230 240 250
MPRYDASNEN KHGTRCAGEV AAAANNSHCT VGIAFNAKIG GVRMLDGDVT
260 270 280 290 300
DMVEAKSVSF NPQHVHIYSA SWGPDDDGKT VDGPAPLTRQ AFENGVRMGR
310 320 330 340 350
RGLGSVFVWA SGNGGRSKDH CSCDGYTNSI YTISISSTAE SGKKPWYLEE
360 370 380 390 400
CSSTLATTYS SGESYDKKII TTDLRQRCTD NHTGTSASAP MAAGIIALAL
410 420 430 440 450
EANPFLTWRD VQHVIVRTSR AGHLNANDWK TNAAGFKVSH LYGFGLMDAE
460 470 480 490 500
AMVMEAEKWT TVPRQHVCVE STDRQIKTIR PNSAVRSIYK ASGCSDNPNR
510 520 530 540 550
HVNYLEHVVV RITITHPRRG DLAIYLTSPS GTRSQLLANR LFDHSMEGFK
560 570 580 590 600
NWEFMTIHCW GERAAGDWVL EVYDTPSQLR NFKTPGKLKE WSLVLYGTSV
610 620 630 640 650
QPYSPTNEFP KVERFRYSRV EDPTDDYGTE DYAGPCDPEC SEVGCDGPGP
660 670 680 690 700
DHCNDCLHYY YKLKNNTRIC VSSCPPGHYH ADKKRCRKCA PNCESCFGSH
710 720 730 740 750
GDQCMSCKYG YFLNEETNSC VTHCPDGSYQ DTKKNLCRKC SENCKTCTEF
760 770 780 790 800
HNCTECRDGL SLQGSRCSVS CEDGRYFNGQ DCQPCHRFCA TCAGAGADGC
810 820 830 840 850
INCTEGYFME DGRCVQSCSI SYYFDHSSEN GYKSCKKCDI SCLTCNGPGF
860 870 880 890 900
KNCTSCPSGY LLDLGMCQMG AICKDGEYVD EHGHCQTCEA SCAKCQGPTQ
910 920 930 940 950
EDCTTCPMTR IFDDGRCVSN CPSWKFEFEN QCHPCHHTCQ RCQGSGPTHC
960 970 980 990 1000
TSCGADNYGR EHFLYQGECG DSCPEGHYAT EGNTCLPCPD NCELCHSVHV
1010 1020 1030 1040 1050
CTRCMKGYFI APTNHTCQKL ECGQGEVQDP DYEECVPCEE GCLGCSLDDP
1060 1070 1080 1090 1100
GTCTSCAMGY YRFDHHCYKT CPEKTYSEEV ECKACDSNCG SCDQNGCYWC
1110 1120 1130 1140 1150
EEGFFLLGGS CVRKCGPGFY GDQEMGECES CHRACETCTG PGHDECSSCQ
1160 1170 1180 1190 1200
EGLQLLRGMC VHATKTQEEG KFWNDILRKL QPCHSSCKTC NGSATLCTSC
1210 1220 1230 1240 1250
PKGAYLLAQA CVSSCPQGTW PSVRSGSCEN CTEACAICSG ADLCKKCQMQ
1260 1270 1280 1290 1300
PGHPLFLHEG RCYSKCPEGS YAEDGICERC SSPCRTCEGN ATNCHSCEGG
1310 1320 1330 1340 1350
HVLHHGVCQE NCPERHVAVK GVCKHCPEMC QDCIHEKTCK ECTPEFFLHD
1360 1370 1380 1390 1400
DMCHQSCPRG FYADSRHCVP CHKDCLECSG PKADDCELCL ESSWVLYDGL
1410 1420 1430 1440 1450
CLEECPAGTY YEKETKECRD CHKSCLTCSS SGTCTTCQKG LIMNPRGSCM
1460 1470 1480 1490 1500
ANEKCSPSEY WDEDAPGCKP CHVKCFHCMG PAEDQCQTCP MNSLLLNTTC
1510 1520 1530 1540 1550
VKDCPEGYYA DEDSNRCAHC HSSCRTCEGR HSRQCHSCRP GWFQLGKECL
1560 1570 1580 1590 1600
LQCREGYYAD NSTGRCERCN RSCKGCQGPR PTDCLSCDRF FFLLRSKGEC
1610 1620 1630 1640 1650
HRSCPDHYYV EQSTQTCERC HPTCDQCKGK GALNCLSCVW SYHLMGGICT
1660 1670 1680 1690 1700
SDCLVGEYRV GEGEKFNCEK CHESCMECKG PGAKNCTLCP ANLVLHMDDS
1710 1720 1730 1740 1750
HCLHCCNTSD PPSAQECCDC QDTTDECILR TSKVRPATEH FKTALFITSS
1760 1770 1780 1790 1800
MMLVLLLGAA VVVWKKSRGR VQPAAKAGYE KLADPNKSYS SYKSSYREST
1810 1820 1830 1840 1850
SFEEDQVIEY RDRDYDEDDD DDIVYMGQDG TVYRKFKYGL LDDDDIDELE
1860
YDDESYSYYQ
Length:1,860
Mass (Da):206,942
Last modified:November 16, 2011 - v4
Checksum:i96B3E7C8215BCC85
GO
Isoform PC6A (identifier: Q92824-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     876-913: GEYVDEHGHC...TTCPMTRIFD → ATEESWAEGG...LCCKTCTFQG
     914-1860: Missing.

