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Q6UW60

- PCSK4_HUMAN

UniProt

Q6UW60 - PCSK4_HUMAN

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
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    • History
      Entry version 97 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    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

    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

    GO - Cellular componenti

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

    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

    ArrayExpressiQ6UW60.
    BgeeiQ6UW60.
    CleanExiHS_PCSK4.
    GenevestigatoriQ6UW60.

    Organism-specific databases

    HPAiHPA005572.

    Interactioni

    Protein-protein interaction databases

    BioGridi120136. 2 interactions.
    STRINGi9606.ENSP00000300954.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6UW60.
    SMRiQ6UW60. Positions 118-581, 650-690.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

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

    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.
    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

    MRPAPIALWL RLVLALALVR PRAVGWAPVR APIYVSSWAV QVSQGNREVE    50
    RLARKFGFVN LGPIFPDGQY FHLRHRGVVQ QSLTPHWGHR LHLKKNPKVQ 100
    WFQQQTLQRR VKRSVVVPTD PWFSKQWYMN SEAQPDLSIL QAWSQGLSGQ 150
    GIVVSVLDDG IEKDHPDLWA NYDPLASYDF NDYDPDPQPR YTPSKENRHG 200
    TRCAGEVAAM ANNGFCGVGV AFNARIGGVR MLDGTITDVI EAQSLSLQPQ 250
    HIHIYSASWG PEDDGRTVDG PGILTREAFR RGVTKGRGGL GTLFIWASGN 300
    GGLHYDNCNC DGYTNSIHTL SVGSTTQQGR VPWYSEACAS TLTTTYSSGV 350
    ATDPQIVTTD LHHGCTDQHT GTSASAPLAA GMIALALEAN PFLTWRDMQH 400
    LVVRASKPAH LQAEDWRTNG VGRQVSHHYG YGLLDAGLLV DTARTWLPTQ 450
    PQRKCAVRVQ SRPTPILPLI YIRENVSACA GLHNSIRSLE HVQAQLTLSY 500
    SRRGDLEISL TSPMGTRSTL VAIRPLDVST EGYNNWVFMS THFWDENPQG 550
    VWTLGLENKG YYFNTGTLYR YTLLLYGTAE DMTARPTGPQ VTSSACVQRD 600
    TEGLCQACDG PAYILGQLCL AYCPPRFFNH TRLVTAGPGH TAAPALRVCS 650
    SCHASCYTCR GGSPRDCTSC PPSSTLDQQQ GSCMGPTTPD SRPRLRAAAC 700
    PHHRCPASAM VLSLLAVTLG GPVLCGMSMD LPLYAWLSRA RATPTKPQVW 750
    LPAGT 755

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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, 650-690.
    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.
    HOGENOMi HOG000192536.
    HOVERGENi HBG008705.
    InParanoidi Q6UW60.
    KOi K08671.
    OMAi HVQVQLS.
    OrthoDBi EOG7BW0JD.
    PhylomeDBi Q6UW60.
    TreeFami TF314277.

    Enzyme and pathway databases

    SignaLinki Q6UW60.

    Miscellaneous databases

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

    Gene expression databases

    ArrayExpressi Q6UW60.
    Bgeei Q6UW60.
    CleanExi HS_PCSK4.
    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

    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: October 1, 2014
    This is version 97 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