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Protein

Proprotein convertase subtilisin/kexin type 4

Gene

Pcsk4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei155 – 1551Charge relay systemBy similarity
Active sitei196 – 1961Charge relay systemBy similarity
Active sitei370 – 3701Charge relay systemBy similarity

GO - Molecular functioni

  1. serine-type endopeptidase activity Source: GO_Central

GO - Biological processi

  1. acrosome reaction Source: MGI
  2. binding of sperm to zona pellucida Source: MGI
  3. fertilization Source: MGI
  4. proteolysis Source: GO_Central
  5. sperm capacitation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

ReactomeiREACT_206713. NGF processing.

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):
KEX2-like endoprotease 3
Neuroendocrine convertase 3
Short name:
NEC 3
Prohormone convertase 3
Gene namesi
Name:Pcsk4
Synonyms:Nec-3, Nec3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 10

Organism-specific databases

MGIiMGI:97514. Pcsk4.

Subcellular locationi

GO - Cellular componenti

  1. acrosomal membrane Source: MGI
  2. endoplasmic reticulum lumen Source: Reactome
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626By similarityAdd
BLAST
Propeptidei27 – 11084Sequence AnalysisPRO_0000027098Add
BLAST
Chaini111 – 655545Proprotein convertase subtilisin/kexin type 4PRO_0000027099Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi472 – 4721N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

PRIDEiP29121.

PTM databases

PhosphoSiteiP29121.

Expressioni

Tissue specificityi

Expressed abundantly in the testis.1 Publication

Developmental stagei

Detected only after the 20th day of postnatal development. Mainly expressed in the round spermatids. Expressed mainly in the early stages of spermiogenesis.1 Publication

Gene expression databases

BgeeiP29121.
CleanExiMM_PCSK4.
ExpressionAtlasiP29121. baseline and differential.
GenevestigatoriP29121.

Interactioni

Protein-protein interaction databases

BioGridi202060. 1 interaction.
STRINGi10090.ENSMUSP00000020340.

Structurei

3D structure databases

ProteinModelPortaliP29121.
SMRiP29121. Positions 115-580.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini150 – 436287Peptidase S8Add
BLAST

Sequence similaritiesi

Belongs to the peptidase S8 family. Furin subfamily.Curated
Contains 1 peptidase S8 domain.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG4935.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP29121.
KOiK08671.
OMAiHVQVQLS.
OrthoDBiEOG7BW0JD.
PhylomeDBiP29121.
TreeFamiTF314277.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR008979. Galactose-bd-like.
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.
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]

Sequences (8)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 8 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P29121-1) [UniParc]FASTAAdd to Basket

Also known as: mPC4-A

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

        10         20         30         40         50
MRPSQTELWL GLTLTLALLA VRWASAQAPI YVSSWAVRVT KGYQEAERLA
60 70 80 90 100
RKFGFVNLGQ IFPDDQYFHL RHRGVAQQSL TPHWGHRLRL KKDPKVRWFE
110 120 130 140 150
QQTLRRRVKR SLVVPTDPWF SKQWYMNKEI QQDLNILKAW NQGLTGRGVV
160 170 180 190 200
ISILDDGIEK DHPDLWANYD PLASYDFNDY DPDPQPRYTP NDENRHGTRC
210 220 230 240 250
AGEVSATANN GFCGAGVAFN ARIGGVRMLD GAITDIVEAQ SLSLQPQHIH
260 270 280 290 300
IYSASWGPED DGRTVDGPGL LTQEAFRRGV TKGRQGLGTL FIWASGNGGL
310 320 330 340 350
HYDNCNCDGY TNSIHTLSVG STTRQGRVPW YSEACASTFT TTFSSGVVTD
360 370 380 390 400
PQIVTTDLHH QCTDKHTGTS ASAPLAAGMI ALALEANPLL TWRDLQHLVV
410 420 430 440 450
RASRPAQLQA EDWRINGVGR QVSHHYGYGL LDAGLLVDLA RVWLPTKPQK
460 470 480 490 500
KCAIRVVHTP TPILPRMLVP KNVTACSDGS RRRLIRSLEH VQVQLSLSYS
510 520 530 540 550
RRGDLEIFLT SPMGTRSTLV AIRPLDISGQ GYNNWIFMST HYWDEDPQGL
560 570 580 590 600
WTLGLENKGY YFNTGTLYYY TLLLYGTAED MTARPQAPQV TSRARACVQR
610 620 630 640 650
DTEGLCQESH SPLSILAGLC LISSQQWWWL YSHPQQPVTE GQASCHPPVT

