[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1021/bi00357a017; PubMed=3521732 [NCBI, ExPASy, EBI, Israel, Japan] Chung D.W., Fujikawa K., McMullen B.A., Davie E.W.; "Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats."; Biochemistry 25:2410-2417(1986).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-143; GLN-202 AND PRO-208. DOI=10.1006/geno.2000.6330; PubMed=11031105 [NCBI, ExPASy, EBI, Israel, Japan] Yu H., Anderson P.J., Freedman B.I., Rich S.S., Bowden D.W.; "Genomic structure of the human plasma prekallikrein gene, identification of allelic variants, and analysis in end-stage renal disease."; Genomics 69:225-234(2000).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-143; THR-178; GLN-202; CYS-269; VAL-311; ALA-358; ALA-381; PRO-442 AND GLN-560. SeattleSNPs program for genomic applications; Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Colon; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	PARTIAL PROTEIN SEQUENCE, AND DISULFIDE BONDS. DOI=10.1021/bi00222a007; PubMed=1998666 [NCBI, ExPASy, EBI, Israel, Japan] McMullen B.A., Fujikawa K., Davie E.W.; "Location of the disulfide bonds in human plasma prekallikrein: the presence of four novel apple domains in the amino-terminal portion of the molecule."; Biochemistry 30:2050-2056(1991).
[6]	GLYCOSYLATION AT ASN-453. DOI=10.1038/nbt827; PubMed=12754519 [NCBI, ExPASy, EBI, Israel, Japan] Zhang H., Li X.-J., Martin D.B., Aebersold R.; "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."; Nat. Biotechnol. 21:660-666(2003).
[7]	GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-127; ASN-308; ASN-396; ASN-453 AND ASN-494, AND MASS SPECTROMETRY. TISSUE=Plasma; DOI=10.1021/pr0502065; PubMed=16335952 [NCBI, ExPASy, EBI, Israel, Japan] Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.; "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."; J. Proteome Res. 4:2070-2080(2005).

Comments

FUNCTION: 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 ACTIVITY: Cleaves selectively Arg-|-Xaa and Lys-|-Xaa bonds, including Lys-|-Arg and Arg-|-Ser bonds in (human) kininogen to release bradykinin.
SUBUNIT: 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.
SUBCELLULAR LOCATION: Secreted.
DISEASE: Defects in KLKB1 are the cause of Fletcher factor deficiency [MIM:229000]; a blood coagulation defect.
SIMILARITY: Belongs to the peptidase S1 family. Plasma kallikrein subfamily [view classification].
SIMILARITY: Contains 4 apple domains.
SIMILARITY: Contains 1 peptidase S1 domain [view classification].
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/klkb1/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M13143; AAA60153.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232742; AAF79940.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232734; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232735; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232736; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232737; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232738; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232739; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232740; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF232741; AAF79940.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY190920; AAN84794.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC117349; AAI17350.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A00921; KQHUP.

NP_000883.2; -.

3D structure databases

PDB

2ANW; X-ray; 1.85 A; A=391-631.	[ExPASy / RCSB / EBI]
2ANY; X-ray; 1.40 A; A=391-631.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

2ANW; -.
2ANY; -.

ModBase

P03952.

Protein family/group databases

MEROPS

S01.212; -.

Enzyme and pathway databases

Reactome

REACT_604; Hemostasis.

Organism-specific databases

HIX0031513; -.

HGNC:6371; KLKB1.

HPA005634; -.

229000; gene+phenotype. [NCBI / EBI]

Orphanet

749; Prekallikrein deficiency, congenital.

PharmGKB

PA30160; -.

GeneCards

P03952.

Gene expression databases

ArrayExpress

P03952; -.

CleanEx

HS_KLK3; -.
HS_KLKB1; -.

GermOnline

ENSG00000164344; Homo sapiens.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from direct assay from HPA).
GO:0005576;	Cellular component: extracellular region (non-traceable author statement from UniProtKB).
GO:0004252;	Molecular function: serine-type endopeptidase activity (traceable author statement from ProtInc).
GO:0006508;	Biological process: proteolysis (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR000177; Apple.
IPR003014; PAN.
IPR003609; Pan_app.
IPR001254; Peptidase_S1_S6.
IPR001314; Peptidase_S1A.
Graphical view of domain structure.

Pfam

PF00024; PAN_1; 4.
PF00089; Trypsin; 1.
Pfam graphical view of domain structure.

PRINTS

PR00005; APPLEDOMAIN.
PR00722; CHYMOTRYPSIN.

SMART

SM00223; APPLE; 4.
SM00020; Tryp_SPc; 1.
SMART graphical view of domain structure.

PROSITE

PS00495; APPLE; 4.
PS50948; PAN; 4.
PS50240; TRYPSIN_DOM; 1.
PS00134; TRYPSIN_HIS; 1.
PS00135; TRYPSIN_SER; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSG00000164344; Homo sapiens. [Contig view]

GeneID

3818; -.

KEGG

hsa:3818; -.

Phylogenomic databases

HOVERGEN

P03952; -.

Other

NextBio

15011; -.

SOURCE

KLKB1; Homo sapiens.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Blood coagulation; Direct protein sequencing; Fibrinolysis; Glycoprotein; Hydrolase; Inflammatory response; Polymorphism; Protease; Repeat; Secreted; Serine protease; Signal; Zymogen.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 19`	`19`
`CHAIN`	`20 390`	`371`	`Plasma kallikrein heavy chain.`	`PRO_0000028021`
`CHAIN`	`391 638`	`248`	`Plasma kallikrein light chain.`	`PRO_0000028022`
`DOMAIN`	`21 104`	`84`	`Apple 1.`
`DOMAIN`	`111 194`	`84`	`Apple 2.`
`DOMAIN`	`201 284`	`84`	`Apple 3.`
`DOMAIN`	`292 375`	`84`	`Apple 4.`
`DOMAIN`	`391 626`	`236`	`Peptidase S1.`
`ACT_SITE`	`434 434`		`Charge relay system.`
`ACT_SITE`	`483 483`		`Charge relay system.`
`ACT_SITE`	`578 578`		`Charge relay system.`
`CARBOHYD`	`127 127`		`N-linked (GlcNAc...).`
`CARBOHYD`	`308 308`		`N-linked (GlcNAc...).`
`CARBOHYD`	`396 396`		`N-linked (GlcNAc...).`
`CARBOHYD`	`453 453`		`N-linked (GlcNAc...).`
`CARBOHYD`	`494 494`		`N-linked (GlcNAc...).`
`DISULFID`	`21 104`
`DISULFID`	`47 77`
`DISULFID`	`51 57`
`DISULFID`	`111 194`
`DISULFID`	`137 166`
`DISULFID`	`141 147`
`DISULFID`	`201 284`
`DISULFID`	`227 256`
`DISULFID`	`231 237`
`DISULFID`	`292 375`
`DISULFID`	`318 347`
`DISULFID`	`322 328`
`DISULFID`	`340 345`
`DISULFID`	`383 503`
`DISULFID`	`419 435`
`DISULFID`	`517 584`
`DISULFID`	`548 563`
`DISULFID`	`574 602`
`VARIANT`	`143 143`	`1`	`N -> S (common polymorphism; dbSNP:rs3733402 [NCBI]).`	`VAR_013598`
`VARIANT`	`178 178`	`1`	`A -> T (in dbSNP:rs4253257 [NCBI]).`	`VAR_016280`
`VARIANT`	`202 202`	`1`	`H -> Q (in dbSNP:rs4253373 [NCBI]).`	`VAR_013599`
`VARIANT`	`208 208`	`1`	`H -> P.`	`VAR_013600`
`VARIANT`	`210 210`	`1`	`A -> E (in dbSNP:rs2278542 [NCBI]).`	`VAR_020180`
`VARIANT`	`269 269`	`1`	`S -> C (in dbSNP:rs4253376 [NCBI]).`	`VAR_016281`
`VARIANT`	`311 311`	`1`	`F -> V (in dbSNP:rs4253377 [NCBI]).`	`VAR_016282`
`VARIANT`	`358 358`	`1`	`T -> A (in dbSNP:rs4253379 [NCBI]).`	`VAR_016283`
`VARIANT`	`381 381`	`1`	`S -> A (in dbSNP:rs4253301 [NCBI]).`	`VAR_016284`
`VARIANT`	`442 442`	`1`	`Q -> P (in dbSNP:rs4253316 [NCBI]).`	`VAR_016285 [3D]`
`VARIANT`	`560 560`	`1`	`R -> Q (in dbSNP:rs4253325 [NCBI]).`	`VAR_016286 [3D]`
`STRAND`	`405 425`	`21`
`STRAND`	`428 431`	`4`
`HELIX`	`433 436`	`4`
`STRAND`	`446 448`	`3`
`HELIX`	`454 456`	`3`
`STRAND`	`466 471`	`6`
`STRAND`	`479 482`	`4`
`STRAND`	`485 491`	`7`
`STRAND`	`515 523`	`9`
`STRAND`	`536 543`	`8`
`HELIX`	`545 549`	`5`
`STRAND`	`561 564`	`4`
`STRAND`	`581 584`	`4`
`STRAND`	`591 598`	`8`
`STRAND`	`600 603`	`4`
`STRAND`	`609 613`	`5`
`HELIX`	`614 617`	`4`
`HELIX`	`618 625`	`8`