Show »
Length:913
Mass (Da):101,649
Checksum:i7A2E63EFC49104BC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2G → D in AAC50643 (PubMed:8755538).Curated1
Sequence conflicti4G → E in AAC50643 (PubMed:8755538).Curated1
Sequence conflicti118F → S in AAC50643 (PubMed:8755538).Curated1
Sequence conflicti121A → V in AAC50643 (PubMed:8755538).Curated1
Sequence conflicti511R → A in AAA91807 (Ref. 7) Curated1
Sequence conflicti601Q → R in AAC50643 (PubMed:8755538).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042017876 – 913GEYVD…TRIFD → ATEESWAEGGFCMLVKKNNL CQRKVLQQLCCKTCTFQG in isoform PC6A. 4 PublicationsAdd BLAST38
Alternative sequenceiVSP_042018914 – 1860Missing in isoform PC6A. 4 PublicationsAdd BLAST947

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U56387 mRNA Translation: AAC50643.2
AL834522 mRNA Translation: CAD39178.1
AL359253 Genomic DNA No translation available.
AL353607 Genomic DNA No translation available.
AL391868 Genomic DNA No translation available.
AL589653 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62575.1
BC012064 mRNA Translation: AAH12064.1
U49114 mRNA Translation: AAA91807.1
AK122718 mRNA No translation available.
CCDSiCCDS55320.1 [Q92824-1]
CCDS6652.1 [Q92824-2]
PIRiG02428
JC6148
RefSeqiNP_001177411.1, NM_001190482.1 [Q92824-1]
NP_006191.2, NM_006200.5 [Q92824-2]
UniGeneiHs.368542
Hs.732073

Genome annotation databases

EnsembliENST00000376752; ENSP00000365943; ENSG00000099139 [Q92824-2]
ENST00000545128; ENSP00000446280; ENSG00000099139 [Q92824-1]
GeneIDi5125
KEGGihsa:5125
UCSCiuc004ajz.5 human [Q92824-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPCSK5_HUMAN
AccessioniPrimary (citable) accession number: Q92824
Secondary accession number(s): F5H2G7, Q13527, Q96EP4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 16, 2011
Last modified: May 23, 2018
This is version 182 of the entry and version 4 of the sequence. See 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
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Main funding by: National Institutes of Health