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. This protein is functionally conserved in ... See more...

Aliases for KLK1 Gene

Aliases for KLK1 Gene

  • Kallikrein 1 2 3 5
  • Kidney/Pancreas/Salivary Gland Kallikrein 3 4
  • Kallikrein 1, Renal/Pancreas/Salivary 2 3
  • Tissue Kallikrein 3 4
  • Kallikrein-1 3 4
  • EC 3.4.21.35 4 51
  • Klk6 2 3
  • Kallikrein Serine Protease 1 3
  • Glandular Kallikrein 1 3
  • EC 3.4.21 51
  • KLKR 3
  • KLK1 5
  • HK1 3

External Ids for KLK1 Gene

Previous GeneCards Identifiers for KLK1 Gene

  • GC19M051951
  • GC19M051683
  • GC19M055998
  • GC19M056014
  • GC19M051322
  • GC19M047656

Summaries for KLK1 Gene

Entrez Gene Summary for KLK1 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. This protein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. [provided by RefSeq, Jul 2008]

GeneCards Summary for KLK1 Gene

KLK1 (Kallikrein 1) is a Protein Coding gene. Diseases associated with KLK1 include Kallikrein, Decreased Urinary Activity Of and Hereditary Angioedema. Among its related pathways are Formation of Fibrin Clot (Clotting Cascade) and Metabolism of proteins. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is KLK2.

UniProtKB/Swiss-Prot Summary for KLK1 Gene

  • Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.

Gene Wiki entry for KLK1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KLK1 Gene

Genomics for KLK1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KLK1 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
GH19J050819 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE 256 +1.8 1825 4.3 IKZF1 ZEB1 ZIC2 ARNT ZNF740 VEZF1 TRIM22 TRIM25 ELF1 EBF1 KLK1 HSALNG0127140 POLD1 NUP62 SIGLEC6 LINC01869 VRK3 LOC105372440
GH19J050824 Enhancer 0.2 Ensembl 250.7 -0.5 -514 0.2 KLK1 piR-43665 KLK15
GH19J050720 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 10.4 +100.3 100342 5.9 TBP ZBTB10 MNT IKZF1 SMAD5 IRF2 MBD2 ZNF217 CTCF BHLHE40 CLEC11A NUP62 ZNF175 CTU1 C19orf48 GPR32 ENSG00000268047 AKT1S1 SNORD88A SNORD88B
GH19J050727 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas 10.4 +95.3 95348 1.4 TBP SIX5 MNT IKZF1 IRF2 BHLHE40 NONO THAP11 HCFC1 VEZF1 SHANK1 SYT3 ENSG00000267890 GPR32 IGLON5 LRRC4B SNORD88A SNORD88B SNORD88C LINC01869
GH19J050802 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 6.9 +19.5 19504 4.2 CHD2 ZBTB10 SP1 MXD4 FEZF1 CEBPA MNT SMAD5 ETS1 IRF2 LINC01869 C19orf48 HSALNG0127138 LINC01869-001 SNORD88C lnc-KLK1-2 NUP62 PTOV1-AS2 ZNF175 POLD1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KLK1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KLK1

Top Transcription factor binding sites by QIAGEN in the KLK1 gene promoter:
  • c-Myc
  • Max1
  • NF-kappaB
  • NF-kappaB1

Genomic Locations for KLK1 Gene

Latest Assembly
chr19:50,819,146-50,823,787
(GRCh38/hg38)
Size:
4,642 bases
Orientation:
Minus strand

Previous Assembly
chr19:51,322,402-51,327,043
(GRCh37/hg19 by Entrez Gene)
Size:
4,642 bases
Orientation:
Minus strand

chr19:51,322,404-51,327,043
(GRCh37/hg19 by Ensembl)
Size:
4,640 bases
Orientation:
Minus strand

Genomic View for KLK1 Gene

Genes around KLK1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLK1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLK1 Gene

Proteins for KLK1 Gene

  • Protein details for KLK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P06870-KLK1_HUMAN
    Recommended name:
    Kallikrein-1
    Protein Accession:
    P06870
    Secondary Accessions:
    • Q66US9
    • Q86U61
    • Q8TCV8
    • Q9BS53
    • Q9NQU4
    • Q9UD19
    • Q9UMJ1

    Protein attributes for KLK1 Gene

    Size:
    262 amino acids
    Molecular mass:
    28890 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for KLK1 Gene

    Alternative splice isoforms for KLK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLK1 Gene

Selected DME Specific Peptides for KLK1 Gene

P06870:
  • LEGGKDTC
  • GSTCLASGWGS
  • VLTAAHC
  • GDSGGPL
  • LQGVTSWG
  • CDGVLQG
  • PDDLQCV
  • PPIQSRI
  • WVLTAAH

Post-translational modifications for KLK1 Gene

  • The O-linked polysaccharides on Ser-93, Ser-104 and Ser-167 are probably the mucin type linked to GalNAc. In PubMed:3163150, GalNAc was detected with the corresponding peptides but not located.
  • Glycosylation at Ser93, Asn102, Ser104, Asn108, Asn165, and Ser167
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • KLK1_HUMAN (172)

Other Protein References for KLK1 Gene

Domains & Families for KLK1 Gene

Gene Families for KLK1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • FDA approved drug targets
  • Predicted secreted proteins

Protein Domains for KLK1 Gene

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

Suggested Antigen Peptide Sequences for KLK1 Gene

GenScript: Design optimal peptide antigens:
  • Tissue kallikrein (KLK1_HUMAN)
  • Kallikrein 1, renal/pancreas/salivary, isoform CRA_c (Q6T776_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P06870

UniProtKB/Swiss-Prot:

KLK1_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 KLK1: view

Function for KLK1 Gene

Molecular function for KLK1 Gene

UniProtKB/Swiss-Prot Function:
Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa.; EC=3.4.21.35;.
GENATLAS Biochemistry:
kallikrein 1,renal/pancreas/salivary

Enzyme Numbers (IUBMB) for KLK1 Gene

Phenotypes From GWAS Catalog for KLK1 Gene

Gene Ontology (GO) - Molecular Function for KLK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity TAS,NAS 7749372
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with KLK1: view
genes like me logo Genes that share phenotypes with KLK1: view

miRNA for KLK1 Gene

miRTarBase miRNAs that target KLK1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLK1

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for KLK1 Gene

Localization for KLK1 Gene

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 KLK1 gene
Compartment Confidence
extracellular 5
nucleus 5
plasma membrane 2
cytoskeleton 2
cytosol 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for KLK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 19232384
GO:0030141 secretory granule IBA 21873635
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with KLK1: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Subcellular locations from the Human Protein Atlas (HPA) for KLK1 Gene

Pathways & Interactions for KLK1 Gene

PathCards logo

SuperPathways for KLK1 Gene

genes like me logo Genes that share pathways with KLK1: view

Pathways by source for KLK1 Gene

1 GeneGo (Thomson Reuters) pathway for KLK1 Gene
  • Cell adhesion_ECM remodeling
3 Qiagen pathways for KLK1 Gene
  • Blood Coagulation Cascade
  • Intrinsic Prothrombin Activation Pathway
  • MSP-RON Signaling

Gene Ontology (GO) - Biological Process for KLK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003073 regulation of systemic arterial blood pressure IBA 21873635
GO:0006508 proteolysis IEA --
GO:0031638 zymogen activation IBA 21873635
genes like me logo Genes that share ontologies with KLK1: view

No data available for SIGNOR curated interactions for KLK1 Gene

Drugs & Compounds for KLK1 Gene

(11) Drugs for KLK1 Gene - From: DrugBank, DGIdb, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Aluminium Approved, Investigational Pharma Target, inhibitor 0
Aluminium phosphate Approved, Investigational Pharma Target 0
Aluminum acetate Approved, Investigational Pharma Target 0
Aprotinin Approved, Investigational, Withdrawn Pharma Target Inhibitor of bovine pancreatic trypsin 27
Ecallantide Approved, Investigational Pharma inhibitor 13

(3) Additional Compounds for KLK1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with KLK1: view

Transcripts for KLK1 Gene

mRNA/cDNA for KLK1 Gene

1 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLK1

Alternative Splicing Database (ASD) splice patterns (SP) for KLK1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5
SP1:
SP2:

Relevant External Links for KLK1 Gene

GeneLoc Exon Structure for
KLK1

Expression for KLK1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KLK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KLK1 Gene

This gene is overexpressed in Pancreas (x47.6).

Protein differential expression in normal tissues from HIPED for KLK1 Gene

This gene is overexpressed in Urine (34.8) and Pancreatic juice (21.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KLK1 Gene



Protein tissue co-expression partners for KLK1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KLK1

SOURCE GeneReport for Unigene cluster for KLK1 Gene:

Hs.123107

mRNA Expression by UniProt/SwissProt for KLK1 Gene:

P06870-KLK1_HUMAN
Tissue specificity: Isoform 2 is expressed in pancreas, salivary glands, kidney, colon, prostate gland, testis, spleen and the colon adenocarcinoma cell line T84.

Evidence on tissue expression from TISSUES for KLK1 Gene

  • Pancreas(4.8)
  • Kidney(4.7)
  • Urine(4.4)
  • Skin(2.8)
  • Blood(2.3)
  • Intestine(2.2)
  • Heart(2.2)
  • Muscle(2.1)
  • Nervous system(2.1)
genes like me logo Genes that share expression patterns with KLK1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for KLK1 Gene

Orthologs for KLK1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KLK1 Gene

Organism Taxonomy Gene Similarity Type Details
Dog
(Canis familiaris)
Mammalia KLK1 30
  • 81.79 (n)
Cow
(Bos Taurus)
Mammalia KLK1 30
  • 80.9 (n)
-- 31
  • 26 (a)
ManyToMany
Rat
(Rattus norvegicus)
Mammalia LOC100911764 30
  • 71.28 (n)
Mouse
(Mus musculus)
Mammalia Klk1 31
  • 65 (a)
ManyToMany
Klk1b5 31
  • 64 (a)
ManyToMany
Klk1b1 31
  • 62 (a)
ManyToMany
Klk1b4 31
  • 62 (a)
ManyToMany
Klk1b11 31
  • 62 (a)
ManyToMany
Klk1b22 31
  • 61 (a)
ManyToMany
Klk1b9 31
  • 60 (a)
ManyToMany
Klk1b24 31
  • 59 (a)
ManyToMany
Klk1b26 31
  • 59 (a)
ManyToMany
Klk1b8 31
  • 59 (a)
ManyToMany
Klk1b27 31
  • 59 (a)
ManyToMany
Klk1b21 31
  • 59 (a)
ManyToMany
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 40 (a)
OneToMany
Species where no ortholog for KLK1 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)
  • Chimpanzee (Pan troglodytes)
  • 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)
  • 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 KLK1 Gene

ENSEMBL:
Gene Tree for KLK1 (if available)
TreeFam:
Gene Tree for KLK1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLK1: view image

Paralogs for KLK1 Gene

Paralogs for KLK1 Gene

Pseudogenes.org Pseudogenes for KLK1 Gene

genes like me logo Genes that share paralogs with KLK1: view

Variants for KLK1 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for KLK1 Gene

KLK1_HUMAN-P06870
Genetic variations in KLK1 are the cause of a decreased in urinary kallikrein activity [MIM:615953]. The His-77 mutation dramatically reduces the activity of the enzyme in the urine. There is a 50 to 60% reduction in urinary kallikrein activity in His-77 individuals, but renal and hormonal adaptation to dietary changes in sodium and potassium are unaffected. However, in studies of brachial artery function, His-77 individuals consistently exhibited an increase in wall shear stress and a paradoxical reduction in artery diameter and lumen compared to Arg-77 individuals. This partial genetic deficiency in kallikrein activity is associated with a form of arterial dysfunction involving inappropriate inward remodeling of the brachial artery despite a chronic increase in shear stress.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KLK1 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
rs191306706 Benign: not provided 50,823,725(-) G/A
NM_002257.4(KLK1):c.24C>T (p.Leu8=)
SYNONYMOUS
rs3212857 Benign: not provided 50,819,965(-) G/A
NM_002257.4(KLK1):c.567C>T (p.His189=)
SYNONYMOUS
rs5515 Affects: Kallikrein, decreased urinary activity of. - 50,820,420(-) C/Tp.Arg77His
NM_002257.4(KLK1):c.230G>A (p.Arg77His)
MISSENSE
rs5516 - p.Glu145Gln
rs5517 - p.Lys186Glu

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for KLK1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for KLK1 Gene

Variant ID Type Subtype PubMed ID
dgv203n21 CNV loss 19592680
dgv204n21 CNV loss 19592680
esv3583463 CNV loss 25503493
esv3583464 CNV loss 25503493
nsv1140251 OTHER inversion 24896259

Variation tolerance for KLK1 Gene

Residual Variation Intolerance Score: 79.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.43; 77.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLK1 Gene

Human Gene Mutation Database (HGMD)
KLK1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLK1

SNP Genotyping and Copy Number Assays for research

Disorders for KLK1 Gene

MalaCards: The human disease database

(4) MalaCards diseases for KLK1 Gene - From: OMI, GTR, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards
Search KLK1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for KLK1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with KLK1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KLK1 Gene

Publications for KLK1 Gene

  1. KLK1 gene polymorphisms are not associated with lupus nephritis in a Chinese Han population. (PMID: 20516044) Zhou XJ … Zhang H (The Journal of rheumatology 2010) 3 23 41
  2. A coding polymorphism of the kallikrein 1 gene is associated with essential hypertension: a tagging SNP-based association study in a Chinese Han population. (PMID: 17762646) Zhao W … Gu D (Journal of hypertension 2007) 3 23 41
  3. Genetic analysis of 22 candidate genes for hypertension in the Japanese population. (PMID: 15167446) Iwai N … Shioji K (Journal of hypertension 2004) 3 23 41
  4. Significance of the tissue kallikrein promoter and transforming growth factor-beta1 polymorphisms with renal progression in children with vesicoureteral reflux. (PMID: 15086490) Lee-Chen GJ … Lin CY (Kidney international 2004) 3 23 41
  5. Loss-of-function polymorphism of the human kallikrein gene with reduced urinary kallikrein activity. (PMID: 11912256) Slim R … Alhenc-Gelas F (Journal of the American Society of Nephrology : JASN 2002) 3 4 41

Products for KLK1 Gene

Sources for KLK1 Gene