Human Gene KNG1 (ENST00000644859.2) from GENCODE V43
  Description: Homo sapiens kininogen 1 (KNG1), transcript variant 1, mRNA. (from RefSeq NM_001102416)
RefSeq Summary (NM_001102416): 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. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reduces or depletes angiotensin converting enzyme 2 (ACE2), which results in an increase in levels of des-Arg(9)-bradykinin, a bioactive metabolite of bradykinin that is associated with lung injury and inflammation. [provided by RefSeq, Jul 2020].
Gencode Transcript: ENST00000644859.2
Gencode Gene: ENSG00000113889.14
Transcript (Including UTRs)
   Position: hg38 chr3:186,717,359-186,744,410 Size: 27,052 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg38 chr3:186,717,543-186,742,331 Size: 24,789 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-02-17 13:02:02

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr3:186,717,359-186,744,410)mRNA (may differ from genome)Protein (644 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Kininogen-1; AltName: Full=Alpha-2-thiol proteinase inhibitor; AltName: Full=Fitzgerald factor; AltName: Full=High molecular weight kininogen; Short=HMWK; AltName: Full=Williams-Fitzgerald-Flaujeac factor; Contains: RecName: Full=Kininogen-1 heavy chain; Contains: RecName: Full=T-kinin; AltName: Full=Ile-Ser-Bradykinin; Contains: RecName: Full=Bradykinin; AltName: Full=Kallidin I; Contains: RecName: Full=Lysyl-bradykinin; AltName: Full=Kallidin II; Contains: RecName: Full=Kininogen-1 light chain; Contains: RecName: Full=Low molecular weight growth-promoting factor; Flags: Precursor;
FUNCTION: (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin- induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW- kininogen is in contrast to HMW-kininogen not involved in blood clotting.
SUBCELLULAR LOCATION: Secreted, extracellular space.
TISSUE SPECIFICITY: Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors.
PTM: Bradykinin is released from kininogen by plasma kallikrein.
PTM: Hydroxylation of Pro-383 occurs prior to the release of bradykinin.
PTM: Phosphorylation sites are present in the extracellular medium.
PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.
POLYMORPHISM: The T-kinin peptide is missing residues 378 to 380, probably as a result of a naturally occurring variant. The complete sequence of the T-kinin peptide is therefore ISRPPGFSPFR. This peptide is associated with malignant tumors but not with benign ones.
DISEASE: Defects in KNG1 are the cause of high molecular weight kininogen deficiency (HMWK deficiency) [MIM:228960]. HMWK deficiency is an autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis.
SIMILARITY: Contains 3 cystatin kininogen-type domains.
WEB RESOURCE: Name=Wikipedia; Note=High molecular weight kininogen entry; URL="";
WEB RESOURCE: Name=SeattleSNPs; URL="";

-  Primer design for this transcript

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Click here to load the transcript sequence and exon structure into Primer3Plus

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: KNG1
Diseases sorted by gene-association score: high molecular weight kininogen deficiency* (370), hereditary angioedema (19), c1 inhibitor deficiency (18), angioedema (17), brain edema (13), whiplash (12), diffuse scleroderma (12), allergic rhinitis (10), chronic inflammatory demyelinating polyneuritis (10), congestive heart failure (9), pleural disease (8), interstitial cystitis (8), renal hypertension (7), rhinitis (7), neurodermatitis (7), malignant secondary hypertension (6), cystitis (6), angina pectoris (6), pulpitis (6), phototoxic dermatitis (6), allergic urticaria (6), coronary artery vasospasm (6), retinal ischemia (5), hydrops, lactic acidosis, and sideroblastic anemia (5), impotence (5), vascular disease (4), coronary artery disease (4), lemierre's syndrome (4), ischemia (4), malignant essential hypertension (4), hypertension, essential (4), ventricular fibrillation, familial, 1 (4), asthma (3), cholera (3), myocardial infarction (3), heart disease (2), autonomic nervous system neoplasm (1), peripheral nervous system neoplasm (1), neuroblastoma (1), hypercholesterolemia, familial (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 325.83 RPKM in Liver
Total median expression: 379.40 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -51.40184-0.279 Picture PostScript Text
3' UTR -517.802079-0.249 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002395 - Kininogen
IPR000010 - Prot_inh_cystat
IPR018073 - Prot_inh_cystat_CS

Pfam Domains:
PF00031 - Cystatin domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2WOK - X-ray 4ECB - X-ray 4ECC - X-ray

ModBase Predicted Comparative 3D Structure on P01042
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004869 cysteine-type endopeptidase inhibitor activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0008201 heparin binding
GO:0008270 zinc ion binding
GO:0030414 peptidase inhibitor activity

Biological Process:
GO:0002576 platelet degranulation
GO:0006954 inflammatory response
GO:0007162 negative regulation of cell adhesion
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007596 blood coagulation
GO:0007597 blood coagulation, intrinsic pathway
GO:0007599 hemostasis
GO:0010466 negative regulation of peptidase activity
GO:0010951 negative regulation of endopeptidase activity
GO:0030195 negative regulation of blood coagulation
GO:0031640 killing of cells of other organism
GO:0042311 vasodilation
GO:0043065 positive regulation of apoptotic process
GO:0043687 post-translational protein modification
GO:0044267 cellular protein metabolic process
GO:0045861 negative regulation of proteolysis
GO:0050880 regulation of blood vessel size

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005788 endoplasmic reticulum lumen
GO:0005886 plasma membrane
GO:0031012 extracellular matrix
GO:0031093 platelet alpha granule lumen
GO:0070062 extracellular exosome
GO:0072562 blood microparticle

-  Descriptions from all associated GenBank mRNAs
  AK303768 - Homo sapiens cDNA FLJ56836 complete cds, highly similar to Kininogen-1 precursor.
AK298440 - Homo sapiens cDNA FLJ53075 complete cds, highly similar to Kininogen-1 precursor.
AK315230 - Homo sapiens cDNA, FLJ96228, Homo sapiens kininogen (KNG), mRNA.
AK290839 - Homo sapiens cDNA FLJ77940 complete cds, highly similar to Human alpha-2-thiol proteinase inhibitor mRNA.
BC060039 - Homo sapiens kininogen 1, mRNA (cDNA clone MGC:61989 IMAGE:4593077), complete cds.
AK223589 - Homo sapiens mRNA for kininogen 1 variant, clone: FCC130F01.
K02566 - Human alpha-2-thiol proteinase inhibitor mRNA, complete coding sequence.
JD514541 - Sequence 495565 from Patent EP1572962.
BC026253 - Homo sapiens kininogen 1, mRNA (cDNA clone IMAGE:4716671), complete cds.
CU687392 - Synthetic construct Homo sapiens gateway clone IMAGE:100022316 5' read KNG1 mRNA.
KJ897102 - Synthetic construct Homo sapiens clone ccsbBroadEn_06496 KNG1 gene, encodes complete protein.
KR711282 - Synthetic construct Homo sapiens clone CCSBHm_00022176 KNG1 (KNG1) mRNA, encodes complete protein.
JD138328 - Sequence 119352 from Patent EP1572962.
JD175974 - Sequence 156998 from Patent EP1572962.
JD175975 - Sequence 156999 from Patent EP1572962.
JD332461 - Sequence 313485 from Patent EP1572962.
JD332462 - Sequence 313486 from Patent EP1572962.
JD189002 - Sequence 170026 from Patent EP1572962.
JD518432 - Sequence 499456 from Patent EP1572962.
JD052093 - Sequence 33117 from Patent EP1572962.
JD322241 - Sequence 303265 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04610 - Complement and coagulation cascades

BioCarta from NCI Cancer Genome Anatomy Project
h_biopeptidesPathway - Bioactive Peptide Induced Signaling Pathway
h_LairPathway - Cells and Molecules involved in local acute inflammatory response
h_no1Pathway - Actions of Nitric Oxide in the Heart
h_intrinsicPathway - Intrinsic Prothrombin Activation Pathway

Reactome (by CSHL, EBI, and GO)

Protein P01042 (Reactome details) participates in the following event(s):

R-HSA-158354 kininogen + C1q binding protein tetramer -> kininogen:C1q binding protein tetramer
R-HSA-374331 Bradykinin receptors B1 and B2 bind to bradykinin
R-HSA-158311 kallikrein:kininogen:C1q binding protein tetramer -> kallikrein + activated kininogen:C1q binding protein tetramer + bradykinin
R-HSA-481007 Exocytosis of platelet alpha granule contents
R-HSA-158218 prekallikrein + kininogen:C1q binding protein tetramer -> prekallikrein:kininogen:C1q binding protein tetramer
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-749452 The Ligand:GPCR:Gq complex dissociates
R-HSA-158251 prekallikrein:kininogen:C1q binding protein tetramer -> kallikrein:kininogen:C1q binding protein tetramer
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-749448 Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq
R-HSA-8952289 FAM20C phosphorylates FAM20C substrates
R-HSA-158313 factor XII -> factor XIIa
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-379048 Liganded Gq/11-activating GPCRs act as GEFs for Gq/11
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-114608 Platelet degranulation
R-HSA-140877 Formation of Fibrin Clot (Clotting Cascade)
R-HSA-418594 G alpha (i) signalling events
R-HSA-416476 G alpha (q) signalling events
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-76005 Response to elevated platelet cytosolic Ca2+
R-HSA-109582 Hemostasis
R-HSA-388396 GPCR downstream signalling
R-HSA-500792 GPCR ligand binding
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-372790 Signaling by GPCR
R-HSA-392499 Metabolism of proteins
R-HSA-597592 Post-translational protein modification
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A8K474, B2RCR2, BDK, ENST00000644859.1, KNG, KNG1_HUMAN, NM_001102416, P01042, P01043, Q53EQ0, Q6PAU9, Q7M4P1, uc285utq.1
UCSC ID: ENST00000644859.2
RefSeq Accession: NM_001102416
Protein: P01042 (aka KNG1_HUMAN)
CCDS: CCDS43183.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.