Reviewed, UniProtKB/Swiss-Prot P07288 (KLK3_HUMAN)

Names and origin

Protein names

Recommended name:
    Prostate-specific antigen
      Short name=PSA
    EC=3.4.21.77
Alternative name(s):
    Kallikrein-3
    Semenogelase
    Gamma-seminoprotein
      Short name=Seminin
    P-30 antigen

Gene names

Name:	KLK3
Synonyms:	APS

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	261 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	Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.
Catalytic activity	Preferential cleavage: -Tyr-|-Xaa-.
Subcellular location	Secreted.
Sequence similarities	Belongs to the peptidase S1 family. Kallikrein subfamily. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	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	negative regulation of angiogenesis Non-traceable author statement. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from direct assay. Source: HPA extracellular region Non-traceable author statement. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular function	serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Ref.15

Propeptide

18 – 24

7

Activation peptide Ref.13 Ref.14

PRO_0000027931

Chain

25 – 261

237

Prostate-specific antigen

PRO_0000027932

Regions

Domain

25 – 258

234

Peptidase S1

Sites

Active site

65

1

Charge relay system

Active site

120

1

Charge relay system

Active site

213

1

Charge relay system

Amino acid modifications

Glycosylation

69

1

N-linked (GlcNAc...)

Disulfide bond

31 ↔ 173

Disulfide bond

50 ↔ 66

Disulfide bond

152 ↔ 219

Disulfide bond

184 ↔ 198

Disulfide bond

209 ↔ 234

Natural variations

Natural variant

32

1

E → K: dbSNP rs2271092.

VAR_021941

Natural variant

132

1

L → I: dbSNP rs2003783.

VAR_021942

Natural variant

179

1

I → T: dbSNP rs17632542.

VAR_051852

Experimental info

Sequence conflict

64

1

A → T Ref.12

Sequence conflict

69

1

N → KC in AAA60193. Ref.6

Sequence conflict

94

1

H → T AA sequence Ref.13

Sequence conflict

136

1

V → M Ref.12

Sequence conflict

165 – 168

4

FLTP → HLLYDQM AA sequence Ref.13

Sequence conflict

175

1

D → Q AA sequence Ref.13

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

261

Helix Strand Turn

Details...

