ID   PCSK5_HUMAN             Reviewed;        1860 AA.
AC   Q92824; F5H2G7; Q13527; Q96EP4;
DT   11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   16-NOV-2011, sequence version 4.
DT   27-MAR-2024, entry version 217.
DE   RecName: Full=Proprotein convertase subtilisin/kexin type 5;
DE            EC=3.4.21.-;
DE   AltName: Full=Proprotein convertase 5;
DE            Short=PC5;
DE   AltName: Full=Proprotein convertase 6;
DE            Short=PC6;
DE            Short=hPC6;
DE   AltName: Full=Subtilisin/kexin-like protease PC5;
DE   Flags: Precursor;
GN   Name=PCSK5; Synonyms=PC5, PC6;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PC6A), AND ALTERNATIVE SPLICING.
RC   TISSUE=T-cell;
RX   PubMed=8755538; DOI=10.1073/pnas.93.15.7695;
RA   Miranda L., Wolf J., Pichuantes S., Duke R., Franzusoff A.;
RT   "Isolation of the human PC6 gene encoding the putative host protease for
RT   HIV-1 gp160 processing in CD4+ T lymphocytes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:7695-7700(1996).
RN   [2]
RP   SEQUENCE REVISION.
RA   Franzusoff A., Miranda L., Wolf J., Pichuantes S., Lu Y., Duke R.;
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PC6A).
RC   TISSUE=Lymph node;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PC6A).
RC   TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 15-913 (ISOFORM PC6A).
RA   Reudelhuber T.L.;
RL   Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1166-1860 (ISOFORM PC6B).
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   FUNCTION IN PREGNANCY ESTABLISHMENT.
RX   PubMed=19764806; DOI=10.1021/pr900381a;
RA   Kilpatrick L.M., Stephens A.N., Hardman B.M., Salamonsen L.A., Li Y.,
RA   Stanton P.G., Nie G.;
RT   "Proteomic identification of caldesmon as a physiological substrate of
RT   proprotein convertase 6 in human uterine decidual cells essential for
RT   pregnancy establishment.";
RL   J. Proteome Res. 8:4983-4992(2009).
RN   [10]
RP   FUNCTION IN PREGNANCY ESTABLISHMENT.
RX   PubMed=20555025; DOI=10.1210/en.2010-0326;
RA   Heng S., Paule S., Hardman B., Li Y., Singh H., Rainczuk A., Stephens A.N.,
RA   Nie G.;
RT   "Posttranslational activation of bone morphogenetic protein 2 is mediated
RT   by proprotein convertase 6 during decidualization for pregnancy
RT   establishment.";
RL   Endocrinology 151:3909-3917(2010).
RN   [11]
RP   FUNCTION.
RX   PubMed=22740495; DOI=10.1093/humrep/des203;
RA   Paule S., Aljofan M., Simon C., Rombauts L.J., Nie G.;
RT   "Cleavage of endometrial alpha-integrins into their functional forms is
RT   mediated by proprotein convertase 5/6.";
RL   Hum. Reprod. 27:2766-2774(2012).
CC   -!- FUNCTION: Serine endoprotease that processes various proproteins by
CC       cleavage at paired basic amino acids, recognizing the RXXX[KR]R
CC       consensus motif. Likely functions in the constitutive and regulated
CC       secretory pathways. Plays an essential role in pregnancy establishment
CC       by proteolytic activation of a number of important factors such as
CC       BMP2, CALD1 and alpha-integrins. {ECO:0000269|PubMed:19764806,
CC       ECO:0000269|PubMed:20555025, ECO:0000269|PubMed:22740495}.
