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Protein

Proprotein convertase subtilisin/kexin type 4

Gene

PCSK4

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

Functioni

Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues (By similarity). In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (By similarity). Plays also a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (PubMed:16040806). May also participate in folliculogenesis in the ovaries (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei158Charge relay systemBy similarity1
Active sitei199Charge relay systemBy similarity1
Active sitei373Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BRENDAi3.4.21.B24. 2681.
3.4.21.B25. 2681.
SignaLinkiQ6UW60.

Protein family/group databases

MEROPSiS08.074.

Names & Taxonomyi

Protein namesi
Recommended name:
Proprotein convertase subtilisin/kexin type 4 (EC:3.4.21.-)
Alternative name(s):
Proprotein convertase 4
Short name:
PC4
Gene namesi
Name:PCSK4Imported
Synonyms:PC41 Publication
ORF Names:UNQ2757/PRO6496
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:8746. PCSK4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei709 – 729HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi373S → A: No effect on interaction with HSPA5. 1 Publication1

Organism-specific databases

DisGeNETi54760.
OpenTargetsiENSG00000115257.
PharmGKBiPA33092.

Chemistry databases

ChEMBLiCHEMBL4861.
GuidetoPHARMACOLOGYi2384.

Polymorphism and mutation databases

BioMutaiPCSK4.
DMDMi296439263.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
PropeptideiPRO_000024677826 – 113Sequence analysisBy similarityAdd BLAST88
ChainiPRO_0000246779114 – 755Proprotein convertase subtilisin/kexin type 4Sequence analysisBy similarityAdd BLAST642

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi475N-linked (GlcNAc...)Sequence analysis1
Glycosylationi629N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication
Synthesized in the endoplasmic reticulum as a zymogen, is matured by autocatalytic cleavage between the prodomain and the catalytic domain.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ6UW60.
PRIDEiQ6UW60.

PTM databases

iPTMnetiQ6UW60.
PhosphoSitePlusiQ6UW60.

Expressioni

Tissue specificityi

Placenta.1 Publication

Developmental stagei

Localized predominantly in the cytotrophoblast layer of trophoblast cells during the first trimester of pregnancy, and to the syncytiotrophoblast and stroma cells during the third trimester.1 Publication

Gene expression databases

BgeeiENSG00000115257.
CleanExiHS_PCSK4.
ExpressionAtlasiQ6UW60. baseline and differential.
GenevisibleiQ6UW60. HS.

Organism-specific databases

HPAiHPA005572.

Interactioni

Subunit structurei

The proPCSK4 form interacts with HSPA5; the interaction takes place at the endoplasmic reticulum.1 Publication

Protein-protein interaction databases

BioGridi120136. 1 interactor.
STRINGi9606.ENSP00000300954.

Chemistry databases

BindingDBiQ6UW60.

Structurei

3D structure databases

ProteinModelPortaliQ6UW60.
SMRiQ6UW60.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini153 – 439Peptidase S8Add BLAST287

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiQ6UW60.
KOiK08671.
OMAiYTPSDEN.
OrthoDBiEOG091G05HI.
PhylomeDBiQ6UW60.
TreeFamiTF314277.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
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. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 2 hits.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SMARTiSM00261. FU. 1 hit.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

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 11 Publication (identifier: Q6UW60-1) [UniParc]FASTAAdd to basket

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
MRPAPIALWL RLVLALALVR PRAVGWAPVR APIYVSSWAV QVSQGNREVE
60 70 80 90 100
RLARKFGFVN LGPIFPDGQY FHLRHRGVVQ QSLTPHWGHR LHLKKNPKVQ
110 120 130 140 150
WFQQQTLQRR VKRSVVVPTD PWFSKQWYMN SEAQPDLSIL QAWSQGLSGQ
160 170 180 190 200
GIVVSVLDDG IEKDHPDLWA NYDPLASYDF NDYDPDPQPR YTPSKENRHG
210 220 230 240 250
TRCAGEVAAM ANNGFCGVGV AFNARIGGVR MLDGTITDVI EAQSLSLQPQ
260 270 280 290 300
HIHIYSASWG PEDDGRTVDG PGILTREAFR RGVTKGRGGL GTLFIWASGN
310 320 330 340 350
GGLHYDNCNC DGYTNSIHTL SVGSTTQQGR VPWYSEACAS TLTTTYSSGV
360 370 380 390 400
ATDPQIVTTD LHHGCTDQHT GTSASAPLAA GMIALALEAN PFLTWRDMQH
410 420 430 440 450
LVVRASKPAH LQAEDWRTNG VGRQVSHHYG YGLLDAGLLV DTARTWLPTQ
460 470 480 490 500
PQRKCAVRVQ SRPTPILPLI YIRENVSACA GLHNSIRSLE HVQAQLTLSY
510 520 530 540 550
SRRGDLEISL TSPMGTRSTL VAIRPLDVST EGYNNWVFMS THFWDENPQG
560 570 580 590 600
VWTLGLENKG YYFNTGTLYR YTLLLYGTAE DMTARPTGPQ VTSSACVQRD
610 620 630 640 650
TEGLCQACDG PAYILGQLCL AYCPPRFFNH TRLVTAGPGH TAAPALRVCS
660 670 680 690 700
SCHASCYTCR GGSPRDCTSC PPSSTLDQQQ GSCMGPTTPD SRPRLRAAAC
710 720 730 740 750
PHHRCPASAM VLSLLAVTLG GPVLCGMSMD LPLYAWLSRA RATPTKPQVW

