Q9Y5K2 (KLK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kallikrein-4
EC=3.4.21.-

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

Gene names

Name:	KLK4
Synonyms:	EMSP1, PRSS17, PSTS

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	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)

Function	Involved in enamel formation. Ref.11
Subcellular location	Secreted.
Tissue specificity	Expressed in prostate.
Involvement in disease	Amelogenesis imperfecta, hypomaturation type, 2A1 (AI2A1) [MIM:204700]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry. 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 Reference proteome
Gene Ontology (GO)
Biological_process	amelogenesis Inferred from mutant phenotype Ref.11. Source: UniProtKB proteolysis Non-traceable author statement Ref.3. Source: UniProtKB
Cellular_component	extracellular region Traceable author statement Ref.1. Source: ProtInc
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Non-traceable author statement Ref.3. Source: UniProtKB
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. Ref.11
Corresponds to variant rs1654551 [ dbSNP | Ensembl ].

VAR_028364

Natural variant

159

1

G → D.
Corresponds to variant rs34626614 [ dbSNP | Ensembl ].

VAR_033009

Natural variant

197

1

H → Q. Ref.2 Ref.3 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10
Corresponds to variant rs2569527 [ dbSNP | Ensembl ].

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

157 – 160

4

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

226 – 229

4

Beta strand

235 – 238

4

Helix

240 – 242

3

Helix

244 – 252

9

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5K2 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 9C5E4722AFF70CB8	FASTA	254	27,032
	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 FCAGGGHDQK 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-197.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-197.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, VARIANT GLN-197.
[6]	Korkmaz K.S., Korkmaz C.G., Saatcioglu F. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-197. 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-197.
[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, VARIANT GLN-197.
[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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 31-35, X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 31-253, ACTIVE SITE, ZINC-BINDING SITES, DISULFIDE BONDS, VARIANT GLN-197.
[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] [Europe PMC] [Abstract] Cited for: FUNCTION, 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. NM_004917.3.

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	[»]

ProteinModelPortal

Q9Y5K2.

SMR

Q9Y5K2. Positions 31-253.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000326159.

Protein family/group databases

MEROPS

S01.251.

Polymorphism databases

DMDM

9296995.

Proteomic databases

PaxDb

Q9Y5K2.

PRIDE

Q9Y5K2.

Protocols and materials databases

DNASU

9622.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000324041; ENSP00000326159; ENSG00000167749.

GeneID

9622.

KEGG

hsa:9622.

UCSC

uc002pua.1. human.

Organism-specific databases

CTD

9622.

GeneCards

GC19M051409.

H-InvDB

HIX0039968.

HGNC

HGNC:6365. KLK4.

HPA

HPA051839.

MIM

204700. phenotype.
603767. gene.

neXtProt

NX_Q9Y5K2.

Orphanet

100033. Hypomaturation amelogenesis imperfecta.

PharmGKB

PA30154.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOGENOM

HOG000251820.

HOVERGEN

HBG013304.

InParanoid

Q9Y5K2.

KO

K08666.

OMA

NGEDCSP.

OrthoDB

EOG4TQM9S.

PhylomeDB

Q9Y5K2.

Gene expression databases

ArrayExpress

Q9Y5K2.

Bgee

Q9Y5K2.

CleanEx

HS_KLK4.

Genevestigator

Q9Y5K2.

GermOnline

ENSG00000167749. 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

Q9Y5K2.

ChEMBL

CHEMBL4446.

EvolutionaryTrace

Q9Y5K2.

GenomeRNAi

9622.

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:	January 11, 2011
Last modified:	May 1, 2013
This is version 116 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.