PCSK6_RAT
ID PCSK6_RAT Reviewed; 937 AA.
AC Q63415;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 155.
DE RecName: Full=Proprotein convertase subtilisin/kexin type 6;
DE EC=3.4.21.-;
DE AltName: Full=Paired basic amino acid cleaving enzyme 4;
DE AltName: Full=Subtilisin-like proprotein convertase 4;
DE Short=SPC4;
DE AltName: Full=Subtilisin/kexin-like protease PACE4;
DE Flags: Precursor;
GN Name=Pcsk6; Synonyms=Pace4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Hypothalamus, and Pituitary;
RX PubMed=8070361; DOI=10.1210/endo.135.3.8070361;
RA Johnson R.C., Darlington D.N., Hand T.A., Bloomquist B.T., Mains R.E.;
RT "PACE4: a subtilisin-like endoprotease prevalent in the anterior pituitary
RT and regulated by thyroid status.";
RL Endocrinology 135:1178-1185(1994).
RN [2]
RP CLEAVAGE OF SIGNAL PEPTIDE AFTER ALA-45, CLEAVAGE OF PROPEPTIDE AFTER
RP ARG-132, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=26479776; DOI=10.1021/acs.jproteome.5b00820;
RA Tsuchiya T., Osaki T., Minamino N., Sasaki K.;
RT "Peptidomics for studying limited proteolysis.";
RL J. Proteome Res. 14:4921-4931(2015).
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, with unique restricted distribution in both neuroendocrine and
CC non-neuroendocrine tissues.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000305};
CC -!- SUBUNIT: The precursor protein seems to exist in the reticulum
CC endoplasmic as both a monomer and a dimer-sized complex whereas mature
CC form exists only as a monomer, suggesting that propeptide cleavage
CC affects its tertiary or quaternary structure. Interacts (immature form
CC including the propeptide) with RCN3; probably involved in the
CC maturation and the secretion of PCSK6. {ECO:0000250|UniProtKB:P29122}.
CC -!- TISSUE SPECIFICITY: High expression in the anterior pituitary and in
CC several brain regions, the atrium, and the ventricle.
CC -!- DOMAIN: The propeptide domain acts as an intramolecular chaperone
CC assisting the folding of the zymogen within the endoplasmic reticulum.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR EMBL; L31894; AAA61987.1; -; mRNA.
DR PIR; I53282; I53282.
DR RefSeq; NP_037131.1; NM_012999.1.
DR AlphaFoldDB; Q63415; -.
DR SMR; Q63415; -.
DR STRING; 10116.ENSRNOP00000015845; -.
DR BindingDB; Q63415; -.
DR ChEMBL; CHEMBL5507; -.
DR MEROPS; S08.075; -.
DR GlyGen; Q63415; 3 sites.
DR PaxDb; Q63415; -.
DR GeneID; 25507; -.
DR KEGG; rno:25507; -.
DR UCSC; RGD:3246; rat.
DR CTD; 5046; -.
DR RGD; 3246; Pcsk6.
DR eggNOG; KOG3525; Eukaryota.
DR InParanoid; Q63415; -.
DR OrthoDB; 473018at2759; -.
DR PhylomeDB; Q63415; -.
DR BRENDA; 3.4.21.B25; 5301.
DR Reactome; R-RNO-167060; NGF processing.
DR Reactome; R-RNO-8963889; Assembly of active LPL and LIPC lipase complexes.
DR PRO; PR:Q63415; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0008201; F:heparin binding; ISO:RGD.
DR GO; GO:0048406; F:nerve growth factor binding; ISO:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR GO; GO:0009100; P:glycoprotein metabolic process; ISO:RGD.
DR GO; GO:0032902; P:nerve growth factor production; ISO:RGD.
DR GO; GO:0016486; P:peptide hormone processing; IEP:RGD.
DR GO; GO:0016485; P:protein processing; ISO:RGD.
DR GO; GO:0032940; P:secretion by cell; ISO:RGD.
DR GO; GO:0007354; P:zygotic determination of anterior/posterior axis, embryo; ISO:RGD.