LPAGT
Note: No experimental confirmation available.Curated
Length:755
Mass (Da):82,795
Last modified:May 18, 2010 - v2
Checksum:i29E9D2CD579C1CEF
GO
Isoform 21 Publication (identifier: Q6UW60-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-513: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:242
Mass (Da):26,118
Checksum:iF0F8977EDB6BEE61
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66P → S in AAQ89322 (PubMed:12975309).Curated1
Sequence conflicti66P → S in AAH36354 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061772267T → M.Corresponds to variant rs36123574dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0520971 – 513Missing in isoform 2. 1 PublicationAdd BLAST513

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358963 mRNA. Translation: AAQ89322.1.
AC027307 Genomic DNA. No translation available.
BC036354 mRNA. Translation: AAH36354.1.
AL133566 mRNA. Translation: CAB63719.3.
CCDSiCCDS12069.2. [Q6UW60-1]
PIRiT43487.
RefSeqiNP_060043.2. NM_017573.4. [Q6UW60-1]
UniGeneiHs.46884.

Genome annotation databases

EnsembliENST00000300954; ENSP00000300954; ENSG00000115257. [Q6UW60-1]
GeneIDi54760.
KEGGihsa:54760.
UCSCiuc002ltb.3. human. [Q6UW60-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358963 mRNA. Translation: AAQ89322.1.
AC027307 Genomic DNA. No translation available.
BC036354 mRNA. Translation: AAH36354.1.
AL133566 mRNA. Translation: CAB63719.3.
CCDSiCCDS12069.2. [Q6UW60-1]
PIRiT43487.
RefSeqiNP_060043.2. NM_017573.4. [Q6UW60-1]
UniGeneiHs.46884.

3D structure databases

ProteinModelPortaliQ6UW60.
SMRiQ6UW60.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120136. 1 interactor.
STRINGi9606.ENSP00000300954.

Chemistry databases

BindingDBiQ6UW60.
ChEMBLiCHEMBL4861.
GuidetoPHARMACOLOGYi2384.

Protein family/group databases

MEROPSiS08.074.

PTM databases

iPTMnetiQ6UW60.
PhosphoSitePlusiQ6UW60.

Polymorphism and mutation databases

BioMutaiPCSK4.
DMDMi296439263.

Proteomic databases

PaxDbiQ6UW60.
PRIDEiQ6UW60.

Protocols and materials databases

DNASUi54760.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300954; ENSP00000300954; ENSG00000115257. [Q6UW60-1]
GeneIDi54760.
KEGGihsa:54760.
UCSCiuc002ltb.3. human. [Q6UW60-1]

Organism-specific databases

CTDi54760.
DisGeNETi54760.
GeneCardsiPCSK4.
H-InvDBHIX0014587.
HGNCiHGNC:8746. PCSK4.
HPAiHPA005572.
MIMi600487. gene.
neXtProtiNX_Q6UW60.
OpenTargetsiENSG00000115257.
PharmGKBiPA33092.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
COG4935. LUCA.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiQ6UW60.
KOiK08671.
OMAiYTPSDEN.
OrthoDBiEOG091G05HI.
PhylomeDBiQ6UW60.
TreeFamiTF314277.

Enzyme and pathway databases

BRENDAi3.4.21.B24. 2681.
3.4.21.B25. 2681.
SignaLinkiQ6UW60.

Miscellaneous databases

ChiTaRSiPCSK4. human.
GeneWikiiPCSK4.
GenomeRNAii54760.
PROiQ6UW60.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115257.
CleanExiHS_PCSK4.
ExpressionAtlasiQ6UW60. baseline and differential.
GenevisibleiQ6UW60. HS.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.30.70.850. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR006212. Furin_repeat.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
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. Propept_inh.
IPR002884. PrprotnconvertsP.
IPR032815. S8_pro-domain.
[Graphical view]
PANTHERiPTHR10795. PTHR10795. 2 hits.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
PF16470. S8_pro-domain. 1 hit.
[Graphical view]
PRINTSiPR00723. SUBTILISIN.
SMARTiSM00261. FU. 1 hit.
[Graphical view]
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPCSK4_HUMAN
AccessioniPrimary (citable) accession number: Q6UW60
Secondary accession number(s): Q8IY88, Q9UF79
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 116 of the entry and version 2 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 19
    Human chromosome 19: 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
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

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.