Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P06870 (KLK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kallikrein-1

EC=3.4.21.35
Alternative name(s):
Kidney/pancreas/salivary gland kallikrein
Tissue kallikrein
Gene names
Name:KLK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length262 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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.

Tissue specificity

Isoform 2 is expressed in pancreas, salivary glands, kidney, colon, prostate gland, testis, spleen and the colon adenocarcinoma cell line T84. Ref.4

Post-translational modification

The O-linked polysaccharides on Ser-93, Ser-104 and Ser-167 are probably the mucin type linked to GalNAc. In Ref.13, GalNAc was detected with the corresponding peptides but not located.

Sequence similarities

Belongs to the peptidase S1 family. Kallikrein subfamily.

Contains 1 peptidase S1 domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P06870-1)

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.
Isoform 2 (identifier: P06870-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Probable
Propeptide19 – 246Activation peptide Probable
PRO_0000027923
Chain25 – 262238Kallikrein-1
PRO_0000027924

Regions

Domain25 – 259235Peptidase S1

Sites

Active site651Charge relay system
Active site1201Charge relay system
Active site2141Charge relay system

Amino acid modifications

Glycosylation931O-linked (GalNAc...) Ref.13
Glycosylation1021N-linked (GlcNAc...) Ref.13
Glycosylation1041O-linked (GalNAc...) Ref.13
Glycosylation1081N-linked (GlcNAc...) Ref.13 Ref.17
Glycosylation1651N-linked (GlcNAc...); partial Ref.13
Glycosylation1671O-linked (GalNAc...) Ref.13
Disulfide bond31 ↔ 174 Ref.17
Disulfide bond50 ↔ 66 Ref.17
Disulfide bond153 ↔ 220 Ref.17
Disulfide bond185 ↔ 199 Ref.17
Disulfide bond210 ↔ 235 Ref.17

Natural variations

Alternative sequence1 – 6969MWFLV…HCISD → MLPCPIPFSPSRLLIPPFPS FPS in isoform 2.
VSP_037483
Natural variant771R → H.
Corresponds to variant rs5515 [ dbSNP | Ensembl ].
VAR_014567
Natural variant1451E → Q. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12
Corresponds to variant rs5516 [ dbSNP | Ensembl ].
VAR_006625
Natural variant1861K → E. Ref.1 Ref.7 Ref.12
Corresponds to variant rs5517 [ dbSNP | Ensembl ].
VAR_006626
Natural variant1931V → E.
Corresponds to variant rs5518 [ dbSNP | Ensembl ].
VAR_014568

Experimental info

Sequence conflict1141D → N in AAU12569. Ref.7
Sequence conflict1391V → F in AAU12569. Ref.7
Sequence conflict1881A → V in AAP35917. Ref.8
Sequence conflict1881A → V in AAH05313. Ref.11

Secondary structure

......................................... 262
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 24, 2009. Version 2.
Checksum: 7D8A715E9E104D60

FASTA26228,890
        10         20         30         40         50         60 
MWFLVLCLAL SLGGTGAAPP IQSRIVGGWE CEQHSQPWQA ALYHFSTFQC GGILVHRQWV 

        70         80         90        100        110        120 
LTAAHCISDN YQLWLGRHNL FDDENTAQFV HVSESFPHPG FNMSLLENHT RQADEDYSHD 

       130        140        150        160        170        180 
LMLLRLTEPA DTITDAVKVV ELPTEEPEVG STCLASGWGS IEPENFSFPD DLQCVDLKIL 

       190        200        210        220        230        240 
PNDECKKAHV QKVTDFMLCV GHLEGGKDTC VGDSGGPLMC DGVLQGVTSW GYVPCGTPNK 

       250        260 
PSVAVRVLSY VKWIEDTIAE NS 

« Hide

Isoform 2 [UniParc].

Checksum: 8FD0C1CEB83D6750
Show »

