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Protein

Kallikrein-14

Gene

KLK14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine-type endopeptidase with a dual trypsin-like and chymotrypsin-like substrate specificity. May activate/inactivate the proteinase-activated receptors F2R, F2RL1 and F2RL3 and other kallikreins including KLK1, KLK3, KLK5 and KLK11. May function in seminal clot liquefaction through direct cleavage of the semenogelin SEMG1 and SEMG2 and activation of KLK3. May function through desmoglein DSG1 cleavage in epidermal desquamation a process by which the most superficial corneocytes are shed from the skin surface. May be involved in several aspects of tumor progression including growth, invasion and angiogenesis.6 Publications

Caution

It is uncertain whether Met-1 or Met-17 is the initiator.Curated

Activity regulationi

Inhibited by SERPINA1, SERPINC1, SERPINE1, SERPINF2, aprotinin, soybean, trypsin inhibitor and leupeptin. Inhibited by serine protease inhibitor SPINK5. Has an autoproteolytic activity which may have a regulatory effect. Activated by citrate and inhibited by zinc and to a lower extent by manganese.3 Publications

Kineticsi

Has a higher catalytic efficiency for the trypsin-like enzyme substrates S-2288, S-2222 and S-2302 compared to S-2586 a chymotrypsin-like enzyme substrate. Has a lower catalytic activity compared to trypsin towards S-2288, S-2222 and S-2302. Cleaves preferentially after Arg residues.
  1. KM=0.3 mM for S-22882 Publications
  2. KM=0.2 mM for S-22222 Publications
  3. KM=0.2 mM for S-23022 Publications
  4. KM=0.7 mM for S-25862 Publications
  5. KM=0.045 mM for Gln-Ala-Arg synthetic peptide2 Publications
  6. KM=0.043 mM for Val-Pro-Arg synthetic peptide2 Publications
  7. KM=0.09 mM for Pro-Phe-Arg synthetic peptide2 Publications
  8. KM=0.278 mM for Phe-Ser-Arg synthetic peptide2 Publications
  9. KM=0.0577 mM for Leu-Gly-Arg synthetic peptide2 Publications
  10. KM=0.139 mM for Gln-Gly-Arg synthetic peptide2 Publications
  11. KM=0.173 mM for Gly-Pro-Arg synthetic peptide2 Publications
  12. KM=0.0268 mM for Gln-Arg-Arg synthetic peptide2 Publications
  13. KM=0.130 mM for Gly-Gly-Arg synthetic peptide2 Publications
  14. KM=0.578 mM for Val-Leu-Lys synthetic peptide2 Publications

    pH dependencei

    Optimum pH is 8.0.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei83Charge relay systemBy similarity1
    Active sitei127Charge relay systemBy similarity1
    Active sitei220Charge relay systemBy similarity1

    GO - Molecular functioni

    • serine-type endopeptidase activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase, Protease, Serine protease

    Enzyme and pathway databases

    BRENDAi3.4.21.B45 2681
    ReactomeiR-HSA-6809371 Formation of the cornified envelope

    Protein family/group databases

    MEROPSiS01.029

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Kallikrein-14 (EC:3.4.21.-)
    Short name:
    hK14
    Alternative name(s):
    Kallikrein-like protein 6
    Short name:
    KLK-L6
    Gene namesi
    Name:KLK14
    Synonyms:KLKL6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000129437.9
    HGNCiHGNC:6362 KLK14
    MIMi606135 gene
    neXtProtiNX_Q9P0G3

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi43847
    OpenTargetsiENSG00000129437
    PharmGKBiPA30151

    Chemistry databases

    ChEMBLiCHEMBL2641
    GuidetoPHARMACOLOGYi2866

    Polymorphism and mutation databases

    BioMutaiKLK14
    DMDMi251757292

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 34Add BLAST34
    PropeptideiPRO_000002795835 – 40Activation peptide1 Publication6
    ChainiPRO_000002795941 – 267Kallikrein-14Add BLAST227

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi47 ↔ 180PROSITE-ProRule annotation
    Disulfide bondi68 ↔ 84PROSITE-ProRule annotation
    Disulfide bondi159 ↔ 226PROSITE-ProRule annotation
    Disulfide bondi191 ↔ 205PROSITE-ProRule annotation
    Disulfide bondi216 ↔ 241PROSITE-ProRule annotation

    Post-translational modificationi

    Proteolytic cleavage of the activation peptide produces the active enzyme.1 Publication

    Keywords - PTMi

    Autocatalytic cleavage, Disulfide bond, Zymogen

    Proteomic databases

    PaxDbiQ9P0G3
    PeptideAtlasiQ9P0G3
    PRIDEiQ9P0G3
    ProteomicsDBi83548

    PTM databases

    iPTMnetiQ9P0G3
    PhosphoSitePlusiQ9P0G3

    Miscellaneous databases

    PMAP-CutDBiQ9P0G3

    Expressioni

    Tissue specificityi

    Highly expressed in CNS, bone marrow and fetal liver. Also expressed in breast, thyroid, kidney, colon, pancreas, spleen, prostate, uterus, small intestine, placenta and skeletal muscle. Among 40 tissues tested, the highest expression is detected in skin followed by breast and prostate (at protein level). Expressed in stratum corneum by sweat ducts and sweat glands and detected in sweat (at protein level).6 Publications

