Gene name: ALOX5

Uniprot entry:

P09917

Protein names:

Polyunsaturated fatty acid 5-lipoxygenase (EC 1.13.11.-) (Arachidonate 5-lipoxygenase) (5-LO) (5-lipoxygenase) (EC 1.13.11.34)

Protein sequence:

1_MPSYT 6_ VTVAT 11_ GSQWF 16_ AGTDD 21_ YIYLS 26_ LVGSA 31_ GCSEK 36_ HLLDK 41_ PFYND 46_ FERGA 51_ VDSYD 56_ VTVDE 61_ ELGEI 66_ QLVRI 71_ EKRKY 76_ WLNDD 81_ WYLKY 86_ ITLKT 91_ PHGDY 96_ IEFPC 101_ YRWIT 106_ GDVEV 111_ VLRDG 116_ RAKLA 121_ RDDQI 126_ HILKQ 131_ HRRKE 136_ LETRQ 141_ KQYRW 146_ MEWNP 151_ GFPLS 156_ IDAKC 161_ HKDLP 166_ RDIQF 171_ DSEKG 176_ VDFVL 181_ NYSKA 186_ MENLF 191_ INRFM 196_ HMFQS 201_ SWNDF 206_ ADFEK 211_ IFVKI 216_ SNTIS 221_ ERVMN 226_ HWQED 231_ LMFGY 236_ QFLNG 241_ CNPVL 246_ IRRCT 251_ ELPEK 256_ LPVTT 261_ EMVEC 266_ SLERQ 271_ LSLEQ 276_ EVQQG 281_ NIFIV 286_ DFELL 291_ DGIDA 296_ NKTDP 301_ CTLQF 306_ LAAPI 311_ CLLYK 316_ NLANK 321_ IVPIA 326_ IQLNQ 331_ IPGDE 336_ NPIFL 341_ PSDAK 346_ YDWLL 351_ AKIWV 356_ RSSDF 361_ HVHQT 366_ ITHLL 371_ RTHLV 376_ SEVFG 381_ IAMYR 386_ QLPAV 391_ HPIFK 396_ LLVAH 401_ VRFTI 406_ AINTK 411_ AREQL 416_ ICECG 421_ LFDKA 426_ NATGG 431_ GGHVQ 436_ MVQRA 441_ MKDLT 446_ YASLC 451_ FPEAI 456_ KARGM 461_ ESKED 466_ IPYYF 471_ YRDDG 476_ LLVWE 481_ AIRTF 486_ TAEVV 491_ DIYYE 496_ GDQVV 501_ EEDPE 506_ LQDFV 511_ NDVYV 516_ YGMRG 521_ RKSSG 526_ FPKSV 531_ KSREQ 536_ LSEYL 541_ TVVIF 546_ TASAQ 551_ HAAVN 556_ FGQYD 561_ WCSWI 566_ PNAPP 571_ TMRAP 576_ PPTAK 581_ GVVTI 586_ EQIVD 591_ TLPDR 596_ GRSCW 601_ HLGAV 606_ WALSQ 611_ FQENE 616_ LFLGM 621_ YPEEH 626_ FIEKP 631_ VKEAM 636_ ARFRK 641_ NLEAI 646_ VSVIA 651_ ERNKK 656_ KQLPY 661_ YYLSP 666_DRIPN

Protein annotations

Protein functions:

1: Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:8615788). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity)