FAP Q12884

脯氨酰内肽酶 FAP (EC 3.4.21.26) (170 kDa 黑色素瘤膜结合明胶酶) (二肽基肽酶 FAP) (EC 3.4.14.5) (成纤维细胞激活蛋白 alpha) (FAPalpha) (明胶降解蛋白酶 FAP) (EC 3.4.21.-) (整合膜丝氨酸蛋白酶) (脯氨酸后切割酶) (丝氨酸整合膜蛋白酶) (SIMP) (表面表达蛋白酶) (Seprase) [切割为：抗纤溶酶切割酶 FAP，可溶形式 (APCE) (EC 3.4.14.5) (EC 3.4.21.-) (EC 3.4.21.26)]

功能描述

细胞表面糖蛋白丝氨酸蛋白酶，参与细胞外基质降解，并参与许多细胞过程，包括组织重塑、纤维化、伤口愈合、炎症和肿瘤生长。质膜形式和可溶形式均表现出脯氨酸后切割内肽酶活性，对底物如alpha-2-抗纤溶酶SERPINF2和SPRY2上的Ala/Ser-Gly-Pro-Ser/Asn/Ala共有序列具有显著偏好 (PubMed:14751930, PubMed:16223769, PubMed:16410248, PubMed:16480718, PubMed:17381073, PubMed:18095711, PubMed:21288888, PubMed:24371721)。也能降解明胶、热变性I型胶原，但不能降解天然I型和IV型胶原、玻连蛋白、肌腱蛋白、层粘连蛋白、纤连蛋白、纤维蛋白或酪蛋白 (PubMed:10347120, PubMed:10455171, PubMed:12376466, PubMed:16223769, PubMed:16651416, PubMed:18095711, PubMed:2172980, PubMed:7923219, PubMed:9065413)。还具有二肽基肽酶活性，表现出水解合成二肽底物N端第二个残基脯氨酰键的能力，前提是倒数第二位残基是脯氨酸，偏好Ala-Pro、Ile-Pro、Gly-Pro、Arg-Pro和Pro-Pro (PubMed:10347120, PubMed:10593948, PubMed:16175601, PubMed:16223769, PubMed:16410248, PubMed:16651416, PubMed:17381073, PubMed:21314817, PubMed:24371721, PubMed:24717288)。二肽基肽酶的天然神经肽激素是神经肽Y (NPY)、肽YY (PYY)、P物质 (TAC1) 和脑利钠肽32 (NPPB) (PubMed:21314817)。质膜形式与DPP4、PLAUR或整合素结合，参与细胞外基质 (ECM) 的细胞周蛋白水解，从而促进细胞粘附、迁移和穿过ECM的侵袭。在发育和伤口愈合过程中在组织重塑中发挥作用。参与恶性黑色素瘤癌症中细胞对ECM的侵袭。通过增加血管生成、胶原纤维降解和细胞凋亡以及降低免疫系统的抗肿瘤反应来增强肿瘤生长进程。通过降解蛋白聚糖brevican促进胶质瘤细胞穿过脑实质的侵袭。通过以不依赖丝氨酸蛋白酶活性的方式调节细胞增殖和存活，在黑色素细胞中充当肿瘤抑制因子。 {ECO:0000250|UniProtKB:P97321, ECO:0000269|PubMed:10347120, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:10593948, ECO:0000269|PubMed:12376466, ECO:0000269|PubMed:14751930, ECO:0000269|PubMed:16175601, ECO:0000269|PubMed:16223769, ECO:0000269|PubMed:16410248, ECO:0000269|PubMed:16480718, ECO:0000269|PubMed:16651416, ECO:0000269|PubMed:17105646, ECO:0000269|PubMed:17381073, ECO:0000269|PubMed:18095711, ECO:0000269|PubMed:20707604, ECO:0000269|PubMed:21288888, ECO:0000269|PubMed:21314817, ECO:0000269|PubMed:2172980, ECO:0000269|PubMed:24371721, ECO:0000269|PubMed:24717288, ECO:0000269|PubMed:7923219, ECO:0000269|PubMed:9065413}.

组织特异性

Expressed in adipose tissue. Expressed in the dermal fibroblasts in the fetal skin. Expressed in the granulation tissue of healing wounds and on reactive stromal fibroblast in epithelial cancers. Expressed in activated fibroblast-like synoviocytes from inflamed synovial tissues. Expressed in activated hepatic stellate cells (HSC) and myofibroblasts from cirrhotic liver, but not detected in normal liver. Expressed in glioma cells (at protein level). Expressed in glioblastomas and glioma cells. Isoform 1 and isoform 2 are expressed in melanoma, carcinoma and fibroblast cell lines.

亚细胞定位

[Prolyl endopeptidase FAP]: Cell surface