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Identification
HMDB Protein ID HMDBP02063
Secondary Accession Numbers
  • 7542
Name Kininogen-1
Synonyms
  1. Alpha-2-thiol proteinase inhibitor
  2. Bradykinin
  3. Fitzgerald factor
  4. HMWK
  5. High molecular weight kininogen
  6. Ile-Ser-Bradykinin
  7. Kallidin I
  8. Kallidin II
  9. Kininogen-1 heavy chain
  10. Kininogen-1 light chain
  11. Low molecular weight growth-promoting factor
  12. Lysyl-bradykinin
  13. T-kinin
  14. Williams-Fitzgerald-Flaujeac factor
Gene Name KNG1
Protein Type Enzyme
Biological Properties
General Function Involved in cysteine-type endopeptidase inhibitor activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
Function
cysteine-type endopeptidase inhibitor activity
peptidase inhibitor activity
endopeptidase inhibitor activity
enzyme regulator activity
enzyme inhibitor activity
Cellular Location
  1. Secreted
  2. extracellular space
Gene Properties
Chromosome Location Chromosome:3
Locus 3q27
SNPs KNG1
Gene Sequence
>1935 bp
ATGAAACTAATTACCATCCTTTTCCTCTGCTCCAGGCTGCTACTAAGTTTAACCCAGGAA
TCACAGTCCGAGGAAATTGACTGCAATGACAAGGATTTATTTAAAGCTGTGGATGCTGCT
CTGAAGAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTACCGCATAACT
GAAGCCACTAAGACGGTTGGCTCTGACACGTTTTATTCCTTCAAGTACGAAATCAAGGAG
GGGGATTGTCCTGTTCAAAGTGGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGCA
AAAGCAGCCACTGGAGAATGCACGGCAACCGTGGGGAAGAGGAGCAGTACGAAATTCTCC
GTGGCTACCCAGACCTGCCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCCAGTAC
GACTGCCTCGGCTGTGTGCATCCTATATCAACGCAGAGCCCAGACCTGGAGCCCATTCTG
AGACACGGCATTCAGTACTTTAACAACAACACTCAACATTCCTCCCTCTTCATGCTTAAT
GAAGTAAAACGGGCCCAAAGACAGGTGGTGGCTGGATTGAACTTTCGAATTACCTACTCA
ATTGTGCAAACGAATTGTTCCAAAGAGAATTTTCTGTTCTTAACTCCAGACTGCAAGTCC
CTTTGGAATGGTGATACCGGTGAATGTACAGATAATGCATACATCGATATTCAGCTACGA
ATTGCTTCCTTCTCACAGAACTGTGACATTTATCCAGGGAAGGATTTTGTACAACCACCT
ACCAAGATTTGCGTGGGCTGCCCCAGAGATATACCCACCAACAGCCCAGAGCTGGAGGAG
ACACTGACTCACACCATCACAAAGCTTAATGCAGAGAATAACGCAACTTTCTATTTCAAG
ATTGACAATGTGAAAAAAGCAAGAGTACAGGTGGTGGCTGGCAAGAAATATTTTATTGAC
TTCGTGGCCAGGGAAACCACATGTTCCAAGGAAAGTAATGAAGAGTTGACCGAAAGCTGT
GAGACCAAAAAACTTGGCCAAAGCCTAGATTGCAACGCTGAAGTTTATGTGGTACCCTGG
GAGAAAAAAATTTACCCTACTGTCAACTGTCAACCACTGGGAATGATCTCACTGATGAAA
AGGCCTCCAGGTTTTTCACCTTTCCGATCATCACGAATAGGGGAAATAAAAGAAGAAACA
ACTGTAAGTCCACCCCACACTTCCATGGCACCTGCACAAGATGAAGAGCGGGATTCAGGA
AAAGAACAAGGGCATACTCGTAGACATGACTGGGGCCATGAAAAACAAAGAAAACATAAT
CTTGGCCATGGCCATAAACATGAACGTGACCAAGGGCATGGGCACCAAAGAGGACATGGC
CTTGGCCATGGACACGAACAACAGCATGGTCTTGGTCATGGACATAAGTTCAAACTTGAT
GATGATCTTGAACACCAAGGGGGCCATGTCCTTGACCATGGACATAAGCATAAGCATGGT
CATGGCCACGGAAAACATAAAAATAAAGGCAAAAAGAATGGAAAGCACAATGGTTGGAAA
ACAGAGCATTTGGCAAGCTCTTCTGAAGACAGTACTACACCTTCTGCACAGACACAAGAG
AAGACAGAAGGGCCAACACCCATCCCTTCCCTAGCCAAGCCAGGTGTAACAGTTACCTTT
TCTGACTTTCAGGACTCTGATCTCATTGCAACTATGATGCCTCCTATATCACCAGCTCCC
ATACAGAGTGATGACGATTGGATCCCTGATATCCAGATAGACCCAAATGGCCTTTCATTT
AACCCAATATCAGATTTTCCAGACACGACCTCCCCAAAATGTCCTGGACGCCCCTGGAAG
TCAGTTAGTGAAATTAATCCAACCACACAAATGAAAGAATCTTATTATTTCGATCTCACT
GATGGCCTTTCTTAA
Protein Properties
Number of Residues 644
Molecular Weight 71957.0
Theoretical pI 6.8
Pfam Domain Function
Signals
  • 1-18
Transmembrane Regions
  • None
Protein Sequence
>Kininogen-1
MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYRIT
EATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSSTKFS
VATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPDLEPILRHGIQYFNNNTQHSSLFMLN
EVKRAQRQVVAGLNFRITYSIVQTNCSKENFLFLTPDCKSLWNGDTGECTDNAYIDIQLR
IASFSQNCDIYPGKDFVQPPTKICVGCPRDIPTNSPELEETLTHTITKLNAENNATFYFK
IDNVKKARVQVVAGKKYFIDFVARETTCSKESNEELTESCETKKLGQSLDCNAEVYVVPW
EKKIYPTVNCQPLGMISLMKRPPGFSPFRSSRIGEIKEETTVSPPHTSMAPAQDEERDSG
KEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGLGHGHEQQHGLGHGHKFKLD
DDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGWKTEHLASSSEDSTTPSAQTQE
KTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPPISPAPIQSDDDWIPDIQIDPNGLSF
NPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESYYFDLTDGLS
GenBank ID Protein 156231037
UniProtKB/Swiss-Prot ID P01042
UniProtKB/Swiss-Prot Entry Name KNG1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001102416.2
GeneCard ID KNG1
GenAtlas ID KNG1
HGNC ID HGNC:6383
References
General References
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  4. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [PubMed:16335952 ]
  5. Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics. 2004 Feb;4(2):454-65. [PubMed:14760718 ]
  6. Nilsson J, Ruetschi U, Halim A, Hesse C, Carlsohn E, Brinkmalm G, Larson G: Enrichment of glycopeptides for glycan structure and attachment site identification. Nat Methods. 2009 Nov;6(11):809-11. doi: 10.1038/nmeth.1392. Epub 2009 Oct 18. [PubMed:19838169 ]
  7. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed:12754519 ]
  8. Zhou W, Ross MM, Tessitore A, Ornstein D, Vanmeter A, Liotta LA, Petricoin EF 3rd: An initial characterization of the serum phosphoproteome. J Proteome Res. 2009 Dec;8(12):5523-31. doi: 10.1021/pr900603n. [PubMed:19824718 ]
  9. Ohkubo I, Kurachi K, Takasawa T, Shiokawa H, Sasaki M: Isolation of a human cDNA for alpha 2-thiol proteinase inhibitor and its identity with low molecular weight kininogen. Biochemistry. 1984 Nov 20;23(24):5691-7. [PubMed:6441591 ]
  10. Takagaki Y, Kitamura N, Nakanishi S: Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens. Primary structures of two human prekininogens. J Biol Chem. 1985 Jul 15;260(14):8601-9. [PubMed:2989293 ]
  11. Kellermann J, Lottspeich F, Henschen A, Muller-Esterl W: Completion of the primary structure of human high-molecular-mass kininogen. The amino acid sequence of the entire heavy chain and evidence for its evolution by gene triplication. Eur J Biochem. 1986 Jan 15;154(2):471-8. [PubMed:3484703 ]
  12. Wunderer G, Walter I, Muller E, Henschen A: Human Ile-Ser-bradykinin, identical with rat T-kinin, is a major permeability factor in ovarian carcinoma ascites. Biol Chem Hoppe Seyler. 1986 Dec;367(12):1231-4. [PubMed:3828072 ]
  13. Wunderer G, Walter I, Eschenbacher B, Lang M, Kellermann J, Kindermann G: Ile-Ser-bradykinin is an aberrant permeability factor in various human malignant effusions. Biol Chem Hoppe Seyler. 1990 Oct;371(10):977-81. [PubMed:2076202 ]
  14. Lottspeich F, Kellermann J, Henschen A, Foertsch B, Muller-Esterl W: The amino acid sequence of the light chain of human high-molecular-mass kininogen. Eur J Biochem. 1985 Oct 15;152(2):307-14. [PubMed:4054110 ]
  15. Kato H, Matsumura Y, Maeda H: Isolation and identification of hydroxyproline analogues of bradykinin in human urine. FEBS Lett. 1988 May 9;232(1):252-4. [PubMed:3366244 ]
  16. Pierce JV: Structural features of plasma kinins and kininogens. Fed Proc. 1968 Jan-Feb;27(1):52-7. [PubMed:4952632 ]
  17. Straczek J, Maachi F, Le Nguyen D, Becchi M, Heulin MH, Nabet P, Belleville F: Purification from human plasma of a tetrapeptide that potentiates insulin-like growth factor-I activity in chick embryo cartilage. FEBS Lett. 1995 Oct 16;373(3):207-11. [PubMed:7589467 ]
  18. Kitamura N, Kitagawa H, Fukushima D, Takagaki Y, Miyata T, Nakanishi S: Structural organization of the human kininogen gene and a model for its evolution. J Biol Chem. 1985 Jul 15;260(14):8610-7. [PubMed:2989294 ]
  19. Maeda H, Matsumura Y, Kato H: Purification and identification of [hydroxyprolyl3]bradykinin in ascitic fluid from a patient with gastric cancer. J Biol Chem. 1988 Nov 5;263(31):16051-4. [PubMed:3182782 ]