PCSK4_RAT
ID PCSK4_RAT Reviewed; 678 AA.
AC Q78EH2; A1A4C9; Q07213; Q07214;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 115.
DE RecName: Full=Proprotein convertase subtilisin/kexin type 4;
DE Short=PC4;
DE EC=3.4.21.-;
DE AltName: Full=KEX2-like endoprotease 3;
DE AltName: Full=Neuroendocrine convertase 3;
DE Short=NEC 3;
DE AltName: Full=Prohormone convertase 3;
DE Flags: Precursor;
GN Name=Pcsk4; Synonyms=Nec-3, Nec3;
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] (ISOFORMS 1; 2; 3; 4 AND 5), TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RC TISSUE=Testis;
RX PubMed=1448111; DOI=10.1210/mend.6.10.1448111;
RA Seidah N.G., Day R., Hamelin J., Gaspar A., Collard M.W., Chretien M.;
RT "Testicular expression of PC4 in the rat: molecular diversity of a novel
RT germ cell-specific Kex2/subtilisin-like proprotein convertase.";
RL Mol. Endocrinol. 6:1559-1570(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Testis;
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 [3]
RP SUBCELLULAR LOCATION.
RX PubMed=21080038; DOI=10.1007/s11010-010-0635-y;
RA Gyamera-Acheampong C., Sirois F., Denis N.J., Mishra P., Figeys D.,
RA Basak A., Mbikay M.;
RT "The precursor to the germ cell-specific PCSK4 proteinase is inefficiently
RT activated in transfected somatic cells: evidence of interaction with the
RT BiP chaperone.";
RL Mol. Cell. Biochem. 348:43-52(2011).
CC -!- FUNCTION: Proprotein convertase involved in the processing of hormone
CC and other protein precursors at sites comprised of pairs of basic amino
CC acid residues. In males, important for ADAM2 processing as well as
CC other acrosomal proteins with roles in fertilization and critical for
CC normal fertilization events such as sperm capacitation, acrosome
CC reaction and binding of sperm to zona pellucida (By similarity). Plays
CC also a role in female fertility, involved in the regulation of
CC trophoblast migration and placental development, may be through the
CC proteolytical processing and activation of proteins such as IGF2 (By
CC similarity). May also participate in folliculogenesis in the ovaries
CC (By similarity). {ECO:0000250|UniProtKB:P29121,
CC ECO:0000250|UniProtKB:Q6UW60}.
CC -!- SUBUNIT: The proPCSK4 form interacts with HSPA5; the interaction takes
CC place at the endoplasmic reticulum. {ECO:0000250|UniProtKB:Q6UW60}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, acrosome
CC membrane {ECO:0000305|PubMed:21080038}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q78EH2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q78EH2-2; Sequence=VSP_011273;
CC Name=3; Synonyms=rPC4-A;
CC IsoId=Q78EH2-3; Sequence=VSP_011274;
CC Name=4; Synonyms=rPC4-B;
CC IsoId=Q78EH2-4; Sequence=VSP_011275;
CC Name=5; Synonyms=rPC4-C;
CC IsoId=Q78EH2-5; Sequence=VSP_011276;
CC -!- TISSUE SPECIFICITY: Expressed abundantly in the testis. High levels
CC seen in germ cells but not in Leydig, Sertoli or peritubular cells.
CC Expressed in the pachytene spermatocytes and the round spermatids but
CC not in the elongating spermatids. May be expressed within hormonally
CC stimulated ovaries. {ECO:0000269|PubMed:1448111}.
CC -!- DEVELOPMENTAL STAGE: First expressed postnatally between days 19 and 22
CC coinciding with the early stages of spermiogenesis. The levels increase
CC up to postnatal day 60. {ECO:0000269|PubMed:1448111}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q6UW60}.
CC -!- PTM: Synthesized in the endoplasmic reticulum as a zymogen, is matured
CC by autocatalytic cleavage between the prodomain and the catalytic
CC domain. {ECO:0000250|UniProtKB:Q6UW60}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
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DR EMBL; L14937; AAA41814.1; -; mRNA.
DR EMBL; L14937; AAA41815.1; -; mRNA.
DR EMBL; L14937; AAA41816.1; -; mRNA.
DR EMBL; BC097288; AAH97288.1; -; mRNA.
DR PIR; A45357; A45357.
DR RefSeq; NP_598243.1; NM_133559.1. [Q78EH2-3]
DR AlphaFoldDB; Q78EH2; -.
DR SMR; Q78EH2; -.
DR STRING; 10116.ENSRNOP00000022358; -.
DR MEROPS; S08.074; -.
DR GlyGen; Q78EH2; 1 site.
DR PaxDb; Q78EH2; -.
DR GeneID; 171085; -.