CC   -!- INTERACTION:
CC       Q92824; O76003: GLRX3; NbExp=3; IntAct=EBI-751290, EBI-374781;
CC       Q92824; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-751290, EBI-10172290;
CC       Q92824; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-751290, EBI-10171774;
CC       Q92824; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-751290, EBI-739863;
CC       Q92824; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-751290, EBI-3958099;
CC       Q92824; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-751290, EBI-10245291;
CC       Q92824; P50222: MEOX2; NbExp=3; IntAct=EBI-751290, EBI-748397;
CC       Q92824; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-751290, EBI-945833;
CC       Q92824; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-751290, EBI-1210753;
CC       Q92824; O75716: STK16; NbExp=3; IntAct=EBI-751290, EBI-749295;
CC       Q92824-2; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-11956269, EBI-10173507;
CC       Q92824-2; Q8WW18: C17orf50; NbExp=3; IntAct=EBI-11956269, EBI-12877892;
CC       Q92824-2; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-11956269, EBI-7317823;
CC       Q92824-2; Q02930-3: CREB5; NbExp=6; IntAct=EBI-11956269, EBI-10192698;
CC       Q92824-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11956269, EBI-3867333;
CC       Q92824-2; Q8NFT6-2: DBF4B; NbExp=3; IntAct=EBI-11956269, EBI-12205861;
CC       Q92824-2; Q92608: DOCK2; NbExp=3; IntAct=EBI-11956269, EBI-448771;
CC       Q92824-2; Q9NVL1-2: FAM86C1P; NbExp=3; IntAct=EBI-11956269, EBI-12845222;
CC       Q92824-2; O95363: FARS2; NbExp=3; IntAct=EBI-11956269, EBI-2513774;
CC       Q92824-2; O43559: FRS3; NbExp=3; IntAct=EBI-11956269, EBI-725515;
CC       Q92824-2; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-11956269, EBI-11978177;
CC       Q92824-2; P49639: HOXA1; NbExp=5; IntAct=EBI-11956269, EBI-740785;
CC       Q92824-2; P17482: HOXB9; NbExp=3; IntAct=EBI-11956269, EBI-745290;
CC       Q92824-2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-11956269, EBI-6509505;
CC       Q92824-2; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-11956269, EBI-11959885;
CC       Q92824-2; P60410: KRTAP10-8; NbExp=6; IntAct=EBI-11956269, EBI-10171774;
CC       Q92824-2; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-11956269, EBI-10172052;
CC       Q92824-2; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-11956269, EBI-1052037;
CC       Q92824-2; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-11956269, EBI-10176379;
CC       Q92824-2; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-11956269, EBI-10241252;
CC       Q92824-2; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-11956269, EBI-12196745;
CC       Q92824-2; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-11956269, EBI-9996449;
CC       Q92824-2; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-11956269, EBI-751260;
CC       Q92824-2; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-11956269, EBI-3958099;
CC       Q92824-2; Q5T752: LCE1D; NbExp=6; IntAct=EBI-11956269, EBI-11741311;
CC       Q92824-2; Q5T754: LCE1F; NbExp=3; IntAct=EBI-11956269, EBI-11958008;
CC       Q92824-2; Q5TA81: LCE2C; NbExp=6; IntAct=EBI-11956269, EBI-11973993;
CC       Q92824-2; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-11956269, EBI-10245291;
CC       Q92824-2; Q9BYE3: LCE3D; NbExp=3; IntAct=EBI-11956269, EBI-6658837;
CC       Q92824-2; Q99750: MDFI; NbExp=3; IntAct=EBI-11956269, EBI-724076;
CC       Q92824-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11956269, EBI-16439278;
CC       Q92824-2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-11956269, EBI-22310682;
CC       Q92824-2; Q6NSM0: NR1D2; NbExp=3; IntAct=EBI-11956269, EBI-10250949;
CC       Q92824-2; Q92570: NR4A3; NbExp=3; IntAct=EBI-11956269, EBI-13644623;
CC       Q92824-2; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-11956269, EBI-1210753;
CC       Q92824-2; P32242: OTX1; NbExp=5; IntAct=EBI-11956269, EBI-740446;
CC       Q92824-2; P29122: PCSK6; NbExp=3; IntAct=EBI-11956269, EBI-2683528;
CC       Q92824-2; Q9NRQ2: PLSCR4; NbExp=3; IntAct=EBI-11956269, EBI-769257;
CC       Q92824-2; Q12837: POU4F2; NbExp=6; IntAct=EBI-11956269, EBI-17236143;
CC       Q92824-2; Q9NUL5-4: SHFL; NbExp=3; IntAct=EBI-11956269, EBI-11955083;
CC       Q92824-2; P49901: SMCP; NbExp=3; IntAct=EBI-11956269, EBI-750494;
CC       Q92824-2; O43609: SPRY1; NbExp=3; IntAct=EBI-11956269, EBI-3866665;
CC       Q92824-2; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-11956269, EBI-750487;
CC       Q92824-2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-11956269, EBI-11741437;
CC       Q92824-2; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-11956269, EBI-3650647;
CC       Q92824-2; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-11956269, EBI-492476;
CC       Q92824-2; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-11956269, EBI-5235829;
CC       Q92824-2; Q15645: TRIP13; NbExp=3; IntAct=EBI-11956269, EBI-358993;
CC       Q92824-2; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-11956269, EBI-11975223;
CC       Q92824-2; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-11956269, EBI-11957216;
CC       Q92824-2; Q8IVP9: ZNF547; NbExp=3; IntAct=EBI-11956269, EBI-12895421;
CC       Q92824-2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-11956269, EBI-625509;
CC       Q92824-2; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-11956269, EBI-11962574;
CC   -!- SUBCELLULAR LOCATION: [Isoform PC6A]: Secreted. Note=Secreted through
CC       the regulated secretory pathway. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Isoform PC6B]: Endomembrane system; Single-pass
CC       type I membrane protein. Note=Type I membrane protein localized to a
CC       paranuclear post-Golgi network compartment in communication with early
CC       endosomes. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=PC6B; Synonyms=Long;
CC         IsoId=Q92824-1; Sequence=Displayed;
CC       Name=PC6A; Synonyms=Short;
CC         IsoId=Q92824-2; Sequence=VSP_042017, VSP_042018;
CC   -!- TISSUE SPECIFICITY: Expressed in T-lymphocytes.
CC   -!- DOMAIN: The propeptide domain acts as an intramolecular chaperone
CC       assisting the folding of the zymogen within the endoplasmic reticulum.
CC   -!- DOMAIN: AC 1 and AC 2 (clusters of acidic amino acids) contain sorting
CC       information. AC 1 directs TGN localization and interacts with the TGN
CC       sorting protein PACS-1 (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR   EMBL; U56387; AAC50643.2; -; mRNA.
DR   EMBL; AL834522; CAD39178.1; -; mRNA.
DR   EMBL; AL359253; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL353607; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL391868; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL589653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471089; EAW62575.1; -; Genomic_DNA.
DR   EMBL; BC012064; AAH12064.1; -; mRNA.
DR   EMBL; U49114; AAA91807.1; -; mRNA.
DR   EMBL; AK122718; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS55320.1; -. [Q92824-1]
DR   CCDS; CCDS6652.1; -. [Q92824-2]
DR   PIR; G02428; G02428.
DR   PIR; JC6148; JC6148.
DR   RefSeq; NP_001177411.1; NM_001190482.1. [Q92824-1]
DR   RefSeq; NP_006191.2; NM_006200.5. [Q92824-2]
DR   AlphaFoldDB; Q92824; -.
DR   SMR; Q92824; -.
DR   BioGRID; 111152; 113.
DR   IntAct; Q92824; 79.
DR   STRING; 9606.ENSP00000446280; -.
DR   BindingDB; Q92824; -.
DR   ChEMBL; CHEMBL2826; -.
DR   GuidetoPHARMACOLOGY; 2385; -.
DR   MEROPS; S08.076; -.
DR   GlyCosmos; Q92824; 12 sites, No reported glycans.
DR   GlyGen; Q92824; 12 sites.
DR   iPTMnet; Q92824; -.
DR   PhosphoSitePlus; Q92824; -.
DR   BioMuta; PCSK5; -.
DR   DMDM; 357529585; -.
DR   MassIVE; Q92824; -.
DR   PaxDb; 9606-ENSP00000446280; -.
DR   PeptideAtlas; Q92824; -.
DR   ProteomicsDB; 75502; -. [Q92824-1]
DR   ProteomicsDB; 75503; -. [Q92824-2]
DR   Antibodypedia; 27199; 220 antibodies from 26 providers.
DR   DNASU; 5125; -.
DR   Ensembl; ENST00000376752.9; ENSP00000365943.4; ENSG00000099139.14. [Q92824-2]
DR   Ensembl; ENST00000545128.5; ENSP00000446280.1; ENSG00000099139.14. [Q92824-1]
DR   GeneID; 5125; -.
DR   KEGG; hsa:5125; -.
DR   UCSC; uc004ajz.5; human. [Q92824-1]
DR   AGR; HGNC:8747; -.
DR   CTD; 5125; -.
DR   DisGeNET; 5125; -.
DR   GeneCards; PCSK5; -.
DR   HGNC; HGNC:8747; PCSK5.
DR   HPA; ENSG00000099139; Tissue enhanced (intestine).
DR   MIM; 600488; gene.
DR   neXtProt; NX_Q92824; -.
DR   OpenTargets; ENSG00000099139; -.
DR   PharmGKB; PA33093; -.
