ID LOXL2_HUMAN Reviewed; 774 AA. AC Q9Y4K0; B2R5Q0; Q53HV3; Q9BW70; Q9Y5Y8; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 204. DE RecName: Full=Lysyl oxidase homolog 2; DE EC=1.4.3.13 {ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596, ECO:0000269|PubMed:29581294}; DE AltName: Full=Lysyl oxidase-like protein 2; DE AltName: Full=Lysyl oxidase-related protein 2; DE AltName: Full=Lysyl oxidase-related protein WS9-14; DE Flags: Precursor; GN Name=LOXL2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9079631; DOI=10.1074/jbc.272.13.8157; RA Saito H., Papaconstantinou J., Sato H., Goldstein S.; RT "Regulation of a novel gene encoding a lysyl oxidase-related protein in RT cellular adhesion and senescence."; RL J. Biol. Chem. 272:8157-8160(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-570. RC TISSUE=Adipose tissue; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-570. RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 202-774, AND TISSUE SPECIFICITY. RC TISSUE=Placenta, and Spleen; RX PubMed=10212285; DOI=10.1074/jbc.274.18.12939; RA Jourdan-Le Saux C., Tronecker H., Bogic L., Bryant-Greenwood G.D., RA Boyd C.D., Csiszar K.; RT "The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed RT at high levels in reproductive tissues."; RL J. Biol. Chem. 274:12939-12944(1999). RN [7] RP FUNCTION, AND INTERACTION WITH SNAI1. RX PubMed=16096638; DOI=10.1038/sj.emboj.7600781; RA Peinado H., Del Carmen Iglesias-de la Cruz M., Olmeda D., Csiszar K., RA Fong K.S., Vega S., Nieto M.A., Cano A., Portillo F.; RT "A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and RT tumor progression."; RL EMBO J. 24:3446-3458(2005). RN [8] RP FUNCTION, AND INDUCTION. RX PubMed=20026874; DOI=10.1074/jbc.m109.042424; RA Schietke R., Warnecke C., Wacker I., Schodel J., Mole D.R., Campean V., RA Amann K., Goppelt-Struebe M., Behrens J., Eckardt K.U., Wiesener M.S.; RT "The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress RT E-cadherin in hypoxia: insights into cellular transformation processes RT mediated by HIF-1."; RL J. Biol. Chem. 285:6658-6669(2010). RN [9] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION. RX PubMed=20439985; DOI=10.1074/jbc.m109.094136; RA Rodriguez H.M., Vaysberg M., Mikels A., McCauley S., Velayo A.C., RA Garcia C., Smith V.; RT "Modulation of lysyl oxidase-like 2 enzymatic activity by an allosteric RT antibody inhibitor."; RL J. Biol. Chem. 285:20964-20974(2010). RN [10] RP ACTIVITY REGULATION. RX PubMed=20818376; DOI=10.1038/nm.2208; RA Barry-Hamilton V., Spangler R., Marshall D., McCauley S., Rodriguez H.M., RA Oyasu M., Mikels A., Vaysberg M., Ghermazien H., Wai C., Garcia C.A., RA Velayo A.C., Jorgensen B., Biermann D., Tsai D., Green J., RA Zaffryar-Eilot S., Holzer A., Ogg S., Thai D., Neufeld G., RA Van Vlasselaer P., Smith V.; RT "Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a RT pathologic microenvironment."; RL Nat. Med. 16:1009-1017(2010). RN [11] RP FUNCTION. RX PubMed=21835952; DOI=10.1182/blood-2010-10-313296; RA Bignon M., Pichol-Thievend C., Hardouin J., Malbouyres M., Brechot N., RA Nasciutti L., Barret A., Teillon J., Guillon E., Etienne E., Caron M., RA Joubert-Caron R., Monnot C., Ruggiero F., Muller L., Germain S.; RT "Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV RT collagen assembly in the endothelial basement membrane."; RL Blood 118:3979-3989(2011). RN [12] RP ROLE IN TUMOR PROGRESSION. RX PubMed=21233336; DOI=10.1158/0008-5472.can-10-2868; RA Barker H.E., Chang J., Cox T.R., Lang G., Bird D., Nicolau M., Evans H.R., RA Gartland A., Erler J.T.; RT "LOXL2-mediated matrix remodeling in metastasis and mammary gland RT involution."; RL Cancer Res. 71:1561-1572(2011). RN [13] RP ROLE IN TUMOR PROGRESSION. RX PubMed=21732535; DOI=10.1002/emmm.201100156; RA Moreno-Bueno G., Salvador F., Martin A., Floristan A., Cuevas E.P., RA Santos V., Montes A., Morales S., Castilla M.A., Rojo-Sebastian A., RA Martinez A., Hardisson D., Csiszar K., Portillo F., Peinado H., RA Palacios J., Cano A.; RT "Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required RT for metastatic dissemination of basal-like breast carcinomas."; RL EMBO Mol. Med. 3:528-544(2011). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=20306300; DOI=10.1007/s11033-010-0088-0; RA Kim Y.M., Kim E.C., Kim Y.; RT "The human lysyl oxidase-like 2 protein functions as an amine oxidase RT toward collagen and elastin."; RL Mol. Biol. Rep. 38:145-149(2011). RN [15] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=22204712; DOI=10.1016/j.humpath.2011.07.027; RA Li T.Y., Xu L.Y., Wu Z.Y., Liao L.D., Shen J.H., Xu X.E., Du Z.P., Zhao Q., RA Li E.M.; RT "Reduced nuclear and ectopic cytoplasmic expression of lysyl oxidase-like 2 RT is associated with lymph node metastasis and poor prognosis in esophageal RT squamous cell carcinoma."; RL Hum. Pathol. 43:1068-1076(2012). RN [16] RP MUTAGENESIS OF TYR-689. RX PubMed=22157764; DOI=10.1074/jbc.m111.261016; RA Lugassy J., Zaffryar-Eilot S., Soueid S., Mordoviz A., Smith V., RA Kessler O., Neufeld G.; RT "The enzymatic activity of lysyl oxidas-like-2 (LOXL2) is not required for RT LOXL2-induced inhibition of keratinocyte differentiation."; RL J. Biol. Chem. 287:3541-3549(2012). RN [17] RP RETRACTED PAPER. RX PubMed=22483618; DOI=10.1016/j.molcel.2012.03.002; RA Herranz N., Dave N., Millanes-Romero A., Morey L., Diaz V.M., RA Lorenz-Fonfria V., Gutierrez-Gallego R., Jeronimo C., Di Croce L., RA Garcia de Herreros A., Peiro S.; RT "Lysyl oxidase-like 2 deaminates lysine 4 in histone H3."; RL Mol. Cell 46:369-376(2012). RN [18] RP RETRACTION NOTICE OF PUBMED:22483618. RX PubMed=27392148; DOI=10.1016/j.molcel.2016.06.013; RA Herranz N., Dave N., Millanes-Romero A., Morey L., Diaz V.M., RA Lorenz-Fonfria V., Gutierrez-Gallego R., Jeronimo C., Di Croce L., RA Garcia de Herreros A., Peiro S.; RL Mol. Cell 63:180-180(2016). RN [19] RP INTERACTION WITH EFEMP2. RX PubMed=27339457; DOI=10.1016/j.matbio.2016.06.003; RA Sasaki T., Hanisch F.G., Deutzmann R., Sakai L.Y., Sakuma T., Miyamoto T., RA Yamamoto T., Hannappel E., Chu M.L., Lanig H., von der Mark K.; RT "Functional consequence of fibulin-4 missense mutations associated with RT vascular and skeletal abnormalities and cutis laxa."; RL Matrix Biol. 56:132-149(2016). RN [20] RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, RP GLYCOSYLATION AT ASN-455 AND ASN-644, MUTAGENESIS OF ASN-455 AND ASN-644, RP CROSS-LINK FORMATION, AND SUBCELLULAR LOCATION. RX PubMed=23319596; DOI=10.1074/jbc.c112.421768; RA Xu L., Go E.P., Finney J., Moon H., Lantz M., Rebecchi K., Desaire H., RA Mure M.; RT "Post-translational modifications of recombinant human lysyl oxidase-like 2 RT (rhLOXL2) secreted from Drosophila S2 cells."; RL J. Biol. Chem. 288:5357-5363(2013). RN [21] RP FUNCTION. RX PubMed=24239292; DOI=10.1016/j.molcel.2013.10.015; RA Millanes-Romero A., Herranz N., Perrera V., Iturbide A., RA Loubat-Casanovas J., Gil J., Jenuwein T., Garcia de Herreros A., Peiro S.; RT "Regulation of heterochromatin transcription by Snail1/LOXL2 during RT epithelial-to-mesenchymal transition."; RL Mol. Cell 52:746-757(2013). RN [22] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 626-HIS--HIS-628. RX PubMed=24414204; DOI=10.1242/bio.20146841; RA Cuevas E.P., Moreno-Bueno G., Canesin G., Santos V., Portillo F., Cano A.; RT "LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal RT transition."; RL Biol. Open 3:129-137(2014). RN [23] RP FUNCTION, AND INTERACTION WITH TAF10. RX PubMed=25959397; DOI=10.1016/j.molcel.2015.04.012; RA Iturbide A., Pascual-Reguant L., Fargas L., Cebria J.P., Alsina B., RA Garcia de Herreros A., Peiro S.; RT "LOXL2 oxidizes methylated TAF10 and controls TFIID-dependent genes during RT neural progenitor differentiation."; RL Mol. Cell 58:755-766(2015). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 626-HIS--HIS-628. RX PubMed=27735137; DOI=10.1111/febs.13922; RA Herranz N., Dave N., Millanes-Romero A., Pascual-Reguant L., Morey L., RA Diaz V.M., Lorenz-Fonfria V., Gutierrez-Gallego R., Jeronimo C., RA Iturbide A., Di Croce L., Garcia de Herreros A., Peiro S.; RT "Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone RT H3."; RL FEBS J. 283:4263-4273(2016). RN [25] RP INTERACTION WITH HSPA5, AND SUBCELLULAR LOCATION. RX PubMed=28332555; DOI=10.1038/srep44988; RA Cuevas E.P., Eraso P., Mazon M.J., Santos V., Moreno-Bueno G., Cano A., RA Portillo F.; RT "LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 RT signalling pathway."; RL Sci. Rep. 7:44988-44988(2017). RN [26] {ECO:0007744|PDB:5ZE3} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 318-774 IN COMPLEX WITH ZINC AND RP CALCIUM, CATALYTIC ACTIVITY, COFACTOR, GLYCOSYLATION AT ASN-644, DISULFIDE RP BONDS, MUTAGENESIS OF HIS-626; HIS-628; HIS-630; LYS-653 AND TYR-689, RP CROSS-LINK FORMATION, TOPAQUINONE FORMATION, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=29581294; DOI=10.1073/pnas.1720859115; RA Zhang X., Wang Q., Wu J., Wang J., Shi Y., Liu M.; RT "Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor RT state."; RL Proc. Natl. Acad. Sci. U.S.A. 115:3828-3833(2018). CC -!- FUNCTION: Mediates the post-translational oxidative deamination of CC lysine residues on target proteins leading to the formation of CC deaminated lysine (allysine) (PubMed:27735137). Acts as a transcription CC corepressor and specifically mediates deamination of trimethylated CC 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic CC transcriptional activation (PubMed:27735137). Shows no activity against CC histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27' CC (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated CC (H3K4me2) (PubMed:27735137). Also mediates deamination of methylated CC TAF10, a member of the transcription factor IID (TFIID) complex, which CC induces release of TAF10 from promoters, leading to inhibition of CC TFIID-dependent transcription (PubMed:25959397). LOXL2-mediated CC deamination of TAF10 results in transcriptional repression of genes CC required for embryonic stem cell pluripotency including POU5F1/OCT4, CC NANOG, KLF4 and SOX2 (By similarity). Involved in epithelial to CC mesenchymal transition (EMT) via interaction with SNAI1 and CC participates in repression of E-cadherin CDH1, probably by mediating CC deamination of histone H3 (PubMed:16096638, PubMed:27735137, CC PubMed:24414204). During EMT, involved with SNAI1 in negatively CC regulating pericentromeric heterochromatin transcription CC (PubMed:24239292). SNAI1 recruits LOXL2 to pericentromeric regions to CC oxidize histone H3 and repress transcription which leads to release of CC heterochromatin component CBX5/HP1A, enabling chromatin reorganization CC and acquisition of mesenchymal traits (PubMed:24239292). Interacts with CC the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1 CC pathway of the unfolded protein response, leading to expression of CC several transcription factors involved in EMT and subsequent EMT CC induction (PubMed:28332555). Involved in E-cadherin repression CC following hypoxia, a hallmark of EMT believed to amplify tumor CC aggressiveness, suggesting that it may play a role in tumor progression CC (PubMed:20026874). When secreted into the extracellular matrix, CC promotes cross-linking of extracellular matrix proteins by mediating CC oxidative deamination of peptidyl lysine residues in precursors to CC fibrous collagen and elastin (PubMed:20306300). Acts as a regulator of CC sprouting angiogenesis, probably via collagen IV scaffolding CC (PubMed:21835952). Acts as a regulator of chondrocyte differentiation, CC probably by regulating expression of factors that control chondrocyte CC differentiation (By similarity). {ECO:0000250|UniProtKB:P58022, CC ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20026874, CC ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:21835952, CC ECO:0000269|PubMed:24239292, ECO:0000269|PubMed:24414204, CC ECO:0000269|PubMed:25959397, ECO:0000269|PubMed:27735137}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-lysyl-[protein] + O2 = (S)-2-amino-6-oxohexanoyl- CC [protein] + H2O2 + NH4(+); Xref=Rhea:RHEA:24544, Rhea:RHEA-COMP:9752, CC Rhea:RHEA-COMP:12448, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:131803; EC=1.4.3.13; CC Evidence={ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:20439985, CC ECO:0000269|PubMed:23319596, ECO:0000269|PubMed:29581294}; CC -!- COFACTOR: CC Name=Cu cation; Xref=ChEBI:CHEBI:23378; CC Evidence={ECO:0000269|PubMed:29581294}; CC -!- COFACTOR: CC Name=lysine tyrosylquinone residue; Xref=ChEBI:CHEBI:20489; CC Evidence={ECO:0000269|PubMed:29581294}; CC Note=Contains 1 lysine tyrosylquinone. {ECO:0000250|UniProtKB:P33072}; CC -!- ACTIVITY REGULATION: According to some reports, it is inhibited by CC beta-aminopropionitrile (BAPN) (PubMed:20439985, PubMed:23319596). CC According to another report, it is not inhibited by beta- CC aminopropionitrile (BAPN) (PubMed:20306300). Specifically inhibited by CC a mouse monoclonal antibody AB0023, inhibition occurs in a non- CC competitive manner. {ECO:0000269|PubMed:20306300, CC ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:20818376, CC ECO:0000269|PubMed:23319596}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.01 mM for 1,5-diaminopentane {ECO:0000269|PubMed:20439985, CC ECO:0000269|PubMed:23319596}; CC KM=1.05 mM for spermine {ECO:0000269|PubMed:20439985, CC ECO:0000269|PubMed:23319596}; CC KM=0.59 uM for tropoelastin (without the first three SRCR domains) CC {ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596}; CC KM=0.62 uM for tropoelastin (without all four SRCR domains) CC {ECO:0000269|PubMed:20439985, ECO:0000269|PubMed:23319596}; CC Note=kcat is 2.04 min(-1) with tropoelastin as substrate (without the CC first three SRCR domains). kcat is 0.62 min(-1) with tropoelastin as CC substrate (without all four SRCR domains).; CC -!- SUBUNIT: Component of some chromatin repressor complex. Interacts with CC SNAI1 (PubMed:16096638). Interacts with TAF10 (PubMed:25959397). CC Interacts with HSPA5 (PubMed:28332555). Interacts with EFEMP2 CC (PubMed:27339457). {ECO:0000269|PubMed:16096638, CC ECO:0000269|PubMed:25959397, ECO:0000269|PubMed:27339457, CC ECO:0000269|PubMed:28332555}. CC -!- INTERACTION: CC Q9Y4K0; P17655: CAPN2; NbExp=2; IntAct=EBI-7172227, EBI-1028956; CC Q9Y4K0; P15502-2: ELN; NbExp=2; IntAct=EBI-7172227, EBI-7882008; CC Q9Y4K0; P02751: FN1; NbExp=2; IntAct=EBI-7172227, EBI-1220319; CC Q9Y4K0; P49006: MARCKSL1; NbExp=4; IntAct=EBI-7172227, EBI-4289961; CC Q9Y4K0; P08670: VIM; NbExp=6; IntAct=EBI-7172227, EBI-353844; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix, basement membrane {ECO:0000269|PubMed:23319596}. Nucleus CC {ECO:0000269|PubMed:22204712, ECO:0000269|PubMed:24414204}. Chromosome CC {ECO:0000269|PubMed:27735137}. Endoplasmic reticulum CC {ECO:0000269|PubMed:28332555}. Note=Associated with chromatin CC (PubMed:27735137). It is unclear how LOXL2 is nuclear as it contains a CC signal sequence and has been shown to be secreted (PubMed:23319596). CC However, a number of reports confirm its intracellular location and its CC key role in transcription regulation (PubMed:22204712, CC PubMed:22483618). {ECO:0000269|PubMed:22204712, CC ECO:0000269|PubMed:23319596, ECO:0000269|PubMed:24414204, CC ECO:0000269|PubMed:27735137}. CC -!- TISSUE SPECIFICITY: Expressed in many tissues (PubMed:10212285). CC Highest expression in reproductive tissues, placenta, uterus and CC prostate (PubMed:10212285). In esophageal epithelium, expressed in the CC basal, prickle and granular cell layers (PubMed:22204712). Up-regulated CC in a number of cancers cells and tissues. {ECO:0000269|PubMed:10212285, CC ECO:0000269|PubMed:22204712}. CC -!