PAAAA
Length:655
Mass (Da):73,214
Last modified:December 1, 1992 - v1
Checksum:i4E4E32CEDECBCB59
GO
Isoform 2 (identifier: P29121-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     273-282: Missing.

Show »
Length:645
Mass (Da):72,040
Checksum:iF640E51A4B932CCC
GO
Isoform 3 (identifier: P29121-3) [UniParc]FASTAAdd to Basket

Also known as: mPC4-B

The sequence of this isoform differs from the canonical sequence as follows:
     590-655: VTSRARACVQ...HPPVTPAAAA → KVTVPSPSWQDSASSPASSGGGSTATHSSQ

Show »
Length:619
Mass (Da):68,946
Checksum:iBFFA404AC3B0309C
GO
Isoform 4 (identifier: P29121-4) [UniParc]FASTAAdd to Basket

Also known as: mPC4-C

The sequence of this isoform differs from the canonical sequence as follows:
     590-655: VTSRARACVQ...HPPVTPAAAA → DSASSPASSGGGSTATHSSQ

Show »
Length:609
Mass (Da):67,835
Checksum:iE6836850549C8B4B
GO
Isoform 5 (identifier: P29121-5) [UniParc]FASTAAdd to Basket

Also known as: E

The sequence of this isoform differs from the canonical sequence as follows:
     22-60: Missing.

Show »
Length:616
Mass (Da):68,790
Checksum:iE6C5935CDB59CED5
GO
Isoform 6 (identifier: P29121-6) [UniParc]FASTAAdd to Basket

Also known as: D

The sequence of this isoform differs from the canonical sequence as follows:
     51-60: Missing.

Show »
Length:645
Mass (Da):72,066
Checksum:i98D75378E95BB1E7
GO
Isoform 7 (identifier: P29121-7) [UniParc]FASTAAdd to Basket

Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     590-608: Missing.

Show »
Length:636
Mass (Da):71,109
Checksum:i9CAE7A7D05A0848E
GO
Isoform 8 (identifier: P29121-8) [UniParc]FASTAAdd to Basket

Also known as: C

The sequence of this isoform differs from the canonical sequence as follows:
     590-617: Missing.

Show »
Length:627
Mass (Da):70,203
Checksum:iF990EE7C2FF4EC95
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti65 – 651D → N in AAA39973. (PubMed:8020970)Curated
Sequence conflicti87 – 871R → P in AAA39973. (PubMed:8020970)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei22 – 6039Missing in isoform 5. 1 PublicationVSP_011266Add
BLAST
Alternative sequencei51 – 6010Missing in isoform 6. 1 PublicationVSP_011267
Alternative sequencei273 – 28210Missing in isoform 2. 1 PublicationVSP_011268
Alternative sequencei590 – 65566VTSRA…PAAAA → KVTVPSPSWQDSASSPASSG GGSTATHSSQ in isoform 3. 1 PublicationVSP_011271Add
BLAST
Alternative sequencei590 – 65566VTSRA…PAAAA → DSASSPASSGGGSTATHSSQ in isoform 4. 1 PublicationVSP_011272Add
BLAST
Alternative sequencei590 – 61728Missing in isoform 8. 1 PublicationVSP_011270Add
BLAST
Alternative sequencei590 – 60819Missing in isoform 7. 1 PublicationVSP_011269Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D01093 mRNA. Translation: BAA00877.1.
L21221
, L21210, L21211, L21212, L21213, L21214, L21215, L21216, L21217, L21218, L21219, L21220, L21222, L21223 Genomic DNA. Translation: AAA39973.1.
CCDSiCCDS24018.1. [P29121-1]
PIRiA54306.
RefSeqiNP_032819.1. NM_008793.2. [P29121-1]
UniGeneiMm.299916.

