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Q9P0G3 (KLK14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kallikrein-14

Short name=hK14
EC=3.4.21.-
Alternative name(s):
Kallikrein-like protein 6
Short name=KLK-L6
Gene names
Name:KLK14
Synonyms:KLKL6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length267 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18

Enzyme regulation

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. Ref.10 Ref.14 Ref.15

Subcellular location

Secretedextracellular space Ref.10 Ref.13 Ref.14.

Tissue specificity

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). Ref.1 Ref.2 Ref.7 Ref.11 Ref.13 Ref.14

Induction

Up-regulated by steroid hormone. Ref.8 Ref.10 Ref.14 Ref.15

Post-translational modification

Proteolytic cleavage of the activation peptide produces the active enzyme.

Sequence similarities

Belongs to the peptidase S1 family. Kallikrein subfamily.

Contains 1 peptidase S1 domain.

Caution

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

Biophysicochemical properties

Kinetic parameters:

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.

KM=0.3 mM for S-2288 Ref.10 Ref.14

KM=0.2 mM for S-2222

KM=0.2 mM for S-2302

KM=0.7 mM for S-2586

KM=0.045 mM for Gln-Ala-Arg synthetic peptide

KM=0.043 mM for Val-Pro-Arg synthetic peptide

KM=0.09 mM for Pro-Phe-Arg synthetic peptide

KM=0.278 mM for Phe-Ser-Arg synthetic peptide

KM=0.0577 mM for Leu-Gly-Arg synthetic peptide

KM=0.139 mM for Gln-Gly-Arg synthetic peptide

KM=0.173 mM for Gly-Pro-Arg synthetic peptide

KM=0.0268 mM for Gln-Arg-Arg synthetic peptide

KM=0.130 mM for Gly-Gly-Arg synthetic peptide

KM=0.578 mM for Val-Leu-Lys synthetic peptide

pH dependence:

Optimum pH is 8.0.

Sequence caution

The sequence AAD50773.2 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAG23260.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAK48523.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAK48524.1 differs from that shown. Reason: Erroneous initiation.

The sequence ABU63131.1 differs from that shown. Reason: Erroneous gene model prediction.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434
Propeptide35 – 406Activation peptide
PRO_0000027958
Chain41 – 267227Kallikrein-14
PRO_0000027959

Regions

Domain41 – 265225Peptidase S1

Sites

Active site831Charge relay system By similarity
Active site1271Charge relay system By similarity
Active site2201Charge relay system By similarity

Amino acid modifications

Disulfide bond47 ↔ 180 By similarity
Disulfide bond68 ↔ 84 By similarity
Disulfide bond159 ↔ 226 By similarity
Disulfide bond191 ↔ 205 By similarity
Disulfide bond216 ↔ 241 By similarity

Natural variations

Natural variant331Q → R. Ref.6
Corresponds to variant rs35287116 [ dbSNP | Ensembl ].
VAR_058018
Natural variant451H → Y. Ref.6
Corresponds to variant rs2569491 [ dbSNP | Ensembl ].
VAR_058019
Natural variant641R → H.
Corresponds to variant rs2569490 [ dbSNP | Ensembl ].
VAR_058020

Sequences

Sequence LengthMass (Da)Tools
Q9P0G3 [UniParc].

Last modified July 7, 2009. Version 2.
Checksum: 0CE085DA7BD1D92B

FASTA26729,122
        10         20         30         40         50         60 
MSLRVLGSGT WPSAPKMFLL LTALQVLAIA MTQSQEDENK IIGGHTCTRS SQPWQAALLA 

        70         80         90        100        110        120 
GPRRRFLCGG ALLSGQWVIT AAHCGRPILQ VALGKHNLRR WEATQQVLRV VRQVTHPNYN 

       130        140        150        160        170        180 
SRTHDNDLML LQLQQPARIG RAVRPIEVTQ ACASPGTSCR VSGWGTISSP IARYPASLQC 

       190        200        210        220        230        240 
VNINISPDEV CQKAYPRTIT PGMVCAGVPQ GGKDSCQGDS GGPLVCRGQL QGLVSWGMER 

       250        260 
CALPGYPGVY TNLCKYRSWI EETMRDK 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of a new member of the human kallikrein gene family, KLK14, which is down-regulated in different malignancies."
Yousef G.M., Magklara A., Chang A., Jung K., Katsaros D., Diamandis E.P.
Cancer Res. 61:3425-3431(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[2]"Identification and characterization of KLK14, a novel kallikrein serine protease gene located on human chromosome 19q13.4 and expressed in prostate and skeletal muscle."
Hooper J.D., Bui L.T., Rae F.K., Harvey T.J., Myers S.A., Ashworth L.K., Clements J.A.
Genomics 73:117-122(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
[3]"Understanding the accuracy of statistical haplotype inference with sequence data of known phase."
Andres A.M., Clark A.G., Shimmin L., Boerwinkle E., Sing C.F., Hixson J.E.
Genet. Epidemiol. 31:659-671(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-33 AND TYR-45.
Tissue: Lung.
[7]"Tissue-specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4."
Harvey T.J., Hooper J.D., Myers S.A., Stephenson S.A., Ashworth L.K., Clements J.A.
J. Biol. Chem. 275:37397-37406(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Steroid hormone regulation and prognostic value of the human kallikrein gene 14 in ovarian cancer."
Yousef G.M., Fracchioli S., Scorilas A., Borgono C.A., Iskander L., Puopolo M., Massobrio M., Diamandis E.P., Katsaros D.
Am. J. Clin. Pathol. 119:346-355(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY STEROID HORMONE.
[9]"Enzymatic profiling of human kallikrein 14 using phage-display substrate technology."
Felber L.M., Borgono C.A., Cloutier S.M., Kuendig C., Kishi T., Ribeiro Chagas J., Jichlinski P., Gygi C.M., Leisinger H.-J., Diamandis E.P., Deperthes D.
Biol. Chem. 386:291-298(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[10]"A proteolytic cascade of kallikreins in the stratum corneum."
Brattsand M., Stefansson K., Lundh C., Haasum Y., Egelrud T.
J. Invest. Dermatol. 124:198-203(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[11]"Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum."
Stefansson K., Brattsand M., Ny A., Glas B., Egelrud T.
Biol. Chem. 387:761-768(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 41-55, TISSUE SPECIFICITY.
[12]"Proteinase-activated receptors, targets for kallikrein signaling."
Oikonomopoulou K., Hansen K.K., Saifeddine M., Tea I., Blaber M., Blaber S.I., Scarisbrick I., Andrade-Gordon P., Cottrell G.S., Bunnett N.W., Diamandis E.P., Hollenberg M.D.
J. Biol. Chem. 281:32095-32112(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN G PROTEIN-COUPLED RECEPTOR SIGNALING.
[13]"Quantification of eight tissue kallikreins in the stratum corneum and sweat."
Komatsu N., Tsai B., Sidiropoulos M., Saijoh K., Levesque M.A., Takehara K., Diamandis E.P.
J. Invest. Dermatol. 126:925-929(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[14]"Expression and functional characterization of the cancer-related serine protease, human tissue kallikrein 14."
Borgono C.A., Michael I.P., Shaw J.L.V., Luo L.-Y., Ghosh M.C., Soosaipillai A., Grass L., Katsaros D., Diamandis E.P.
J. Biol. Chem. 282:2405-2422(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PROTEOLYTIC PROCESSING, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[15]"A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation."
Borgono C.A., Michael I.P., Komatsu N., Jayakumar A., Kapadia R., Clayman G.L., Sotiropoulou G., Diamandis E.P.
J. Biol. Chem. 282:3640-3652(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
[16]"Human kallikrein-related peptidase 14 (KLK14) is a new activator component of the KLK proteolytic cascade. Possible function in seminal plasma and skin."
Emami N., Diamandis E.P.
J. Biol. Chem. 283:3031-3041(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"Major role of human KLK14 in seminal clot liquefaction."
Emami N., Deperthes D., Malm J., Diamandis E.P.
J. Biol. Chem. 283:19561-19569(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"Activation of proteinase-activated receptor-2 by human kallikrein-related peptidases."
Stefansson K., Brattsand M., Roosterman D., Kempkes C., Bocheva G., Steinhoff M., Egelrud T.
J. Invest. Dermatol. 128:18-25(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS12823.2.
RefSeqNP_071329.2. NM_022046.4.
XP_006723288.1. XM_006723225.1.
UniGeneHs.283925.

3D structure databases

ProteinModelPortalQ9P0G3.
SMRQ9P0G3. Positions 41-265.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000156499.

Chemistry

BindingDBQ9P0G3.
ChEMBLCHEMBL2641.

Protein family/group databases

MEROPSS01.029.

PTM databases

PhosphoSiteQ9P0G3.

Polymorphism databases

DMDM251757292.

Proteomic databases

PaxDbQ9P0G3.
PRIDEQ9P0G3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000156499; ENSP00000156499; ENSG00000129437.
ENST00000391802; ENSP00000375678; ENSG00000129437.
GeneID43847.
KEGGhsa:43847.
UCSCuc002pvs.1. human.

Organism-specific databases

CTD43847.
GeneCardsGC19M051580.
HGNCHGNC:6362. KLK14.
HPACAB026228.
MIM606135. gene.
neXtProtNX_Q9P0G3.
PharmGKBPA30151.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidQ9P0G3.
KOK09622.
OMAGMERCAQ.
OrthoDBEOG7MKW6Q.
PhylomeDBQ9P0G3.
TreeFamTF331065.

Gene expression databases

BgeeQ9P0G3.
CleanExHS_KLK14.
GenevestigatorQ9P0G3.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiKLK14.
GenomeRNAi43847.
NextBio53000.
PMAP-CutDBQ9P0G3.
PROQ9P0G3.
SOURCESearch...

Entry information

Entry nameKLK14_HUMAN
AccessionPrimary (citable) accession number: Q9P0G3
Secondary accession number(s): A7UNK5, Q1RMZ2, Q6B089
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: July 7, 2009
Last modified: July 9, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM