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Protein

Kallikrein-4

Gene

KLK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has a major role in enamel formation (PubMed:15235027). Required during the maturation stage of tooth development for clearance of enamel proteins and normal structural patterning of the crystalline matrix (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi40Zinc1 Publication1
Active sitei71Charge relay system1 Publication1
Metal bindingi91Zinc1 Publication1
Active sitei116Charge relay system1 Publication1
Active sitei207Charge relay system1 Publication1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • serine-type endopeptidase activity Source: InterPro
  • serine-type peptidase activity Source: UniProtKB

GO - Biological processi

  • amelogenesis Source: UniProtKB
  • biomineral tissue development Source: UniProtKB-KW
  • proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Biomineralization

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000167749-MONOMER.
BRENDAi3.4.21.B12. 2681.

Protein family/group databases

MEROPSiS01.251.

Names & Taxonomyi

Protein namesi
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 namesi
Name:KLK4
Synonyms:EMSP1, PRSS17, PSTS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6365. KLK4.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Amelogenesis imperfecta, hypomaturation type, 2A1 (AI2A1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:204700

Keywords - Diseasei

Amelogenesis imperfecta

Organism-specific databases

DisGeNETi9622.
MalaCardsiKLK4.
MIMi204700. phenotype.
OpenTargetsiENSG00000167749.
Orphaneti100033. Hypomaturation amelogenesis imperfecta.
PharmGKBiPA30154.

Chemistry databases

ChEMBLiCHEMBL4446.
GuidetoPHARMACOLOGYi2374.

Polymorphism and mutation databases

BioMutaiKLK4.
DMDMi317373372.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
PropeptideiPRO_000002793727 – 301 Publication4
ChainiPRO_000002793831 – 254Kallikrein-4Add BLAST224

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi37 ↔ 167PROSITE-ProRule annotation1 Publication
Disulfide bondi56 ↔ 72PROSITE-ProRule annotation1 Publication
Disulfide bondi141 ↔ 241PROSITE-ProRule annotation1 Publication
Disulfide bondi148 ↔ 213PROSITE-ProRule annotation1 Publication
Glycosylationi169N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi178 ↔ 192PROSITE-ProRule annotation1 Publication
Disulfide bondi203 ↔ 228PROSITE-ProRule annotation1 Publication

Post-translational modificationi

N-glycosylated. The N-glycan structures are of complex diantennary or triantennary type, which may be further modified with up to 2 sialic acid residues.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiQ9Y5K2.
PaxDbiQ9Y5K2.
PeptideAtlasiQ9Y5K2.
PRIDEiQ9Y5K2.

PTM databases

PhosphoSitePlusiQ9Y5K2.

Expressioni

Tissue specificityi

Expressed in prostate.

Gene expression databases

BgeeiENSG00000167749.
CleanExiHS_KLK4.
ExpressionAtlasiQ9Y5K2. baseline and differential.
GenevisibleiQ9Y5K2. HS.

Organism-specific databases

HPAiHPA051839.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TYRO3Q064183EBI-10224152,EBI-3951628

Protein-protein interaction databases

BioGridi114982. 4 interactors.
IntActiQ9Y5K2. 1 interactor.
STRINGi9606.ENSP00000326159.

Chemistry databases

BindingDBiQ9Y5K2.

Structurei

Secondary structure

1254
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi45 – 50Combined sources6
Beta strandi53 – 62Combined sources10
Beta strandi65 – 68Combined sources4
Helixi70 – 72Combined sources3
Beta strandi75 – 82Combined sources8
Beta strandi84 – 86Combined sources3
Helixi88 – 90Combined sources3
Beta strandi95 – 99Combined sources5
Beta strandi101 – 104Combined sources4
Turni106 – 109Combined sources4
Beta strandi118 – 121Combined sources4
Beta strandi130 – 132Combined sources3
Beta strandi147 – 154Combined sources8
Beta strandi157 – 160Combined sources4
Beta strandi166 – 172Combined sources7
Helixi175 – 182Combined sources8
Turni183 – 185Combined sources3
Beta strandi190 – 193Combined sources4
Beta strandi210 – 213Combined sources4
Beta strandi216 – 227Combined sources12
Beta strandi235 – 239Combined sources5
Helixi240 – 242Combined sources3
Helixi244 – 252Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BDGX-ray1.95A/B31-247[»]
2BDHX-ray3.00A/B/C/D31-247[»]
2BDIX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P31-247[»]
4K1EX-ray1.30A31-253[»]
4K8YX-ray1.00A31-253[»]
4KELX-ray1.15A31-253[»]
4KGAX-ray2.32A/B31-253[»]
ProteinModelPortaliQ9Y5K2.
SMRiQ9Y5K2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y5K2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 252Peptidase S1PROSITE-ProRule annotationAdd BLAST222

Sequence similaritiesi

Belongs to the peptidase S1 family. Kallikrein subfamily.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiQ9Y5K2.
KOiK08666.
PhylomeDBiQ9Y5K2.
TreeFamiTF331065.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y5K2-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MATAGNPWGW FLGYLILGVA GSLVSGSCSQ IINGEDCSPH SQPWQAALVM
60 70 80 90 100
ENELFCSGVL VHPQWVLSAA HCFQNSYTIG LGLHSLEADQ EPGSQMVEAS
110 120 130 140 150
LSVRHPEYNR PLLANDLMLI KLDESVSESD TIRSISIASQ CPTAGNSCLV
160 170 180 190 200
SGWGLLANGR MPTVLQCVNV SVVSEEVCSK LYDPLYHPSM FCAGGGHDQK
210 220 230 240 250
DSCNGDSGGP LICNGYLQGL VSFGKAPCGQ VGVPGVYTNL CKFTEWIEKT

VQAS
Length:254
Mass (Da):27,032
Last modified:January 11, 2011 - v2
Checksum:i9C5E4722AFF70CB8
GO
Isoform 2 (identifier: Q9Y5K2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.
     160-254: Missing.

Show »
Length:110
Mass (Da):11,858
Checksum:iB6F9C135EA93B116
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02836422S → A.1 PublicationCorresponds to variant rs1654551dbSNPEnsembl.1
Natural variantiVAR_033009159G → D.Corresponds to variant rs34626614dbSNPEnsembl.1
Natural variantiVAR_028365197H → Q.7 PublicationsCorresponds to variant rs2569527dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0566291 – 49Missing in isoform 2. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_056630160 – 254Missing in isoform 2. 1 PublicationAdd BLAST95

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AF259971 mRNA. Translation: AAK71706.1.
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.
CCDSiCCDS12809.1. [Q9Y5K2-1]
RefSeqiNP_001289890.1. NM_001302961.1.
NP_004908.4. NM_004917.4.
UniGeneiHs.218366.

Genome annotation databases

EnsembliENST00000431178; ENSP00000399448; ENSG00000167749. [Q9Y5K2-2]
GeneIDi9622.
KEGGihsa:9622.
UCSCiuc002pty.2. human. [Q9Y5K2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AF259971 mRNA. Translation: AAK71706.1.
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.
CCDSiCCDS12809.1. [Q9Y5K2-1]
RefSeqiNP_001289890.1. NM_001302961.1.
NP_004908.4. NM_004917.4.
UniGeneiHs.218366.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BDGX-ray1.95A/B31-247[»]
2BDHX-ray3.00A/B/C/D31-247[»]
2BDIX-ray3.00A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P31-247[»]
4K1EX-ray1.30A31-253[»]
4K8YX-ray1.00A31-253[»]
4KELX-ray1.15A31-253[»]
4KGAX-ray2.32A/B31-253[»]
ProteinModelPortaliQ9Y5K2.
SMRiQ9Y5K2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114982. 4 interactors.
IntActiQ9Y5K2. 1 interactor.
STRINGi9606.ENSP00000326159.

Chemistry databases

BindingDBiQ9Y5K2.
ChEMBLiCHEMBL4446.
GuidetoPHARMACOLOGYi2374.

Protein family/group databases

MEROPSiS01.251.

PTM databases

PhosphoSitePlusiQ9Y5K2.

Polymorphism and mutation databases

BioMutaiKLK4.
DMDMi317373372.

Proteomic databases

EPDiQ9Y5K2.
PaxDbiQ9Y5K2.
PeptideAtlasiQ9Y5K2.
PRIDEiQ9Y5K2.

Protocols and materials databases

DNASUi9622.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000431178; ENSP00000399448; ENSG00000167749. [Q9Y5K2-2]
GeneIDi9622.
KEGGihsa:9622.
UCSCiuc002pty.2. human. [Q9Y5K2-1]

Organism-specific databases

CTDi9622.
DisGeNETi9622.
GeneCardsiKLK4.
H-InvDBHIX0039968.
HGNCiHGNC:6365. KLK4.
HPAiHPA051839.
MalaCardsiKLK4.
MIMi204700. phenotype.
603767. gene.
neXtProtiNX_Q9Y5K2.
OpenTargetsiENSG00000167749.
Orphaneti100033. Hypomaturation amelogenesis imperfecta.
PharmGKBiPA30154.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOGENOMiHOG000251820.
HOVERGENiHBG013304.
InParanoidiQ9Y5K2.
KOiK08666.
PhylomeDBiQ9Y5K2.
TreeFamiTF331065.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000167749-MONOMER.
BRENDAi3.4.21.B12. 2681.

Miscellaneous databases

ChiTaRSiKLK4. human.
EvolutionaryTraceiQ9Y5K2.
GeneWikiiKLK4.
GenomeRNAii9622.
PROiQ9Y5K2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167749.
CleanExiHS_KLK4.
ExpressionAtlasiQ9Y5K2. baseline and differential.
GenevisibleiQ9Y5K2. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKLK4_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5K2
Secondary accession number(s): Q4VB16
, Q96RU5, Q9GZL6, Q9UBJ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 11, 2011
Last modified: November 2, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.