Genome annotation databases

EnsembliENSMUST00000020340; ENSMUSP00000020340; ENSMUSG00000020131. [P29121-1]
GeneIDi18551.
KEGGimmu:18551.
UCSCiuc007gcs.2. mouse. [P29121-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D01093 mRNA. Translation: BAA00877.1.
L21221
, L21210, L21211, L21212, L21213, L21214, L21215, L21216, L21217, L21218, L21219, L21220, L21222, L21223 Genomic DNA. Translation: AAA39973.1.
CCDSiCCDS24018.1. [P29121-1]
PIRiA54306.
RefSeqiNP_032819.1. NM_008793.2. [P29121-1]
UniGeneiMm.299916.

3D structure databases

ProteinModelPortaliP29121.
SMRiP29121. Positions 115-580.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202060. 1 interaction.
STRINGi10090.ENSMUSP00000020340.

Protein family/group databases

MEROPSiS08.074.

PTM databases

PhosphoSiteiP29121.

Proteomic databases

PRIDEiP29121.

Protocols and materials databases

DNASUi18551.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020340; ENSMUSP00000020340; ENSMUSG00000020131. [P29121-1]
GeneIDi18551.
KEGGimmu:18551.
UCSCiuc007gcs.2. mouse. [P29121-1]

Organism-specific databases

CTDi54760.
MGIiMGI:97514. Pcsk4.

Phylogenomic databases

eggNOGiCOG4935.
GeneTreeiENSGT00750000117358.
HOGENOMiHOG000192536.
HOVERGENiHBG008705.
InParanoidiP29121.
KOiK08671.
OMAiHVQVQLS.
OrthoDBiEOG7BW0JD.
PhylomeDBiP29121.
TreeFamiTF314277.

Enzyme and pathway databases

ReactomeiREACT_206713. NGF processing.

Miscellaneous databases

NextBioi294352.
PROiP29121.
SOURCEiSearch...

Gene expression databases

BgeeiP29121.
CleanExiMM_PCSK4.
ExpressionAtlasiP29121. baseline and differential.
GenevestigatoriP29121.

Family and domain databases

Gene3Di2.60.120.260. 1 hit.
3.40.50.200. 1 hit.
InterProiIPR008979. Galactose-bd-like.
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.
SUPFAMiSSF49785. SSF49785. 1 hit.
SSF52743. SSF52743. 1 hit.
SSF54897. SSF54897. 1 hit.
PROSITEiPS00136. SUBTILASE_ASP. 1 hit.
PS00137. SUBTILASE_HIS. 1 hit.
PS00138. SUBTILASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Identification of the fourth member of the mammalian endoprotease family homologous to the yeast Kex2 protease. Its testis-specific expression."
    Nakayama K., Kim W.-S., Torii S., Hosaka M., Nakagawa T., Ikemizu J., Baba T., Murakami K.
    J. Biol. Chem. 267:5897-5900(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Testis.
  2. "Testicular expression of PC4 in the rat: molecular diversity of a novel germ cell-specific Kex2/subtilisin-like proprotein convertase."
    Seidah N.G., Day R., Hamelin J., Gaspar A., Collard M.W., Chretien M.
    Mol. Endocrinol. 6:1559-1570(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4).
    Tissue: Testis.
  3. "Structure of the gene for the testis-specific proprotein convertase 4 and of its alternate messenger RNA isoforms."
    Mbikay M., Raffin-Sanson M.-L., Tadros H., Sirois F., Seidah N.G., Chretien M.
    Genomics 20:231-237(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 5; 6; 7 AND 8).
    Strain: C57BL/6.
    Tissue: Liver.

Entry informationi

Entry nameiPCSK4_MOUSE
AccessioniPrimary (citable) accession number: P29121
Secondary accession number(s): Q62094
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: February 4, 2015
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.