KLK4_MOUSE
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 03-AUG-2022, entry version 158.
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},
GN KLK-L1 {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 GlyGen; Q9Z0M1; 2 sites.
DR PhosphoSitePlus; Q9Z0M1; -.
DR PaxDb; Q9Z0M1; -.
DR PRIDE; Q9Z0M1; -.
DR ProteomicsDB; 264852; -.
DR Antibodypedia; 18932; 292 antibodies from 35 providers.
DR DNASU; 56640; -.
DR Ensembl; ENSMUST00000007161; ENSMUSP00000007161; ENSMUSG00000006948.
DR GeneID; 56640; -.
DR KEGG; mmu:56640; -.
DR UCSC; uc009gny.1; mouse.
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; TEDEFFC; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9Z0M1; -.
DR TreeFam; TF331065; -.
DR BRENDA; 3.4.21.B12; 3474.
DR BioGRID-ORCS; 56640; 2 hits in 75 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 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; -; 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 Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 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
