ID   KLK4_MOUSE              Reviewed;         255 AA.
AC   Q9Z0M1; Q9JIS2;
DT   13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 167.
DE   RecName: Full=Kallikrein-4 {ECO:0000250|UniProtKB:Q9Y5K2};
DE            EC=3.4.21.- {ECO:0000255|PROSITE-ProRule:PRU00274};
DE   AltName: Full=Enamel matrix serine proteinase 1 {ECO:0000303|PubMed:10690663};
DE   AltName: Full=Kallikrein-like protein 1 {ECO:0000250|UniProtKB:Q9Y5K2};
DE   AltName: Full=Serine protease 17 {ECO:0000303|PubMed:10863090};
DE   Flags: Precursor;
GN   Name=Klk4 {ECO:0000312|MGI:MGI:1861379};
GN   Synonyms=EMSP1 {ECO:0000303|PubMed:10690663}, KLK-L1
GN   {ECO:0000312|MGI:MGI:1861379}, Prss17 {ECO:0000303|PubMed:10863090};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1] {ECO:0000312|EMBL:AAF85937.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RC   STRAIN=129/SvJ {ECO:0000312|EMBL:AAF85937.1};
RX   PubMed=10863090; DOI=10.1016/s0378-1119(00)00203-1;
RA   Hu J.C.-C., Zhang C., Sun X., Yang Y., Cao X., Ryu O., Simmer J.P.;
RT   "Characterization of the mouse and human PRSS17 genes, their relationship
RT   to other serine proteases, and the expression of PRSS17 in developing mouse
RT   incisors.";
RL   Gene 251:1-8(2000).
RN   [2] {ECO:0000312|EMBL:AAC98894.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC   STRAIN=Swiss Webster {ECO:0000312|EMBL:AAC98894.1};
RC   TISSUE=Ameloblast {ECO:0000312|EMBL:AAC98894.1};
RX   PubMed=10690663; DOI=10.1177/00220345000790011301;
RA   Hu J.C.-C., Ryu O.H., Chen J.J., Uchida T., Wakida K., Murakami C.,
RA   Jiang H., Qian Q., Zhang C., Ottmers V., Bartlett J.D., Simmer J.P.;
RT   "Localization of EMSP1 expression during tooth formation and cloning of
RT   mouse cDNA.";
RL   J. Dent. Res. 79:70-76(2000).
RN   [3] {ECO:0000312|Proteomes:UP000000589}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J {ECO:0000312|Proteomes:UP000000589};
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4] {ECO:0000312|Proteomes:UP000000589}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5] {ECO:0000312|EMBL:AAI00717.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [6] {ECO:0000305}
RP   FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX   PubMed=19578120; DOI=10.1074/jbc.m109.013623;
RA   Simmer J.P., Hu Y., Lertlam R., Yamakoshi Y., Hu J.C.;
RT   "Hypomaturation enamel defects in Klk4 knockout/LacZ knockin mice.";
RL   J. Biol. Chem. 284:19110-19121(2009).
RN   [7] {ECO:0000305}
RP   GLYCOSYLATION.
RX   PubMed=22243251; DOI=10.1111/j.1600-0722.2011.00863.x;
RA   Yamakoshi Y., Yamakoshi F., Hu J.C., Simmer J.P.;
RT   "Characterization of kallikrein-related peptidase 4 glycosylations.";
RL   Eur. J. Oral Sci. 119:234-240(2011).
CC   -!- FUNCTION: Has a major role in enamel formation. Required during the
CC       maturation stage of tooth development for clearance of enamel proteins
CC       and normal structural patterning of the crystalline matrix.
CC       {ECO:0000269|PubMed:19578120}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- DEVELOPMENTAL STAGE: In developing teeth, expressed in ameloblasts
CC       during transition and maturation stages (PubMed:10863090,
CC       PubMed:10690663, PubMed:19578120). Expressed weakly in odontoblasts
CC       (PubMed:10863090). Not detected in odontoblasts (PubMed:19578120).
CC       Detected in the epithelium surrounding the erupted first molar
CC       (PubMed:10690663). {ECO:0000269|PubMed:10690663,
CC       ECO:0000269|PubMed:10863090, ECO:0000269|PubMed:19578120}.
CC   -!- PTM: N-glycosylated. The N-glycan structures are of complex diantennary
CC       or triantennary type, which may be further modified with up to 2 sialic
CC       acid residues. {ECO:0000269|PubMed:22243251}.
CC   -!- DISRUPTION PHENOTYPE: Viable and fertile, when reared on a soft diet.
CC       Tooth morphology is grossly normal but the enamel surface is fragile
CC       and rapidly abraded. Although formation of the enamel layer is
CC       initially normal, the crystallites fail to thicken and interlock. The
CC       enamel proteins enamelin and amelogenin are not cleared and persist in
CC       the matrix during the maturation stage. {ECO:0000269|PubMed:19578120}.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AF198031; AAF85937.1; -; Genomic_DNA.
DR   EMBL; AF019979; AAC98894.1; -; mRNA.
