Reviewed, UniProtKB/Swiss-Prot P06870 (KLK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Kallikrein-1
    EC=3.4.21.35
Alternative name(s):
    Tissue kallikrein
    Kidney/pancreas/salivary gland kallikrein

Gene names

Name:

KLK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	262 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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.12, 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.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Molecular function	serine-type endopeptidase activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Probable

Propeptide

19 – 24

6

Activation peptide Probable

PRO_0000027923

Chain

25 – 262

238

Kallikrein-1

PRO_0000027924

Regions

Domain

25 – 259

235

Peptidase S1

Sites

Active site

65

1

Charge relay system

Active site

120

1

Charge relay system

Active site

214

1

Charge relay system

Amino acid modifications

Glycosylation

93

1

O-linked (GalNAc...) Ref.12

Glycosylation

102

1

N-linked (GlcNAc...) Ref.12

Glycosylation

104

1

O-linked (GalNAc...) Ref.12

Glycosylation

108

1

N-linked (GlcNAc...) Ref.12

Glycosylation

165

1

N-linked (GlcNAc...); partial Ref.12

Glycosylation

167

1

O-linked (GalNAc...) Ref.12

Disulfide bond

31 ↔ 174

By similarity

Disulfide bond

50 ↔ 66

By similarity

Disulfide bond

153 ↔ 220

By similarity

Disulfide bond

185 ↔ 199

By similarity

Disulfide bond

210 ↔ 235

By similarity

Natural variations

Alternative sequence

1 – 69

69

MWFLV…HCISD → MLPCPIPFSPSRLLIPPFPS FPS in isoform 2.

VSP_037483

Natural variant

77

1

R → H: dbSNP rs5515.

VAR_014567

Natural variant

145

1

Q → E: dbSNP rs5516.

VAR_006625

Natural variant

186

1

E → K: dbSNP rs5517. Ref.6

VAR_006626

Natural variant

193

1

V → E: dbSNP rs5518.

VAR_014568

Experimental info

Sequence conflict

114

1

D → N in AAU12569. Ref.7

Sequence conflict

139

1

V → F in AAU12569. Ref.7

Sequence conflict

188

1

A → V in AAP35917. Ref.8

Sequence conflict

188

1

A → V in AAH05313. Ref.10

Secondary structure

1

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262

Helix Strand Turn

Details...

Beta strand

39 – 44

6

Beta strand

47 – 56

10

Beta strand

59 – 62

4

Helix

64 – 66

3

Beta strand

69 – 76

8

Beta strand

88 – 90

3

Beta strand

92 – 97

6

Helix

103 – 106

4

Turn

112 – 114

3

Beta strand

122 – 128

7

Beta strand

152 – 159

8

Beta strand

161 – 165

5

Beta strand

173 – 180

8

Helix

182 – 188

7

Beta strand

197 – 201

5

Beta strand

206 – 208

3

Beta strand

217 – 220

4

Beta strand

223 – 230

8

Beta strand

242 – 246

5

Helix

247 – 250

4

Helix

251 – 260

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: 772AD14A93A496C0	FASTA	262	28,890
	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 ELPTQEPEVG STCLASGWGS IEPENFSFPD DLQCVDLKIL 190 200 210 220 230 240 PNDECEKAHV QKVTDFMLCV GHLEGGKDTC VGDSGGPLMC DGVLQGVTSW GYVPCGTPNK 250 260 PSVAVRVLSY VKWIEDTIAE NS
	Isoform 2. Checksum: 857061DAB589BCF0	FASTA	216	23,835
	10 20 30 40 50 60 MLPCPIPFSP SRLLIPPFPS FPSNYQLWLG RHNLFDDENT AQFVHVSESF PHPGFNMSLL 70 80 90 100 110 120 ENHTRQADED YSHDLMLLRL TEPADTITDA VKVVELPTQE PEVGSTCLAS GWGSIEPENF 130 140 150 160 170 180 SFPDDLQCVD LKILPNDECE KAHVQKVTDF MLCVGHLEGG KDTCVGDSGG PLMCDGVLQG 190 200 210 VTSWGYVPCG TPNKPSVAVR VLSYVKWIED TIAENS

References

	« Hide 'large scale' referencesShow '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: 3004571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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: 2898948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. 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: 2686621] [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: 7749372] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, VARIANT LYS-186.
[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: 11006094] [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: 11054574] [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).
[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 LYS-186.
[9]	SeattleSNPs variation discovery resource Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-186.
[10]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Pancreas.
[11]	"Human kidney kallikrein: cDNA cloning and sequence analysis." Baker A.R., Shine J. DNA 4:445-450(1985) [PubMed: 3853975] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 18-262 (ISOFORM 1). Tissue: Kidney.
[12]	"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: 3163150] [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.
[13]	"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: 2666327] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-262 (ISOFORM 1). Tissue: Urine.
[14]	"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: 393608] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-55 (ISOFORM 1). Tissue: Urine.
[15]	"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: 3635530] [Abstract] Cited for: PROTEIN SEQUENCE OF 28-47 (ISOFORM 1). Tissue: Urine.
+	Additional computationally mapped references.

Web resources

Wikipedia

Kallikrein entry

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
BC005313 mRNA. Translation: AAH05313.1.
M12706 mRNA. Translation: AAA59201.1.

IPI

IPI00304808.

PIR

KQHU. A24696.
B24696.

RefSeq

NP_002248.1.

UniGene

Hs.123107

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SPJ	X-ray	1.70	A	25-262	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S01.160.

PTM databases

GlycoSuiteDB

P06870.

Genome annotation databases

Ensembl

ENSG00000167748. Homo sapiens. [Contig view]

GeneID

3816.

KEGG

hsa:3816.

Organism-specific databases

GeneCards

GC19M056014.

HGNC

HGNC:6357. KLK1.

MIM

147910. gene+phenotype.

PharmGKB

PA224.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P06870.

HOVERGEN

P06870.

Enzyme and pathway databases

BRENDA

3.4.21.35. 247.

Gene expression databases

Bgee

P06870.

CleanEx

HS_KLK1.

GermOnline

ENSG00000167748. Homo sapiens.

Family and domain databases

InterPro

IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00009. Alteplase.
DB00029. Anistreplase.
DB00015. Reteplase.
DB00031. Tenecteplase.

NextBio

15001.

SOURCE

Search...

Entry information

Entry name

KLK1_HUMAN

Accession

Primary (citable) accession number: P06870
Secondary accession number(s): Q66US9 , Q86U61, Q8TCV8, Q9BS53, Q9NQU4, Q9UD19, Q9UMJ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	June 16, 2009
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)