Beta strand

39 – 56

18

Beta strand

59 – 62

4

Helix

64 – 66

3

Beta strand

72 – 76

5

Beta strand

78 – 82

5

Beta strand

88 – 97

10

Helix

103 – 106

4

Beta strand

107 – 110

4

Beta strand

122 – 128

7

Beta strand

151 – 157

7

Beta strand

160 – 164

5

Beta strand

172 – 179

8

Helix

181 – 187

7

Beta strand

189 – 191

3

Beta strand

196 – 200

5

Beta strand

216 – 229

14

Beta strand

241 – 245

5

Helix

246 – 249

4

Helix

250 – 258

9

Sequences

	Sequence		Length	Mass (Da)
	P07288-1 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: AE9E732AF872141A	FASTA	261	28,741
	10 20 30 40 50 60 MWVPVVFLTL SVTWIGAAPL ILSRIVGGWE CEKHSQPWQV LVASRGRAVC GGVLVHPQWV 70 80 90 100 110 120 LTAAHCIRNK SVILLGRHSL FHPEDTGQVF QVSHSFPHPL YDMSLLKNRF LRPGDDSSHD 130 140 150 160 170 180 LMLLRLSEPA ELTDAVKVMD LPTQEPALGT TCYASGWGSI EPEEFLTPKK LQCVDLHVIS 190 200 210 220 230 240 NDVCAQVHPQ KVTKFMLCAG RWTGGKSTCS GDSGGPLVCN GVLQGITSWG SEPCALPERP 250 260 SLYTKVVHYR KWIKDTIVAN P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human prostate specific antigen cDNA." Lundwall A., Lilja H. FEBS Lett. 214:317-322(1987) [PubMed: 2436946] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Prostate.
[2]	"Human prostate specific antigen (PSA) gene: structure and linkage to the kallikrein-like gene, hGK-1." Digby M.R., Zhang X.Y., Richard R.I. Nucleic Acids Res. 17:2137-2137(1989) [PubMed: 2467258] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Prostate.
[3]	"Genomic sequence of human prostate specific antigen (PSA)." Klobeck H.-G., Combriato G., Schulz P., Arbusow V., Fittler F. Nucleic Acids Res. 17:3981-3981(1989) [PubMed: 2471958] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Characterization of the gene for prostate-specific antigen, a human glandular kallikrein." Lundwall A. Biochem. Biophys. Res. Commun. 161:1151-1159(1989) [PubMed: 2472789] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Leukocyte.
[5]	"cDNA coding for the entire human prostate specific antigen shows high homologies to the human tissue kallikrein genes." Henttu P., Vihko P. Biochem. Biophys. Res. Commun. 160:903-910(1989) [PubMed: 2470373] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Prostate.
[6]	"Characterization of the prostate-specific antigen gene: a novel human kallikrein-like gene." Riegman P.H.J., Vlietstra R.J., van der Korput J.A.G.M., Romijn J.C., Trapman J. Biochem. Biophys. Res. Commun. 159:95-102(1989) [PubMed: 2466464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Prostate.
[7]	"A comparative analysis of prostate specific antigen gene sequence in benign and malignant prostate tissue." Monne M.M., Moreno J.M., Mele C.M., Mulholland G.M., Gomella L.G. Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Prostate.
[8]	"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].
[9]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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]. Tissue: PNS and Prostate.
[11]	"Molecular characterization of prostate-specific antigen messenger RNA expressed in breast tumors." Monne M., Croce C.M., Yu H., Diamandis E.P. Cancer Res. 54:6344-6347(1994) [PubMed: 7527295] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-176.
[12]	"Sequence of a cDNA clone encompassing the complete mature human prostate specific antigen (PSA) and an unspliced leader sequence." Schulz P., Stucka R., Feldmann H., Combriato G., Klobeck H.-G., Fittler F. Nucleic Acids Res. 16:6226-6226(1988) [PubMed: 2456523] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-261.
[13]	"Human prostate-specific antigen: structural and functional similarity with serine proteases." Watt K.W.K., Lee P.J., M'Timkulu T., Chan W.P., Loor R. Proc. Natl. Acad. Sci. U.S.A. 83:3166-3170(1986) [PubMed: 2422647] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-261.
[14]	"Isolation, characterization and amino-acid sequence of gamma-seminoprotein, a glycoprotein from human seminal plasma." Schaller J., Akiyama K., Tsuda R., Hara M., Marti T., Rickli E.E. Eur. J. Biochem. 170:111-120(1987) [PubMed: 3691515] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-261.
[15]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-32.
[16]	"A structural model for the prostate disease marker, human prostate-specific antigen." Villoutreix B.O., Getzoff E.D., Griffin J.H. Protein Sci. 3:2033-2044(1994) [PubMed: 7535613] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[17]	"Substrate specificity of prostate-specific antigen (PSA)." Coombs G.S., Bergstrom R.C., Pellequer J.L., Baker S.I., Navre M., Smith M.M., Tainer J.A., Madison E.L., Corey D.R. Chem. Biol. 5:475-488(1998) [PubMed: 9751643] [Abstract] Cited for: 3D-STRUCTURE MODELING.
+	Additional computationally mapped references.

Web resources

Wikipedia

Prostate-specific antigen entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X05332 mRNA. Translation: CAA28947.1.
X13940 Genomic DNA. Translation: CAA32123.1.
X13941 Genomic DNA. Translation: CAA32124.1. Sequence problems.
X13942 Genomic DNA. Translation: CAB46487.1.
X13943 Genomic DNA. Translation: CAA32126.1.
X13944 Genomic DNA. Translation: CAA32127.1.
X14810 Genomic DNA. Translation: CAA32915.1.
M27274 Genomic DNA. Translation: AAA60192.1.
M26663 mRNA. Translation: AAA58802.1.
M24543 Genomic DNA. Translation: AAA60193.1.
U17040 mRNA. Translation: AAA56764.1.
AF243527 Genomic DNA. Translation: AAG33355.1.
BT019862 mRNA. Translation: AAV38665.1.
BC005307 mRNA. Translation: AAH05307.1.
BC050595 mRNA. Translation: AAH50595.2.
BC056665 mRNA. Translation: AAH56665.1.
S75755 mRNA. Translation: AAD14185.1. Different initiation.
X07730 mRNA. No translation available.

IPI

IPI00010858.

PIR

A32297.

RefSeq

NP_001025218.1.
NP_001025219.1.
NP_001025220.1.
NP_001639.1.

UniGene

Hs.171995

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PFA	model	-	A	10-261	[»]
2PSA	model	-	A	25-261	[»]
2ZCH	X-ray	2.83	P	25-261	[»]
2ZCK	X-ray	3.10	P	25-261	[»]
2ZCL	X-ray	3.25	P	25-261	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S01.162.

PTM databases

PhosphoSite

P07288.

Genome annotation databases

Ensembl

ENSG00000142515. Homo sapiens. [Contig view]

GeneID

354.

KEGG

hsa:354.

Organism-specific databases

GeneCards

GC19P056049.

H-InvDB

HIX0015369.

HGNC

HGNC:6364. KLK3.

HPA

CAB000070.
HPA000764.

MIM

176820. gene.

PharmGKB

PA30153.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P07288.

HOVERGEN

P07288.

OMA

P07288. GSEPCAL.

Enzyme and pathway databases

BRENDA

3.4.21.77. 247.

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.
hnf3apathway. FOXA1 transcription factor network.
ar_tf_pathway. Regulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

P07288.

Bgee

P07288.

CleanEx

HS_KLK3.

GermOnline

ENSG00000142515. 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

NextBio

1459.

PMAP-CutDB

P07288.

SOURCE

Search...

Entry information

Entry name

KLK3_HUMAN

Accession

Primary (citable) accession number: P07288
Secondary accession number(s): Q16272, Q86TG8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	July 1, 1989
Last modified:	May 26, 2009
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)