DR CDD; cd00064; FU; 4.
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; 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; IPR010909; PLAC.
DR InterPro; IPR032815; S8_pro-domain.
DR InterPro; IPR038466; S8_pro-domain_sf.
DR Pfam; PF14843; GF_recep_IV; 1.
DR Pfam; PF01483; P_proprotein; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF08686; PLAC; 1.
DR Pfam; PF16470; S8_pro-domain; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00261; FU; 5.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS51829; P_HOMO_B; 1.
DR PROSITE; PS50900; PLAC; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Calcium; Cleavage on pair of basic residues; Glycoprotein; Hydrolase;
KW Protease; Reference proteome; Repeat; Serine protease; Signal; Zymogen.
FT SIGNAL 1..45
FT /evidence="ECO:0000269|PubMed:26479776"
FT PROPEP 46..132
FT /evidence="ECO:0000269|PubMed:26479776"
FT /id="PRO_0000027112"
FT CHAIN 133..937
FT /note="Proprotein convertase subtilisin/kexin type 6"
FT /id="PRO_0000027113"
FT DOMAIN 149..468
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 476..616
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT REPEAT 660..707
FT /note="FU 1"
FT REPEAT 711..758
FT /note="FU 2"
FT REPEAT 762..806
FT /note="FU 3"
FT REPEAT 810..855
FT /note="FU 4"
FT REPEAT 863..911
FT /note="FU 5"
FT DOMAIN 899..937
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 621..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 680..898
FT /note="CRM (Cys-rich motif)"
FT MOTIF 534..536
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..18
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 186
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 227
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 401
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT SITE 132..133
FT /note="Cleavage; by autolysis"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 882
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 900
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 937 AA; 104053 MW; F3865557C33705C8 CRC64;
MPPRAPPAPG PRPPPRAAGR HGLSPLAPRP WRWLLLLALP AVCSALPPPR PVYTNHWAVQ
VLGGPGAADR VAAAHGYLNL GQIGNLDDYY HFYHSKTFKR STLSSRGPHT FLRMDPQVKW
LQQQEVKRRV KRQARSDSLY FNDPIWSNMW YMHCADKNSR CRSEMNVQAA WKRGYTGKNV
VVTILDDGIE RNHPDLAPNY DSYASYDVNG NDYDPSPRYD ASNENKHGTR CAGEVAASAN
NSYCIVGIAY NAKIGGIRML DGDVTDVVEA KSLGIRPNYI DIYSASWGPD DDGKTVDGPG
RLAKQAFEYG IKKGRQGLGS IFVWASGNGG REGDHCSCDG YTNSIYTISV SSTTENGHKP
WYLEECASTL ATTYSSGAFY ERKIVTTDLR QRCTDGHTGT SVSAPMVAGI IALALEANNQ
LTWRDVQHLL VKTSRPAHLK ASDWKVNGAG HKVSHLYGFG LVDAEALVLE ARKWTAVPSQ
HMCVATADKR PRSIPVVQVL RTTALTNACA DHSDQRVVYL EHVVVRISIS HPRRGDLQIH
LISPSGTKSQ LLAKRLLDFS NEGFTNWEFM TVHCWGEKAE GEWTLEVQDI PSQVRNPEKQ
GKLKEWSLIL YGTAEHPYRT FSSHQSRSRM LELSVPEQEP LKAEGPPPQA ETPEEEEEYT
GVCHPECGDK GCDGPSADQC LNCVHFSLGN SKTNRKCVSE CPLGYFGDTA ARRCRRCHKG
CETCTGRSPT QCLSCRRGFY HHQETNTCVT LCPAGLYADE SQRLCLRCHP SCQKCVDEPE
KSTVCKEGFS LARGSCIPDC EPGTYFDSEL IRCGECHHTC RTCVGPSREE CIHCAKSFHF
QDWKCVPACG EGFYPEEMPG LPHKVCRRCD ENCLSCEGSS RNCSRCKAGF TQLGTSCITN
HTCSNADETF CEMVKSNRLC ERKLFIQFCC RTCLLAG
