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Q6UW60

- PCSK4_HUMAN

UniProt

Q6UW60 - PCSK4_HUMAN

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Protein

Proprotein convertase subtilisin/kexin type 4

Gene

PCSK4

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

Functioni

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei158 – 1581Charge relay systemBy similarity
Active sitei199 – 1991Charge relay systemBy similarity
Active sitei373 – 3731Charge relay systemBy similarity

GO - Molecular functioni

  1. serine-type endopeptidase activity Source: RefGenome

GO - Biological processi

  1. acrosome reaction Source: Ensembl
  2. binding of sperm to zona pellucida Source: Ensembl
  3. proteolysis Source: RefGenome
  4. sperm capacitation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

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
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:8746. PCSK4.

Subcellular locationi

Membrane Sequence Analysis; Single-pass membrane protein Sequence Analysis

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei709 – 72921HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. acrosomal membrane Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33092.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Propeptidei26 – 11388By similaritySequence AnalysisPRO_0000246778Add
BLAST
Chaini114 – 755642Proprotein convertase subtilisin/kexin type 4By similaritySequence AnalysisPRO_0000246779Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi475 – 4751N-linked (GlcNAc...)Sequence Analysis
Glycosylationi629 – 6291N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ6UW60.
PRIDEiQ6UW60.

PTM databases

PhosphoSiteiQ6UW60.

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

BgeeiQ6UW60.
CleanExiHS_PCSK4.
ExpressionAtlasiQ6UW60. baseline.
GenevestigatoriQ6UW60.

Organism-specific databases

HPAiHPA005572.

Interactioni

Protein-protein interaction databases

BioGridi120136. 2 interactions.
STRINGi9606.ENSP00000300954.

Structurei

3D structure databases

ProteinModelPortaliQ6UW60.
SMRiQ6UW60. Positions 118-581.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini153 – 439287Peptidase S8Add
BLAST

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

eggNOGiCOG4935.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiQ6UW60.
KOiK08671.
OMAiHVQVQLS.
OrthoDBiEOG7BW0JD.
PhylomeDBiQ6UW60.
TreeFamiTF314277.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR006212. 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]
PANTHERiPTHR10795. PTHR10795. 1 hit.
PfamiPF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti66 – 661P → S in AAQ89322. (PubMed:12975309)Curated
Sequence conflicti66 – 661P → S in AAH36354. (PubMed:15489334)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti267 – 2671T → M.
Corresponds to variant rs36123574 [ dbSNP | Ensembl ].
VAR_061772

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 513513Missing in isoform 2. 1 PublicationVSP_052097Add
BLAST

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.
UCSCiuc002lsz.2. human. [Q6UW60-2]
uc002ltb.1. human. [Q6UW60-1]

Polymorphism databases

DMDMi296439263.

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 .
CCDSi CCDS12069.2. [Q6UW60-1 ]
PIRi T43487.
RefSeqi NP_060043.2. NM_017573.4. [Q6UW60-1 ]
UniGenei Hs.46884.

3D structure databases

ProteinModelPortali Q6UW60.
SMRi Q6UW60. Positions 118-581.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 120136. 2 interactions.
STRINGi 9606.ENSP00000300954.

Chemistry

ChEMBLi CHEMBL4861.

Protein family/group databases

MEROPSi S08.074.

PTM databases

PhosphoSitei Q6UW60.

Polymorphism databases

DMDMi 296439263.

Proteomic databases

PaxDbi Q6UW60.
PRIDEi Q6UW60.

Protocols and materials databases

DNASUi 54760.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000300954 ; ENSP00000300954 ; ENSG00000115257 . [Q6UW60-1 ]
GeneIDi 54760.
KEGGi hsa:54760.
UCSCi uc002lsz.2. human. [Q6UW60-2 ]
uc002ltb.1. human. [Q6UW60-1 ]

Organism-specific databases

CTDi 54760.
GeneCardsi GC19M001481.
H-InvDB HIX0014587.
HGNCi HGNC:8746. PCSK4.
HPAi HPA005572.
MIMi 600487. gene.
neXtProti NX_Q6UW60.
PharmGKBi PA33092.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG4935.
GeneTreei ENSGT00750000117358.
HOGENOMi HOG000192536.
HOVERGENi HBG008705.
InParanoidi Q6UW60.
KOi K08671.
OMAi HVQVQLS.
OrthoDBi EOG7BW0JD.
PhylomeDBi Q6UW60.
TreeFami TF314277.

Enzyme and pathway databases

SignaLinki Q6UW60.

Miscellaneous databases

ChiTaRSi PCSK4. human.
GeneWikii PCSK4.
GenomeRNAii 54760.
NextBioi 57393.
PROi Q6UW60.
SOURCEi Search...

Gene expression databases

Bgeei Q6UW60.
CleanExi HS_PCSK4.
ExpressionAtlasi Q6UW60. baseline.
Genevestigatori Q6UW60.

Family and domain databases

Gene3Di 2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProi 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 ]
PANTHERi PTHR10795. PTHR10795. 1 hit.
Pfami PF01483. P_proprotein. 1 hit.
PF00082. Peptidase_S8. 1 hit.
[Graphical view ]
PRINTSi PR00723. SUBTILISIN.
SMARTi SM00261. FU. 1 hit.
[Graphical view ]
SUPFAMi SSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEi PS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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: BrainImported.
  4. 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.

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 26, 2014
This is version 99 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

External Data

Dasty 3