    Inductioni

    Up-regulated by steroid hormone.1 Publication

    Gene expression databases

    BgeeiENSG00000129437 Expressed in 83 organ(s), highest expression level in ectocervix
    CleanExiHS_KLK14
    ExpressionAtlasiQ9P0G3 baseline and differential
    GenevisibleiQ9P0G3 HS

    Organism-specific databases

    HPAiCAB026228

    Interactioni

    Protein-protein interaction databases

    BioGridi119063, 2 interactors
    STRINGi9606.ENSP00000156499

    Chemistry databases

    BindingDBiQ9P0G3

    Structurei

    3D structure databases

    ProteinModelPortaliQ9P0G3
    SMRiQ9P0G3
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini41 – 265Peptidase S1PROSITE-ProRule annotationAdd BLAST225

    Sequence similaritiesi

    Belongs to the peptidase S1 family. Kallikrein subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG3627 Eukaryota
    COG5640 LUCA
    GeneTreeiENSGT00760000118862
    HOGENOMiHOG000251820
    HOVERGENiHBG013304
    InParanoidiQ9P0G3
    KOiK09622
    OMAiSAPKMFL
    OrthoDBiEOG091G0AH5
    PhylomeDBiQ9P0G3
    TreeFamiTF331065

    Family and domain databases

    CDDicd00190 Tryp_SPc, 1 hit
    InterProiView protein in InterPro
    IPR009003 Peptidase_S1_PA
    IPR001314 Peptidase_S1A
    IPR001254 Trypsin_dom
    IPR018114 TRYPSIN_HIS
    IPR033116 TRYPSIN_SER
    PfamiView protein in Pfam
    PF00089 Trypsin, 1 hit
    PRINTSiPR00722 CHYMOTRYPSIN
    SMARTiView protein in SMART
    SM00020 Tryp_SPc, 1 hit
    SUPFAMiSSF50494 SSF50494, 1 hit
    PROSITEiView protein in PROSITE
    PS50240 TRYPSIN_DOM, 1 hit
    PS00134 TRYPSIN_HIS, 1 hit
    PS00135 TRYPSIN_SER, 1 hit

    Sequencei

    Sequence statusi: Complete.

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

    Q9P0G3-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MSLRVLGSGT WPSAPKMFLL LTALQVLAIA MTQSQEDENK IIGGHTCTRS
    60 70 80 90 100
    SQPWQAALLA GPRRRFLCGG ALLSGQWVIT AAHCGRPILQ VALGKHNLRR
    110 120 130 140 150
    WEATQQVLRV VRQVTHPNYN SRTHDNDLML LQLQQPARIG RAVRPIEVTQ
    160 170 180 190 200
    ACASPGTSCR VSGWGTISSP IARYPASLQC VNINISPDEV CQKAYPRTIT
    210 220 230 240 250
    PGMVCAGVPQ GGKDSCQGDS GGPLVCRGQL QGLVSWGMER CALPGYPGVY
    260
    TNLCKYRSWI EETMRDK
    Length:267
    Mass (Da):29,122
    Last modified:July 7, 2009 - v2
    Checksum:i0CE085DA7BD1D92B
    GO

    Sequence cautioni

    The sequence AAD50773 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence AAG23260 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence AAK48523 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence AAK48524 differs from that shown. Reason: Erroneous initiation.Curated
    The sequence ABU63131 differs from that shown. Reason: Erroneous gene model prediction.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_05801833Q → R1 PublicationCorresponds to variant dbSNP:rs35287116Ensembl.1
    Natural variantiVAR_05801945H → Y1 PublicationCorresponds to variant dbSNP:rs2569491Ensembl.1
    Natural variantiVAR_05802064R → H. Corresponds to variant dbSNP:rs2569490Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF161221 Genomic DNA Translation: AAD50773.2 Sequence problems.
    AF283669 Genomic DNA Translation: AAK48523.1 Sequence problems.
    AF283670 mRNA Translation: AAK48524.1 Different initiation.
    EU091477 Genomic DNA Translation: ABU63131.1 Sequence problems.
    AC011473 Genomic DNA Translation: AAG23260.1 Sequence problems.
    CH471135 Genomic DNA Translation: EAW71982.1
    BC074904 mRNA Translation: AAH74904.2
    BC074905 mRNA Translation: AAH74905.2
    BC114614 mRNA Translation: AAI14615.2
    CCDSiCCDS12823.2
    RefSeqiNP_001298111.1, NM_001311182.1
    NP_071329.2, NM_022046.5
    UniGeneiHs.283925

    Genome annotation databases

    EnsembliENST00000156499; ENSP00000156499; ENSG00000129437
    ENST00000391802; ENSP00000375678; ENSG00000129437
    GeneIDi43847
    KEGGihsa:43847
    UCSCiuc002pvs.1 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiKLK14_HUMAN
    AccessioniPrimary (citable) accession number: Q9P0G3
    Secondary accession number(s): A7UNK5, Q1RMZ2, Q6B089
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: July 7, 2009
    Last modified: September 12, 2018
    This is version 147 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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