KLKB1 kallikrein B1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KLKB1provided by HGNC
Official Full Name: kallikrein B1provided by HGNC
Primary source: HGNC:HGNC:6371
See related: Ensembl:ENSG00000164344 MIM:229000; AllianceGenome:HGNC:6371
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PKK; PPK; KLK3; PKKD
Summary: This gene encodes a glycoprotein that participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. The encoded preproprotein present in plasma as a non-covalent complex with high molecular weight kininogen undergoes proteolytic processing mediated by activated coagulation factor XII to generate a disulfide-linked, heterodimeric serine protease comprised of heavy and light chains. Certain mutations in this gene cause prekallikrein deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
Expression: Biased expression in liver (RPKM 44.5) and kidney (RPKM 1.2) See more
Orthologs: mouse all
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Genomic context

Location:: 4q35.2

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (186210853..186258471)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (189554481..189598453)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (187148661..187179625)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema.
Title: CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema.
KLKB1 and CLSTN2 are associated with HDL-mediated cholesterol efflux capacity in a genome-wide association study.
Title: KLKB1 and CLSTN2 are associated with HDL-mediated cholesterol efflux capacity in a genome-wide association study.
[Matrix metalloproteinase 14 and plasma kallikrein 1 may be potential biomarkers in the diagnosis and treatment of sepsis: a proteomics and bioinformatics analysis].
Title: [Matrix metalloproteinase 14 and plasma kallikrein 1 may be potential biomarkers in the diagnosis and treatment of sepsis: a proteomics and bioinformatics analysis].
Kallikrein augments the anticoagulant function of the protein C system in thrombin generation.
Title: Kallikrein augments the anticoagulant function of the protein C system in thrombin generation.
c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans.
Title: c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans.
Severe plasma prekallikrein deficiency: Clinical characteristics, novel KLKB1 mutations, and estimated prevalence.
Title: Severe plasma prekallikrein deficiency: Clinical characteristics, novel KLKB1 mutations, and estimated prevalence.
These results highlight a novel and specific approach to target PKK for the treatment of HAE and other diseases involving contact system activation and overproduction of bradykinin.
Title: IONIS-PKK(Rx) a Novel Antisense Inhibitor of Prekallikrein and Bradykinin Production.
Plasma high molecular weight kininogen and prekallikrein concentrations were not associated with incident cardiovascular disease.
Title: Prospective study of plasma high molecular weight kininogen and prekallikrein and incidence of coronary heart disease, ischemic stroke and heart failure.
Kallikrein cleaves central complement component C3 directly to yield active components C3b and C3a. The cleavage site within C3 is identical to that recognized by C3 convertase. Kallikrein-generated C3b forms C3 convertases, which trigger C3 amplification loop. Kallikrein-generated C3 convertases are inhibited by factor H; suggesting activation of the contact system locally enhances complement activation on cell surfaces.
Title: Kallikrein Cleaves C3 and Activates Complement.
We further define the interactions of keratinocyte PKK with TP63 and NF-kappaB signaling, highlighting the importance of this protein as a tumor suppressor in skin squamous cell carcinoma development.
Title: PKK deletion in basal keratinocytes promotes tumorigenesis after chemical carcinogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (39)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Inherited prekallikrein deficiency MedGen: CN305372 OMIM: 612423 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants influencing human serum metabolome among African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association of lipid-lowering response to statins in combined study populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1. EBI GWAS Catalog EBI GWAS CatalogPubMed
Human metabolic individuality in biomedical and pharmaceutical research. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-112359 (e-PCR)
- UniSTS:183838

SHGC4-1080 (e-PCR)
- UniSTS:91460

D4S3236 (e-PCR)
- UniSTS:26698

D4S3127 (e-PCR)
- UniSTS:2248

STS-M13143 (e-PCR)
- UniSTS:13798

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Factor XII activation	TAS Traceable Author Statement more info	PubMed
involved_in blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in fibrinolysis	IEA Inferred from Electronic Annotation more info
involved_in plasminogen activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in zymogen activation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: plasma kallikrein

Names: kallikrein B, plasma (Fletcher factor) 1; kininogenin; plasma prekallikrein

NP_000883.2

EC 3.4.21.34

NP_001305323.1

EC 3.4.21.34

NP_001305325.1

EC 3.4.21.34

XP_011530232.1

EC 3.4.21.34

XP_016863670.1

EC 3.4.21.34

XP_016863671.1

EC 3.4.21.34

XP_016863672.1

EC 3.4.21.34

XP_016863673.1

EC 3.4.21.34

XP_047271617.1

EC 3.4.21.34

XP_054205936.1

EC 3.4.21.34

XP_054205937.1

EC 3.4.21.34

XP_054205938.1

EC 3.4.21.34

XP_054205939.1

EC 3.4.21.34

XP_054205940.1

EC 3.4.21.34

XP_054205941.1

EC 3.4.21.34

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012095.2 RefSeqGene

Range

23529..54493

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_565

mRNA and Protein(s)

NM_000892.5 → NP_000883.2 plasma kallikrein isoform 1 preproprotein

See identical proteins and their annotated locations for NP_000883.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AK292624, AW182528, CN265612, M13143

Consensus CDS

CCDS34120.1

UniProtKB/Swiss-Prot

A6NH96, B2R8H9, P03952, Q17RE8, Q17RE9, Q4W5C3

UniProtKB/TrEMBL

A8K9A9

Related

ENSP00000264690.6, ENST00000264690.11

Conserved Domains (3) summary

smart00223
Location:21 → 104

APPLE; APPLE domain

smart00020
Location:390 → 621

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:391 → 621

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
NM_001318394.2 → NP_001305323.1 plasma kallikrein isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple differences, compared to variant 1. These differences result in a distinct 5' UTR and cause translation initiation at a downstream start codon, compared to variant 1. The encoded protein (isoform 2) is shorter than isoform 1.

Source sequence(s)

AC110771, AK292624, AK297672, AW182528

Consensus CDS

CCDS82982.1

UniProtKB/TrEMBL

B4DMX2, E9PBC5

Related

ENSP00000424469.2, ENST00000513864.2

Conserved Domains (3) summary

smart00223
Location:163 → 246

APPLE; APPLE domain

smart00020
Location:352 → 485

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:353 → 500

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
NM_001318396.2 → NP_001305325.1 plasma kallikrein isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. It encodes isoform 3 which is shorter and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

AC110771, AK292624, AW182528, BC143911

UniProtKB/TrEMBL

A8K9A9

Related

ENST00000511406.5

Conserved Domains (4) summary

smart00223
Location:90 → 173

APPLE; APPLE domain

smart00020
Location:188 → 419

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:189 → 419

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cl00112
Location:51 → 82

PAN_APPLE; PAN/APPLE-like domain; present in N-terminal (N) domains of plasminogen/ hepatocyte growth factor proteins, plasma prekallikrein/coagulation factor XI and microneme antigen proteins, plant receptor-like protein kinases, and various nematode and leech ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

186210853..186258471

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047415661.1 → XP_047271617.1 plasma kallikrein isoform X2

UniProtKB/Swiss-Prot

A6NH96, B2R8H9, P03952, Q17RE8, Q17RE9, Q4W5C3
XM_017008181.2 → XP_016863670.1 plasma kallikrein isoform X1

UniProtKB/TrEMBL

A8K9A9

Conserved Domains (3) summary

smart00223
Location:21 → 104

APPLE; APPLE domain

smart00020
Location:401 → 632

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:402 → 632

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
XM_011531930.3 → XP_011530232.1 plasma kallikrein isoform X1

See identical proteins and their annotated locations for XP_011530232.1

UniProtKB/TrEMBL

A8K9A9

Conserved Domains (3) summary

smart00223
Location:21 → 104

APPLE; APPLE domain

smart00020
Location:401 → 632

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:402 → 632

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
XM_017008182.2 → XP_016863671.1 plasma kallikrein isoform X3

UniProtKB/TrEMBL

B4DMX2
XM_017008183.2 → XP_016863672.1 plasma kallikrein isoform X4

UniProtKB/TrEMBL

B4DMX2
XM_017008184.2 → XP_016863673.1 plasma kallikrein isoform X5

Conserved Domains (4) summary

smart00223
Location:90 → 173

APPLE; APPLE domain

smart00020
Location:188 → 419

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:189 → 419

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cl00112
Location:51 → 82

PAN_APPLE; PAN/APPLE-like domain; present in N-terminal (N) domains of plasminogen/ hepatocyte growth factor proteins, plasma prekallikrein/coagulation factor XI and microneme antigen proteins, plant receptor-like protein kinases, and various nematode and leech ...