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Protein

Kallikrein-1

Gene

KLK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.

Catalytic activityi

Preferential cleavage of Arg-|-Xaa bonds in small molecule substrates. Highly selective action to release kallidin (lysyl-bradykinin) from kininogen involves hydrolysis of Met-|-Xaa or Leu-|-Xaa.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei65Charge relay system1
Active sitei120Charge relay system1
Active sitei214Charge relay system1

GO - Molecular functioni

  • serine-type endopeptidase activity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BioCyciZFISH:HS09620-MONOMER.
BRENDAi3.4.21.35. 2681.
ReactomeiR-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Names & Taxonomyi

Protein namesi
Recommended name:
Kallikrein-1 (EC:3.4.21.35)
Alternative name(s):
Kidney/pancreas/salivary gland kallikrein
Tissue kallikrein
Gene namesi
Name:KLK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:6357. KLK1.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi3816.
MIMi615953. phenotype.
OpenTargetsiENSG00000167748.
PharmGKBiPA224.

Chemistry databases

ChEMBLiCHEMBL2319.
DrugBankiDB06692. Aprotinin.
GuidetoPHARMACOLOGYi2865.

Polymorphism and mutation databases

BioMutaiKLK1.
DMDMi269849612.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18CuratedAdd BLAST18
PropeptideiPRO_000002792319 – 24Activation peptideCurated6
ChainiPRO_000002792425 – 262Kallikrein-1Add BLAST238

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 174PROSITE-ProRule annotation1 Publication
Disulfide bondi50 ↔ 66PROSITE-ProRule annotation1 Publication
Glycosylationi93O-linked (GalNAc...)1 Publication1
Glycosylationi102N-linked (GlcNAc...)1 Publication1
Glycosylationi104O-linked (GalNAc...)1 Publication1
Glycosylationi108N-linked (GlcNAc...)2 Publications1
Disulfide bondi153 ↔ 220PROSITE-ProRule annotation1 Publication
Glycosylationi165N-linked (GlcNAc...); partial1 Publication1
Glycosylationi167O-linked (GalNAc...)1 Publication1
Disulfide bondi185 ↔ 199PROSITE-ProRule annotation1 Publication
Disulfide bondi210 ↔ 235PROSITE-ProRule annotation1 Publication

Post-translational modificationi

The O-linked polysaccharides on Ser-93, Ser-104 and Ser-167 are probably the mucin type linked to GalNAc. In PubMed:3163150, GalNAc was detected with the corresponding peptides but not located.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP06870.
PeptideAtlasiP06870.
PRIDEiP06870.

PTM databases

UniCarbKBiP06870.

Expressioni

Tissue specificityi

Isoform 2 is expressed in pancreas, salivary glands, kidney, colon, prostate gland, testis, spleen and the colon adenocarcinoma cell line T84.1 Publication

Gene expression databases

BgeeiENSG00000167748.
CleanExiHS_KLK1.
ExpressionAtlasiP06870. baseline and differential.
GenevisibleiP06870. HS.

Interactioni

Protein-protein interaction databases

BioGridi110016. 1 interactor.
STRINGi9606.ENSP00000301420.

Chemistry databases

BindingDBiP06870.

Structurei

Secondary structure

1262
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 44Combined sources6
Beta strandi47 – 56Combined sources10
Beta strandi59 – 62Combined sources4
Helixi64 – 66Combined sources3
Beta strandi69 – 76Combined sources8
Beta strandi88 – 90Combined sources3
Beta strandi92 – 97Combined sources6
Helixi103 – 106Combined sources4
Turni112 – 114Combined sources3
Beta strandi122 – 128Combined sources7
Beta strandi152 – 159Combined sources8
Beta strandi161 – 165Combined sources5
Beta strandi173 – 180Combined sources8
Helixi182 – 188Combined sources7
Beta strandi197 – 201Combined sources5
Beta strandi206 – 208Combined sources3
Beta strandi217 – 220Combined sources4
Beta strandi223 – 230Combined sources8
Beta strandi242 – 246Combined sources5
Helixi247 – 250Combined sources4
Helixi251 – 260Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SPJX-ray1.70A25-262[»]
ProteinModelPortaliP06870.
SMRiP06870.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06870.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 259Peptidase S1PROSITE-ProRule annotationAdd BLAST235

