Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In some tissues its expression is hormonal... See more...

Aliases for KLK4 Gene

Aliases for KLK4 Gene

  • Kallikrein Related Peptidase 4 2 3 5
  • Enamel Matrix Serine Proteinase 1 2 3 4
  • KLK-L1 2 3 4
  • EMSP1 2 3 4
  • PSTS 2 3 4
  • Kallikrein-Like Protein 1 3 4
  • Serine Protease 17 3 4
  • Kallikrein-4 3 4
  • Prostase 3 4
  • PRSS17 3 4
  • EMSP 2 3
  • Kallikrein 4 (Prostase, Enamel Matrix, Prostate) 2
  • Enamel Matrix Serine Protease 1 3
  • Androgen-Regulated Message 1 3
  • EC 3.4.21.- 4
  • Kallikrein 3
  • EC 3.4.21 51
  • AI2A1 3
  • ARM1 3
  • KLK4 5

External Ids for KLK4 Gene

Previous HGNC Symbols for KLK4 Gene

  • PRSS17

Previous GeneCards Identifiers for KLK4 Gene

  • GC19M052036
  • GC19M051770
  • GC19M056085
  • GC19M056101
  • GC19M051409
  • GC19M047742

Summaries for KLK4 Gene

Entrez Gene Summary for KLK4 Gene

  • Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]

GeneCards Summary for KLK4 Gene

KLK4 (Kallikrein Related Peptidase 4) is a Protein Coding gene. Diseases associated with KLK4 include Amelogenesis Imperfecta, Hypomaturation Type, Iia1 and Amelogenesis Imperfecta Hypomaturation Type. Among its related pathways are Collagen chain trimerization and MSP-RON Signaling. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and serine-type peptidase activity. An important paralog of this gene is KLK5.

UniProtKB/Swiss-Prot Summary for KLK4 Gene

  • 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).

Gene Wiki entry for KLK4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KLK4 Gene

Genomics for KLK4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KLK4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J050909 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 605.4 +1.3 1344 1.2 NRF1 ZBTB44 KLF9 SP2 HDGF ZBTB48 ZBTB17 NR2F1 ZFX SP1 KLK4 lnc-KLK5-1 KLK2
GH19J050912 Enhancer 0.5 Ensembl 600.7 -1.5 -1456 0.8 ZNF512 YBX1 ZNF335 GLI4 ZNF366 SUZ12 KLF1 EZH2 GLIS2 KLK4 KLK8 PPIAP59 KLK5
GH19J050890 Enhancer 1.1 Ensembl ENCODE dbSUPER 13.5 +19.4 19445 1.8 RELA TCF12 IKZF2 TRIM22 ARID3A DPF2 RELB RUNX3 ZNF157 GATAD2B KLK4 C19orf48 LINC01869 SNORD88C KLK15 KLK1 lnc-KLK2-3 KLKP1 lnc-KLK4-1 HSALNG0127146
GH19J050537 Enhancer 1.1 ENCODE dbSUPER 10.2 +372.9 372866 0.1 CREB1 CTCF TEAD4 IKZF1 RFX5 JUND ZNF143 MTA2 ZSCAN4 REST ASPDH JOSD2 LRRC4B GPR32 SNORD88A SNORD88B SNORD88C NAPSA NR1H2 C19orf48
GH19J050931 Enhancer 0.9 Ensembl ENCODE 12.3 -22.1 -22078 2.9 SP1 CTBP1 NFE2 ZNF316 MAFF MAFK MAFG EHMT2 CTCF FOXA1 KLK4 KLK6 KLK2 KLK15 KLK1 LINC01869 C19orf48 SNORD88C KLK14 CTU1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KLK4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KLK4

Top Transcription factor binding sites by QIAGEN in the KLK4 gene promoter:
  • AhR
  • Arnt
  • GATA-1
  • GR
  • GR-alpha
  • NF-1
  • SRF
  • SRF (504 AA)
  • XBP-1
  • ZIC2

Genomic Locations for KLK4 Gene

Genomic Locations for KLK4 Gene
chr19:50,906,352-50,910,745
(GRCh38/hg38)
Size:
4,394 bases
Orientation:
Minus strand
chr19:51,409,608-51,413,994
(GRCh37/hg19)
Size:
4,387 bases
Orientation:
Minus strand

Genomic View for KLK4 Gene

Genes around KLK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLK4 Gene

Proteins for KLK4 Gene

  • Protein details for KLK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y5K2-KLK4_HUMAN
    Recommended name:
    Kallikrein-4
    Protein Accession:
    Q9Y5K2
    Secondary Accessions:
    • Q4VB16
    • Q96RU5
    • Q9GZL6
    • Q9UBJ6

    Protein attributes for KLK4 Gene

    Size:
    254 amino acids
    Molecular mass:
    27032 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for KLK4 Gene

    Alternative splice isoforms for KLK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLK4 Gene

Selected DME Specific Peptides for KLK4 Gene

Q9Y5K2:
  • CNGDSGGP
  • GDSGGPL
  • WVLSAAHC
  • SGGPLIC

Post-translational modifications for KLK4 Gene

  • 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.
  • Glycosylation at Asn169
  • Modification sites at PhosphoSitePlus

Domains & Families for KLK4 Gene

Gene Families for KLK4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for KLK4 Gene

InterPro:
Blocks:
  • Serine protease, trypsin family
  • Chymotrypsin serine protease family (S1) signature
ProtoNet:

Suggested Antigen Peptide Sequences for KLK4 Gene

GenScript: Design optimal peptide antigens:
  • Kallikrein (B1GRN1_HUMAN)
  • Serine protease 17 (KLK4_HUMAN)
  • Kallikrein-related peptidase 4 (Q4VB17_HUMAN)
  • KLK4 protein (Q4VB18_HUMAN)
  • Kallikrein 4 (Q5BQA0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y5K2

UniProtKB/Swiss-Prot:

KLK4_HUMAN :
  • Belongs to the peptidase S1 family. Kallikrein subfamily.
Family:
  • Belongs to the peptidase S1 family. Kallikrein subfamily.
genes like me logo Genes that share domains with KLK4: view

Function for KLK4 Gene

Molecular function for KLK4 Gene

UniProtKB/Swiss-Prot Function:
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).

Enzyme Numbers (IUBMB) for KLK4 Gene

Phenotypes From GWAS Catalog for KLK4 Gene

Gene Ontology (GO) - Molecular Function for KLK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IEA --
GO:0005515 protein binding IPI 25416956
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity TAS,NAS 10438493
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with KLK4: view
genes like me logo Genes that share phenotypes with KLK4: view

Human Phenotype Ontology for KLK4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for KLK4 Gene

MGI Knock Outs for KLK4:
  • Klk4 Klk4<tm1.1Jpsi>

Animal Model Products

  • Taconic Biosciences Mouse Models for KLK4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLK4

No data available for Transcription Factor Targets and HOMER Transcription for KLK4 Gene

Localization for KLK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLK4 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KLK4 gene
Compartment Confidence
extracellular 5
nucleus 3
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
golgi apparatus 2
peroxisome 1
endosome 1

Gene Ontology (GO) - Cellular Components for KLK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS,IEA --
GO:0030141 secretory granule IBA 21873635
genes like me logo Genes that share ontologies with KLK4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KLK4 Gene

Pathways & Interactions for KLK4 Gene

PathCards logo

SuperPathways for KLK4 Gene

SuperPathway Contained pathways
1 Collagen chain trimerization
.48
.46
2 MSP-RON Signaling
-
genes like me logo Genes that share pathways with KLK4: view

Pathways by source for KLK4 Gene

3 Qiagen pathways for KLK4 Gene
  • Blood Coagulation Cascade
  • Intrinsic Prothrombin Activation Pathway
  • MSP-RON Signaling

SIGNOR curated interactions for KLK4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for KLK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis NAS 10438493
GO:0022617 extracellular matrix disassembly IBA 21873635
GO:0030163 protein catabolic process IEA --
GO:0031214 biomineral tissue development IEA --
GO:0097186 amelogenesis IMP 15235027
genes like me logo Genes that share ontologies with KLK4: view

Drugs & Compounds for KLK4 Gene

(5) Drugs for KLK4 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dihydrogenphosphate Experimental Pharma Target 0
N-[2-(1-Maleimidyl)Ethyl]-7-Diethylaminocoumarin-3-Carboxamide Experimental Pharma Target 0
genes like me logo Genes that share compounds with KLK4: view

Transcripts for KLK4 Gene

mRNA/cDNA for KLK4 Gene

2 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLK4

Alternative Splicing Database (ASD) splice patterns (SP) for KLK4 Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d · 2e ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6a · 6b · 6c
SP1: - -
SP2: -
SP3: - -
SP4:
SP5: - - - - -
SP6: - -
SP7:
SP8: -

Relevant External Links for KLK4 Gene

GeneLoc Exon Structure for
KLK4

Expression for KLK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KLK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KLK4 Gene

This gene is overexpressed in Prostate (x48.1).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KLK4

SOURCE GeneReport for Unigene cluster for KLK4 Gene:

Hs.218366

mRNA Expression by UniProt/SwissProt for KLK4 Gene:

Q9Y5K2-KLK4_HUMAN
Tissue specificity: Expressed in prostate.

Evidence on tissue expression from TISSUES for KLK4 Gene

  • Blood(3.3)
  • Urine(2.9)
  • Kidney(2.8)
  • Nervous system(2.7)
  • Heart(2.7)
  • Saliva(2.5)
  • Muscle(2.4)
  • Skin(2.4)
  • Intestine(2.3)
  • Liver(2.2)
  • Pancreas(2.2)
  • Adrenal gland(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for KLK4 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • skeleton
Regions:
Head and neck:
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • skull
  • tooth
genes like me logo Genes that share expression patterns with KLK4: view

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for KLK4 Gene

Orthologs for KLK4 Gene

This gene was present in the common ancestor of mammals.

Orthologs for KLK4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KLK4 30 31
  • 99.61 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia KLK4 30 31
  • 85.3 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KLK4 30 31
  • 83.86 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Klk4 30
  • 75.76 (n)
Mouse
(Mus musculus)
Mammalia Klk4 30 17 31
  • 74.67 (n)
OneToOne
Species where no ortholog for KLK4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for KLK4 Gene

ENSEMBL:
Gene Tree for KLK4 (if available)
TreeFam:
Gene Tree for KLK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLK4: view image

Paralogs for KLK4 Gene

Paralogs for KLK4 Gene

genes like me logo Genes that share paralogs with KLK4: view

Variants for KLK4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KLK4 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
714810 Benign: not provided 50,908,495(-) C/T MISSENSE_VARIANT
779471 Benign: not provided 50,908,757(-) G/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
782657 Benign: not provided 50,908,754(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
rs104894704 Pathogenic: Amelogenesis imperfecta, hypomaturation type, IIA1 50,908,596(-) C/T NONSENSE,NON_CODING_TRANSCRIPT_VARIANT
rs1654552 Benign: not specified 50,909,410(-) C/A SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for KLK4 Gene

Structural Variations from Database of Genomic Variants (DGV) for KLK4 Gene

Variant ID Type Subtype PubMed ID
esv1633192 CNV deletion 17803354
esv3583473 CNV loss 25503493
nsv1140251 OTHER inversion 24896259

Variation tolerance for KLK4 Gene

Residual Variation Intolerance Score: 58% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.05; 60.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLK4 Gene

Human Gene Mutation Database (HGMD)
KLK4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLK4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLK4 Gene

Disorders for KLK4 Gene

MalaCards: The human disease database

(23) MalaCards diseases for KLK4 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search KLK4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

KLK4_HUMAN
  • 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. {ECO:0000269 PubMed:15235027}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for KLK4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with KLK4: view

No data available for Genatlas for KLK4 Gene

Publications for KLK4 Gene

  1. Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors. (PMID: 10863090) Hu JC … Simmer JP (Gene 2000) 2 3 4 23
  2. 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. (PMID: 10438493) Stephenson SA … Clements JA (The Journal of biological chemistry 1999) 2 3 4 23
  3. Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. (PMID: 10077646) Nelson PS … Wang K (Proceedings of the National Academy of Sciences of the United States of America 1999) 2 3 4 23
  4. Candidate gene approach evaluates association between innate immunity genes and breast cancer risk in Korean women. (PMID: 19372141) Lee JY … Kang D (Carcinogenesis 2009) 3 23 41
  5. Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with other members of the kallikrein family: intracellular localization, alternative cDNA forms, and Regulation by multiple hormones. (PMID: 11506707) Korkmaz KS … Saatcioglu F (DNA and cell biology 2001) 3 4 23

Products for KLK4 Gene

Sources for KLK4 Gene