DR   VEuPathDB; HostDB:ENSG00000099139; -.
DR   eggNOG; KOG3525; Eukaryota.
DR   GeneTree; ENSGT00940000155770; -.
DR   HOGENOM; CLU_003159_0_0_1; -.
DR   InParanoid; Q92824; -.
DR   OrthoDB; 5474719at2759; -.
DR   PhylomeDB; Q92824; -.
DR   TreeFam; TF314277; -.
DR   BRENDA; 3.4.21.B26; 2681.
DR   PathwayCommons; Q92824; -.
DR   Reactome; R-HSA-167060; NGF processing.
DR   Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes.
DR   SignaLink; Q92824; -.
DR   SIGNOR; Q92824; -.
DR   BioGRID-ORCS; 5125; 6 hits in 1145 CRISPR screens.
DR   ChiTaRS; PCSK5; human.
DR   GeneWiki; PCSK5; -.
DR   GenomeRNAi; 5125; -.
DR   Pharos; Q92824; Tchem.
DR   PRO; PR:Q92824; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q92824; Protein.
DR   Bgee; ENSG00000099139; Expressed in buccal mucosa cell and 192 other cell types or tissues.
DR   ExpressionAtlas; Q92824; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; ISS:BHF-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR   GO; GO:0004175; F:endopeptidase activity; EXP:Reactome.
DR   GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR   GO; GO:0042277; F:peptide binding; ISS:BHF-UCL.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IMP:BHF-UCL.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0140447; P:cytokine precursor processing; ISS:BHF-UCL.
DR   GO; GO:0007566; P:embryo implantation; ISS:BHF-UCL.
DR   GO; GO:0048566; P:embryonic digestive tract development; IMP:BHF-UCL.
DR   GO; GO:0048706; P:embryonic skeletal system development; IMP:BHF-UCL.
DR   GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR   GO; GO:0001822; P:kidney development; IMP:BHF-UCL.
DR   GO; GO:0035108; P:limb morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0043043; P:peptide biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0016486; P:peptide hormone processing; IDA:BHF-UCL.
DR   GO; GO:0034369; P:plasma lipoprotein particle remodeling; TAS:Reactome.
DR   GO; GO:0016485; P:protein processing; IDA:MGI.
DR   GO; GO:0002001; P:renin secretion into blood stream; IEP:BHF-UCL.
DR   GO; GO:0030323; P:respiratory tube development; ISS:BHF-UCL.
DR   GO; GO:0006465; P:signal peptide processing; IDA:HGNC-UCL.
DR   GO; GO:0019058; P:viral life cycle; IEP:BHF-UCL.
DR   CDD; cd00064; FU; 16.
DR   CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR   Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR   Gene3D; 3.30.70.850; Peptidase S8, pro-domain; 1.
DR   Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR006212; Furin_repeat.
DR   InterPro; IPR008979; Galactose-bd-like_sf.
DR   InterPro; IPR032778; GF_recep_IV.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR034182; Kexin/furin.
DR   InterPro; IPR002884; P_dom.
DR   InterPro; IPR000209; Peptidase_S8/S53_dom.
DR   InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR   InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR   InterPro; IPR022398; Peptidase_S8_His-AS.
DR   InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR   InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR   InterPro; IPR032815; S8_pro-domain.
DR   InterPro; IPR038466; S8_pro-domain_sf.
DR   PANTHER; PTHR42884:SF13; NEUROENDOCRINE CONVERTASE 2; 1.
DR   PANTHER; PTHR42884; PROPROTEIN CONVERTASE SUBTILISIN/KEXIN-RELATED; 1.
DR   Pfam; PF14843; GF_recep_IV; 1.
DR   Pfam; PF01483; P_proprotein; 1.
DR   Pfam; PF00082; Peptidase_S8; 1.
DR   Pfam; PF16470; S8_pro-domain; 1.
DR   PRINTS; PR00723; SUBTILISIN.
DR   SMART; SM00181; EGF; 16.
DR   SMART; SM01411; Ephrin_rec_like; 8.
DR   SMART; SM00261; FU; 22.
DR   SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 7.
DR   SUPFAM; SSF54897; Protease propeptides/inhibitors; 1.
DR   SUPFAM; SSF52743; Subtilisin-like; 1.
DR   PROSITE; PS51829; P_HOMO_B; 1.
DR   PROSITE; PS51892; SUBTILASE; 1.
DR   PROSITE; PS00136; SUBTILASE_ASP; 1.
DR   PROSITE; PS00137; SUBTILASE_HIS; 1.
DR   PROSITE; PS00138; SUBTILASE_SER; 1.
DR   Genevisible; Q92824; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cleavage on pair of basic residues; Glycoprotein;
KW   Hydrolase; Membrane; Pregnancy; Protease; Reference proteome; Repeat;
KW   Secreted; Serine protease; Signal; Transmembrane; Transmembrane helix;
KW   Zymogen.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000250"
FT   PROPEP          33..114
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000027102"
FT   CHAIN           115..1860
FT                   /note="Proprotein convertase subtilisin/kexin type 5"
FT                   /id="PRO_0000027103"
FT   TOPO_DOM        115..1743
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1744..1764
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1765..1860
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          134..453
FT                   /note="Peptidase S8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   DOMAIN          461..601
FT                   /note="P/Homo B"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT   REPEAT          630..680
FT                   /note="FU 1"
FT   REPEAT          683..730
FT                   /note="FU 2"
FT   REPEAT          734..777
FT                   /note="FU 3"
FT   REPEAT          779..824
FT                   /note="FU 4"
FT   REPEAT          832..879
FT                   /note="FU 5"
FT   DOMAIN          869..913
FT                   /note="PLAC"
FT   REPEAT          882..927
FT                   /note="FU 6"
FT   REPEAT          929..979
FT                   /note="FU 7"
FT   REPEAT          982..1028
FT                   /note="FU 8"
FT   REPEAT          1032..1077
FT                   /note="FU 9"
FT   REPEAT          1079..1121
FT                   /note="FU 10"
FT   REPEAT          1125..1168
FT                   /note="FU 11"
FT   REPEAT          1177..1221
FT                   /note="FU 12"
FT   REPEAT          1225..1272
FT                   /note="FU 13"
FT   REPEAT          1274..1318
FT                   /note="FU 14"
FT   REPEAT          1320..1363
FT                   /note="FU 15"
FT   REPEAT          1365..1411
FT                   /note="FU 16"
FT   REPEAT          1415..1461
FT                   /note="FU 17"
FT   REPEAT          1465..1510
FT                   /note="FU 18"
FT   REPEAT          1514..1559
FT                   /note="FU 19"
FT   REPEAT          1563..1610
FT                   /note="FU 20"
FT   REPEAT          1614..1659
FT                   /note="FU 21"
FT   REPEAT          1665..1712
FT                   /note="FU 22"
FT   REGION          636..1727
FT                   /note="CRM (Cys-rich motif)"
FT   REGION          1807..1826
FT                   /note="AC 1"
FT                   /evidence="ECO:0000250"
FT   REGION          1838..1860
FT                   /note="AC 2"
FT                   /evidence="ECO:0000250"
FT   MOTIF           519..521
FT                   /note="Cell attachment site"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        171
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   ACT_SITE        212
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   ACT_SITE        386
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT   SITE            114..115
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        225
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        381
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        665
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        752
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        802
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        852
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1014
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1191
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1290
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1497
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1685
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        1707
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         876..913
FT                   /note="GEYVDEHGHCQTCEASCAKCQGPTQEDCTTCPMTRIFD -> ATEESWAEGG
FT                   FCMLVKKNNLCQRKVLQQLCCKTCTFQG (in isoform PC6A)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:8755538,
FT                   ECO:0000303|Ref.7"
FT                   /id="VSP_042017"
FT   VAR_SEQ         914..1860
FT                   /note="Missing (in isoform PC6A)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:8755538,
FT                   ECO:0000303|Ref.7"
FT                   /id="VSP_042018"
FT   CONFLICT        2
FT                   /note="G -> D (in Ref. 1; AAC50643)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        4
FT                   /note="G -> E (in Ref. 1; AAC50643)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        118
FT                   /note="F -> S (in Ref. 1; AAC50643)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        121
FT                   /note="A -> V (in Ref. 1; AAC50643)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        511
FT                   /note="R -> A (in Ref. 7; AAA91807)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        601
FT                   /note="Q -> R (in Ref. 1; AAC50643)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1860 AA;  206942 MW;  96B3E7C8215BCC85 CRC64;
     MGWGSRCCCP GRLDLLCVLA LLGGCLLPVC RTRVYTNHWA VKIAGGFPEA NRIASKYGFI
     NIGQIGALKD YYHFYHSRTI KRSVISSRGT HSFISMEPKV EWIQQQVVKK RTKRDYDFSR
     AQSTYFNDPK WPSMWYMHCS DNTHPCQSDM NIEGAWKRGY TGKNIVVTIL DDGIERTHPD
     LMQNYDALAS CDVNGNDLDP MPRYDASNEN KHGTRCAGEV AAAANNSHCT VGIAFNAKIG
     GVRMLDGDVT DMVEAKSVSF NPQHVHIYSA SWGPDDDGKT VDGPAPLTRQ AFENGVRMGR
     RGLGSVFVWA SGNGGRSKDH CSCDGYTNSI YTISISSTAE SGKKPWYLEE CSSTLATTYS
     SGESYDKKII TTDLRQRCTD NHTGTSASAP MAAGIIALAL EANPFLTWRD VQHVIVRTSR
     AGHLNANDWK TNAAGFKVSH LYGFGLMDAE AMVMEAEKWT TVPRQHVCVE STDRQIKTIR
     PNSAVRSIYK ASGCSDNPNR HVNYLEHVVV RITITHPRRG DLAIYLTSPS GTRSQLLANR
     LFDHSMEGFK NWEFMTIHCW GERAAGDWVL EVYDTPSQLR NFKTPGKLKE WSLVLYGTSV
     QPYSPTNEFP KVERFRYSRV EDPTDDYGTE DYAGPCDPEC SEVGCDGPGP DHCNDCLHYY
     YKLKNNTRIC VSSCPPGHYH ADKKRCRKCA PNCESCFGSH GDQCMSCKYG YFLNEETNSC
     VTHCPDGSYQ DTKKNLCRKC SENCKTCTEF HNCTECRDGL SLQGSRCSVS CEDGRYFNGQ
     DCQPCHRFCA TCAGAGADGC INCTEGYFME DGRCVQSCSI SYYFDHSSEN GYKSCKKCDI
     SCLTCNGPGF KNCTSCPSGY LLDLGMCQMG AICKDGEYVD EHGHCQTCEA SCAKCQGPTQ
     EDCTTCPMTR IFDDGRCVSN CPSWKFEFEN QCHPCHHTCQ RCQGSGPTHC TSCGADNYGR
     EHFLYQGECG DSCPEGHYAT EGNTCLPCPD NCELCHSVHV CTRCMKGYFI APTNHTCQKL
     ECGQGEVQDP DYEECVPCEE GCLGCSLDDP GTCTSCAMGY YRFDHHCYKT CPEKTYSEEV
     ECKACDSNCG SCDQNGCYWC EEGFFLLGGS CVRKCGPGFY GDQEMGECES CHRACETCTG
     PGHDECSSCQ EGLQLLRGMC VHATKTQEEG KFWNDILRKL QPCHSSCKTC NGSATLCTSC
     PKGAYLLAQA CVSSCPQGTW PSVRSGSCEN CTEACAICSG ADLCKKCQMQ PGHPLFLHEG
     RCYSKCPEGS YAEDGICERC SSPCRTCEGN ATNCHSCEGG HVLHHGVCQE NCPERHVAVK
     GVCKHCPEMC QDCIHEKTCK ECTPEFFLHD DMCHQSCPRG FYADSRHCVP CHKDCLECSG
     PKADDCELCL ESSWVLYDGL CLEECPAGTY YEKETKECRD CHKSCLTCSS SGTCTTCQKG
     LIMNPRGSCM ANEKCSPSEY WDEDAPGCKP CHVKCFHCMG PAEDQCQTCP MNSLLLNTTC
     VKDCPEGYYA DEDSNRCAHC HSSCRTCEGR HSRQCHSCRP GWFQLGKECL LQCREGYYAD
     NSTGRCERCN RSCKGCQGPR PTDCLSCDRF FFLLRSKGEC HRSCPDHYYV EQSTQTCERC
     HPTCDQCKGK GALNCLSCVW SYHLMGGICT SDCLVGEYRV GEGEKFNCEK CHESCMECKG
     PGAKNCTLCP ANLVLHMDDS HCLHCCNTSD PPSAQECCDC QDTTDECILR TSKVRPATEH
     FKTALFITSS MMLVLLLGAA VVVWKKSRGR VQPAAKAGYE KLADPNKSYS SYKSSYREST
     SFEEDQVIEY RDRDYDEDDD DDIVYMGQDG TVYRKFKYGL LDDDDIDELE YDDESYSYYQ
//