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Protein

Kallikrein-14

Gene

KLK14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

    • epidermis morphogenesis Source: UniProtKB
    • fertilization Source: UniProtKB
    • negative regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
    • positive regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
    • proteolysis Source: UniProtKB
    • seminal clot liquefaction Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000129437-MONOMER.
    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

    HGNCiHGNC:6362. KLK14.

    Subcellular locationi

    GO - Cellular componenti

    • extracellular exosome Source: UniProtKB
    • extracellular space Source: UniProtKB
    Complete GO annotation...

    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.

    PTM databases

    iPTMnetiQ9P0G3.
    PhosphoSitePlusiQ9P0G3.

    Miscellaneous databases

    PMAP-CutDBQ9P0G3.

    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.
    CleanExiHS_KLK14.
    ExpressionAtlasiQ9P0G3. baseline and differential.
    GenevisibleiQ9P0G3. HS.

    Organism-specific databases

    HPAiCAB026228.

    Interactioni

    Protein-protein interaction databases

    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
    Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

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

    Family and domain databases

    CDDicd00190. Tryp_SPc. 1 hit.
    InterProiIPR009003. Peptidase_S1_PA.
    IPR001314. Peptidase_S1A.
    IPR001254. Trypsin_dom.
    IPR018114. TRYPSIN_HIS.
    IPR033116. TRYPSIN_SER.
    [Graphical view]
    PfamiPF00089. Trypsin. 1 hit.
    [Graphical view]
    PRINTSiPR00722. CHYMOTRYPSIN.
    SMARTiSM00020. Tryp_SPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50494. SSF50494. 1 hit.
    PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view]

    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 → R.1 PublicationCorresponds to variant rs35287116dbSNPEnsembl.1
    Natural variantiVAR_05801945H → Y.1 PublicationCorresponds to variant rs2569491dbSNPEnsembl.1
    Natural variantiVAR_05802064R → H.Corresponds to variant rs2569490dbSNPEnsembl.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

    Cross-referencesi

    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.

    3D structure databases

    ProteinModelPortaliQ9P0G3.
    SMRiQ9P0G3.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9606.ENSP00000156499.

    Chemistry databases

    BindingDBiQ9P0G3.
    ChEMBLiCHEMBL2641.
    GuidetoPHARMACOLOGYi2866.

    Protein family/group databases

    MEROPSiS01.029.

    PTM databases

    iPTMnetiQ9P0G3.
    PhosphoSitePlusiQ9P0G3.

    Polymorphism and mutation databases

    BioMutaiKLK14.
    DMDMi251757292.

    Proteomic databases

    PaxDbiQ9P0G3.
    PeptideAtlasiQ9P0G3.
    PRIDEiQ9P0G3.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi43847.
    DisGeNETi43847.
    GeneCardsiKLK14.
    HGNCiHGNC:6362. KLK14.
    HPAiCAB026228.
    MIMi606135. gene.
    neXtProtiNX_Q9P0G3.
    OpenTargetsiENSG00000129437.
    PharmGKBiPA30151.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000129437-MONOMER.
    BRENDAi3.4.21.B45. 2681.
    ReactomeiR-HSA-6809371. Formation of the cornified envelope.

    Miscellaneous databases

    GeneWikiiKLK14.
    GenomeRNAii43847.
    PMAP-CutDBQ9P0G3.
    PROiQ9P0G3.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000129437.
    CleanExiHS_KLK14.
    ExpressionAtlasiQ9P0G3. baseline and differential.
    GenevisibleiQ9P0G3. HS.

    Family and domain databases

    CDDicd00190. Tryp_SPc. 1 hit.
    InterProiIPR009003. Peptidase_S1_PA.
    IPR001314. Peptidase_S1A.
    IPR001254. Trypsin_dom.
    IPR018114. TRYPSIN_HIS.
    IPR033116. TRYPSIN_SER.
    [Graphical view]
    PfamiPF00089. Trypsin. 1 hit.
    [Graphical view]
    PRINTSiPR00722. CHYMOTRYPSIN.
    SMARTiSM00020. Tryp_SPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50494. SSF50494. 1 hit.
    PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiKLK14_HUMAN
    AccessioniPrimary (citable) accession number: Q9P0G3
    Secondary accession number(s): A7UNK5, Q1RMZ2, Q6B089
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: July 7, 2009
    Last modified: November 30, 2016
    This is version 138 of the entry and version 2 of the sequence. [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

    Caution

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

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    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 one 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.