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Q6UW60 (PCSK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 4

EC=3.4.21.-
Alternative name(s):
Proprotein convertase 4
Short name=PC4
Gene names
Name:PCSK4
Synonyms:PC4
ORF Names:UNQ2757/PRO6496
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length755 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Plays a role in transcriptional coactivation. May be involved in stabilizing the multiprotein transcription complex. Ref.5 PubMed 9482861 UniProtKB P29121 PubMed 7628453

Subcellular location

Membrane; Single-pass membrane protein Potential.

Tissue specificity

Placenta. Ref.5

Developmental stage

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. Ref.5

Sequence similarities

Belongs to the peptidase S8 family. Furin subfamily.

Contains 1 FU (furin-like) repeat.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q6UW60-1)

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.
Note: No experimental confirmation available.
Isoform 2 Ref.3 (identifier: Q6UW60-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-513: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Propeptide26 – 11388 Potential UniProtKB P29121
PRO_0000246778
Chain114 – 755642Proprotein convertase subtilisin/kexin type 4 UniProtKB P29121
PRO_0000246779

Regions

Transmembrane709 – 72921Helical; Potential
Repeat646 – 69449FU
Region124 – 417294Catalytic By similarity UniProtKB P29121

Sites

Active site1581Charge relay system By similarity UniProtKB P23188
Active site1991Charge relay system By similarity UniProtKB P23188
Active site3731Charge relay system By similarity

Amino acid modifications

Glycosylation4751N-linked (GlcNAc...) Potential
Glycosylation6291N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 513513Missing in isoform 2. Ref.3
VSP_052097
Natural variant2671T → M.
Corresponds to variant rs36123574 [ dbSNP | Ensembl ].
VAR_061772

Experimental info

Sequence conflict661P → S in AAQ89322. Ref.1
Sequence conflict661P → S in AAH36354. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 29E9D2CD579C1CEF

FASTA75582,795
        10         20         30         40         50         60 
MRPAPIALWL RLVLALALVR PRAVGWAPVR APIYVSSWAV QVSQGNREVE RLARKFGFVN 

        70         80         90        100        110        120 
LGPIFPDGQY FHLRHRGVVQ QSLTPHWGHR LHLKKNPKVQ WFQQQTLQRR VKRSVVVPTD 

       130        140        150        160        170        180 
PWFSKQWYMN SEAQPDLSIL QAWSQGLSGQ GIVVSVLDDG IEKDHPDLWA NYDPLASYDF 

       190        200        210        220        230        240 
NDYDPDPQPR YTPSKENRHG TRCAGEVAAM ANNGFCGVGV AFNARIGGVR MLDGTITDVI 

       250        260        270        280        290        300 
EAQSLSLQPQ HIHIYSASWG PEDDGRTVDG PGILTREAFR RGVTKGRGGL GTLFIWASGN 

       310        320        330        340        350        360 
GGLHYDNCNC DGYTNSIHTL SVGSTTQQGR VPWYSEACAS TLTTTYSSGV ATDPQIVTTD 

       370        380        390        400        410        420 
LHHGCTDQHT GTSASAPLAA GMIALALEAN PFLTWRDMQH LVVRASKPAH LQAEDWRTNG 

       430        440        450        460        470        480 
VGRQVSHHYG YGLLDAGLLV DTARTWLPTQ PQRKCAVRVQ SRPTPILPLI YIRENVSACA 

       490        500        510        520        530        540 
GLHNSIRSLE HVQAQLTLSY SRRGDLEISL TSPMGTRSTL VAIRPLDVST EGYNNWVFMS 

       550        560        570        580        590        600 
THFWDENPQG VWTLGLENKG YYFNTGTLYR YTLLLYGTAE DMTARPTGPQ VTSSACVQRD 

       610        620        630        640        650        660 
TEGLCQACDG PAYILGQLCL AYCPPRFFNH TRLVTAGPGH TAAPALRVCS SCHASCYTCR 

       670        680        690        700        710        720 
GGSPRDCTSC PPSSTLDQQQ GSCMGPTTPD SRPRLRAAAC PHHRCPASAM VLSLLAVTLG 

       730        740        750 
GPVLCGMSMD LPLYAWLSRA RATPTKPQVW LPAGT 

« Hide

Isoform 2 [UniParc].

Checksum: F0F8977EDB6BEE61
Show »

FASTA24226,118

References

« Hide 'large scale' references
[1]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[2]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 526-755 (ISOFORMS 1/2).
Tissue: Testis.
[5]"Role of pro-IGF-II processing by proprotein convertase 4 in human placental development."
Qiu Q., Basak A., Mbikay M., Tsang B.K., Gruslin A.
Proc. Natl. Acad. Sci. U.S.A. 102:11047-11052(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY358963 mRNA. Translation: AAQ89322.1.
AC027307 Genomic DNA. No translation available.
BC036354 mRNA. Translation: AAH36354.1.
AL133566 mRNA. Translation: CAB63719.3.
CCDSCCDS12069.2. [Q6UW60-1]
PIRT43487.
RefSeqNP_060043.2. NM_017573.4. [Q6UW60-1]
UniGeneHs.46884.

3D structure databases

ProteinModelPortalQ6UW60.
SMRQ6UW60. Positions 118-581, 650-690.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120136. 2 interactions.
STRING9606.ENSP00000300954.

Chemistry

ChEMBLCHEMBL4861.

Protein family/group databases

MEROPSS08.074.

PTM databases

PhosphoSiteQ6UW60.

Polymorphism databases

DMDM296439263.

Proteomic databases

PaxDbQ6UW60.
PRIDEQ6UW60.

Protocols and materials databases

DNASU54760.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000300954; ENSP00000300954; ENSG00000115257. [Q6UW60-1]
GeneID54760.
KEGGhsa:54760.
UCSCuc002lsz.2. human. [Q6UW60-2]
uc002ltb.1. human. [Q6UW60-1]

Organism-specific databases

CTD54760.
GeneCardsGC19M001481.
H-InvDBHIX0014587.
HGNCHGNC:8746. PCSK4.
HPAHPA005572.
MIM600487. gene.
neXtProtNX_Q6UW60.
PharmGKBPA33092.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4935.
HOGENOMHOG000192536.
HOVERGENHBG008705.
InParanoidQ6UW60.
KOK08671.
OMAHVQVQLS.
OrthoDBEOG7BW0JD.
PhylomeDBQ6UW60.
TreeFamTF314277.

Enzyme and pathway databases

SignaLinkQ6UW60.

Gene expression databases

ArrayExpressQ6UW60.
BgeeQ6UW60.
CleanExHS_PCSK4.
GenevestigatorQ6UW60.

Family and domain databases

Gene3D2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProIPR006212. 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.
SMARTSM00261. FU. 1 hit.
[Graphical view]
SUPFAMSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPCSK4.
GenomeRNAi54760.
NextBio57393.
PROQ6UW60.
SOURCESearch...

Entry information

Entry namePCSK4_HUMAN
AccessionPrimary (citable) accession number: Q6UW60
Secondary accession number(s): Q8IY88, Q9UF79
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM