KNG1 (kininogen 1)

Gene

• Entrez ID: 3827
• Gene name: Kininogen 1
• Gene symbol: KNG1
• Synonyms: BDK, BK, HAE6, HMWK, KNG
• Chromosome: 3
• Chromosome location: 3q27.3
• 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. 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. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2020]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918131	C>G,T	Pathogenic	Stop gained, missense variant, intron variant, coding sequence variant
rs797044429	A>-	Affects	Frameshift variant, intron variant, coding sequence variant
rs797044430	->C	Affects	Frameshift variant, intron variant, coding sequence variant
rs869320718	TTGTTGTTGTTGTTGTTTGTTTTTTGT>GGTGGTGGTGGTGGTGGTTTGTTTTTGG	Affects	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT021957	hsa-miR-128-3p	Microarray	17612493

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002576	Process	Platelet degranulation	TAS
GO:0004866	Function	Endopeptidase inhibitor activity	IBA	21873635
GO:0004869	Function	Cysteine-type endopeptidase inhibitor activity	IBA	21873635
GO:0004869	Function	Cysteine-type endopeptidase inhibitor activity	IDA	3488317
GO:0005102	Function	Signaling receptor binding	IPI	11290596
GO:0005515	Function	Protein binding	IPI	8710908, 23082758
GO:0005576	Component	Extracellular region	HDA	27068509
GO:0005576	Component	Extracellular region	IBA	21873635
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	3488317
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005886	Component	Plasma membrane	TAS
GO:0006954	Process	Inflammatory response	IEA
GO:0007162	Process	Negative regulation of cell adhesion	IDA	11970955
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IBA	21873635
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IDA	16014619
GO:0007597	Process	Blood coagulation, intrinsic pathway	TAS
GO:0008201	Function	Heparin binding	NAS	12911595
GO:0008270	Function	Zinc ion binding	NAS	12911595
GO:0010951	Process	Negative regulation of endopeptidase activity	IBA	21873635
GO:0030195	Process	Negative regulation of blood coagulation	IBA	21873635
GO:0030195	Process	Negative regulation of blood coagulation	IDA	11970955
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0042311	Process	Vasodilation	IEA
GO:0043065	Process	Positive regulation of apoptotic process	NAS	12715893
GO:0043687	Process	Post-translational protein modification	TAS
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0045861	Process	Negative regulation of proteolysis	IDA	3488317
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	25037231, 27559042, 28675934
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0072562	Component	Blood microparticle	HDA	22516433

Other IDs

• MIM: 612358
• HGNC: 6383
• e!Ensembl: ENSG00000113889

Protein

• UniProt ID: P01042
• Protein name: Kininogen-1 (Alpha-2-thiol proteinase inhibitor) (Fitzgerald factor) (High molecular weight kininogen) (HMWK) (Williams-Fitzgerald-Flaujeac factor) [Cleaved into: Kininogen-1 heavy chain; T-kinin (Ile-Ser-Bradykinin); Bradykinin (Kallidin I); Lysyl-bradykinin (Kallidin II); Kininogen-1 light chain; Low molecular weight growth-promoting factor]
• Protein 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.
• PDB: 1NY2, 2WOK, 4ASQ, 4ASR, 4ECB, 4ECC, 5I25, 6F27, 6F3V, 6F3W, 6F3X, 6F3Y
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00031	Cystatin	21 → 116	Cystatin domain	Domain
  PF00031	Cystatin	144 → 238	Cystatin domain	Domain
  PF00031	Cystatin	266 → 360	Cystatin domain	Domain

• Sequence:

  MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYRIT
  EATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSSTKFS
  VATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPDLEPILRHGIQYFNNNTQHSSLFMLN
  EVKRAQRQVVAGLNFRITYSIVQTNCSKENFLFLTPDCKSLWNGDTGECTDNAYIDIQLR
  IASFSQNCDIYPGKDFVQPPTKICVGCPRDIPTNSPELEETLTHTITKLNAENNATFYFK
  IDNVKKARVQVVAGKKYFIDFVARETTCSKESNEELTESCETKKLGQSLDCNAEVYVVPW
  EKKIYPTVNCQPLGMISLMKRPPGFSPFRSSRIGEIKEETTVSPPHTSMAPAQDEERDSG
  KEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGLGHGHEQQHGLGHGHKFKLD
  DDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGWKTEHLASSSEDSTTPSAQTQE
  KTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPPISPAPIQSDDDWIPDIQIDPNGLSF
  NPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESYYFDLTDGLS

• Sequence length: 644