Reviewed, UniProtKB/Swiss-Prot Q9Y5K2 (KLK4_HUMAN)

Names and origin

Protein names

Recommended name:
    Kallikrein-4
    EC=3.4.21.-
Alternative name(s):
    Prostase
    Kallikrein-like protein 1
      Short name=KLK-L1
    Enamel matrix serine proteinase 1
    Serine protease 17

Gene names

Name:	KLK4
Synonyms:	EMSP1, PRSS17, PSTS

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	254 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)

Subcellular location	Secreted.
Tissue specificity	Expressed in prostate.
Involvement in disease	Defects in KLK4 are the cause of amelogenesis imperfecta hypomaturation type 2A1 (AI2A1) [MIM:204700]. AI2A1 is an autosomal recessive defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. Ref.11
Sequence similarities	Belongs to the peptidase S1 family. Kallikrein subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Amelogenesis imperfecta
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Ref.3 Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Ref.1 Traceable author statement. Source: ProtInc
Molecular function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Potential

Propeptide

27 – 30

4

Potential

PRO_0000027937

Chain

31 – 254

224

Kallikrein-4

PRO_0000027938

Regions

Domain

31 – 252

222

Peptidase S1

Sites

Active site

71

1

Charge relay system Ref.10

Active site

116

1

Charge relay system Ref.10

Active site

207

1

Charge relay system Ref.10

Metal binding

40

1

Zinc

Metal binding

91

1

Zinc

Amino acid modifications

Glycosylation

169

1

N-linked (GlcNAc...) Potential

Disulfide bond

37 ↔ 167

Ref.10

Disulfide bond

56 ↔ 72

Ref.10

Disulfide bond

141 ↔ 241

Ref.10

Disulfide bond

148 ↔ 213

Ref.10

Disulfide bond

178 ↔ 192

Ref.10

Disulfide bond

203 ↔ 228

Ref.10

Natural variations

Natural variant

22

1

S → A: dbSNP rs1654551. Ref.11

VAR_028364

Natural variant

159

1

G → D: dbSNP rs34626614.

VAR_033009

Natural variant

197

1

Q → H: dbSNP rs2569527. Ref.1 Ref.4

VAR_028365

Secondary structure

1

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254

Helix Strand Turn

Details...

Beta strand

45 – 49

5

Beta strand

54 – 62

9

Beta strand

65 – 68

4

Helix

70 – 72

3

Beta strand

75 – 82

8

Beta strand

84 – 86

3

Helix

88 – 90

3

Beta strand

95 – 104

10

Turn

106 – 109

4

Beta strand

118 – 124

7

Beta strand

147 – 153

7

Beta strand

166 – 172

7

Helix

175 – 181

7

Turn

183 – 185

3

Beta strand

190 – 193

4

Beta strand

210 – 213

4

Beta strand

216 – 223

8

Beta strand

235 – 238

4

Helix

240 – 242

3

Helix

244 – 252

9

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5K2-1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 9C475E22B6EE0CB8	FASTA	254	27,023
	10 20 30 40 50 60 MATAGNPWGW FLGYLILGVA GSLVSGSCSQ IINGEDCSPH SQPWQAALVM ENELFCSGVL 70 80 90 100 110 120 VHPQWVLSAA HCFQNSYTIG LGLHSLEADQ EPGSQMVEAS LSVRHPEYNR PLLANDLMLI 130 140 150 160 170 180 KLDESVSESD TIRSISIASQ CPTAGNSCLV SGWGLLANGR MPTVLQCVNV SVVSEEVCSK 190 200 210 220 230 240 LYDPLYHPSM FCAGGGQDQK DSCNGDSGGP LICNGYLQGL VSFGKAPCGQ VGVPGVYTNL 250 CKFTEWIEKT VQAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression." Nelson P.S., Gan L., Ferguson C., Moss P., Gelinas R., Hood L., Wang K. Proc. Natl. Acad. Sci. U.S.A. 96:3114-3119(1999) [PubMed: 10077646] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT HIS-197.
[2]	"Prostase/KLK-L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated." Yousef G.M., Obiezu C.V., Luo L.-Y., Black M.H., Diamandis E.P. Cancer Res. 59:4252-4256(1999) [PubMed: 10485467] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4." Stephenson S.A., Verity K., Ashworth L.K., Clements J.A. J. Biol. Chem. 274:23210-23214(1999) [PubMed: 10438493] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 11054574] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-197.
[5]	"Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors." Hu J.C.-C., Zhang C., Sun X., Yang Y., Cao X., Ryu O., Simmer J.P. Gene 251:1-8(2000) [PubMed: 10863090] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION.
[6]	Korkmaz K.S., Korkmaz C.G., Saatcioglu F. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Prostatic carcinoma.
[7]	"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].
[8]	"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].
[9]	"Cloning and characterization of a cDNA encoding human EMSP1." Simmer J.P., Ryu O.H., Qian Q., Zhang C., Cao X., Sun X., Hu C.-C. (In) Goldberg M. (eds.); Chemistry and biology of mineralized tissues, pp.1-1, American Academy of Orthopaedic Surgeons, Vittel (2000) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-254.
[10]	"Crystal structures of human tissue kallikrein 4: activity modulation by a specific zinc binding site." Debela M., Magdolen V., Grimminger V., Sommerhoff C., Messerschmidt A., Huber R., Friedrich R., Bode W., Goettig P. J. Mol. Biol. 362:1094-1107(2006) [PubMed: 16950394] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-35, X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 31-253, ACTIVE SITE, ZINC-BINDING SITES, DISULFIDE BONDS.
[11]	"Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta." Hart P.S., Hart T.C., Michalec M.D., Ryu O.H., Simmons D., Hong S., Wright J.T. J. Med. Genet. 41:545-549(2004) [PubMed: 15235027] [Abstract] Cited for: INVOLVEMENT IN AI2A1, VARIANT ALA-22.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF113140 mRNA. Translation: AAD21580.1.
AF113141 Genomic DNA. Translation: AAD21581.1.
AF135023 Genomic DNA. Translation: AAD26424.2.
AF148532 Genomic DNA. Translation: AAD38019.1.
AF243527 Genomic DNA. Translation: AAG33357.1.
AF228497 Genomic DNA. Translation: AAF70620.1.
AF259969 mRNA. Translation: AAF81227.1.
AC037199 Genomic DNA. No translation available.
BC069325 mRNA. Translation: AAH69325.1.
BC069403 mRNA. Translation: AAH69403.1.
BC069429 mRNA. Translation: AAH69429.1.
BC069489 mRNA. Translation: AAH69489.1.
BC096175 mRNA. Translation: AAH96175.1.
BC096178 mRNA. Translation: AAH96178.1.
AF126401 mRNA. Translation: AAG43246.1.

IPI

IPI00001559.

RefSeq

NP_004908.3.

UniGene

Hs.218366

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BDG	X-ray	1.95	A/B	31-253	[»]
2BDH	X-ray	3.00	A/B/C/D	31-253	[»]
2BDI	X-ray	3.00	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P	31-253	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q9Y5K2.

Genome annotation databases

Ensembl

ENST00000324041; ENSP00000326159; ENSG00000167749; Homo sapiens. [Genome view]

GeneID

9622.

KEGG

hsa:9622.

Organism-specific databases

CTD

9622.

GeneCards

GC19M056101.

HGNC

HGNC:6365. KLK4.

MIM

204700. phenotype.
603767. gene.

Orphanet

88661. Amelogenesis imperfecta.
100033. Amelogenesis imperfecta, hypomaturation type.

PharmGKB

PA30154.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20294.

HOGENOM

HBG755338.

HOVERGEN

Q9Y5K2.

InParanoid

Q9Y5K2.

Gene expression databases

ArrayExpress

Q9Y5K2.

Bgee

Q9Y5K2.

CleanEx

HS_KLK4.

Genevestigator

Q9Y5K2.

GermOnline

ENSG00000167749. Homo sapiens.

Family and domain databases

InterPro

IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
IPR009003. Ser/Cys_Pept_Trypsin-like.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

36105.

SOURCE

Search...

Entry information

Entry name

KLK4_HUMAN

Accession

Primary (citable) accession number: Q9Y5K2
Secondary accession number(s): Q4VB16, Q9GZL6, Q9UBJ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1999
Last modified:	January 19, 2010
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.