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Protein

Plasma kallikrein

Gene

KLKB1

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

Functioni

The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin.

Catalytic activityi

Cleaves selectively Arg-|-Xaa and Lys-|-Xaa bonds, including Lys-|-Arg and Arg-|-Ser bonds in (human) kininogen to release bradykinin.

Activity regulationi

Inhibited by SERPINA5.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei434Charge relay system1
Active sitei483Charge relay system1
Active sitei578Charge relay system1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processBlood coagulation, Fibrinolysis, Hemostasis, Inflammatory response

Enzyme and pathway databases

BRENDAi3.4.21.34 2681
ReactomeiR-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-1592389 Activation of Matrix Metalloproteinases
SABIO-RKiP03952

Protein family/group databases

MEROPSiS01.212

Names & Taxonomyi

Protein namesi
Recommended name:
Plasma kallikrein (EC:3.4.21.34)
Alternative name(s):
Fletcher factor
Kininogenin
Plasma prekallikrein
Short name:
PKK
Cleaved into the following 2 chains:
Gene namesi
Name:KLKB1
Synonyms:KLK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000164344.15
HGNCiHGNC:6371 KLKB1
MIMi229000 gene
neXtProtiNX_P03952

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

Prekallikrein deficiency (PKK deficiency)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThis disorder is a blood coagulation defect.
See also OMIM:612423
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054907123G → R in PKK deficiency; reduces the binding activity of Apple domain 2 to HMW kininogen. 1 Publication1
Natural variantiVAR_013598143N → S in PKK deficiency; reduces the binding activity of Apple domain 2 to HMW kininogen. 3 PublicationsCorresponds to variant dbSNP:rs3733402Ensembl.1
Natural variantiVAR_054908548C → Y in PKK deficiency. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3818
MalaCardsiKLKB1
MIMi612423 phenotype
Orphaneti749 Congenital prekallikrein deficiency
PharmGKBiPA30160

Chemistry databases

ChEMBLiCHEMBL2000
DrugBankiDB06404 C1 Esterase Inhibitor (Human)
DB09228 C1 Esterase Inhibitor (Recombinant)
DB05311 Ecallantide
GuidetoPHARMACOLOGYi2379

Polymorphism and mutation databases

BioMutaiKLKB1
DMDMi125184

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Add BLAST19
ChainiPRO_000002802120 – 390Plasma kallikrein heavy chainAdd BLAST371
ChainiPRO_0000028022391 – 638Plasma kallikrein light chainAdd BLAST248

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi21 ↔ 1041 Publication
Disulfide bondi47 ↔ 771 Publication
Disulfide bondi51 ↔ 571 Publication
Disulfide bondi111 ↔ 1941 Publication
Glycosylationi127N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi137 ↔ 1661 Publication
Disulfide bondi141 ↔ 1471 Publication
Disulfide bondi201 ↔ 2841 Publication
Disulfide bondi227 ↔ 2561 Publication
Disulfide bondi231 ↔ 2371 Publication
Disulfide bondi292 ↔ 3751 Publication
Glycosylationi308N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi318 ↔ 3471 Publication
Disulfide bondi322 ↔ 3281 Publication
Disulfide bondi340 ↔ 3451 Publication
Disulfide bondi383 ↔ 5031 Publication
Glycosylationi396N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi419 ↔ 4351 Publication
Glycosylationi453N-linked (GlcNAc...) asparagine4 Publications1
Glycosylationi494N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi517 ↔ 5841 Publication
Disulfide bondi548 ↔ 5631 Publication
Disulfide bondi574 ↔ 6021 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP03952
PeptideAtlasiP03952
PRIDEiP03952
ProteomicsDBi51622

PTM databases

GlyConnecti714
iPTMnetiP03952
PhosphoSitePlusiP03952

Expressioni

Gene expression databases

BgeeiENSG00000164344 Expressed in 150 organ(s), highest expression level in liver
CleanExiHS_KLK3
HS_KLKB1
ExpressionAtlasiP03952 baseline and differential
GenevisibleiP03952 HS

Interactioni

Subunit structurei

Forms a heterodimer with SERPINA5. The zymogen is activated by factor XIIa, which cleaves the molecule into a light chain, which contains the active site, and a heavy chain, which associates with HMW kininogen. These chains are linked by one or more disulfide bonds.

Protein-protein interaction databases

BioGridi110018, 6 interactors
IntActiP03952, 1 interactor
STRINGi9606.ENSP00000264690

Chemistry databases

BindingDBiP03952

Structurei

Secondary structure

1638
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP03952
SMRiP03952
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03952

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 104Apple 1PROSITE-ProRule annotationAdd BLAST84
Domaini111 – 194Apple 2PROSITE-ProRule annotationAdd BLAST84
Domaini201 – 284Apple 3PROSITE-ProRule annotationAdd BLAST84
Domaini292 – 375Apple 4PROSITE-ProRule annotationAdd BLAST84
Domaini391 – 626Peptidase S1PROSITE-ProRule annotationAdd BLAST236

Sequence similaritiesi

Belongs to the peptidase S1 family. Plasma kallikrein subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
HOGENOMiHOG000112467
HOVERGENiHBG000399
InParanoidiP03952
KOiK01324
PhylomeDBiP03952
TreeFamiTF343687

Family and domain databases

CDDicd01100 APPLE_Factor_XI_like, 4 hits
cd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR000177 Apple
IPR003609 Pan_app
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR034813 Plasma_kallikrein
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR44459:SF2 PTHR44459:SF2, 1 hit
PfamiView protein in Pfam
PF00024 PAN_1, 4 hits
PF00089 Trypsin, 1 hit
PRINTSiPR00005 APPLEDOMAIN
PR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00223 APPLE, 4 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS00495 APPLE, 4 hits
PS50948 PAN, 4 hits
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

P03952-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MILFKQATYF ISLFATVSCG CLTQLYENAF FRGGDVASMY TPNAQYCQMR
60 70 80 90 100
CTFHPRCLLF SFLPASSIND MEKRFGCFLK DSVTGTLPKV HRTGAVSGHS
110 120 130 140 150
LKQCGHQISA CHRDIYKGVD MRGVNFNVSK VSSVEECQKR CTNNIRCQFF
160 170 180 190 200
SYATQTFHKA EYRNNCLLKY SPGGTPTAIK VLSNVESGFS LKPCALSEIG
210 220 230 240 250
CHMNIFQHLA FSDVDVARVL TPDAFVCRTI CTYHPNCLFF TFYTNVWKIE
260 270 280 290 300
SQRNVCLLKT SESGTPSSST PQENTISGYS LLTCKRTLPE PCHSKIYPGV
310 320 330 340 350
DFGGEELNVT FVKGVNVCQE TCTKMIRCQF FTYSLLPEDC KEEKCKCFLR
360 370 380 390 400
LSMDGSPTRI AYGTQGSSGY SLRLCNTGDN SVCTTKTSTR IVGGTNSSWG
410 420 430 440 450
EWPWQVSLQV KLTAQRHLCG GSLIGHQWVL TAAHCFDGLP LQDVWRIYSG
460 470 480 490 500
ILNLSDITKD TPFSQIKEII IHQNYKVSEG NHDIALIKLQ APLNYTEFQK
510 520 530 540 550
PICLPSKGDT STIYTNCWVT GWGFSKEKGE IQNILQKVNI PLVTNEECQK
560 570 580 590 600
RYQDYKITQR MVCAGYKEGG KDACKGDSGG PLVCKHNGMW RLVGITSWGE
610 620 630
GCARREQPGV YTKVAEYMDW ILEKTQSSDG KAQMQSPA
Length:638
Mass (Da):71,370
Last modified:October 23, 1986 - v1
Checksum:iE62F9C1053838FB4
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YAC1H0YAC1_HUMAN
Plasma kallikrein
KLKB1
686Annotation score:
C9J075C9J075_HUMAN
Plasma kallikrein
KLKB1
148Annotation score:
E9PBC5E9PBC5_HUMAN
Plasma kallikrein
KLKB1
514Annotation score:
C9JCT1C9JCT1_HUMAN
Plasma kallikrein
KLKB1
141Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054907123G → R in PKK deficiency; reduces the binding activity of Apple domain 2 to HMW kininogen. 1 Publication1
Natural variantiVAR_013598143N → S in PKK deficiency; reduces the binding activity of Apple domain 2 to HMW kininogen. 3 PublicationsCorresponds to variant dbSNP:rs3733402Ensembl.1
Natural variantiVAR_016280178A → T1 PublicationCorresponds to variant dbSNP:rs4253257Ensembl.1
Natural variantiVAR_013599202H → Q2 PublicationsCorresponds to variant dbSNP:rs4253373EnsemblClinVar.1
Natural variantiVAR_013600208H → P1 Publication1
Natural variantiVAR_020180210A → E. Corresponds to variant dbSNP:rs2278542Ensembl.1
Natural variantiVAR_016281269S → C1 PublicationCorresponds to variant dbSNP:rs4253376EnsemblClinVar.1
Natural variantiVAR_016282311F → V1 PublicationCorresponds to variant dbSNP:rs4253377Ensembl.1
Natural variantiVAR_016283358T → A1 PublicationCorresponds to variant dbSNP:rs4253379Ensembl.1
Natural variantiVAR_016284381S → A1 PublicationCorresponds to variant dbSNP:rs4253301Ensembl.1
Natural variantiVAR_016285442Q → P1 PublicationCorresponds to variant dbSNP:rs4253316Ensembl.1
Natural variantiVAR_054908548C → Y in PKK deficiency. 1 Publication1
Natural variantiVAR_016286560R → Q2 PublicationsCorresponds to variant dbSNP:rs4253325Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13143 mRNA Translation: AAA60153.1
AF232742
, AF232734, AF232735, AF232736, AF232737, AF232738, AF232739, AF232740, AF232741 Genomic DNA Translation: AAF79940.1
AK313378 mRNA Translation: BAG36176.1
AY190920 Genomic DNA Translation: AAN84794.1
AC110771 Genomic DNA Translation: AAY40900.1
CH471056 Genomic DNA Translation: EAX04623.1
BC117349 mRNA Translation: AAI17350.1
BC117351 mRNA Translation: AAI17352.1
CCDSiCCDS34120.1
PIRiA00921 KQHUP
RefSeqiNP_000883.2, NM_000892.4
UniGeneiHs.237642

