Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4

被引:86
作者
Stephenson, SA
Verity, K
Ashworth, LK
Clements, JA
机构
[1] Queensland Univ Technol, Sch Life Sci, Ctr Mol Biotechnol, Brisbane, Qld 4001, Australia
[2] Prince Henrys Inst Med Res, Clayton, Vic 3168, Australia
[3] Univ Calif Lawrence Livermore Natl Lab, Ctr Human Genome, Livermore, CA 94551 USA
关键词
D O I
10.1074/jbc.274.33.23210
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The human tissue kallikrein (KLK) family of serine proteases, which is important in post-translational processing events, currently consists of just three genes-tissue kallikrein (KLK1), KLK2, and prostate-specific antigen (PSA) (KLK3)-clustered at chromosome 19q13.3-13.4. We identified an expressed sequence tag from an endometrial carcinoma cDNA library with 50% identity to the three known KLK genes. Primers designed to putative exon 2 and exon 3 regions from this novel kallikrein-related sequence were used to polymerase chain reaction-screen five cosmids spanning 130 kb around the KIK locus on chromosome 19. This new gene, which we have named KLK4, is 25 kb downstream of the KLK2 gene and follows a region that includes two other putative KLK-like gene fragments KLK4 spans 5.2 kb, has an identical genomic structure-five exons and four introns-to the other KLK genes and is transcribed on the reverse strand, in the same direction as KLK1 but opposite to that of KLK2 and KLK3. It encodes a 254-amino acid prepro-serine protease that is most similar (78% identical) to pig enamel matrix serine protease but is also 37% identical to PSA. These data suggest that the human kallikrein gene family locus on chromosome 19 is larger than previously thought and also indicate a greater sequence divergence within this family compared with the highly conserved rodent kallikrein genes.
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页码:23210 / 23214
页数:5
相关论文
共 34 条
[1]  
Adams MJ, 1998, BIOCHEM J, V329, P165
[2]   A novel protease homolog differentially expressed in breast and ovarian cancer [J].
Anisowicz, A ;
Sotiropoulou, G ;
Stenman, G ;
Mok, SC ;
Sager, R .
MOLECULAR MEDICINE, 1996, 2 (05) :624-636
[3]   HUMAN-KIDNEY KALLIKREIN - CDNA CLONING AND SEQUENCE-ANALYSIS [J].
BAKER, AR ;
SHINE, J .
DNA-A JOURNAL OF MOLECULAR & CELLULAR BIOLOGY, 1985, 4 (06) :445-450
[4]  
BERG T, 1992, RECENT PROGR KININS, V1, P19
[5]  
CLEMENTS JA, 1997, KININ SYSTEM, P72
[6]   Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter [J].
Cleutjens, KBJM ;
vanEekelen, CCEM ;
vanderKorput, HAGM ;
Brinkmann, AO ;
Trapman, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (11) :6379-6388
[7]   A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and androgen-regulated expression of the endogenous prostate-specific antigen gene in humans [J].
Cleutjens, KBJM ;
vanderKorput, HAGM ;
EhrenvanEekelen, CC ;
Sikes, RA ;
Fasciana, C ;
Chung, LW ;
Trapman, J .
MOLECULAR ENDOCRINOLOGY, 1997, 11 (09) :1256-1265
[8]  
DIGBY MR, 1990, P GEN C LORN AUSTR
[9]   STRUCTURE AND CHROMOSOMAL LOCALIZATION OF THE HUMAN RENAL KALLIKREIN GENE [J].
EVANS, BA ;
YUN, ZX ;
CLOSE, JA ;
TREGEAR, GW ;
KITAMURA, N ;
NAKANISHI, S ;
CALLEN, DF ;
BAKER, E ;
HYLAND, VJ ;
SUTHERLAND, GR ;
RICHARDS, RI .
BIOCHEMISTRY, 1988, 27 (09) :3124-3129
[10]  
EVANS BA, 1987, J BIOL CHEM, V262, P8027