P07288 (KLK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prostate-specific antigen
Short name=PSA
EC=3.4.21.77

Alternative name(s):
Gamma-seminoprotein
Short name=Seminin
Kallikrein-3
P-30 antigen
Semenogelase

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-.
Enzyme regulation	Inhibited by SERPINA5. Activity is strongly inhibited by Zn2+, 100 times more abundant in semen than in serum. This inhibition is relieved by exposure to semenogelins, which are avid zinc binders. Ref.16 Ref.19
Subunit structure	Forms heterodimer with SERPINA5.
Subcellular location	Secreted.
Sequence similarities	Belongs to the peptidase S1 family. Kallikrein subfamily. Contains 1 peptidase S1 domain.
Sequence caution	The sequence AAD14185.1 differs from that shown. Reason: Erroneous initiation.

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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of angiogenesis Non-traceable author statement. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.16. Source: UniProtKB 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

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 Ref.19

Active site

120

1

Charge relay system Ref.19

Active site

213

1

Charge relay system Ref.19

Amino acid modifications

Glycosylation

69

1

N-linked (GlcNAc...)

Disulfide bond

31 ↔ 173

Ref.19

Disulfide bond

50 ↔ 66

Ref.19

Disulfide bond

152 ↔ 219

Ref.19

Disulfide bond

184 ↔ 198

Ref.19

Disulfide bond

209 ↔ 234

Ref.19

Natural variations

Natural variant

32

1

E → K.
Corresponds to variant rs2271092 [ dbSNP | Ensembl ].

VAR_021941

Natural variant

132

1

L → I.
Corresponds to variant rs2003783 [ dbSNP | Ensembl ].

VAR_021942

Natural variant

179

1

I → T.
Corresponds to variant rs17632542 [ dbSNP | Ensembl ].

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

.

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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 [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." Baffa R., Moreno J.G., Monne M., Veronese M.L., Gomella L.G. Urology 47:795-800(1996) [PubMed: 8677566] [Abstract] 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]	"Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen." Espana F., Gilabert J., Estelles A., Romeu A., Aznar J., Cabo A. Thromb. Res. 64:309-320(1991) [PubMed: 1725227] [Abstract] Cited for: ENZYME REGULATION, HETERODIMER WITH SERPINA5.
[17]	"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.
[18]	"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.
[19]	"Crystal structure of a ternary complex between human prostate-specific antigen, its substrate acyl intermediate and an activating antibody." Menez R., Michel S., Muller B.H., Bossus M., Ducancel F., Jolivet-Reynaud C., Stura E.A. J. Mol. Biol. 376:1021-1033(2008) [PubMed: 18187150] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.83 ANGSTROMS) OF 25-261 IN COMPLEX WITH SUBSTRATE AND ACTIVATING ANTIBODY, ENZYME REGULATION, ACTIVE SITE, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

Wikipedia

Prostate-specific antigen entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_001030047.1.
NP_001025219.1. NM_001030048.1.
NP_001639.1. NM_001648.2.

UniGene

Hs.171995.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3QUM	X-ray	3.20	P/Q	25-261	[»]

ProteinModelPortal

P07288.

SMR

P07288. Positions 25-261.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07288. 3 interactions.

STRING

P07288.

Protein family/group databases

Allergome

2836. Hom s PSA.

MEROPS

S01.162.

Polymorphism databases

DMDM

130989.

Proteomic databases

PRIDE

P07288.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000326003; ENSP00000314151; ENSG00000142515.

GeneID

354.

KEGG

hsa:354.

Organism-specific databases

CTD

354.

GeneCards

GC19P051358.

H-InvDB

HIX0015369.

HGNC

HGNC:6364. KLK3.

HPA

CAB000070.
HPA000764.

MIM

176820. gene.

neXtProt

NX_P07288.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04669.

HOGENOM

HBG755338.

HOVERGEN

HBG013304.

InParanoid

P07288.

OMA

RSIGRYR.

PhylomeDB

P07288.

Enzyme and pathway databases

BRENDA

3.4.21.77. 2681.

Pathway_Interaction_DB

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

Reactome

REACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpress

P07288.

Bgee

P07288.

CleanEx

HS_KLK3.

Genevestigator

P07288.

GermOnline

ENSG00000142515. 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

K01351.

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

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:	January 25, 2012
This is version 144 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.