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Protein

Kininogen-1

Gene

KNG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • cysteine-type endopeptidase inhibitor activity Source: UniProtKB
  • heparin binding Source: UniProtKB
  • signaling receptor binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
  • blood coagulation, intrinsic pathway Source: Reactome
  • cellular protein metabolic process Source: Reactome
  • G-protein coupled receptor signaling pathway Source: Reactome
  • inflammatory response Source: UniProtKB-KW
  • killing of cells of other organism Source: UniProtKB
  • negative regulation of blood coagulation Source: UniProtKB
  • negative regulation of cell adhesion Source: UniProtKB
  • negative regulation of proteolysis Source: UniProtKB
  • platelet degranulation Source: Reactome
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of cytosolic calcium ion concentration Source: UniProtKB
  • post-translational protein modification Source: Reactome
  • vasodilation Source: UniProtKB-KW

Keywordsi

Molecular functionProtease inhibitor, Thiol protease inhibitor, Vasoactive, Vasodilator
Biological processBlood coagulation, Hemostasis, Inflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-416476 G alpha (q) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-8957275 Post-translational protein phosphorylation

Protein family/group databases

MEROPSiI25.016

Names & Taxonomyi

Protein namesi
Recommended name:
Kininogen-1
Alternative name(s):
Alpha-2-thiol proteinase inhibitor
Fitzgerald factor
High molecular weight kininogen
Short name:
HMWK
Williams-Fitzgerald-Flaujeac factor
Cleaved into the following 6 chains:
Alternative name(s):
Ile-Ser-Bradykinin
Alternative name(s):
Kallidin I
Alternative name(s):
Kallidin II
Gene namesi
Name:KNG1
Synonyms:BDK, KNG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000113889.11
HGNCiHGNC:6383 KNG1
MIMi612358 gene
neXtProtiNX_P01042

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

High molecular weight kininogen deficiency (HMWK deficiency)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis.
See also OMIM:228960

Organism-specific databases

DisGeNETi3827
MalaCardsiKNG1
MIMi228960 phenotype
OpenTargetsiENSG00000113889
Orphaneti483 Congenital high-molecular-weight kininogen deficiency
PharmGKBiPA225

Chemistry databases

ChEMBLiCHEMBL3638337

Polymorphism and mutation databases

BioMutaiKNG1
DMDMi124056474

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 182 PublicationsAdd BLAST18
ChainiPRO_000000668519 – 644Kininogen-1Add BLAST626
ChainiPRO_000000668619 – 380Kininogen-1 heavy chainAdd BLAST362
PeptideiPRO_0000372485376 – 389T-kininAdd BLAST14
PeptideiPRO_0000006687380 – 389Lysyl-bradykinin10
PeptideiPRO_0000006688381 – 389Bradykinin9
ChainiPRO_0000006689390 – 644Kininogen-1 light chainAdd BLAST255
PeptideiPRO_0000006690431 – 434Low molecular weight growth-promoting factor4

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Pyrrolidone carboxylic acid; in mature formBy similarity1
Disulfide bondi28 ↔ 614Interchain (between heavy and light chains)PROSITE-ProRule annotation1 Publication
Glycosylationi48N-linked (GlcNAc...) (complex) asparagine2 Publications1
Disulfide bondi83 ↔ 94PROSITE-ProRule annotation1 Publication
Disulfide bondi107 ↔ 126PROSITE-ProRule annotation1 Publication
Disulfide bondi142 ↔ 145PROSITE-ProRule annotation1 Publication
Glycosylationi169N-linked (GlcNAc...) asparagine4 Publications1
Glycosylationi205N-linked (GlcNAc...) (complex) asparagine4 Publications1
Disulfide bondi206 ↔ 218PROSITE-ProRule annotation1 Publication
Disulfide bondi229 ↔ 248PROSITE-ProRule annotation1 Publication
Disulfide bondi264 ↔ 267PROSITE-ProRule annotation1 Publication
Glycosylationi294N-linked (GlcNAc...) (complex) asparagine6 Publications1
Disulfide bondi328 ↔ 340PROSITE-ProRule annotation1 Publication
Modified residuei332Phosphoserine; by FAM20CCombined sources1 Publication1
Disulfide bondi351 ↔ 370PROSITE-ProRule annotation1 Publication
Modified residuei3834-hydroxyproline; partial2 Publications1
Glycosylationi401O-linked (GalNAc...) threonine1
Glycosylationi533O-linked (GalNAc...) threonine1 Publication1
Glycosylationi542O-linked (GalNAc...) threonine1
Glycosylationi546O-linked (GalNAc...) threonine1 Publication1
Glycosylationi557O-linked (GalNAc...) threonine1
Glycosylationi571O-linked (GalNAc...) threonine1
Glycosylationi577O-linked (GalNAc...) serine1
Glycosylationi628O-linked (GalNAc...) threonine1

Post-translational modificationi

Bradykinin is released from kininogen by plasma kallikrein.
Hydroxylation of Pro-383 occurs prior to the release of bradykinin.2 Publications
Phosphorylated by FAM20C in the extracellular medium.1 Publication
N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei48Not glycosylated1 Publication1
Sitei379 – 380Cleavage; by kallikrein2
Sitei389 – 390Cleavage; by kallikrein2

Keywords - PTMi

Disulfide bond, Glycoprotein, Hydroxylation, Phosphoprotein, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiP01042
PeptideAtlasiP01042
PRIDEiP01042

2D gel databases

SWISS-2DPAGEiP01042

PTM databases

CarbonylDBiP01042
GlyConnecti741 [P01042-2]
810
iPTMnetiP01042
PhosphoSitePlusiP01042

Miscellaneous databases

PMAP-CutDBiB2RCR2

Expressioni

Tissue specificityi

Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors.1 Publication

Gene expression databases

BgeeiENSG00000113889
CleanExiHS_KNG1
GenevisibleiP01042 HS

Organism-specific databases

HPAiCAB009809
HPA001616
HPA001645

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • signaling receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110026, 33 interactors
IntActiP01042, 13 interactors
MINTiP01042
STRINGi9606.ENSP00000265023

Chemistry databases

BindingDBiP01042

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NY2X-ray2.304381-385[»]
2WOKX-ray1.70B381-389[»]
4ASQX-ray1.99P381-389[»]
4ASRX-ray1.90P381-389[»]
4ECBX-ray2.20A/B498-507[»]
4ECCX-ray2.20A498-510[»]
5I25X-ray2.85B601-608[»]
6F27NMR-A380-388[»]
6F3VNMR-A381-389[»]
6F3WNMR-A381-389[»]
6F3XNMR-A380-388[»]
6F3YNMR-A380-388[»]
ProteinModelPortaliP01042
SMRiP01042
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01042

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 132Cystatin kininogen-type 1PROSITE-ProRule annotationAdd BLAST105
Domaini151 – 254Cystatin kininogen-type 2PROSITE-ProRule annotationAdd BLAST104
Domaini273 – 376Cystatin kininogen-type 3PROSITE-ProRule annotationAdd BLAST104
Repeati420 – 449Add BLAST30
Repeati450 – 479Add BLAST30
Repeati480 – 510Add BLAST31

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni120 – 153O-glycosylated at one site onlyAdd BLAST34

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi420 – 510His-richAdd BLAST91

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKIQ Eukaryota
ENOG4111ZQ8 LUCA
GeneTreeiENSGT00440000039713
HOGENOMiHOG000113239
HOVERGENiHBG006224
InParanoidiP01042
KOiK03898
OMAiGECTATV
OrthoDBiEOG091G0SH2
PhylomeDBiP01042
TreeFamiTF351852

Family and domain databases

CDDicd00042 CY, 3 hits
InterProiView protein in InterPro
IPR000010 Cystatin_dom
IPR002395 Kininogen
IPR027358 Kininogen-type_cystatin_dom
IPR018073 Prot_inh_cystat_CS
PfamiView protein in Pfam
PF00031 Cystatin, 3 hits
PRINTSiPR00334 KININOGEN
SMARTiView protein in SMART
SM00043 CY, 3 hits
PROSITEiView protein in PROSITE
PS00287 CYSTATIN, 2 hits
PS51647 CYSTATIN_KININOGEN, 3 hits

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform HMW (identifier: P01042-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKLITILFLC SRLLLSLTQE SQSEEIDCND KDLFKAVDAA LKKYNSQNQS
60 70 80 90 100
NNQFVLYRIT EATKTVGSDT FYSFKYEIKE GDCPVQSGKT WQDCEYKDAA
110 120 130 140 150
KAATGECTAT VGKRSSTKFS VATQTCQITP AEGPVVTAQY DCLGCVHPIS
160 170 180 190 200
TQSPDLEPIL RHGIQYFNNN TQHSSLFMLN EVKRAQRQVV AGLNFRITYS
210 220 230 240 250
IVQTNCSKEN FLFLTPDCKS LWNGDTGECT DNAYIDIQLR IASFSQNCDI
260 270 280 290 300
YPGKDFVQPP TKICVGCPRD IPTNSPELEE TLTHTITKLN AENNATFYFK
310 320 330 340 350
IDNVKKARVQ VVAGKKYFID FVARETTCSK ESNEELTESC ETKKLGQSLD
360 370 380 390 400
CNAEVYVVPW EKKIYPTVNC QPLGMISLMK RPPGFSPFRS SRIGEIKEET
410 420 430 440 450
TVSPPHTSMA PAQDEERDSG KEQGHTRRHD WGHEKQRKHN LGHGHKHERD
460 470 480 490 500
QGHGHQRGHG LGHGHEQQHG LGHGHKFKLD DDLEHQGGHV LDHGHKHKHG
510 520 530 540 550
HGHGKHKNKG KKNGKHNGWK TEHLASSSED STTPSAQTQE KTEGPTPIPS
560 570 580 590 600
LAKPGVTVTF SDFQDSDLIA TMMPPISPAP IQSDDDWIPD IQIDPNGLSF
610 620 630 640
NPISDFPDTT SPKCPGRPWK SVSEINPTTQ MKESYYFDLT DGLS
Length:644
Mass (Da):71,957
Last modified:January 23, 2007 - v2
Checksum:i3132B4DF2954C24E
GO
Isoform LMW (identifier: P01042-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     402-427: VSPPHTSMAPAQDEERDSGKEQGHTR → SHLRSCEYKGRPPKAGAEPASEREVS
     428-644: Missing.

Show »
Length:427
Mass (Da):47,883
Checksum:iC8B398F00BE38BE9
GO
Isoform 3 (identifier: P01042-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     189-224: Missing.
     402-643: VSPPHTSMAP...SYYFDLTDGL → SHLRSCEYKGRPPKAGAEPASEREV

Note: Gene prediction based on EST data.
Show »
Length:391
Mass (Da):43,822
Checksum:iE2126218B3462290
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33L → F in BAF83528 (PubMed:14702039).Curated1
Sequence conflicti311V → A in BAF83528 (PubMed:14702039).Curated1
Sequence conflicti593I → T in AAO61092 (Ref. 5) Curated1
Sequence conflicti593I → T AA sequence (PubMed:4054110).Curated1

Polymorphismi

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.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019277163G → S1 PublicationCorresponds to variant dbSNP:rs5030015Ensembl.1
Natural variantiVAR_019278178M → T3 PublicationsCorresponds to variant dbSNP:rs1656922Ensembl.1
Natural variantiVAR_028937197I → M1 PublicationCorresponds to variant dbSNP:rs2304456Ensembl.1
Natural variantiVAR_019279212L → P1 PublicationCorresponds to variant dbSNP:rs5030024Ensembl.1
Natural variantiVAR_055233378 – 380Missing in T-kinin peptide. 2 Publications3
Natural variantiVAR_048853430D → E. Corresponds to variant dbSNP:rs5030084Ensembl.1
Natural variantiVAR_048854581I → T. Corresponds to variant dbSNP:rs710446Ensembl.1
Natural variantiVAR_048855642G → A. Corresponds to variant dbSNP:rs5030087Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047307189 – 224Missing in isoform 3. CuratedAdd BLAST36
Alternative sequenceiVSP_047308402 – 643VSPPH…LTDGL → SHLRSCEYKGRPPKAGAEPA SEREV in isoform 3. CuratedAdd BLAST242
Alternative sequenceiVSP_001261402 – 427VSPPH…QGHTR → SHLRSCEYKGRPPKAGAEPA SEREVS in isoform LMW. 4 PublicationsAdd BLAST26
Alternative sequenceiVSP_001262428 – 644Missing in isoform LMW. 4 PublicationsAdd BLAST217

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02566 mRNA Translation: AAA35497.1
M11437
, M11438, M11521, M11522, M11523, M11524, M11525, M11526, M11527, M11528 Genomic DNA Translation: AAB59550.1
M11437
, M11438, M11521, M11522, M11523, M11524, M11525, M11526, M11527, M11528 Genomic DNA Translation: AAB59551.1
AK315230 mRNA Translation: BAG37659.1
AK290839 mRNA Translation: BAF83528.1
AK223589 mRNA Translation: BAD97309.1
AY248697 Genomic DNA Translation: AAO61092.1
AC109780 Genomic DNA No translation available.
AC112907 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW78179.1
BC060039 mRNA Translation: AAH60039.1
CCDSiCCDS3281.1 [P01042-2]
CCDS43183.1 [P01042-1]
CCDS54695.1 [P01042-3]
PIRiA01279 KGHUH1
A01280 KGHUL1
S13279
RefSeqiNP_000884.1, NM_000893.3 [P01042-2]
NP_001095886.1, NM_001102416.2 [P01042-1]
NP_001159923.1, NM_001166451.1 [P01042-3]
UniGeneiHs.77741

Genome annotation databases

EnsembliENST00000265023; ENSP00000265023; ENSG00000113889 [P01042-1]
ENST00000287611; ENSP00000287611; ENSG00000113889 [P01042-2]
ENST00000447445; ENSP00000396025; ENSG00000113889 [P01042-3]
GeneIDi3827
KEGGihsa:3827
UCSCiuc003fqr.4 human [P01042-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKNG1_HUMAN
AccessioniPrimary (citable) accession number: P01042
Secondary accession number(s): A8K474
, B2RCR2, C9JEX1, P01043, Q53EQ0, Q6PAU9, Q7M4P1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 208 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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