Sequence similaritiesi

Belongs to the peptidase S1 family. Kallikrein subfamily.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOVERGENiHBG013304.
InParanoidiP06870.
KOiK01325.
OMAiQFVHVSE.
OrthoDBiEOG091G0DF7.
PhylomeDBiP06870.
TreeFamiTF331065.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[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 1 (identifier: P06870-1) [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
MWFLVLCLAL SLGGTGAAPP IQSRIVGGWE CEQHSQPWQA ALYHFSTFQC
60 70 80 90 100
GGILVHRQWV LTAAHCISDN YQLWLGRHNL FDDENTAQFV HVSESFPHPG
110 120 130 140 150
FNMSLLENHT RQADEDYSHD LMLLRLTEPA DTITDAVKVV ELPTEEPEVG
160 170 180 190 200
STCLASGWGS IEPENFSFPD DLQCVDLKIL PNDECKKAHV QKVTDFMLCV
210 220 230 240 250
GHLEGGKDTC VGDSGGPLMC DGVLQGVTSW GYVPCGTPNK PSVAVRVLSY
260
VKWIEDTIAE NS
Length:262
Mass (Da):28,890
Last modified:November 24, 2009 - v2
Checksum:i7D8A715E9E104D60
GO
Isoform 2 (identifier: P06870-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: MWFLVLCLAL...VLTAAHCISD → MLPCPIPFSPSRLLIPPFPSFPS

Show »
Length:216
Mass (Da):23,835
Checksum:i8FD0C1CEB83D6750
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti114D → N in AAU12569 (Ref. 7) Curated1
Sequence conflicti139V → F in AAU12569 (Ref. 7) Curated1
Sequence conflicti188A → V in AAP35917 (Ref. 8) Curated1
Sequence conflicti188A → V in AAH05313 (PubMed:15489334).Curated1

Polymorphismi

Genetic variations in KLK1 are the cause of a decreased in urinary kallikrein activity [MIMi:615953]. The His-77 mutation dramatically reduces the activity of the enzyme in the urine. There is a 50 to 60% reduction in urinary kallikrein activity in His-77 individuals, but renal and hormonal adaptation to dietary changes in sodium and potassium are unaffected. However, in studies of brachial artery function, His-77 individuals consistently exhibited an increase in wall shear stress and a paradoxical reduction in artery diameter and lumen compared to Arg-77 individuals. This partial genetic deficiency in kallikrein activity is associated with a form of arterial dysfunction involving inappropriate inward remodeling of the brachial artery despite a chronic increase in shear stress.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01456777R → H Polymorphism; associated with a significant decrease in urinary kallikrein activity. 1 PublicationCorresponds to variant rs5515dbSNPEnsembl.1
Natural variantiVAR_006625145E → Q Polymorphism; not associated with changes in urinary kallikrein activity. 8 PublicationsCorresponds to variant rs5516dbSNPEnsembl.1
Natural variantiVAR_006626186K → E.3 PublicationsCorresponds to variant rs5517dbSNPEnsembl.1
Natural variantiVAR_014568193V → E.Corresponds to variant rs5518dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0374831 – 69MWFLV…HCISD → MLPCPIPFSPSRLLIPPFPS FPS in isoform 2. 1 PublicationAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25629 mRNA. Translation: AAA36136.1.
M33109
, M33105, M33106, M33107, M33108 Genomic DNA. Translation: AAA59455.1.
X13561 mRNA. Translation: CAA31912.1.
AF277050 Genomic DNA. Translation: AAF86333.1.
AF243527 Genomic DNA. Translation: AAG33353.1.
AY703451 mRNA. Translation: AAU12569.1.
BT007253 mRNA. Translation: AAP35917.1.
AY094609 Genomic DNA. Translation: AAM11874.1.
AC010325 Genomic DNA. No translation available.
BC005313 mRNA. Translation: AAH05313.1.
M12706 mRNA. Translation: AAA59201.1.
CCDSiCCDS12804.1. [P06870-1]
PIRiA24696. KQHU.
B24696.
RefSeqiNP_002248.1. NM_002257.3. [P06870-1]
UniGeneiHs.123107.

Genome annotation databases

EnsembliENST00000301420; ENSP00000301420; ENSG00000167748. [P06870-1]
GeneIDi3816.
KEGGihsa:3816.
UCSCiuc002ptk.3. human. [P06870-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Kallikrein entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25629 mRNA. Translation: AAA36136.1.
M33109
, M33105, M33106, M33107, M33108 Genomic DNA. Translation: AAA59455.1.
X13561 mRNA. Translation: CAA31912.1.
AF277050 Genomic DNA. Translation: AAF86333.1.
AF243527 Genomic DNA. Translation: AAG33353.1.
AY703451 mRNA. Translation: AAU12569.1.
BT007253 mRNA. Translation: AAP35917.1.
AY094609 Genomic DNA. Translation: AAM11874.1.
AC010325 Genomic DNA. No translation available.
BC005313 mRNA. Translation: AAH05313.1.
M12706 mRNA. Translation: AAA59201.1.
CCDSiCCDS12804.1. [P06870-1]
PIRiA24696. KQHU.
B24696.
RefSeqiNP_002248.1. NM_002257.3. [P06870-1]
UniGeneiHs.123107.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SPJX-ray1.70A25-262[»]
ProteinModelPortaliP06870.
SMRiP06870.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110016. 1 interactor.
STRINGi9606.ENSP00000301420.

Chemistry databases

BindingDBiP06870.
ChEMBLiCHEMBL2319.
DrugBankiDB06692. Aprotinin.
GuidetoPHARMACOLOGYi2865.

PTM databases

UniCarbKBiP06870.

Polymorphism and mutation databases

BioMutaiKLK1.
DMDMi269849612.

Proteomic databases

PaxDbiP06870.
PeptideAtlasiP06870.
PRIDEiP06870.

Protocols and materials databases

DNASUi3816.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301420; ENSP00000301420; ENSG00000167748. [P06870-1]
GeneIDi3816.
KEGGihsa:3816.
UCSCiuc002ptk.3. human. [P06870-1]

Organism-specific databases

CTDi3816.
DisGeNETi3816.
GeneCardsiKLK1.
HGNCiHGNC:6357. KLK1.
MIMi147910. gene.
615953. phenotype.
neXtProtiNX_P06870.
OpenTargetsiENSG00000167748.
PharmGKBiPA224.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118862.
HOVERGENiHBG013304.
InParanoidiP06870.
KOiK01325.
OMAiQFVHVSE.
OrthoDBiEOG091G0DF7.
PhylomeDBiP06870.
TreeFamiTF331065.

Enzyme and pathway databases

BioCyciZFISH:HS09620-MONOMER.
BRENDAi3.4.21.35. 2681.
ReactomeiR-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).

Miscellaneous databases

ChiTaRSiKLK1. human.
EvolutionaryTraceiP06870.
GeneWikiiKLK1.
GenomeRNAii3816.
PROiP06870.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167748.
CleanExiHS_KLK1.
ExpressionAtlasiP06870. baseline and differential.
GenevisibleiP06870. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKLK1_HUMAN
AccessioniPrimary (citable) accession number: P06870
Secondary accession number(s): Q66US9
, Q86U61, Q8TCV8, Q9BS53, Q9NQU4, Q9UD19, Q9UMJ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 24, 2009
Last modified: November 2, 2016
This is version 178 of the entry and version 2 of the sequence. [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 19
    Human chromosome 19: 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
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.