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Protein

Kininogen-1

Gene

Kng1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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: RGD
  • protease binding Source: RGD

GO - Biological processi

  • blood coagulation Source: UniProtKB-KW
  • inflammatory response Source: UniProtKB-KW
  • negative regulation of endopeptidase activity Source: GOC
  • negative regulation of lymphocyte proliferation Source: RGD
  • negative regulation of MAP kinase activity Source: RGD
  • negative regulation of proteolysis Source: RGD
  • negative regulation of T cell proliferation Source: RGD
  • positive regulation of endothelial cell proliferation Source: RGD
  • positive regulation of fibroblast proliferation Source: RGD
  • positive regulation of MAPK cascade Source: RGD
  • regulation of endopeptidase activity Source: RGD
  • vasodilation Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Thiol protease inhibitor, Vasoactive, Vasodilator

Keywords - Biological processi

Blood coagulation, Hemostasis, Inflammatory response

Protein family/group databases

MEROPSiI25.018.

Names & Taxonomyi

Protein namesi
Recommended name:
Kininogen-1
Cleaved into the following 3 chains:
Gene namesi
Name:Kng1
Synonyms:Kng
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2980. Kng1.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: RGD
  • intracellular membrane-bounded organelle Source: RGD
  • perikaryon Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Add
BLAST
Chaini19 – 639621Kininogen-1PRO_0000006695Add
BLAST
Chaini19 – 380362Kininogen-1 heavy chainPRO_0000006696Add
BLAST
Peptidei381 – 3899BradykininPRO_0000006697
Chaini390 – 639250Kininogen-1 light chainPRO_0000006698Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Pyrrolidone carboxylic acidBy similarity
Disulfide bondi28 ↔ 609Interchain (between heavy and light chains)PROSITE-ProRule annotation
Glycosylationi82 – 821N-linked (GlcNAc...)Sequence analysis
Disulfide bondi83 ↔ 94PROSITE-ProRule annotation
Disulfide bondi107 ↔ 126PROSITE-ProRule annotation
Glycosylationi127 – 1271N-linked (GlcNAc...)Sequence analysis
Disulfide bondi142 ↔ 145PROSITE-ProRule annotation
Glycosylationi169 – 1691N-linked (GlcNAc...)Sequence analysis
Glycosylationi205 – 2051N-linked (GlcNAc...)Sequence analysis
Disulfide bondi206 ↔ 218PROSITE-ProRule annotation
Disulfide bondi229 ↔ 248PROSITE-ProRule annotation
Disulfide bondi264 ↔ 267PROSITE-ProRule annotation
Glycosylationi294 – 2941N-linked (GlcNAc...)Sequence analysis
Disulfide bondi328 ↔ 340PROSITE-ProRule annotation
Modified residuei332 – 3321PhosphoserineBy similarity
Disulfide bondi351 ↔ 370PROSITE-ProRule annotation
Glycosylationi529 – 5291N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Bradykinin is released from kininogen by plasma kallikrein.
Phosphorylated by FAM20C in the extracellular medium.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiP08934.
PRIDEiP08934.

Miscellaneous databases

PMAP-CutDBP08934.

Expressioni

Tissue specificityi

Plasma.

Interactioni

GO - Molecular functioni

  • protease binding Source: RGD

Protein-protein interaction databases

IntActiP08934. 1 interaction.
STRINGi10116.ENSRNOP00000065146.

Structurei

3D structure databases

ProteinModelPortaliP08934.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 132105Cystatin kininogen-type 1PROSITE-ProRule annotationAdd
BLAST
Domaini151 – 254104Cystatin kininogen-type 2PROSITE-ProRule annotationAdd
BLAST
Domaini273 – 376104Cystatin kininogen-type 3PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi439 – 51476His-richAdd
BLAST

Sequence similaritiesi

Contains 3 cystatin kininogen-type domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IKIQ. Eukaryota.
ENOG4111ZQ8. LUCA.
HOVERGENiHBG006224.
InParanoidiP08934.
KOiK03898.

Family and domain databases

InterProiIPR000010. Cystatin_dom.
IPR002395. Kininogen.
IPR027358. Kininogen-type_cystatin_dom.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PfamiPF00031. Cystatin. 3 hits.
[Graphical view]
PRINTSiPR00334. KININOGEN.
SMARTiSM00043. CY. 3 hits.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 2 hits.
PS51647. CYSTATIN_KININOGEN. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform HMW (identifier: P08934-1) [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
MKLITILLLC SRLLPSLAQE EDAQEMDCND ESLFQAVDTA LKKYNAGLKS
60 70 80 90 100
GNQFVLYQVT EGTKKDGSKT FYSFKYQIKE GNCSVQSGFA WQDCDFKDAE
110 120 130 140 150
EAATGECTAT LEKRRNNKFS IATQICNITP GKGPIVTNEY HCLGCMHPIS
160 170 180 190 200
VDSPELGPVL KHAVEHFNNN TKHTHLFALG EVKSADRQVV AGMNYQIIYS
210 220 230 240 250
IVQTNCSKED FPSLHEDCVP LPSGDDGECK GNAFVDIHKT IAGFSDSCEF
260 270 280 290 300
YPGDDLFELL PEDCPGCPRN IPVDSPELKE ALGHSIAQLN AENNHTFYFK
310 320 330 340 350
IDTVKKATSQ VVAGTKYVIE FIARETKCSK ESNAELTADC ETKRLGQSLN
360 370 380 390 400
CNANVYMRPW ENKVVPTVKC KVLDMTSVIR RPPGFSPFRA PRVKKPKEST
410 420 430 440 450
TVSPSYIARV QEERDPGNEQ GPIHGHGWLH AKQIKNKNHQ GHKHGHGIGH
460 470 480 490 500
GHQKPHGLGH GHQLKLDDLK QQREDGYDHR HPVGHGHGQR HGHGHGHGHG
510 520 530 540 550
RDKHTNKDKN NVKHTDQRRA PLTSSSEDNT TSTQIQGRTE GFTLNPPLAQ
560 570 580 590 600
PAVISRGFQD SGFTEGVIAT TSPYDTETHD DLIPDIHVQP DSLSFKLISD
610 620 630
FPEATSHKCP GRPWKPVSRK DPTIETTEFS DFDLLDALS
Length:639
Mass (Da):70,933
Last modified:November 1, 1988 - v1
Checksum:iD3172DF94FF56AF5
GO
Isoform LMW (identifier: P08934-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     402-433: VSPSYIARVQEERDPGNEQGPIHGHGWLHAKQ → RLLNSCEYKGRLLKAGAGPAPERQAEASTVTP
     434-639: Missing.