Genome annotation databases

EnsembliENST00000264690; ENSP00000264690; ENSG00000164344
GeneIDi3818
KEGGihsa:3818
UCSCiuc003iyy.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13143 mRNA Translation: AAA60153.1
AF232742
, AF232734, AF232735, AF232736, AF232737, AF232738, AF232739, AF232740, AF232741 Genomic DNA Translation: AAF79940.1
AK313378 mRNA Translation: BAG36176.1
AY190920 Genomic DNA Translation: AAN84794.1
AC110771 Genomic DNA Translation: AAY40900.1
CH471056 Genomic DNA Translation: EAX04623.1
BC117349 mRNA Translation: AAI17350.1
BC117351 mRNA Translation: AAI17352.1
CCDSiCCDS34120.1
PIRiA00921 KQHUP
RefSeqiNP_000883.2, NM_000892.4
UniGeneiHs.237642

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ANWX-ray1.85A391-631[»]
2ANYX-ray1.40A391-631[»]
4OGXX-ray2.40A391-631[»]
4OGYX-ray2.10A/B391-631[»]
5F8TX-ray1.75A391-629[»]
5F8XX-ray1.55A391-629[»]
5F8ZX-ray1.50A391-629[»]
5TJXX-ray1.41A376-638[»]
5TZ9X-ray1.70E376-638[»]
ProteinModelPortaliP03952
SMRiP03952
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110018, 6 interactors
IntActiP03952, 1 interactor
STRINGi9606.ENSP00000264690

Chemistry databases

BindingDBiP03952
ChEMBLiCHEMBL2000
DrugBankiDB06404 C1 Esterase Inhibitor (Human)
DB09228 C1 Esterase Inhibitor (Recombinant)
DB05311 Ecallantide
GuidetoPHARMACOLOGYi2379

Protein family/group databases

MEROPSiS01.212

PTM databases

GlyConnecti714
iPTMnetiP03952
PhosphoSitePlusiP03952

Polymorphism and mutation databases

BioMutaiKLKB1
DMDMi125184

Proteomic databases

PaxDbiP03952
PeptideAtlasiP03952
PRIDEiP03952
ProteomicsDBi51622

Protocols and materials databases

DNASUi3818
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264690; ENSP00000264690; ENSG00000164344
GeneIDi3818
KEGGihsa:3818
UCSCiuc003iyy.4 human

Organism-specific databases

CTDi3818
DisGeNETi3818
EuPathDBiHostDB:ENSG00000164344.15
GeneCardsiKLKB1
HGNCiHGNC:6371 KLKB1
MalaCardsiKLKB1
MIMi229000 gene
612423 phenotype
neXtProtiNX_P03952
Orphaneti749 Congenital prekallikrein deficiency
PharmGKBiPA30160
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627 Eukaryota
COG5640 LUCA
HOGENOMiHOG000112467
HOVERGENiHBG000399
InParanoidiP03952
KOiK01324
PhylomeDBiP03952
TreeFamiTF343687

Enzyme and pathway databases

BRENDAi3.4.21.34 2681
ReactomeiR-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation
R-HSA-1592389 Activation of Matrix Metalloproteinases
SABIO-RKiP03952

Miscellaneous databases

ChiTaRSiKLKB1 human
EvolutionaryTraceiP03952
GeneWikiiKLKB1
GenomeRNAii3818
PROiPR:P03952
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164344 Expressed in 150 organ(s), highest expression level in liver
CleanExiHS_KLK3
HS_KLKB1
ExpressionAtlasiP03952 baseline and differential
GenevisibleiP03952 HS

Family and domain databases

CDDicd01100 APPLE_Factor_XI_like, 4 hits
cd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR000177 Apple
IPR003609 Pan_app
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR034813 Plasma_kallikrein
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PANTHERiPTHR44459:SF2 PTHR44459:SF2, 1 hit
PfamiView protein in Pfam
PF00024 PAN_1, 4 hits
PF00089 Trypsin, 1 hit
PRINTSiPR00005 APPLEDOMAIN
PR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00223 APPLE, 4 hits
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS00495 APPLE, 4 hits
PS50948 PAN, 4 hits
PS50240 TRYPSIN_DOM, 1 hit
PS00134 TRYPSIN_HIS, 1 hit
PS00135 TRYPSIN_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKLKB1_HUMAN
AccessioniPrimary (citable) accession number: P03952
Secondary accession number(s): A6NH96
, B2R8H9, Q17RE8, Q17RE9, Q4W5C3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 1986
Last sequence update: October 23, 1986
Last modified: October 10, 2018
This is version 201 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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