P06870 (KLK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kallikrein-1
EC=3.4.21.35

Alternative name(s):
Kidney/pancreas/salivary gland kallikrein
Tissue 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. 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.

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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	serine-type endopeptidase activity Non-traceable author statement Ref.4. Source: UniProtKB
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.13

Glycosylation

102

1

N-linked (GlcNAc...) Ref.13

Glycosylation

104

1

O-linked (GalNAc...) Ref.13

Glycosylation

108

1

N-linked (GlcNAc...) Ref.13 Ref.17

Glycosylation

165

1

N-linked (GlcNAc...); partial Ref.13

Glycosylation

167

1

O-linked (GalNAc...) Ref.13

Disulfide bond

31 ↔ 174

Ref.17

Disulfide bond

50 ↔ 66

Ref.17

Disulfide bond

153 ↔ 220

Ref.17

Disulfide bond

185 ↔ 199

Ref.17

Disulfide bond

210 ↔ 235

Ref.17

Natural variations

Alternative sequence

1 – 69

69

MWFLV…HCISD → MLPCPIPFSPSRLLIPPFPS FPS in isoform 2.

VSP_037483

Natural variant

77

1

R → H.
Corresponds to variant rs5515 [ dbSNP | Ensembl ].

VAR_014567

Natural variant

145

1

E → Q. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12
Corresponds to variant rs5516 [ dbSNP | Ensembl ].

VAR_006625

Natural variant

186

1

K → E. Ref.1 Ref.7 Ref.12
Corresponds to variant rs5517 [ dbSNP | Ensembl ].

VAR_006626

Natural variant

193

1

V → E.
Corresponds to variant rs5518 [ dbSNP | Ensembl ].

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.11

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 November 24, 2009. Version 2. Checksum: 7D8A715E9E104D60	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 ELPTEEPEVG STCLASGWGS IEPENFSFPD DLQCVDLKIL 190 200 210 220 230 240 PNDECKKAHV QKVTDFMLCV GHLEGGKDTC VGDSGGPLMC DGVLQGVTSW GYVPCGTPNK 250 260 PSVAVRVLSY VKWIEDTIAE NS
	Isoform 2 [UniParc]. Checksum: 8FD0C1CEB83D6750	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 VKVVELPTEE PEVGSTCLAS GWGSIEPENF 130 140 150 160 170 180 SFPDDLQCVD LKILPNDECK 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), 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: 2898948] [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: 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.
[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), 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. , 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: 15057824] [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: 15489334] [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: 3853975] [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: 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.
[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: 2666327] [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: 393608] [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: 3635530] [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: 15651049] [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 , 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.

IPI

IPI00304808.
IPI00930404.

PIR

KQHU. A24696.
B24696.

RefSeq

NP_002248.1. NM_002257.2.

UniGene

Hs.123107.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P06870.

SMR

P06870. Positions 25-262.

ModBase

Search...

Protein-protein interaction databases

STRING

P06870.

Protein family/group databases

MEROPS

S01.160.

PTM databases

GlycoSuiteDB

P06870.

Polymorphism databases

DMDM

269849612.

Proteomic databases

PRIDE

P06870.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301420; ENSP00000301420; ENSG00000167748.

GeneID

3816.

KEGG

hsa:3816.

Organism-specific databases

CTD

3816.

GeneCards

GC19M051322.

HGNC

HGNC:6357. KLK1.

MIM

147910. gene+phenotype.

neXtProt

NX_P06870.

PharmGKB

PA224.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15164.

HOVERGEN

HBG013304.

InParanoid

P06870.

OMA

VISHLEW.

OrthoDB

EOG4DZ1VW.

PhylomeDB

P06870.

Enzyme and pathway databases

BRENDA

3.4.21.35. 2681.

Gene expression databases

ArrayExpress

P06870.

Bgee

P06870.

CleanEx

HS_KLK1.

Genevestigator

P06870.

GermOnline

ENSG00000167748. Homo sapiens.

Family and domain databases

InterPro

IPR009003. Pept_cys/ser_Trypsin-like.
IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

KO

K01325.

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

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:	November 24, 2009
Last modified:	January 25, 2012
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.