PCSK7_HUMAN
ID PCSK7_HUMAN Reviewed; 785 AA.
AC Q16549; B0YJ60; Q3C1X1; Q53GM4; Q96FK8; Q9UL57;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Proprotein convertase subtilisin/kexin type 7;
DE EC=3.4.21.-;
DE AltName: Full=Lymphoma proprotein convertase;
DE AltName: Full=Prohormone convertase 7;
DE AltName: Full=Proprotein convertase 7;
DE Short=PC7;
DE AltName: Full=Proprotein convertase 8;
DE Short=PC8;
DE Short=hPC8;
DE AltName: Full=Subtilisin/kexin-like protease PC7;
DE Flags: Precursor;
GN Name=PCSK7; Synonyms=LPC, PC7, PC8, SPC7;
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].
RC TISSUE=Lung carcinoma;
RX PubMed=8615762; DOI=10.1042/bj3140727;
RA Bruzzaniti A., Goodge K., Jay P., Taviaux S.A., Lam M.H.C., Berta P.,
RA Martin T.J., Moseley J.M., Gillespie M.T.;
RT "PC8, a new member of the convertase family.";
RL Biochem. J. 314:727-731(1996).
RN [2]
RP ERRATUM OF PUBMED:8615762.
RA Bruzzaniti A., Goodge K., Jay P., Taviaux S.A., Lam M.H.C., Berta P.,
RA Martin T.J., Moseley J.M., Gillespie M.T.;
RL Biochem. J. 316:1007-1007(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=T-cell lymphoma;
RX PubMed=8564950;
RA Meerabux J., Yaspo M.-L., Roebroek A.J.M., Van de Ven W.J.M., Lister T.A.,
RA Young B.D.;
RT "A new member of the proprotein convertase gene family (LPC) is located at
RT a chromosome translocation breakpoint in lymphomas.";
RL Cancer Res. 56:448-451(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 527-785.
RX PubMed=10362256; DOI=10.1038/sj.onc.1202645;
RA Lecointe N., Meerabux J., Ebihara M., Hill A., Young B.D.;
RT "Molecular analysis of an unstable genomic region at chromosome band 11q23
RT reveals a disruption of the gene encoding the alpha2 subunit of platelet-
RT activating factor acetylhydrolase (Pafah1a2) in human lymphoma.";
RL Oncogene 18:2852-2859(1999).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 574-655.
RA Totoki Y., Yada T., Sakaki Y., Takeda T.;
RT "Identification of novel human genes predicted by combining multiple gene-
RT finders.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP GLYCOSYLATION, AND PALMITOYLATION.
RX PubMed=9341152; DOI=10.1074/jbc.272.43.27116;
RA Van de Loo J.-W.H.P., Creemers J.W.M., Bright N.A., Young B.D.,
RA Roebroek A.J.M., Van de Ven W.J.M.;
RT "Biosynthesis, distinct post-translational modifications, and functional
RT characterization of lymphoma proprotein convertase.";
RL J. Biol. Chem. 272:27116-27123(1997).
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 secretory
CC pathway.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by zinc and copper. {ECO:0000250}.
CC -!- INTERACTION:
CC Q16549; P14136: GFAP; NbExp=3; IntAct=EBI-8059854, EBI-744302;
CC Q16549; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-8059854, EBI-1055254;
CC Q16549; Q92876: KLK6; NbExp=3; IntAct=EBI-8059854, EBI-2432309;
CC Q16549; P19404: NDUFV2; NbExp=3; IntAct=EBI-8059854, EBI-713665;
CC Q16549; P29474: NOS3; NbExp=3; IntAct=EBI-8059854, EBI-1391623;
CC Q16549; P16284: PECAM1; NbExp=3; IntAct=EBI-8059854, EBI-716404;
CC Q16549; P17612: PRKACA; NbExp=3; IntAct=EBI-8059854, EBI-476586;
CC Q16549; P50454: SERPINH1; NbExp=3; IntAct=EBI-8059854, EBI-350723;
CC Q16549; P37173: TGFBR2; NbExp=3; IntAct=EBI-8059854, EBI-296151;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
CC Note=Seems to be localized intracellularly to the trans Golgi network.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in spleen, thymus, prostate, testis,
CC ovary, small intestine, colon and peripheral blood leukocyte.