Sequence information

Length: 638 AA [This is the length of the unprocessed precursor]

Molecular weight: 71370 Da [This is the MW of the unprocessed precursor]

CRC64: E62F9C1053838FB4 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MILFKQATYF ISLFATVSCG CLTQLYENAF FRGGDVASMY TPNAQYCQMR CTFHPRCLLF 

        70         80         90        100        110        120 
SFLPASSIND MEKRFGCFLK DSVTGTLPKV HRTGAVSGHS LKQCGHQISA CHRDIYKGVD 

       130        140        150        160        170        180 
MRGVNFNVSK VSSVEECQKR CTNNIRCQFF SYATQTFHKA EYRNNCLLKY SPGGTPTAIK 

       190        200        210        220        230        240 
VLSNVESGFS LKPCALSEIG CHMNIFQHLA FSDVDVARVL TPDAFVCRTI CTYHPNCLFF 

       250        260        270        280        290        300 
TFYTNVWKIE SQRNVCLLKT SESGTPSSST PQENTISGYS LLTCKRTLPE PCHSKIYPGV 

       310        320        330        340        350        360 
DFGGEELNVT FVKGVNVCQE TCTKMIRCQF FTYSLLPEDC KEEKCKCFLR LSMDGSPTRI 

       370        380        390        400        410        420 
AYGTQGSSGY SLRLCNTGDN SVCTTKTSTR IVGGTNSSWG EWPWQVSLQV KLTAQRHLCG 

       430        440        450        460        470        480 
GSLIGHQWVL TAAHCFDGLP LQDVWRIYSG ILNLSDITKD TPFSQIKEII IHQNYKVSEG 

       490        500        510        520        530        540 
NHDIALIKLQ APLNYTEFQK PICLPSKGDT STIYTNCWVT GWGFSKEKGE IQNILQKVNI 

       550        560        570        580        590        600 
PLVTNEECQK RYQDYKITQR MVCAGYKEGG KDACKGDSGG PLVCKHNGMW RLVGITSWGE 

       610        620        630 
GCARREQPGV YTKVAEYMDW ILEKTQSSDG KAQMQSPA

P03952 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools