KLK-4

Kallikrein-related peptidase 4


Eigenschaften des menschlichen Proteins
Masse/Länge Primärstruktur	224 Aminosäuren
Kofaktor	Zn²⁺
Bezeichner
Gen-Name	KLK4
Externe IDs	OMIM: 603767 UniProt: Q9Y5K2 MGI: 1861379
Enzymklassifikation
EC, Kategorie	3.4.21.- Serinprotease
MEROPS	S01.251
Orthologe
	Mensch	Maus
Entrez	9622	56640
Ensembl	ENSG00000167749	ENSMUSG00000006948
UniProt	Q9Y5K2
Refseq (mRNA)	XM_001134318	NM_019928
Refseq (Protein)	XP_001134318	NP_064312
Genlocus	Chr chr19: 56.1 – 56.11 Mb	Chr chr7: 43.75 – 43.75 Mb
PubMed-Suche	9622	56640

Kallikrein-related peptidase 4, auch bekannt als KLK4 oder EMSP1, ist ein menschliches Protein.^[1]^[2]

Nomenklatur und Genetik

Kallikreine sind eine Untergruppe der Serinproteasen und haben verschiedene biologische Funktionen. Zu den Kallikreinen gehört der Tumormarker Prostataspezifisches Antigen, der in der Kallikreinnomenklatur als KLK-3 bezeichnet wird. KLK4 ist beim Menschen eines der 15 bislang bekannten Mitglieder der auf Chromosom 19 lokalisierten Kallikrein-Familie.^[3]^[4]^[5]^[6] Die Anzahl der Maus-Gene ist nicht genau bekannt und wird auf 13-26 geschätzt.^[6]

Tumorbiologische Aspekte

In jüngster Zeit haben sich die Hinweise verdichtet, dass neben dem PSA auch andere Kallikreine in der Krebsentstehung eine Rolle spielen.^[7]^[8] So scheint KLK-4 den PSA-Vorläufer pro-PSA und den urokinase-ähnlichen Plasminaktivator uPA aktivieren zu können.^[9] Man vermutet daher, dass es bei der Entstehung des Prostata-Karzinoms beteiligt ist.^[10] Zudem ist in Prostata- und Brustdrüsen-Gewebe die Expression von KLK-4 hormonell reguliert. Auch diese Beobachtung spricht für die Annahme, dass es für die Tumorentstehung in diesen Geweben eine Rolle spielt.^[11]^[12] Aufgrund der gewebespezifischen Expression des KLK-4 Proteins wurde untersucht, ob es sich für eine Tumorvaccine gegen das Prostatakarzinom eignet.^[13]

Zahnentwicklung

Das Maus-Homolog von KLK4 wird in den Zahnanlagen exprimiert. Es konnte dabei in Odontoblasten und Ameloblasten nachgewiesen werden.^[14] Dies stütz die Annahme, dass KLK4 eine Rolle bei der Degradation der Zahnschmelzproteine spielt, da es eine 78 % Sequenzhomologie mit der Enamel Matrix Serinprotease I des Schweins aufzeigt, die eine solche Funktion ausübt.^[15] Mutationen am KLK4-Gen können die Ursache für Amelogenesis imperfecta (AIPH) sein.^[16]^[17]

Weiterführende Literatur zu Chromosom 19

Strausberg RL, Feingold EA, Grouse LH, et al.: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. in: Proc. Natl. Acad. Sci. USA vol. 99,26 pg. 16899–903 (2003) PMID 12477932
Grimwood J, Gordon LA, Olsen A, et al.: The DNA sequence and biology of human chromosome 19. in: Nature vol. 428,6982 pg. 529–35 (2004) PMID 15057824
Gerhard DS, Wagner L, Feingold EA, et al.: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). in: Genome Res. vol. 14,10B pg. 2121–7 (2004) PMID 15489334

