P49862 (KLK7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	253 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	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. SCCE cleaves 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.
Catalytic activity	Cleavage of proteins with aromatic side chains in the P1 position.
Enzyme regulation	Inhibited by Zn2+ and Cu2+ at low micromolar concentrations.
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
Sequence similarities	Belongs to the peptidase S1 family. Kallikrein subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	epidermis development Traceable author statement Ref.1. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	epidermal lamellar body Inferred from direct assay PubMed 15675955. Source: UniProtKB extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.1

Propeptide

23 – 29

7

Activation peptide

PRO_0000027942

Chain

30 – 253

224

Kallikrein-7

PRO_0000027943

Regions

Domain

30 – 250

221

Peptidase S1

Sites

Active site

70

1

Charge relay system Ref.8

Active site

112

1

Charge relay system Ref.8

Active site

205

1

Charge relay system Ref.8

Site

109

1

Major binding site for inhibitory zinc or copper

Amino acid modifications

Glycosylation

246

1

N-linked (GlcNAc...) Potential

Disulfide bond

36 ↔ 165

Ref.8 Ref.9

Disulfide bond

55 ↔ 71

Ref.8 Ref.9

Disulfide bond

137 ↔ 239

Ref.8 Ref.9

Disulfide bond

144 ↔ 211

Ref.8 Ref.9

Disulfide bond

176 ↔ 190

Ref.8 Ref.9

Disulfide bond

201 ↔ 226

Ref.8 Ref.9

Natural variations

Alternative sequence

1 – 72

72

Missing in isoform 2.

VSP_013581

Experimental info

Mutagenesis

54

1

H → F: No effect on zinc inhibition. Ref.8

Mutagenesis

109

1

H → A: No zinc inhibition. Ref.8

Sequence conflict

226

1

C → W in AAH32005. Ref.6

Secondary structure

1

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253

Helix Strand Turn

Details...

Beta strand

44 – 49

6

Beta strand

52 – 61

10

Beta strand

64 – 67

4

Helix

69 – 71

3

Beta strand

76 – 81

6

Beta strand

90 – 95

6

Beta strand

97 – 100

4

Turn

106 – 108

3

Beta strand

114 – 117

4

Beta strand

143 – 150

8

Beta strand

152 – 156

5

Beta strand

164 – 171

8

Helix

173 – 180

8

Helix

181 – 183

3

Beta strand

188 – 192

5

Beta strand

208 – 211

4

Beta strand

214 – 221

8

Beta strand

224 – 226

3

Beta strand

233 – 237

5

Helix

238 – 240

3

Helix

242 – 251

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 2D68B6B15A76A668	FASTA	253	27,525
	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
	Isoform 2 (Short) [UniParc]. Checksum: 86A28A03B80C2D78	FASTA	181	19,887
	10 20 30 40 50 60 MNEYTVHLGS DTLGDRRAQR IKASKSFRHP GYSTQTHVND LMLVKLNSQA RLSSMVKKVR 70 80 90 100 110 120 LPSRCEPPGT TCTVSGWGTT TSPDVTFPSD LMCVDVKLIS PQDCTKVYKD LLENSMLCAG 130 140 150 160 170 180 IPDSKKNACN GDSGGPLVCR GTLQGLVSWG TFPCGQPNDP GVYTQVCKFT KWINDTMKKH R

References

	« Hide 'large scale' referencesShow '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]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
BC032005 mRNA. Translation: AAH32005.1.

IPI

IPI00028600.
IPI00556124.

PIR

A53968.

RefSeq

NP_001193982.1. NM_001207053.1.
NP_001230055.1. NM_001243126.1.
NP_005037.1. NM_005046.3.
NP_644806.1. NM_139277.2.

UniGene

Hs.151254.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2QXG	X-ray	2.60	A/B	30-253	[»]
2QXH	X-ray	2.00	A	30-253	[»]
2QXI	X-ray	1.00	A	30-253	[»]
2QXJ	X-ray	2.10	A	30-253	[»]
3BSQ	X-ray	2.80	A/B/C	30-250	[»]

ProteinModelPortal

P49862.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000304791.

Protein family/group databases

MEROPS

S01.300.

PTM databases

PhosphoSite

P49862.

Polymorphism databases

DMDM

1710878.

Proteomic databases

PaxDb

P49862.

PRIDE

P49862.

Protocols and materials databases

DNASU

5650.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000391807; ENSP00000375683; ENSG00000169035.
ENST00000595820; ENSP00000470538; ENSG00000169035.
ENST00000597707; ENSP00000469950; ENSG00000169035.

GeneID

5650.

KEGG

hsa:5650.

UCSC

uc002puo.3. human.

Organism-specific databases

CTD

5650.

GeneCards

GC19M051479.

HGNC

HGNC:6368. KLK7.

HPA

CAB026342.
HPA018994.

MIM

604438. gene.

neXtProt

NX_P49862.

PharmGKB

PA30157.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

P49862.

KO

K08668.

OMA

VLVNERW.

OrthoDB

EOG42V8H2.

PhylomeDB

P49862.

Enzyme and pathway databases

BRENDA

3.4.21.117. 1154.

Gene expression databases

ArrayExpress

P49862.

Bgee

P49862.

CleanEx

HS_KLK7.

Genevestigator

P49862.

GermOnline

ENSG00000169035. Homo sapiens.

Family and domain databases

InterPro

IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

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

BindingDB

P49862.

ChEMBL

CHEMBL2443.

EvolutionaryTrace

P49862.

GenomeRNAi

5650.

NextBio

21952.

PMAP-CutDB

P49862.

SOURCE

Search...

Entry information

Entry name

KLK7_HUMAN

Accession

Primary (citable) accession number: P49862
Secondary accession number(s): Q8N5N9, Q8NFV7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 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.