DR KEGG; rno:171085; -.
DR UCSC; RGD:620325; rat. [Q78EH2-1]
DR CTD; 54760; -.
DR RGD; 620325; Pcsk4.
DR eggNOG; KOG3525; Eukaryota.
DR InParanoid; Q78EH2; -.
DR OrthoDB; 473018at2759; -.
DR PhylomeDB; Q78EH2; -.
DR BRENDA; 3.4.21.B24; 5301.
DR BRENDA; 3.4.21.B25; 5301.
DR PRO; PR:Q78EH2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0002080; C:acrosomal membrane; ISS:UniProtKB.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0007340; P:acrosome reaction; ISS:UniProtKB.
DR GO; GO:0007339; P:binding of sperm to zona pellucida; ISS:UniProtKB.
DR GO; GO:0009566; P:fertilization; ISS:UniProtKB.
DR GO; GO:0016486; P:peptide hormone processing; IBA:GO_Central.
DR GO; GO:0016485; P:protein processing; ISS:UniProtKB.
DR GO; GO:0022414; P:reproductive process; ISS:UniProtKB.
DR GO; GO:0048240; P:sperm capacitation; ISS:UniProtKB.
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; 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 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; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Glycoprotein; Hydrolase; Membrane; Protease;
KW Reference proteome; Serine protease; Signal; Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..110
FT /evidence="ECO:0000255"
FT /id="PRO_0000027100"
FT CHAIN 111..678
FT /note="Proprotein convertase subtilisin/kexin type 4"
FT /id="PRO_0000027101"
FT DOMAIN 123..437
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 446..580
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT ACT_SITE 155
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 196
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 370
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT CARBOHYD 472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 590..678
FT /note="ESHCPLSIVAELCLISSKQWWWLYSHTQQPVTKGQDSCHPPTTPARQLDQRL
FT HCLFPAPHAGSASEPLQGLSPLAAILAISLGPWCCPC -> VTSCAHACAEGHRGAVPG
FT KSLSPLHCGRTLPHLQQAVVVALQPHTAASDQGTGQLSPSYHTCSAA (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:1448111"
FT /id="VSP_011274"
FT VAR_SEQ 590..678
FT /note="ESHCPLSIVAELCLISSKQWWWLYSHTQQPVTKGQDSCHPPTTPARQLDQRL
FT HCLFPAPHAGSASEPLQGLSPLAAILAISLGPWCCPC -> KVIVPSPLWQNSASSPAS
FT SGGGSTATHSSQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:1448111,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_011275"
FT VAR_SEQ 590..678
FT /note="ESHCPLSIVAELCLISSKQWWWLYSHTQQPVTKGQDSCHPPTTPARQLDQRL
FT HCLFPAPHAGSASEPLQGLSPLAAILAISLGPWCCPC -> NSASSPASSGGGSTATHS
FT SQ (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:1448111"
FT /id="VSP_011276"
FT VAR_SEQ 590..599
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1448111"
FT /id="VSP_011273"
SQ SEQUENCE 678 AA; 75740 MW; BB5C7DC1BD19E6BA CRC64;
MRPSQTALWL GLVLSLALLA VGWASARPPI YVSSWAVRVT KGYQEAERLA RKFGFVNLGQ
IFPDDQYFHL RHRGVAQQSL TPHWGHRLRL KKEPKVRWFE QQTLRRRVKR SLVVPTDPWF
SKQWYMNKEI EQDLNILKVW NQGLTGRGVV VSILDDGIEK DHPDLWANYD PLASYDFNDY
DPDPQPRYTP NDENRHGTRC AGEVSATANN GFCGAGVAFN ARIGGVRMLD GAITDIVEAQ
SLSLQPQHIH IYSASWGPED DGRTVDGPGL LTQEAFRRGV TKGRQGLGTL FIWASGNGGL
HYDNCNCDGY TNSIHTLSVG STTRQGRVPW YSEACASTFT TTFSSGVVTD PQIVTTDLHH
QCTDKHTGTS ASAPLAAGMI ALALEANPLL TWRDLQHLVV RASRPAQLQA EDWRINGVGR
QVSHHYGYGL LDAGLLVDLA RVWLPTKPQK KCTIRVVHTP TPILPRMLVP KNVTVCCDGS
RRRLIRSLEH VQVQLSLSYS RRGDLEIFLT SPMGTRSTLV AIRPLDISGQ GYNNWIFMST
HYWDEDPQGL WTLGLENKGY YYNTGTLYYC TLLLYGTAED MTARPQTPQE SHCPLSIVAE
LCLISSKQWW WLYSHTQQPV TKGQDSCHPP TTPARQLDQR LHCLFPAPHA GSASEPLQGL
SPLAAILAIS LGPWCCPC