Einzelnachweise

↑ Entrez Gene: KLK4 kallikrein-related peptidase 4. Abgerufen am 7. Januar 2011.
↑ Simmer JP, Fukae M, Tanabe T, et al.: Purification, characterization, and cloning of enamel matrix serine proteinase 1. in: J. Dent. Res. vol. 77,2 pg. 377–86 (1998) PMID 9465170
↑ Gan L, Lee I, Smith R, et al.: Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. in: Gene vol. 257,1 pg. 119–30 (2001) PMID 11054574
↑ Stephenson SA, Verity K, Ashworth LK, Clements JA: 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. in: J. Biol. Chem. vol. 274,33 pg. 23210–4 (1999) PMID 10438493
↑ DuPont BR, Hu CC, Reveles X, Simmer JP: Assignment of serine protease 17 (PRSS17) to human chromosome bands 19q13.3→q13.4 by in situ hybridization. in: Cytogenet. Cell Genet. vol. 86,3-4 pg. 212–3 (2000) PMID 10575207
↑ ^6,0 ^6,1 Clements J, Hooper J, Dong Y, Harvey T: The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. in: Biol. Chem. vol. 382,1 pg. 5–14 (2001) PMID 11258672
↑ Veveris-Lowe TL, Lawrence MG, Collard RL, et al.: Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells. in: Endocr. Relat. Cancer vol. 12,3 pg. 631–43 (2005) PMID 16172196
↑ Xi Z, Klokk TI, Korkmaz K, et al.: Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. in: Cancer Res. vol. 64,7 pg. 2365–70 (2004) PMID 15059887
↑ Takayama TK, McMullen BA, Nelson PS, et al.: Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. in: Biochemistry vol. 40,50 pg. 15341–8 (2002) PMID 11735417
↑ Takayama TK, Carter CA, Deng T: Activation of prostate-specific antigen precursor (pro-PSA) by prostin, a novel human prostatic serine protease identified by degenerate PCR. in: Biochemistry vol. 40,6 pg. 1679–87 (2001) PMID 11327827
↑ Yousef GM, Obiezu CV, Luo LY, et al.: Prostase/KLK-L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated. in: Cancer Res. vol. 59,17 pg. 4252–6 (1999) PMID 10485467
↑ Korkmaz KS, Korkmaz CG, Pretlow TG, Saatcioglu F: Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with other members of the kallikrein family: intracellular localization, alternative cDNA forms, and Regulation by multiple hormones. in: DNA Cell Biol. vol. 20,7 pg. 435–45 (2001) PMID 11506707
↑ Hural JA, Friedman RS, McNabb A, et al.: Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation. in: J. Immunol. vol. 169,1 pg. 557–65 (2002) PMID 12077288
↑ Hu JC, Zhang C, Sun X, et al.: Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors. in: Gene vol. 251,1 pg. 1–8 (2000) PMID 10863090
↑ Nelson PS, Gan L, Ferguson C, et al.: Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. in: Proc. Natl. Acad. Sci. U.S.A. vol. 96,6 pg. 3114–9 (1999) PMID 10077646
↑ AIPH. In: {{Modul:Vorlage:lang}} Modul:Multilingual:149: attempt to index field 'data' (a nil value). (englisch).
↑ Hart PS, Hart TC, Michalec MD, et al.: Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. in: J. Med. Genet. vol. 41,7 pg. 545–9 (2004) PMID 15235027

[entrez-1] Entrez Gene: KLK4 kallikrein-related peptidase 4. Abgerufen am 7. Januar 2011.

[2] Simmer JP, Fukae M, Tanabe T, et al.: Purification, characterization, and cloning of enamel matrix serine proteinase 1. in: J. Dent. Res. vol. 77,2 pg. 377–86 (1998) PMID 9465170

[3] Gan L, Lee I, Smith R, et al.: Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. in: Gene vol. 257,1 pg. 119–30 (2001) PMID 11054574

[4] Stephenson SA, Verity K, Ashworth LK, Clements JA: 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. in: J. Biol. Chem. vol. 274,33 pg. 23210–4 (1999) PMID 10438493

[5] DuPont BR, Hu CC, Reveles X, Simmer JP: Assignment of serine protease 17 (PRSS17) to human chromosome bands 19q13.3→q13.4 by in situ hybridization. in: Cytogenet. Cell Genet. vol. 86,3-4 pg. 212–3 (2000) PMID 10575207

[Clements_5-14-6] 6,0 ^6,1 Clements J, Hooper J, Dong Y, Harvey T: The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. in: Biol. Chem. vol. 382,1 pg. 5–14 (2001) PMID 11258672

[7] Veveris-Lowe TL, Lawrence MG, Collard RL, et al.: Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells. in: Endocr. Relat. Cancer vol. 12,3 pg. 631–43 (2005) PMID 16172196

[8] Xi Z, Klokk TI, Korkmaz K, et al.: Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. in: Cancer Res. vol. 64,7 pg. 2365–70 (2004) PMID 15059887

[9] Takayama TK, McMullen BA, Nelson PS, et al.: Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. in: Biochemistry vol. 40,50 pg. 15341–8 (2002) PMID 11735417

[10] Takayama TK, Carter CA, Deng T: Activation of prostate-specific antigen precursor (pro-PSA) by prostin, a novel human prostatic serine protease identified by degenerate PCR. in: Biochemistry vol. 40,6 pg. 1679–87 (2001) PMID 11327827

[11] Yousef GM, Obiezu CV, Luo LY, et al.: Prostase/KLK-L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated. in: Cancer Res. vol. 59,17 pg. 4252–6 (1999) PMID 10485467

[12] Korkmaz KS, Korkmaz CG, Pretlow TG, Saatcioglu F: Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with other members of the kallikrein family: intracellular localization, alternative cDNA forms, and Regulation by multiple hormones. in: DNA Cell Biol. vol. 20,7 pg. 435–45 (2001) PMID 11506707

[13] Hural JA, Friedman RS, McNabb A, et al.: Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation. in: J. Immunol. vol. 169,1 pg. 557–65 (2002) PMID 12077288

[14] Hu JC, Zhang C, Sun X, et al.: Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors. in: Gene vol. 251,1 pg. 1–8 (2000) PMID 10863090

[15] Nelson PS, Gan L, Ferguson C, et al.: Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. in: Proc. Natl. Acad. Sci. U.S.A. vol. 96,6 pg. 3114–9 (1999) PMID 10077646

[16] AIPH. In: {{Modul:Vorlage:lang}} Modul:Multilingual:149: attempt to index field 'data' (a nil value). (englisch).

[17] Hart PS, Hart TC, Michalec MD, et al.: Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. in: J. Med. Genet. vol. 41,7 pg. 545–9 (2004) PMID 15235027

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