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P49862 (KLK7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kallikrein-7

Short name=hK7
EC=3.4.21.117
Alternative name(s):
Serine protease 6
Stratum corneum chymotryptic enzyme
Short name=hSCCE
Gene names
Name:KLK7
Synonyms:PRSS6, SCCE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length253 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. Cleaves insulin A chain at '14-Tyr-|-Gln-15' and insulin B chain at '6-Leu-|-Cys-7', '16-Tyr-|-Leu-17', '25-Phe-|-Tyr-26' and '26-Tyr-|-Thr-27'. Could play a role in the activation of precursors to inflammatory cytokines. Ref.11

Catalytic activity

Cleavage of proteins with aromatic side chains in the P1 position.

Enzyme regulation

Inhibited by Zn2+ and Cu2+ at low micromolar concentrations. Inhibited by SERPINA12. Ref.11

Subcellular location

Secreted. Note: In ovarian carcinoma, secreted and also observed at the apical membrane and in cytoplasm at the invasive front. Ref.5

Tissue specificity

Abundantly expressed in the skin and is expressed by keratinocytes in the epidermis. Also expressed in the brain, mammary gland, cerebellum, spinal cord and kidney. Lower levels in salivary glands, uterus, thymus, thyroid, placenta, trachea and testis. Up-regulated in ovarian carcinoma, especially late-stage serous carcinoma, compared with normal ovaries and benign adenomas (at protein level). Ref.2 Ref.5

Induction

By estrogens and glucocorticoids in a breast carcinoma cell line. Ref.2 Ref.11

Sequence similarities

Belongs to the peptidase S1 family. Kallikrein subfamily.

Contains 1 peptidase S1 domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49862-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P49862-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.1
Propeptide23 – 297Activation peptide
PRO_0000027942
Chain30 – 253224Kallikrein-7
PRO_0000027943

Regions

Domain30 – 250221Peptidase S1

Sites

Active site701Charge relay system Ref.12
Active site1121Charge relay system Ref.12
Active site2051Charge relay system Ref.12
Site1091Major binding site for inhibitory zinc or copper

Amino acid modifications

Glycosylation2461N-linked (GlcNAc...) Potential
Disulfide bond36 ↔ 165 Ref.12 Ref.13
Disulfide bond55 ↔ 71 Ref.12 Ref.13
Disulfide bond137 ↔ 239 Ref.12 Ref.13
Disulfide bond144 ↔ 211 Ref.12 Ref.13
Disulfide bond176 ↔ 190 Ref.12 Ref.13
Disulfide bond201 ↔ 226 Ref.12 Ref.13

Natural variations

Alternative sequence1 – 7272Missing in isoform 2.
VSP_013581

Experimental info

Mutagenesis541H → F: No effect on zinc inhibition. Ref.12
Mutagenesis1091H → A: No zinc inhibition. Ref.12
Sequence conflict2261C → W in AAH32005. Ref.9

Secondary structure

......................................... 253
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 2D68B6B15A76A668

FASTA25327,525
        10         20         30         40         50         60 
MARSLLLPLQ ILLLSLALET AGEEAQGDKI IDGAPCARGS HPWQVALLSG NQLHCGGVLV 

        70         80         90        100        110        120 
NERWVLTAAH CKMNEYTVHL GSDTLGDRRA QRIKASKSFR HPGYSTQTHV NDLMLVKLNS 

       130        140        150        160        170        180 
QARLSSMVKK VRLPSRCEPP GTTCTVSGWG TTTSPDVTFP SDLMCVDVKL ISPQDCTKVY 

       190        200        210        220        230        240 
KDLLENSMLC AGIPDSKKNA CNGDSGGPLV CRGTLQGLVS WGTFPCGQPN DPGVYTQVCK 

       250 
FTKWINDTMK KHR 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 86A28A03B80C2D78
Show »

FASTA18119,887

References

« Hide 'large scale' references
[1]"Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase."
Hansson L., Stroemqvist M., Baeckman A., Wallbrandt P., Carlstein A., Egelrud T.
J. Biol. Chem. 269:19420-19426(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 23-53.
Tissue: Skin.
[2]"The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family -- genomic characterization, mapping, tissue expression and hormonal regulation."
Yousef G.M., Scorilas A., Magklara A., Soosaipillai A., Diamandis E.P.
Gene 254:119-128(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, INDUCTION.
Tissue: Keratinocyte.
[3]"Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region."
Gan L., Lee I., Smith R., Argonza-Barrett R., Lei H., McCuaig J., Moss P., Paeper B., Wang K.
Gene 257:119-130(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Epidermal overexpression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis."
Hansson L., Backman A., Ny A., Edlund M., Ekholm E., Ekstrand Hammarstrom B., Tornell J., Wallbrandt P., Wennbo H., Egelrud T.
J. Invest. Dermatol. 118:444-449(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers."
Dong Y., Kaushal A., Brattsand M., Nicklin J., Clements J.A.
Clin. Cancer Res. 9:1710-1720(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Ovarian carcinoma.
[6]"Prostate epithelial cells KLK7 protein."
Mo Z., Yang X.
Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Prostate.
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Amygdala.
[8]Mural R.J., Istrail S., Sutton 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].
[9]"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] (ISOFORM 1).
Tissue: Skin.
[10]"Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme."
Skytt A., Stroemqvist M., Egelrud T.
Biochem. Biophys. Res. Commun. 211:586-589(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[11]"Vaspin inhibits kallikrein 7 by serpin mechanism."
Heiker J.T., Kloting N., Kovacs P., Kuettner E.B., Strater N., Schultz S., Kern M., Stumvoll M., Bluher M., Beck-Sickinger A.G.
Cell. Mol. Life Sci. 70:2569-2583(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CLEAVAGE SPECIFICITY FOR INSULIN, ENZYME REGULATION.
[12]"Chymotryptic specificity determinants in the 1.0 A structure of the zinc-inhibited human tissue kallikrein 7."
Debela M., Hess P., Magdolen V., Schechter N.M., Steiner T., Huber R., Bode W., Goettig P.
Proc. Natl. Acad. Sci. U.S.A. 104:16086-16091(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 30-253 IN COMPLEX WITH ZINC OR COPPER, ACTIVE SITE, DISULFIDE BONDS, MUTAGENESIS OF HIS-54 AND HIS-109.
[13]"Crystal structure of human epidermal kallikrein 7 (hK7) synthesized directly in its native state in E. coli: insights into the atomic basis of its inhibition by LEKTI domain 6 (LD6)."
Fernandez I.S., Standker L., Magert H.J., Forssmann W.G., Gimenez-Gallego G., Romero A.
J. Mol. Biol. 377:1488-1497(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-250, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L33404 mRNA. Translation: AAC37551.1.
AF166330 Genomic DNA. Translation: AAD49718.1.
AF243527 Genomic DNA. Translation: AAG33360.1.
AF332583 Genomic DNA. Translation: AAK69624.1.
AF411214 mRNA. Translation: AAN03662.1.
AF411215 mRNA. Translation: AAN03663.1.
AY601109 mRNA. Translation: AAU04540.1.
AK289660 mRNA. Translation: BAF82349.1.
CH471135 Genomic DNA. Translation: EAW71959.1.
BC032005 mRNA. Translation: AAH32005.1.
PIRA53968.
RefSeqNP_001193982.1. NM_001207053.1.
NP_001230055.1. NM_001243126.1.
NP_005037.1. NM_005046.3.
NP_644806.1. NM_139277.2.
UniGeneHs.151254.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QXGX-ray2.60A/B30-253[»]
2QXHX-ray2.00A30-253[»]
2QXIX-ray1.00A30-253[»]
2QXJX-ray2.10A30-253[»]
3BSQX-ray2.80A/B/C30-250[»]
ProteinModelPortalP49862.
SMRP49862. Positions 30-253.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111631. 3 interactions.
STRING9606.ENSP00000304791.

Chemistry

BindingDBP49862.
ChEMBLCHEMBL2443.

Protein family/group databases

MEROPSS01.300.

PTM databases

PhosphoSiteP49862.

Polymorphism databases

DMDM1710878.

Proteomic databases

PaxDbP49862.
PRIDEP49862.

Protocols and materials databases

DNASU5650.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000391807; ENSP00000375683; ENSG00000169035. [P49862-1]
ENST00000595820; ENSP00000470538; ENSG00000169035. [P49862-1]
ENST00000597707; ENSP00000469950; ENSG00000169035. [P49862-2]
GeneID5650.
KEGGhsa:5650.
UCSCuc002puo.3. human. [P49862-1]

Organism-specific databases

CTD5650.
GeneCardsGC19M051479.
HGNCHGNC:6368. KLK7.
HPACAB026342.
HPA018994.
MIM604438. gene.
neXtProtNX_P49862.
PharmGKBPA30157.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidP49862.
KOK08668.
OMAVLVNERW.
PhylomeDBP49862.
TreeFamTF331065.

Enzyme and pathway databases

BRENDA3.4.21.117. 1154.
ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressP49862.
BgeeP49862.
CleanExHS_KLK7.
GenevestigatorP49862.

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

EvolutionaryTraceP49862.
GeneWikiKLK7.
GenomeRNAi5650.
NextBio21952.
PMAP-CutDBP49862.
PROP49862.
SOURCESearch...

Entry information

Entry nameKLK7_HUMAN
AccessionPrimary (citable) accession number: P49862
Secondary accession number(s): A8K0U5, Q8N5N9, Q8NFV7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 130 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 19

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