Show »
Length:433
Mass (Da):47,891
Checksum:i6D584348595166ED
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti61 – 611E → K (PubMed:2413018).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei402 – 43332VSPSY…LHAKQ → RLLNSCEYKGRLLKAGAGPA PERQAEASTVTP in isoform LMW. 2 PublicationsVSP_001265Add
BLAST
Alternative sequencei434 – 639206Missing in isoform LMW. 2 PublicationsVSP_001266Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29428 mRNA. Translation: AAA41486.1.
M11884 mRNA. Translation: AAA41487.1.
M14369 Genomic DNA. Translation: AAA41484.1.
M14369 Genomic DNA. Translation: AAA41485.1. Sequence problems.
M16455 Genomic DNA. Translation: AAA41482.1.
PIRiA25486.
A28055.
C25486.
RefSeqiNP_036873.1. NM_012741.1. [P08934-1]
UniGeneiRn.128333.
Rn.44576.

Genome annotation databases

GeneIDi25087.
KEGGirno:25087.
UCSCiRGD:2980. rat. [P08934-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29428 mRNA. Translation: AAA41486.1.
M11884 mRNA. Translation: AAA41487.1.
M14369 Genomic DNA. Translation: AAA41484.1.
M14369 Genomic DNA. Translation: AAA41485.1. Sequence problems.
M16455 Genomic DNA. Translation: AAA41482.1.
PIRiA25486.
A28055.
C25486.
RefSeqiNP_036873.1. NM_012741.1. [P08934-1]
UniGeneiRn.128333.
Rn.44576.

3D structure databases

ProteinModelPortaliP08934.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP08934. 1 interaction.
STRINGi10116.ENSRNOP00000065146.

Protein family/group databases

MEROPSiI25.018.

Proteomic databases

PaxDbiP08934.
PRIDEiP08934.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25087.
KEGGirno:25087.
UCSCiRGD:2980. rat. [P08934-1]

Organism-specific databases

CTDi385643.
RGDi2980. Kng1.

Phylogenomic databases

eggNOGiENOG410IKIQ. Eukaryota.
ENOG4111ZQ8. LUCA.
HOVERGENiHBG006224.
InParanoidiP08934.
KOiK03898.

Miscellaneous databases

NextBioi605354.
PMAP-CutDBP08934.
PROiP08934.

Family and domain databases

InterProiIPR000010. Cystatin_dom.
IPR002395. Kininogen.
IPR027358. Kininogen-type_cystatin_dom.
IPR018073. Prot_inh_cystat_CS.
[Graphical view]
PfamiPF00031. Cystatin. 3 hits.
[Graphical view]
PRINTSiPR00334. KININOGEN.
SMARTiSM00043. CY. 3 hits.
[Graphical view]
PROSITEiPS00287. CYSTATIN. 2 hits.
PS51647. CYSTATIN_KININOGEN. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Differing expression patterns and evolution of the rat kininogen gene family."
    Kitagawa H., Kitamura N., Hayashida H., Miyata T., Nakanishi S.
    J. Biol. Chem. 262:2190-2198(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HMW AND LMW).
  2. "Primary structures of the mRNAs encoding the rat precursors for bradykinin and T-kinin. Structural relationship of kininogens with major acute phase protein and alpha 1-cysteine proteinase inhibitor."
    Furuto-Kato S., Matsumoto A., Kitamura N., Nakanishi S.
    J. Biol. Chem. 260:12054-12059(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LMW).
  3. "Structure and expression of the genes for major acute phase alpha 1-protein (thiostatin) and kininogen in the rat."
    Fung W.-P., Schreiber G.
    J. Biol. Chem. 262:9298-9308(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65.
    Strain: Buffalo.
  4. "Differing utilization of homologous transcription initiation sites of rat K and T kininogen genes under inflammation condition."
    Kageyama R., Kitamura N., Ohkubo H., Nakanishi S.
    J. Biol. Chem. 262:2345-2351(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
    Strain: Wistar.
    Tissue: Liver.

Entry informationi

Entry nameiKNG1_RAT
AccessioniPrimary (citable) accession number: P08934
Secondary accession number(s): P08933
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: May 11, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Rats express four types of kininogens: the classical HMW/LMW kininogens and two additional LMW-like kininogens: T-I and T-II.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.