FASTA21623,835

References

« Hide 'large scale' references
[1]"Nucleotide sequence of cloned cDNA for human pancreatic kallikrein."
Fukushima D., Kitamura N., Nakanishi S.
Biochemistry 24:8037-8043(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLN-145 AND GLU-186.
Tissue: Pancreas.
[2]"Structure and chromosomal localization of the human renal kallikrein gene."
Evans B.A., Yun Z.X., Close J.A., Tregear G.W., Kitamura N., Nakanishi S., Callen D.F., Baker E., Hyland V.J., Sutherland G.R., Richards R.I.
Biochemistry 27:3124-3129(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-145.
Tissue: Kidney.
[3]"Cloning and expression of human salivary-gland kallikrein in Escherichia coli."
Angermann A., Bergmann C., Appelhans H.
Biochem. J. 262:787-793(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Salivary gland.
[4]"Molecular cloning and characterization of a novel kallikrein transcript in colon and its distribution in human tissues."
Chen L.-M., Murray S.R., Chai K.X., Chao L., Chao J.
Braz. J. Med. Biol. Res. 27:1829-1838(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[5]"Genomic organization of the human kallikrein gene family on chromosome 19q13.3-q13.4."
Yousef G.M., Chang A., Scorilas A., Diamandis E.P.
Biochem. Biophys. Res. Commun. 276:125-133(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region."
Gan L., Lee I., Smith R., Argonza-Barrett R., Lei H., McCuaig J., Moss P., Paeper B., Wang K.
Gene 257:119-130(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Kallikrein cDNA from the pancreas of a Chinese patient."
Li T., Du G., Dai Y.
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLN-145 AND GLU-186.
[8]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-145.
[9]SeattleSNPs variation discovery resource
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-145.
[10]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-145.
Tissue: Pancreas.
[12]"Human kidney kallikrein: cDNA cloning and sequence analysis."
Baker A.R., Shine J.
DNA 4:445-450(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-262 (ISOFORM 1), VARIANTS GLN-145 AND GLU-186.
Tissue: Kidney.
[13]"Human urinary kallikrein -- amino acid sequence and carbohydrate attachment sites."
Kellermann J., Lottspeich F., Geiger R., Deutzmann R.
Protein Seq. Data Anal. 1:177-182(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-262 (ISOFORM 1), GLYCOSYLATION AT SER-93; ASN-102; SER-104; ASN-108; ASN-165 AND SER-167.
Tissue: Urine.
[14]"Human urinary kallikrein. Complete amino acid sequence and sites of glycosylation."
Lu H.S., Lin F.-K., Chao L., Chao J.
Int. J. Pept. Protein Res. 33:237-249(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-262 (ISOFORM 1).
Tissue: Urine.
[15]"N-terminal amino acid sequence of human urinary kallikrein homology with other serine proteases."
Lottspeich F., Geiger R., Henschen A., Kutzbach C.
Hoppe-Seyler's Z. Physiol. Chem. 360:1947-1950(1979) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 25-55 (ISOFORM 1).
Tissue: Urine.
[16]"N-terminal amino acid sequence of human urinary prokallikrein."
Takahashi S., Irie A., Katayama Y., Ito K., Miyake Y.
J. Biochem. 99:989-992(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 28-47 (ISOFORM 1).
Tissue: Urine.
[17]"1.70 A X-ray structure of human apo kallikrein 1: structural changes upon peptide inhibitor/substrate binding."
Laxmikanthan G., Blaber S.I., Bernett M.J., Scarisbrick I.A., Juliano M.A., Blaber M.
Proteins 58:802-814(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 25-262, GLYCOSYLATION AT ASN-108, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Wikipedia

Kallikrein entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M25629 mRNA. Translation: AAA36136.1.
M33109 expand/collapse EMBL AC list , 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.
CCDSCCDS12804.1. [P06870-1]
PIRKQHU. A24696.
B24696.
RefSeqNP_002248.1. NM_002257.3. [P06870-1]
UniGeneHs.123107.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SPJX-ray1.70A25-262[»]
ProteinModelPortalP06870.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110016. 1 interaction.
STRING9606.ENSP00000301420.

Chemistry

ChEMBLCHEMBL2319.
DrugBankDB00009. Alteplase.
DB00029. Anistreplase.
DB00015. Reteplase.
DB00031. Tenecteplase.

PTM databases

UniCarbKBP06870.

Polymorphism databases

DMDM269849612.

Proteomic databases

PaxDbP06870.
PRIDEP06870.

Protocols and materials databases

DNASU3816.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301420; ENSP00000301420; ENSG00000167748. [P06870-1]
GeneID3816.
KEGGhsa:3816.
UCSCuc002ptk.1. human. [P06870-1]

Organism-specific databases

CTD3816.
GeneCardsGC19M051322.
HGNCHGNC:6357. KLK1.
MIM147910. gene+phenotype.
neXtProtNX_P06870.
PharmGKBPA224.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOVERGENHBG013304.
InParanoidP06870.
KOK01325.
OMALWLGRHN.
PhylomeDBP06870.
TreeFamTF331065.

Enzyme and pathway databases

BRENDA3.4.21.35. 2681.
ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressP06870.
BgeeP06870.
CleanExHS_KLK1.
GenevestigatorP06870.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP06870.
GeneWikiKLK1.
GenomeRNAi3816.
NextBio15001.
PROP06870.
SOURCESearch...

Entry information

Entry nameKLK1_HUMAN
AccessionPrimary (citable) accession number: P06870
Secondary accession number(s): Q66US9 expand/collapse secondary AC list , Q86U61, Q8TCV8, Q9BS53, Q9NQU4, Q9UD19, Q9UMJ1
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 24, 2009
Last modified: July 9, 2014
This is version 158 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM