Q9P0G3 (KLK14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	267 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › extracellular 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.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	epidermis morphogenesis Inferred from direct assay Ref.15. Source: UniProtKB fertilization Inferred from direct assay Ref.17. Source: UniProtKB negative regulation of G-protein coupled receptor protein signaling pathway Inferred from direct assay Ref.12. Source: UniProtKB positive regulation of G-protein coupled receptor protein signaling pathway Inferred from direct assay Ref.12. Source: UniProtKB proteolysis Inferred from direct assay Ref.10Ref.14Ref.15Ref.17. Source: UniProtKB seminal clot liquefaction Inferred from direct assay Ref.17. Source: UniProtKB
Cellular component	extracellular space Inferred from direct assay Ref.10Ref.14. Source: UniProtKB
Molecular function	serine-type endopeptidase activity Inferred from direct assay Ref.10Ref.12Ref.14Ref.15. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 34	34
	Propeptide	35 – 40	6	Activation peptide		PRO_0000027958
	Chain	41 – 267	227	Kallikrein-14		PRO_0000027959
Regions
	Domain	41 – 265	225	Peptidase S1
Sites
	Active site	83	1	Charge relay system By similarity
	Active site	127	1	Charge relay system By similarity
	Active site	220	1	Charge relay system By similarity
Amino acid modifications
	Disulfide bond	47 ↔ 180		By similarity
	Disulfide bond	68 ↔ 84		By similarity
	Disulfide bond	159 ↔ 226		By similarity
	Disulfide bond	191 ↔ 205		By similarity
	Disulfide bond	216 ↔ 241		By similarity
Natural variations
	Natural variant	33	1	Q → R. Ref.6 Corresponds to variant rs35287116 [ dbSNP | Ensembl ].		VAR_058018
	Natural variant	45	1	H → Y. Ref.6 Corresponds to variant rs2569491 [ dbSNP | Ensembl ].		VAR_058019
	Natural variant	64	1	R → H. Corresponds to variant rs2569490 [ dbSNP | Ensembl ].		VAR_058020

Sequences

	Sequence		Length	Mass (Da)
	Q9P0G3 [UniParc]. Last modified July 7, 2009. Version 2. Checksum: 0CE085DA7BD1D92B	FASTA	267	29,122
	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

References

	« Hide 'large scale' referencesShow '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: 11309303] [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: 11352573] [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: 17922479] [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. , 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: 15057824] [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. , 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: 15489334] [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: 10969073] [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: 12645335] [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: 15843175] [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: 15654974] [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: 16800737] [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: 16885167] [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: 16456535] [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: 17110383] [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: 17158887] [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: 18056261] [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: 18482984] [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: 17625593] [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.
IPI	IPI00000700.
RefSeq	NP_071329.2. NM_022046.4.
UniGene	Hs.283925.
3D structure databases
ProteinModelPortal	Q9P0G3.
SMR	Q9P0G3. Positions 2-266.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9P0G3.
Protein family/group databases
MEROPS	S01.029.
Polymorphism databases
DMDM	251757292.
Proteomic databases
PRIDE	Q9P0G3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000156499; ENSP00000156499; ENSG00000129437. ENST00000391802; ENSP00000375678; ENSG00000129437.
GeneID	43847.
KEGG	hsa:43847.
Organism-specific databases
CTD	43847.
GeneCards	GC19M051580.
HGNC	HGNC:6362. KLK14.
HPA	CAB026228.
MIM	606135. gene.
neXtProt	NX_Q9P0G3.
PharmGKB	PA30151.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00580000081320.
HOGENOM	HBG755338.
HOVERGEN	HBG013304.
InParanoid	Q9P0G3.
OMA	SAPKMFL.
OrthoDB	EOG43BMPJ.
PhylomeDB	Q9P0G3.
Gene expression databases
ArrayExpress	Q9P0G3.
Bgee	Q9P0G3.
CleanEx	HS_KLK14.
Genevestigator	Q9P0G3.
GermOnline	ENSG00000129437. Homo sapiens.
Family and domain databases
InterPro	IPR009003. Pept_cys/ser_Trypsin-like. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
KO	K09622.
Pfam	PF00089. Trypsin. 1 hit. [Graphical view]
PRINTS	PR00722. CHYMOTRYPSIN.
SMART	SM00020. Tryp_SPc. 1 hit. [Graphical view]
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit.
PROSITE	PS50240. TRYPSIN_DOM. 1 hit. PS00134. TRYPSIN_HIS. 1 hit. PS00135. TRYPSIN_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
PMAP-CutDB	Q9P0G3.
SOURCE	Search...

Entry information

Entry name

KLK14_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.