| IED ID | IndEnz0002002992 |
| Enzyme Type ID | protease002992 |
| 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 |
| Gene Name | KNG1 BDK KNG |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYRITEATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSSTKFSVATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPDLEPILRHGIQYFNNNTQHSSLFMLNEVKRAQRQVVAGLNFRITYSIVQTNCSKENFLFLTPDCKSLWNGDTGECTDNAYIDIQLRIASFSQNCDIYPGKDFVQPPTKICVGCPRDIPTNSPELEETLTHTITKLNAENNATFYFKIDNVKKARVQVVAGKKYFIDFVARETTCSKESNEELTESCETKKLGQSLDCNAEVYVVPWEKKIYPTVNCQPLGMISLMKRPPGFSPFRSSRIGEIKEETTVSPPHTSMAPAQDEERDSGKEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGLGHGHEQQHGLGHGHKFKLDDDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGWKTEHLASSSEDSTTPSAQTQEKTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPPISPAPIQSDDDWIPDIQIDPNGLSFNPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESYYFDLTDGLS |
| Enzyme Length | 644 |
| Uniprot Accession Number | P01042 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | 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. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (4); Chain (3); Compositional bias (4); Disulfide bond (9); Domain (3); Glycosylation (12); Modified residue (3); Natural variant (8); Peptide (4); Region (2); Repeat (3); Sequence conflict (4); Signal peptide (1); Site (3); Turn (1) |
| Keywords | 3D-structure;Alternative splicing;Blood coagulation;Direct protein sequencing;Disulfide bond;Glycoprotein;Hemostasis;Hydroxylation;Inflammatory response;Phosphoprotein;Protease inhibitor;Pyrrolidone carboxylic acid;Reference proteome;Repeat;Secreted;Signal;Thiol protease inhibitor;Vasoactive;Vasodilator |
| Interact With | Q07021; Q10714; P46663; Q9BYF1; P30411 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space. |
| Modified Residue | MOD_RES 19; /note="Pyrrolidone carboxylic acid; in mature form"; /evidence="ECO:0000250|UniProtKB:P01045"; MOD_RES 332; /note="Phosphoserine; by FAM20C"; /evidence="ECO:0000269|PubMed:26091039, ECO:0007744|PubMed:19824718, ECO:0007744|PubMed:24275569"; MOD_RES 383; /note="4-hydroxyproline; partial"; /evidence="ECO:0000269|PubMed:3182782, ECO:0000269|PubMed:3366244" |
| Post Translational Modification | PTM: Bradykinin is released from kininogen by plasma kallikrein.; PTM: Hydroxylation of Pro-383 occurs prior to the release of bradykinin. {ECO:0000269|PubMed:3182782, ECO:0000269|PubMed:3366244}.; PTM: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269|PubMed:26091039}.; PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:3484703}. |
| Signal Peptide | SIGNAL 1..18; /evidence="ECO:0000269|PubMed:2989293, ECO:0000269|PubMed:3484703" |
| Structure 3D | NMR spectroscopy (5); X-ray crystallography (7) |
| Cross Reference PDB | 1NY2; 2WOK; 4ASQ; 4ASR; 4ECB; 4ECC; 5I25; 6F27; 6F3V; 6F3W; 6F3X; 6F3Y; |
| Mapped Pubmed ID | 10191087; 1066663; 11204562; 11689005; 11792853; 11830581; 11920276; 11970955; 11986212; 12071855; 12082110; 12123826; 12594059; 12598231; 12663668; 12748173; 12761213; 12851878; 12911595; 12944405; 12952972; 1314587; 14506238; 14517215; 14597972; 14629481; 14691562; 14996700; 15044324; 15086463; 16091369; 16140359; 16598774; 16754659; 17065357; 17585065; 17598838; 17635790; 18083112; 18127230; 18156442; 18236494; 18330734; 18455532; 18577758; 18783336; 18810490; 1905813; 19082699; 19086053; 19126685; 19213944; 19330902; 19584173; 19592120; 19691495; 19716087; 19885862; 19913121; 19923143; 19941870; 19966052; 20050188; 20303064; 20628086; 20876611; 21054968; 21270443; 21451024; 21496200; 21527472; 21586566; 21911577; 21982724; 22577144; 22701019; 23000411; 23082758; 23300094; 23505046; 23640497; 23672780; 23808406; 23874198; 24552232; 24688027; 24984152; 2534964; 25477429; 25766502; 26159646; 26420021; 26792617; 26884824; 27006387; 2748346; 28053049; 28321; 2834384; 28651026; 29034546; 29334381; 30068373; 30478260; 3086311; 31059006; 31338581; 31412146; 31473403; 31625351; 31933486; 32114020; 32359101; 32707450; 33129885; 33179332; 33827130; 3521732; 3886654; 500690; 6457647; 6604055; 7391081; 8015379; 8063797; 8195709; 8344943; 8467233; 8664309; 8710908; 874082; 9226169; 9427705; |
| Motif | |
| Gene Encoded By | |
| Mass | 71,957 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |