Identification of Novel ACE2 homologue, collectrin, and its role in renal organogenesis and progressive renal failure.

Collectrin是血管紧张素转化酶相关羧肽酶（ACE 2）的一种新同系物，在肥大期的5/6个消融肾中鉴定到（Zhang H等，J Biol Chem 276（20），17132 - 17139，2001）。通过使用部分肾切除术的动物模型，通过基于PCR的cDNA消减方法分离几个差异表达的基因（Zhang H等，Kidney Int 56（2），549 - 558，1999）。因为其中一个基因是肾脏特异性的，并且高度定位于集合管，所以它被命名为collectrin。序列分析显示，collectrin具有222个氨基酸，具有明显的信号肽和跨膜结构域（下图中的黑框）;该序列在小鼠、大鼠和人中保守，同源性为81.9%。人collectrin与ACE 2的非催化细胞外和胞质结构域（图中的白色框）具有47.8%的同一性，然而，与ACE和ACE 2不同，collectrin缺乏活性二肽基羧肽酶催化结构域。有趣的是，ACE 2和collectrin在同一染色体区域（Xp 22）中彼此靠近，而ACE位于染色体17。collectrin mRNA转录物仅在肾脏中表达。原位杂交显示其mRNA在肾集合管中表达，免疫组织化学显示其定位于集合管的管腔表面和细胞质。

Collectrin, a novel homologue of angiotensin converting enzyme-related carboxypeptidase (ACE2), was identified in 5/6 ablated kidneys at hypertrophic phase (Zhang H et al. J Biol Chem 276(20),17132-17139,2001). By using an animal model of partial nephrectomy, several differentially expressed genes were isolated by the PCR-based cDNA-subtraction method (Zhang H et al. Kidney Int 56(2),549-558,1999). Because one of these genes was kidney-specific and highly localized to the collecting ducts, it was designated as collectrin. The sequence analyses revealed that collectrin with 222 amino acids has an apparent signal peptide and a transmembrane domain (black box in figure shown below) ; the sequence is conserved in mouse, rat and human and shared 81.9% identity. Human collectrin has 47.8% identity with non-catalytic extracellular and cytosolic domains of ACE2 (white box in figure), however, unlike ACE and ACE2, collectrin lacks active dipeptidyl carboxypeptidase catalytic domains. Interestingly, ACE2 and collectrin are located close to each other in the same chromosomal region (Xp22) and whereas ACE is located chromosome 17. The collectrin mRNA transcripts are expressed exclusively in the kidney. In situ hybridization reveals its mRNA expression in renal collecting ducts and immunohistochemistry shows it is localized to the luminal surface and cytoplasm of collecting ducts.