DR   EMBL; AC134858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466603; EDL22687.1; -; Genomic_DNA.
DR   EMBL; BC100716; AAI00717.1; -; mRNA.
DR   EMBL; BC100717; AAI00718.1; -; mRNA.
DR   EMBL; BC100718; AAI00719.1; -; mRNA.
DR   EMBL; BC100719; AAI00720.1; -; mRNA.
DR   CCDS; CCDS21186.1; -.
DR   RefSeq; NP_064312.1; NM_019928.1.
DR   AlphaFoldDB; Q9Z0M1; -.
DR   SMR; Q9Z0M1; -.
DR   STRING; 10090.ENSMUSP00000007161; -.
DR   MEROPS; S01.251; -.
DR   GlyCosmos; Q9Z0M1; 2 sites, No reported glycans.
DR   GlyGen; Q9Z0M1; 3 sites, 1 O-linked glycan (1 site).
DR   PhosphoSitePlus; Q9Z0M1; -.
DR   PaxDb; 10090-ENSMUSP00000007161; -.
DR   ProteomicsDB; 264852; -.
DR   Antibodypedia; 18932; 317 antibodies from 35 providers.
DR   DNASU; 56640; -.
DR   Ensembl; ENSMUST00000007161.8; ENSMUSP00000007161.6; ENSMUSG00000006948.8.
DR   GeneID; 56640; -.
DR   KEGG; mmu:56640; -.
DR   UCSC; uc009gny.1; mouse.
DR   AGR; MGI:1861379; -.
DR   CTD; 9622; -.
DR   MGI; MGI:1861379; Klk4.
DR   VEuPathDB; HostDB:ENSMUSG00000006948; -.
DR   eggNOG; KOG3627; Eukaryota.
DR   GeneTree; ENSGT01020000230389; -.
DR   HOGENOM; CLU_006842_1_1_1; -.
DR   InParanoid; Q9Z0M1; -.
DR   OMA; LICKGSL; -.
DR   OrthoDB; 4629979at2759; -.
DR   PhylomeDB; Q9Z0M1; -.
DR   TreeFam; TF331065; -.
DR   BRENDA; 3.4.21.B12; 3474.
DR   BioGRID-ORCS; 56640; 2 hits in 80 CRISPR screens.
DR   PRO; PR:Q9Z0M1; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q9Z0M1; Protein.
DR   Bgee; ENSMUSG00000006948; Expressed in molar tooth and 18 other cell types or tissues.
DR   ExpressionAtlas; Q9Z0M1; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0097186; P:amelogenesis; IMP:MGI.
DR   GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR   GO; GO:0022617; P:extracellular matrix disassembly; IMP:MGI.
DR   GO; GO:0030163; P:protein catabolic process; IMP:MGI.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR   InterPro; IPR001314; Peptidase_S1A.
DR   InterPro; IPR001254; Trypsin_dom.
DR   InterPro; IPR018114; TRYPSIN_HIS.
DR   InterPro; IPR033116; TRYPSIN_SER.
DR   PANTHER; PTHR24264:SF65; PEPTIDASE S1 DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR24264; TRYPSIN-RELATED; 1.
DR   Pfam; PF00089; Trypsin; 1.
DR   PRINTS; PR00722; CHYMOTRYPSIN.
DR   SMART; SM00020; Tryp_SPc; 1.
DR   SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR   PROSITE; PS50240; TRYPSIN_DOM; 1.
DR   PROSITE; PS00134; TRYPSIN_HIS; 1.
DR   PROSITE; PS00135; TRYPSIN_SER; 1.
PE   1: Evidence at protein level;
KW   Biomineralization; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding;
KW   Protease; Reference proteome; Secreted; Serine protease; Signal; Zinc;
KW   Zymogen.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..31
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5K2"
FT                   /id="PRO_0000436024"
FT   CHAIN           32..255
FT                   /note="Kallikrein-4"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_5006493980"
FT   DOMAIN          32..253
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        72
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        117
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   ACT_SITE        208
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   BINDING         41
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5K2"
FT   BINDING         92
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5K2"
FT   CARBOHYD        124
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        170
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        57..73
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        149..214
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        179..193
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   DISULFID        204..229
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   CONFLICT        15
FT                   /note="C -> Y (in Ref. 1; AAF85937)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        251
FT                   /note="I -> T (in Ref. 1; AAF85937)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   255 AA;  27488 MW;  6FD2E7DEA0660A2A CRC64;
     MMVTARTPWG WFLGCLILEV TGASASSVSS RIIQGQDCSP HSQPWQAALF SEDGFFCSGV
     LVHPQWVLSA AHCLQESYIV GLGLHNLKGS QEPGSRMLEA HLSIQHPNFN DPSFANDLML
     IKLNESVIES NTIRSIPVAT QCPTPGDTCL VSGWGQLKNG KLPSLLQCVN LSVASEETCR
     LLYDPVYHLS MFCAGGGQDQ KDSCNGDSGG PIVCNRSLQG LVSMGQGKCG QPGIPSVYTN
     LCKFTNWIQT IIQTN
//