IL4I1 Q96RQ9

L-氨基酸氧化酶 (LAAO) (LAO) (EC 1.4.3.2) (EC 1.4.3.25) (白细胞介素-4诱导蛋白1) (IL4诱导蛋白1) (hIL4I1) (Fig-1蛋白) (hFIG1)

功能描述

分泌型L-氨基酸氧化酶，作为关键的免疫调节因子 (PubMed:17356132, PubMed:32818467, PubMed:32866000)。对L-芳香族氨基酸有偏好：分别将苯丙氨酸 (Phe)、酪氨酸 (Tyr) 和色氨酸 (Trp) 转化为苯丙酮酸 (PP)、对羟基苯丙酮酸 (HPP) 和吲哚-3-丙酮酸 (I3P) (PubMed:17356132, PubMed:32818467, PubMed:32866000)。亦具有微弱的L-精氨酸氧化酶活性 (PubMed:26673964)。通过吲哚丙酮途径介导Trp降解，激活转录因子AHR，从而作为抗肿瘤免疫的负调节因子 (PubMed:32818467, PubMed:32866000)。IL4I1介导的Trp分解代谢产生I3P，生成吲哚代谢物（吲哚-3-乙酸 (IAA) 和吲哚-3-甲醛 (I3A)）和犬尿酸，它们作为AHR的配体；AHR是一种配体激活的转录因子，在免疫和癌症中发挥重要作用 (PubMed:32818467, PubMed:32866000)。IL4I1介导的Trp降解后产生的吲哚激活AHR，通过促进癌细胞运动和抑制适应性免疫来增强肿瘤进展 (PubMed:32818467)。在某些免疫细胞中亦具有免疫调节功能，可能通过介导Trp降解并促进下游AHR激活：抑制T细胞活化和增殖，促进初始CD4(+) T细胞分化为FOXP3(+) 调节性T细胞 (Treg)，并调节B细胞的发育和功能 (PubMed:17356132, PubMed:25446972, PubMed:25778793, PubMed:28891065)。亦通过抑制T细胞活化来调节M2型巨噬细胞极化 (By similarity)。亦具有抗菌特性，通过产生NH4(+) 和 H2O2 抑制革兰氏阴性和革兰氏阳性细菌的生长 (PubMed:23355881)。 {ECO:0000250|UniProtKB:O09046, ECO:0000269|PubMed:17356132, ECO:0000269|PubMed:23355881, ECO:0000269|PubMed:25446972, ECO:0000269|PubMed:25778793, ECO:0000269|PubMed:26673964, ECO:0000269|PubMed:28891065, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000}。

组织特异性

Primarily found in immune tissues, with the highest expression in lymph nodes and spleen (PubMed:12031486, PubMed:12446450). Present in germinal center macrophages and inflammatory myeloid cells and antigen-presenting cells (at protein level) (PubMed:17356132). Also present in spermatozoa (at protein level) (PubMed:25767141). Highly expressed in primary mediastinal large B-cell lymphoma, a specific subtype of diffuse large B-cell lymphoma (PubMed:12446450). Expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophages (PubMed:19436310).

亚细胞定位

Secreted