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KNG1 kininogen 1 [ Homo sapiens (human) ]

Gene ID: 3827, updated on 12-Aug-2018

Summary

Official Symbol
KNG1provided by HGNC
Official Full Name
kininogen 1provided by HGNC
Primary source
HGNC:HGNC:6383
See related
Ensembl:ENSG00000113889 MIM:612358; Vega:OTTHUMG00000150348
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
BK; BDK; KNG; HMWK
Summary
This gene uses alternative splicing to generate two different proteins- high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). HMWK is essential for blood coagulation and assembly of the kallikrein-kinin system. Also, bradykinin, a peptide causing numerous physiological effects, is released from HMWK. Bradykinin also functions as an antimicrobial peptide with antibacterial and antifungal activity. In contrast to HMWK, LMWK is not involved in blood coagulation. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2014]
Expression
Restricted expression toward liver (RPKM 432.8) See more
Orthologs

Genomic context

See KNG1 in Genome Data Viewer
Location:
3q27.3
Exon count:
11
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 3 NC_000003.12 (186717309..186744410)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (186435098..186462199)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105374258 Neighboring gene histidine rich glycoprotein Neighboring gene histidine rich glycoprotein pseudogene Neighboring gene uncharacterized LOC105374259 Neighboring gene proteasome 26S subunit, non-ATPase, 10 pseudogene 2

Genomic regions, transcripts, and products

Expression

  • Project title: 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
High molecular weight kininogen deficiency
MedGen: C0272340 OMIM: 228960 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
NHGRI GWA Catalog
Common variants of large effect in F12, KNG1, and HRG are associated with activated partial thromboplastin time.
NHGRI GWA Catalog
Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.
NHGRI GWA Catalog
Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ.
NHGRI GWA Catalog

Pathways from BioSystems

  • ACE Inhibitor Pathway, organism-specific biosystem (from WikiPathways)
    ACE Inhibitor Pathway, organism-specific biosystemThe core of this pathway was elucidated over a century ago and involves the conversion of angiotensinogen to angiotensin I (Ang I) by renin, its subsequent conversion to angiotensin II (Ang II) by an...
  • Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
    Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
  • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
    Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
  • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
    Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement and coagulation cascades, conserved biosystem (from KEGG)
    Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
    Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
  • G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
    G alpha (i) signalling events, organism-specific biosystemThe classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased act...
  • G alpha (q) signalling events, organism-specific biosystem (from REACTOME)
    G alpha (q) signalling events, organism-specific biosystemThe classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides ...
  • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
    GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
  • GPCR ligand binding, organism-specific biosystem (from REACTOME)
    GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
  • Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystem (from REACTOME)
    Gastrin-CREB signalling pathway via PKC and MAPK, organism-specific biosystemGastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic fac...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystem (from REACTOME)
    Intrinsic Pathway of Fibrin Clot Formation, organism-specific biosystemThe intrinsic pathway of blood clotting connects interactions among kininogen (high molecular weight kininogen, HK), prekallikrein (PK), and factor XII to the activation of clotting factor X by a ser...
  • Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
    Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
  • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
    Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
  • Platelet degranulation, organism-specific biosystem (from REACTOME)
    Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
  • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
    Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • Syndecan-2-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    Syndecan-2-mediated signaling events, organism-specific biosystem
    Syndecan-2-mediated signaling events
  • amb2 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
    amb2 Integrin signaling, organism-specific biosystem
    amb2 Integrin signaling

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cysteine-type endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cysteine-type endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
heparin binding NAS
Non-traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
zinc ion binding NAS
Non-traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
G-protein coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
blood coagulation, intrinsic pathway TAS
Traceable Author Statement
more info
 
cellular protein metabolic process TAS
Traceable Author Statement
more info
 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of blood coagulation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of blood coagulation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of endopeptidase activity IEA
Inferred from Electronic Annotation
more info
 
negative regulation of proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
platelet degranulation TAS
Traceable Author Statement
more info
 
positive regulation of apoptotic process NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of cytosolic calcium ion concentration IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of cytosolic calcium ion concentration IDA
Inferred from Direct Assay
more info
PubMed 
post-translational protein modification TAS
Traceable Author Statement
more info
 
vasodilation IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
kininogen-1
Names
alpha-2-thiol proteinase inhibitor
bradykinin
fitzgerald factor
high molecular weight kininogen
williams-Fitzgerald-Flaujeac factor

NCBI Reference Sequences (RefSeq)

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

  1. NG_016009.1 RefSeqGene

    Range
    5051..32102
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_598

mRNA and Protein(s)

  1. NM_000893.4NP_000884.1  kininogen-1 isoform 2 precursor

    See identical proteins and their annotated locations for NP_000884.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice pattern in the 3' coding region, compared to variant 1. The resulting isoform (2), also known as low molecular weight preprokininogen, has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC109780, AC112907, DC362362, K02566
    Consensus CDS
    CCDS3281.1
    UniProtKB/Swiss-Prot
    P01042
    Related
    ENSP00000496167.1, OTTHUMP00000197128, ENST00000645909.1
    Conserved Domains (1) summary
    pfam00031
    Location:266360
    Cystatin; Cystatin domain
  2. NM_001102416.3NP_001095886.1  kininogen-1 isoform 1 precursor

    See identical proteins and their annotated locations for NP_001095886.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1), also known as high molecular weight preprokininogen.
    Source sequence(s)
    AC109780, AC112907, DC362362, K02566
    Consensus CDS
    CCDS43183.1
    UniProtKB/Swiss-Prot
    P01042
    Related
    ENSP00000265023.4, OTTHUMP00000197129, ENST00000265023.9
    Conserved Domains (1) summary
    cd00042
    Location:266370
    CY; Cystatin-like domain; Cystatins are a family of cysteine protease inhibitors that occur mainly as single domain proteins. However some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains.
  3. NM_001166451.1NP_001159923.1  kininogen-1 isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice pattern in the 3' coding region and lacks an alternate in-frame exon, compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus and lacks an internal segment, compared to isoform 1.
    Source sequence(s)
    AC112907, CD014130, DC362362
    Consensus CDS
    CCDS54695.1
    UniProtKB/Swiss-Prot
    P01042
    Related
    ENSP00000396025.1, OTTHUMP00000210109, ENST00000447445.1, OTTHUMT00000344651
    Conserved Domains (1) summary
    pfam00031
    Location:230324
    Cystatin; Cystatin domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p12 Primary Assembly

    Range
    186717309..186744410
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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