- INDUCTION: Strongly induced in hypoxia. Direct transcriptional target CC of HIF1A. {ECO:0000269|PubMed:20026874}. CC -!- DOMAIN: The fourth SRCR domain plays an important role in optimizing CC the catalytic activity of the lysyl-oxidase like (LOX) catalytic CC domain. CC -!- PTM: The lysine tyrosylquinone cross-link (LTQ) is generated by CC condensation of the epsilon-amino group of a lysine with a topaquinone CC produced by oxidation of tyrosine. {ECO:0000269|PubMed:23319596, CC ECO:0000269|PubMed:29581294}. CC -!- PTM: N-glycosylated. N-glycosylation on Asn-455 and Asn-644 may be CC essential for proper folding and secretion; may be composed of a CC fucosylated carbohydrates attached to a trimannose N-linked glycan CC core. {ECO:0000269|PubMed:23319596}. CC -!- MISCELLANEOUS: Its overexpression in a number of cancers and its CC ability to promote epithelial to mesenchymal transition suggest that CC LOXL2 might play a role in tumor progression: expression is correlated CC with metastasis and decreased survival in patients with aggressive CC breast cancer (PubMed:21233336, PubMed:21732535). Allosteric inhibition CC by AB0023 inhibits formation of the tumor microenvironment and reduces CC metastatic tumor burden in xenograft models (PubMed:20818376, CC PubMed:21732535). However, inhibiting the enzyme activity of LOXL2 may CC not be sufficient, since inhibition of keratinocyte differentiation is CC not prevented in mutants that lack enzyme activity nor by inhibition of CC activity by the AB0023 antibody, thereby promoting development of CC squamous cell carcinomas (PubMed:22157764). CC {ECO:0000305|PubMed:20818376, ECO:0000305|PubMed:21233336, CC ECO:0000305|PubMed:21732535, ECO:0000305|PubMed:22157764}. CC -!- SIMILARITY: Belongs to the lysyl oxidase family. {ECO:0000305}. CC -!- CAUTION: The original paper reporting the role of LOXL2 in deamination CC of trimethylated 'Lys-4' of histone H3 was retracted due to CC inappropriate manipulation of figure data (PubMed:22483618, CC PubMed:27392148). However, this role was confirmed in a subsequent CC publication (PubMed:27735137). {ECO:0000269|PubMed:27735137, CC ECO:0000305|PubMed:22483618, ECO:0000305|PubMed:27392148}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD34343.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41192/LOXL2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U89942; AAB49697.1; -; mRNA. DR EMBL; AK312266; BAG35197.1; -; mRNA. DR EMBL; AK222477; BAD96197.1; -; mRNA. DR EMBL; AC090197; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000594; AAH00594.1; -; mRNA. DR EMBL; AF117949; AAD34343.1; ALT_SEQ; mRNA. DR CCDS; CCDS34864.1; -. DR RefSeq; NP_002309.1; NM_002318.2. DR PDB; 5ZE3; X-ray; 2.40 A; A/B=318-774. DR PDBsum; 5ZE3; -. DR AlphaFoldDB; Q9Y4K0; -. DR SMR; Q9Y4K0; -. DR BioGRID; 110201; 443. DR IntAct; Q9Y4K0; 48. DR MINT; Q9Y4K0; -. DR STRING; 9606.ENSP00000373783; -. DR BindingDB; Q9Y4K0; -. DR ChEMBL; CHEMBL3714029; -. DR GuidetoPHARMACOLOGY; 2853; -. DR GlyConnect; 1480; 1 N-Linked glycan (1 site). DR GlyCosmos; Q9Y4K0; 3 sites, 1 glycan. DR GlyGen; Q9Y4K0; 3 sites, 1 N-linked glycan (1 site). DR iPTMnet; Q9Y4K0; -. DR PhosphoSitePlus; Q9Y4K0; -. DR BioMuta; LOXL2; -. DR DMDM; 13878585; -. DR EPD; Q9Y4K0; -. DR jPOST; Q9Y4K0; -. DR MassIVE; Q9Y4K0; -. DR MaxQB; Q9Y4K0; -. DR PaxDb; 9606-ENSP00000373783; -. DR PeptideAtlas; Q9Y4K0; -. DR ProteomicsDB; 86223; -. DR Pumba; Q9Y4K0; -. DR ABCD; Q9Y4K0; 1 sequenced antibody. DR Antibodypedia; 22758; 543 antibodies from 35 providers. DR DNASU; 4017; -. DR Ensembl; ENST00000389131.8; ENSP00000373783.3; ENSG00000134013.16. DR GeneID; 4017; -. DR KEGG; hsa:4017; -. DR MANE-Select; ENST00000389131.8; ENSP00000373783.3; NM_002318.3; NP_002309.1. DR UCSC; uc003xdh.2; human. DR AGR; HGNC:6666; -. DR CTD; 4017; -. DR DisGeNET; 4017; -. DR GeneCards; LOXL2; -. DR HGNC; HGNC:6666; LOXL2. DR HPA; ENSG00000134013; Tissue enhanced (smooth). DR MIM; 606663; gene. DR neXtProt; NX_Q9Y4K0; -. DR OpenTargets; ENSG00000134013; -. DR PharmGKB; PA30429; -. DR VEuPathDB; HostDB:ENSG00000134013; -. DR eggNOG; ENOG502QSX8; Eukaryota. DR GeneTree; ENSGT00940000155874; -. DR HOGENOM; CLU_002555_3_0_1; -. DR InParanoid; Q9Y4K0; -. DR OMA; YCTGKEA; -. DR OrthoDB; 3035117at2759; -. DR PhylomeDB; Q9Y4K0; -. DR TreeFam; TF326061; -. DR BRENDA; 1.4.3.13; 2681. DR PathwayCommons; Q9Y4K0; -. DR Reactome; R-HSA-1566948; Elastic fibre formation. DR Reactome; R-HSA-2243919; Crosslinking of collagen fibrils. DR SignaLink; Q9Y4K0; -. DR SIGNOR; Q9Y4K0; -. DR BioGRID-ORCS; 4017; 9 hits in 1152 CRISPR screens. DR ChiTaRS; LOXL2; human. DR GeneWiki; LOXL2; -. DR GenomeRNAi; 4017; -. DR Pharos; Q9Y4K0; Tchem. DR PRO; PR:Q9Y4K0; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9Y4K0; Protein. DR Bgee; ENSG00000134013; Expressed in stromal cell of endometrium and 145 other cell types or tissues. DR ExpressionAtlas; Q9Y4K0; baseline and differential. DR GO; GO:0005604; C:basement membrane; ISS:UniProtKB. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IEA:InterPro. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0070492; F:oligosaccharide binding; IDA:UniProtKB. DR GO; GO:0004720; F:protein-lysine 6-oxidase activity; IDA:UniProtKB. DR GO; GO:0030199; P:collagen fibril organization; IMP:UniProtKB. DR GO; GO:0043542; P:endothelial cell migration; IMP:UniProtKB. DR GO; GO:0001935; P:endothelial cell proliferation; IMP:UniProtKB. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB. DR GO; GO:0070828; P:heterochromatin organization; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:1902455; P:negative regulation of stem cell population maintenance; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0018057; P:peptidyl-lysine oxidation; IDA:UniProtKB. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; ISS:UniProtKB. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:UniProtKB. DR GO; GO:0036211; P:protein modification process; IDA:UniProtKB. DR GO; GO:0046688; P:response to copper ion; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB. DR GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB. DR Gene3D; 3.10.250.10; SRCR-like domain; 4. DR InterPro; IPR001695; Lysyl_oxidase. DR InterPro; IPR019828; Lysyl_oxidase_CS. DR InterPro; IPR001190; SRCR. DR InterPro; IPR017448; SRCR-like_dom. DR InterPro; IPR036772; SRCR-like_dom_sf. DR PANTHER; PTHR45817:SF1; LYSYL OXIDASE HOMOLOG 2; 1. DR PANTHER; PTHR45817; LYSYL OXIDASE-LIKE-RELATED; 1. DR Pfam; PF01186; Lysyl_oxidase; 1. DR Pfam; PF00530; SRCR; 4. DR PRINTS; PR00074; LYSYLOXIDASE. DR PRINTS; PR00258; SPERACTRCPTR. DR SMART; SM00202; SR; 4. DR SUPFAM; SSF56487; SRCR-like; 4. DR PROSITE; PS00926; LYSYL_OXIDASE; 1. DR PROSITE; PS00420; SRCR_1; 2. DR PROSITE; PS50287; SRCR_2; 4. DR Genevisible; Q9Y4K0; HS. PE 1: Evidence at protein level; KW 3D-structure; Basement membrane; Calcium; Chromatin regulator; Chromosome; KW Copper; Disulfide bond; Endoplasmic reticulum; Extracellular matrix; KW Glycoprotein; LTQ; Metal-binding; Nucleus; Oxidoreductase; KW Reference proteome; Repeat; Repressor; Secreted; Signal; TPQ; KW Transcription; Transcription regulation. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..774 FT /note="Lysyl oxidase homolog 2" FT /id="PRO_0000018532" FT DOMAIN 58..159 FT /note="SRCR 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DOMAIN 188..302 FT /note="SRCR 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DOMAIN 326..425 FT /note="SRCR 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DOMAIN 435..544 FT /note="SRCR 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT REGION 548..751 FT /note="Lysyl-oxidase like" FT BINDING 549 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 550 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 626 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 628 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 630 FT /ligand="Cu cation" FT /ligand_id="ChEBI:CHEBI:23378" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 722 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 724 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 727 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000305|PubMed:29581294" FT BINDING 728 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000305|PubMed:29581294" FT MOD_RES 689 FT /note="2',4',5'-topaquinone" FT /evidence="ECO:0000269|PubMed:29581294" FT CARBOHYD 288 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 455 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:23319596" FT CARBOHYD 644 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:23319596, FT ECO:0000269|PubMed:29581294, ECO:0007744|PDB:5ZE3" FT DISULFID 84..148 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DISULFID 97..158 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DISULFID 128..138 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DISULFID 218..291 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DISULFID 231..301 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DISULFID 265..275 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DISULFID 351..414 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DISULFID 364..424 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196, FT ECO:0000269|PubMed:29581294, ECO:0007744|PDB:5ZE3" FT DISULFID 395..405 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196, FT ECO:0000269|PubMed:29581294, ECO:0007744|PDB:5ZE3" FT DISULFID 464..530 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196, FT ECO:0000269|PubMed:29581294, ECO:0007744|PDB:5ZE3" FT DISULFID 477..543 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196, FT ECO:0000269|PubMed:29581294, ECO:0007744|PDB:5ZE3" FT DISULFID 511..521 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196, FT ECO:0000269|PubMed:29581294, ECO:0007744|PDB:5ZE3" FT DISULFID 573..625 FT /evidence="ECO:0000269|PubMed:29581294, FT ECO:0007744|PDB:5ZE3" FT DISULFID 579..695 FT /evidence="ECO:0000269|PubMed:29581294, FT ECO:0007744|PDB:5ZE3" FT DISULFID 657..673 FT /evidence="ECO:0000269|PubMed:29581294, FT ECO:0007744|PDB:5ZE3" FT DISULFID 663..685 FT /evidence="ECO:0000269|PubMed:29581294, FT ECO:0007744|PDB:5ZE3" FT DISULFID 732..746 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196, FT ECO:0000269|PubMed:29581294, ECO:0007744|PDB:5ZE3" FT CROSSLNK 653..689 FT /note="Lysine tyrosylquinone (Lys-Tyr)" FT /evidence="ECO:0000269|PubMed:23319596, FT ECO:0000269|PubMed:29581294" FT VARIANT 359 FT /note="S -> W (in dbSNP:rs4602894)" FT /id="VAR_050010" FT VARIANT 570 FT /note="M -> L (in dbSNP:rs1063582)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3" FT /id="VAR_024527" FT MUTAGEN 455 FT /note="N->Q: Inhibits secretion." FT /evidence="ECO:0000269|PubMed:23319596" FT MUTAGEN 626..628 FT /note="HRH->ARA: Abolishes oxidase activity and oxidation FT of trimethylated 'Lys-4' of histone H3 but does not affect FT secretion, interaction with SNAI1, binding to the CDH1 FT promoter, repression of CDH1 transcription or ability to FT induce EMT." FT /evidence="ECO:0000269|PubMed:24414204, FT ECO:0000269|PubMed:27735137" FT MUTAGEN 626 FT /note="H->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:29581294" FT MUTAGEN 628 FT /note="H->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:29581294" FT MUTAGEN 630 FT /note="H->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:29581294" FT MUTAGEN 644 FT /note="N->Q: Inhibits secretion." FT /evidence="ECO:0000269|PubMed:23319596" FT MUTAGEN 653 FT /note="K->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:29581294" FT MUTAGEN 689 FT /note="Y->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:29581294" FT MUTAGEN 689 FT /note="Y->F: Does not affect ability to inhibit FT keratinocyte differentiation." FT /evidence="ECO:0000269|PubMed:22157764" FT CONFLICT 184 FT /note="E -> K (in Ref. 2; BAG35197)" FT /evidence="ECO:0000305" FT CONFLICT 239 FT /note="E -> G (in Ref. 3; BAD96197)" FT /evidence="ECO:0000305" FT CONFLICT 295 FT /note="L -> Q (in Ref. 6; AAD34343)" FT /evidence="ECO:0000305" FT CONFLICT 536 FT /note="Q -> R (in Ref. 2; BAG35197)" FT /evidence="ECO:0000305" FT CONFLICT 652 FT /note="H -> Q (in Ref. 6; AAD34343)" FT /evidence="ECO:0000305" FT CONFLICT 746 FT /note="C -> S (in Ref. 6; AAD34343)" FT /evidence="ECO:0000305" FT STRAND 325..333 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 336..343 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 346..351 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 357..366 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 372..376 FT /evidence="ECO:0007829|PDB:5ZE3" FT TURN 378..381 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 388..390 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 404..406 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 421..424 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 434..441 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 445..454 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 457..463 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 470..480 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 484..490 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 504..506 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 518..520 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 534..536 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 540..545 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 550..552 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 554..559 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 562..567 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 568..570 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 572..576 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 582..586 FT /evidence="ECO:0007829|PDB:5ZE3" FT TURN 589..591 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 593..598 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 601..605 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 607..609 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 617..619 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 621..623 FT /evidence="ECO:0007829|PDB:5ZE3" FT TURN 624..627 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 628..641 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 645..649 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 652..656 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 661..664 FT /evidence="ECO:0007829|PDB:5ZE3" FT TURN 674..676 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 685..689 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 697..699 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 705..715 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 728..736 FT /evidence="ECO:0007829|PDB:5ZE3" FT STRAND 741..748 FT /evidence="ECO:0007829|PDB:5ZE3" FT HELIX 754..759 FT /evidence="ECO:0007829|PDB:5ZE3" SQ SEQUENCE 774 AA; 86725 MW; 9DF5D25D4824BCCD CRC64; MERPLCSHLC SCLAMLALLS PLSLAQYDSW PHYPEYFQQP APEYHQPQAP ANVAKIQLRL AGQKRKHSEG RVEVYYDGQW GTVCDDDFSI HAAHVVCREL GYVEAKSWTA SSSYGKGEGP IWLDNLHCTG NEATLAACTS NGWGVTDCKH TEDVGVVCSD KRIPGFKFDN SLINQIENLN IQVEDIRIRA ILSTYRKRTP VMEGYVEVKE GKTWKQICDK HWTAKNSRVV CGMFGFPGER TYNTKVYKMF ASRRKQRYWP FSMDCTGTEA HISSCKLGPQ VSLDPMKNVT CENGLPAVVS CVPGQVFSPD GPSRFRKAYK PEQPLVRLRG GAYIGEGRVE VLKNGEWGTV CDDKWDLVSA SVVCRELGFG SAKEAVTGSR LGQGIGPIHL NEIQCTGNEK SIIDCKFNAE SQGCNHEEDA GVRCNTPAMG LQKKLRLNGG RNPYEGRVEV LVERNGSLVW GMVCGQNWGI VEAMVVCRQL GLGFASNAFQ ETWYWHGDVN SNKVVMSGVK CSGTELSLAH CRHDGEDVAC PQGGVQYGAG VACSETAPDL VLNAEMVQQT TYLEDRPMFM LQCAMEENCL SASAAQTDPT TGYRRLLRFS SQIHNNGQSD FRPKNGRHAW IWHDCHRHYH SMEVFTHYDL LNLNGTKVAE GHKASFCLED TECEGDIQKN YECANFGDQG ITMGCWDMYR HDIDCQWVDI TDVPPGDYLF QVVINPNFEV AESDYSNNIM KCRSRYDGHR IWMYNCHIGG SFSEETEKKF EHFSGLLNNQ LSPQ //