CC -!- PTM: Cysteine residues in the cytoplasmic tail are probably
CC palmitoylated. {ECO:0000269|PubMed:9341152}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9341152}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR EMBL; U40623; AAC50417.1; -; mRNA.
DR EMBL; U33849; AAB03087.1; -; mRNA.
DR EMBL; BT006870; AAP35516.1; -; mRNA.
DR EMBL; AK312429; BAG35338.1; -; mRNA.
DR EMBL; AK222907; BAD96627.1; -; mRNA.
DR EMBL; EF445005; ACA06036.1; -; Genomic_DNA.
DR EMBL; EF445005; ACA06037.1; -; Genomic_DNA.
DR EMBL; CH471065; EAW67305.1; -; Genomic_DNA.
DR EMBL; BC010696; AAH10696.1; -; mRNA.
DR EMBL; AF057710; AAD55137.1; -; Genomic_DNA.
DR EMBL; AB231710; BAE46876.1; -; mRNA.
DR CCDS; CCDS8382.1; -.
DR PIR; S64706; S64706.
DR RefSeq; NP_004707.2; NM_004716.3.
DR AlphaFoldDB; Q16549; -.
DR SMR; Q16549; -.
DR BioGRID; 114604; 2.
DR IntAct; Q16549; 10.
DR MINT; Q16549; -.
DR STRING; 9606.ENSP00000325917; -.
DR BindingDB; Q16549; -.
DR ChEMBL; CHEMBL2232; -.
DR DrugCentral; Q16549; -.
DR GuidetoPHARMACOLOGY; 2387; -.
DR MEROPS; S08.077; -.
DR GlyGen; Q16549; 4 sites.
DR iPTMnet; Q16549; -.
DR PhosphoSitePlus; Q16549; -.
DR SwissPalm; Q16549; -.
DR BioMuta; PCSK7; -.
DR DMDM; 205830663; -.
DR EPD; Q16549; -.
DR jPOST; Q16549; -.
DR MassIVE; Q16549; -.
DR PaxDb; Q16549; -.
DR PeptideAtlas; Q16549; -.
DR PRIDE; Q16549; -.
DR ProteomicsDB; 60909; -.
DR Antibodypedia; 32336; 153 antibodies from 23 providers.
DR DNASU; 9159; -.
DR Ensembl; ENST00000320934.8; ENSP00000325917.3; ENSG00000160613.15.
DR Ensembl; ENST00000524507.6; ENSP00000433841.2; ENSG00000160613.15.
DR Ensembl; ENST00000676339.1; ENSP00000501995.1; ENSG00000160613.15.
DR GeneID; 9159; -.
DR KEGG; hsa:9159; -.
DR MANE-Select; ENST00000320934.8; ENSP00000325917.3; NM_004716.4; NP_004707.2.
DR UCSC; uc001pqr.4; human.
DR CTD; 9159; -.
DR DisGeNET; 9159; -.
DR GeneCards; PCSK7; -.
DR HGNC; HGNC:8748; PCSK7.
DR HPA; ENSG00000160613; Low tissue specificity.
DR MIM; 604872; gene.
DR neXtProt; NX_Q16549; -.
DR OpenTargets; ENSG00000160613; -.
DR PharmGKB; PA33094; -.
DR VEuPathDB; HostDB:ENSG00000160613; -.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000157676; -.
DR InParanoid; Q16549; -.
DR OMA; SFTIFWT; -.
DR OrthoDB; 473018at2759; -.
DR PhylomeDB; Q16549; -.
DR TreeFam; TF314277; -.
DR BRENDA; 3.4.21.B27; 2681.
DR PathwayCommons; Q16549; -.
DR SignaLink; Q16549; -.
DR SIGNOR; Q16549; -.
DR BioGRID-ORCS; 9159; 27 hits in 1076 CRISPR screens.
DR ChiTaRS; PCSK7; human.
DR GeneWiki; PCSK7; -.
DR GenomeRNAi; 9159; -.
DR Pharos; Q16549; Tchem.
DR PRO; PR:Q16549; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q16549; protein.
DR Bgee; ENSG00000160613; Expressed in granulocyte and 177 other tissues.
DR ExpressionAtlas; Q16549; baseline and differential.
DR Genevisible; Q16549; HS.
DR GO; GO:0030173; C:integral component of Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0016486; P:peptide hormone processing; NAS:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:MGI.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 3.30.70.850; -; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR008979; Galactose-bd-like_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; 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 Pfam; PF01483; P_proprotein; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF16470; S8_pro-domain; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51829; P_HOMO_B; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Glycoprotein; Golgi apparatus;
KW Hydrolase; Lipoprotein; Membrane; Palmitate; Protease; Reference proteome;
KW Serine protease; Signal; Transmembrane; Transmembrane helix; Zymogen.
FT SIGNAL 1..37
FT /evidence="ECO:0000250"
FT PROPEP 38..141
FT /evidence="ECO:0000250"
FT /id="PRO_0000027114"
FT CHAIN 142..785
FT /note="Proprotein convertase subtilisin/kexin type 7"
FT /id="PRO_0000027115"
FT TOPO_DOM 142..667
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 668..688
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 689..785
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 153..473
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 481..618
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT REGION 197..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 700..751
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 187
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 228
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 406
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT SITE 141..142
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 511
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 688
FT /note="L -> V (in dbSNP:rs608620)"
FT /id="VAR_044419"
FT VARIANT 689
FT /note="S -> N (in dbSNP:rs45539233)"
FT /id="VAR_044420"
FT VARIANT 700
FT /note="R -> M (in dbSNP:rs45574931)"
FT /id="VAR_044421"
FT VARIANT 708
FT /note="H -> Y (in dbSNP:rs473131)"
FT /id="VAR_044422"
FT VARIANT 711
FT /note="R -> Q (in dbSNP:rs473093)"
FT /id="VAR_044423"
FT CONFLICT 52
FT /note="P -> A (in Ref. 1; AAC50417 and 3; AAB03087)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="A -> P (in Ref. 1; AAC50417 and 3; AAB03087)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="H -> R (in Ref. 6; BAD96627)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="A -> T (in Ref. 7; ACA06037)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 785 AA; 86247 MW; 4A268754766C32DA CRC64;
MPKGRQKVPH LDAPLGLPTC LWLELAGLFL LVPWVMGLAG TGGPDGQGTG GPSWAVHLES
LEGDGEEETL EQQADALAQA AGLVNAGRIG ELQGHYLFVQ PAGHRPALEV EAIRQQVEAV
LAGHEAVRWH SEQRLLRRAK RSVHFNDPKY PQQWHLNNRR SPGRDINVTG VWERNVTGRG
VTVVVVDDGV EHTIQDIAPN YSPEGSYDLN SNDPDPMPHP DVENGNHHGT RCAGEIAAVP
NNSFCAVGVA YGSRIAGIRV LDGPLTDSME AVAFNKHYQI NDIYSCSWGP DDDGKTVDGP
HQLGKAALQH GVIAGRQGFG SIFVVASGNG GQHNDNCNYD GYANSIYTVT IGAVDEEGRM
PFYAEECASM LAVTFSGGDK MLRSIVTTDW DLQKGTGCTE GHTGTSAAAP LAAGMIALML
QVRPCLTWRD VQHIIVFTAT RYEDRRAEWV TNEAGFSHSH QHGFGLLNAW RLVNAAKIWT
SVPYLASYVS PVLKENKAIP QSPRSLEVLW NVSRMDLEMS GLKTLEHVAV TVSITHPRRG
SLELKLFCPS GMMSLIGAPR SMDSDPNGFN DWTFSTVRCW GERARGTYRL VIRDVGDESF
QVGILRQWQL TLYGSVWSAV DIRDRQRLLE SAMSGKYLHD DFALPCPPGL KIPEEDGYTI
TPNTLKTLVL VGCFTVFWTV YYMLEVYLSQ RNVASNQVCR SGPCHWPHRS RKAKEEGTEL
ESVPLCSSKD PDEVETESRG PPTTSDLLAP DLLEQGDWSL SQNKSALDCP HQHLDVPHGK
EEQIC
