ID F8W4B7_DANRE Unreviewed; 1081 AA. AC F8W4B7; A0A8M3BBK8; DT 21-SEP-2011, integrated into UniProtKB/TrEMBL. DT 21-SEP-2011, sequence version 1. DT 27-MAR-2024, entry version 94. DE SubName: Full=Histone deacetylase 6 {ECO:0000313|Ensembl:ENSDARP00000124246, ECO:0000313|RefSeq:XP_009302026.1}; GN Name=hdac6 {ECO:0000313|Ensembl:ENSDARP00000124246, GN ECO:0000313|RefSeq:XP_009302026.1, ECO:0000313|RefSeq:XP_009302027.1, GN ECO:0000313|ZFIN:ZDB-GENE-030131-3232}; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955 {ECO:0000313|Ensembl:ENSDARP00000124246}; RN [1] {ECO:0000313|Ensembl:ENSDARP00000124246} RP IDENTIFICATION. RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000124246}; RG Ensembl; RL Submitted (JUL-2011) to UniProtKB. RN [2] {ECO:0000313|Ensembl:ENSDARP00000124246, ECO:0000313|Proteomes:UP000000437} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000124246}; RX PubMed=23594743; DOI=10.1038/nature12111; RG Genome Reference Consortium Zebrafish; RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M., RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I., RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J., RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y., RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B., RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S., RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M., RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J., RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D., RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B., RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M., RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M., RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J., RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D., RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K., RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R., RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M., RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D., RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M., RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M., RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D., RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J., RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I., RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M., RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M., RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B., RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P., RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R., RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I., RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H., RA Rogers J., Stemple D.L.; RT "The zebrafish reference genome sequence and its relationship to the human RT genome."; RL Nature 496:498-503(2013). RN [3] {ECO:0007829|PDB:5EEF, ECO:0007829|PDB:5EEI} RP X-RAY CRYSTALLOGRAPHY (1.32 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZINC. RX PubMed=27454933; DOI=10.1038/nchembio.2134; RA Hai Y., Christianson D.W.; RT "Histone deacetylase 6 structure and molecular basis of catalysis and RT inhibition."; RL Nat. Chem. Biol. 12:741-747(2016). RN [4] {ECO:0007829|PDB:5G0F, ECO:0007829|PDB:5G0G} RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 41-418 IN COMPLEX WITH ZINC. RX PubMed=27454931; DOI=10.1038/nchembio.2140; RA Miyake Y., Keusch J.J., Wang L., Saito M., Hess D., Wang X., Melancon B.J., RA Helquist P., Gut H., Matthias P.; RT "Structural insights into HDAC6 tubulin deacetylation and its selective RT inhibition."; RL Nat. Chem. Biol. 12:748-754(2016). RN [5] {ECO:0007829|PDB:5WGI, ECO:0007829|PDB:5WGK} RP X-RAY CRYSTALLOGRAPHY (1.05 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=29203661; DOI=10.1073/pnas.1718823114; RA Porter N.J., Mahendran A., Breslow R., Christianson D.W.; RT "Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors."; RL Proc. Natl. Acad. Sci. U.S.A. 114:13459-13464(2017). RN [6] {ECO:0007829|PDB:6MR5} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=30613344; DOI=10.1021/acsmedchemlett.8b00487; RA Porter N.J., Shen S., Barinka C., Kozikowski A.P., Christianson D.W.; RT "Molecular Basis for the Selective Inhibition of Histone Deacetylase 6 by a RT Mercaptoacetamide Inhibitor."; RL ACS Med. Chem. Lett. 9:1301-1305(2018). RN [7] {ECO:0007829|PDB:6CSP, ECO:0007829|PDB:6CSQ} RP X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=29775292; DOI=10.1021/acs.biochem.8b00367; RA Porter N.J., Wagner F.F., Christianson D.W.; RT "Entropy as a Driver of Selectivity for Inhibitor Binding to Histone RT Deacetylase 6."; RL Biochemistry 57:3916-3924(2018). RN [8] {ECO:0007829|PDB:6DVL, ECO:0007829|PDB:6DVM} RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=30118224; DOI=10.1021/acs.jmedchem.8b01013; RA Porter N.J., Osko J.D., Diedrich D., Kurz T., Hooker J.M., Hansen F.K., RA Christianson D.W.; RT "Histone Deacetylase 6-Selective Inhibitors and the Influence of Capping RT Groups on Hydroxamate-Zinc Denticity."; RL J. Med. Chem. 61:8054-8060(2018). RN [9] {ECO:0007829|PDB:6CW8} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=30365892; DOI=10.1021/acs.jmedchem.8b01487; RA Bhatia S., Krieger V., Groll M., Osko J.D., Ressing N., Ahlert H., RA Borkhardt A., Kurz T., Christianson D.W., Hauer J., Hansen F.K.; RT "Discovery of the First-in-Class Dual Histone Deacetylase-Proteasome RT Inhibitor."; RL J. Med. Chem. 61:10299-10309(2018). RN [10] {ECO:0007829|PDB:6UO2, ECO:0007829|PDB:6UO3} RP X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) OF 60-419 IN COMPLEX WITH ZN(2+). RX PubMed=31755702; DOI=10.1021/acs.biochem.9b00934; RA Osko J.D., Christianson D.W.; RT "Structural Basis of Catalysis and Inhibition of HDAC6 CD1, the Enigmatic RT Catalytic Domain of Histone Deacetylase 6."; RL Biochemistry 58:4912-4924(2019). RN [11] {ECO:0007829|PDB:5W5K} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=30645113; DOI=10.1021/acs.jmedchem.8b01090; RA Vogerl K., Ong N., Senger J., Herp D., Schmidtkunz K., Marek M., Muller M., RA Bartel K., Shaik T.B., Porter N.J., Robaa D., Christianson D.W., Romier C., RA Sippl W., Jung M., Bracher F.; RT "Synthesis and Biological Investigation of Phenothiazine-Based RT Benzhydroxamic Acids as Selective Histone Deacetylase 6 Inhibitors."; RL J. Med. Chem. 62:1138-1166(2019). RN [12] {ECO:0007829|PDB:6R0K} RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 440-798. RX PubMed=31414801; DOI=10.1021/acs.jmedchem.9b00946; RA Shen S., Hadley M., Ustinova K., Pavlicek J., Knox T., Noonepalle S., RA Tavares M.T., Zimprich C.A., Zhang G., Robers M.B., Barinka C., RA Kozikowski A.P., Villagra A.; RT "Discovery of a New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 RT Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse RT Models."; RL J. Med. Chem. 62:8557-8577(2019). RN [13] {ECO:0007829|PDB:6THV} RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 440-798. RX PubMed=32435374; DOI=10.1021/acsmedchemlett.9b00560; RA Shen S., Svoboda M., Zhang G., Cavasin M.A., Motlova L., McKinsey T.A., RA Eubanks J.H., Barinka C., Kozikowski A.P.; RT "Structural and in Vivo Characterization of Tubastatin A, a Widely Used RT Histone Deacetylase 6 Inhibitor."; RL ACS Med. Chem. Lett. 11:706-712(2020). RN [14] {ECO:0007829|PDB:6V7A} RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=33214839; DOI=10.1021/acsmedchemlett.0c00395; RA Saraswati A.P., Relitti N., Brindisi M., Osko J.D., Chemi G., Federico S., RA Grillo A., Brogi S., McCabe N.H., Turkington R.C., Ibrahim O., RA O'Sullivan J., Lamponi S., Ghanim M., Kelly V.P., Zisterer D., Amet R., RA Hannon Barroeta P., Vanni F., Ulivieri C., Herp D., Sarno F., RA Di Costanzo A., Saccoccia F., Ruberti G., Jung M., Altucci L., Gemma S., RA Butini S., Christianson D.W., Campiani G.; RT "Spiroindoline-Capped Selective HDAC6 Inhibitors: Design, Synthesis, RT Structural Analysis, and Biological Evaluation."; RL ACS Med. Chem. Lett. 11:2268-2276(2020). RN [15] {ECO:0007829|PDB:6WYO, ECO:0007829|PDB:6WYP} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 61-419 IN COMPLEX WITH ZN(2+). RX PubMed=32880591; DOI=10.1107/s2053230x20010250; RA Osko J.D., Christianson D.W.; RT "Binding of inhibitors to active-site mutants of CD1, the enigmatic RT catalytic domain of histone deacetylase 6."; RL Acta Crystallogr. F Struct. Biol. Commun. 76:428-437(2020). RN [16] {ECO:0007829|PDB:6VNR} RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=32348628; DOI=10.1002/cmdc.202000149; RA Morgen M., Steimbach R.R., Geraldy M., Hellweg L., Sehr P., Ridinger J., RA Witt O., Oehme I., Herbst-Gervasoni C.J., Osko J.D., Porter N.J., RA Christianson D.W., Gunkel N., Miller A.K.; RT "Design and Synthesis of Dihydroxamic Acids as HDAC6/8/10 Inhibitors."; RL ChemMedChem 15:1163-1174(2020). RN [17] {ECO:0007829|PDB:6PZO, ECO:0007829|PDB:6PZR} RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 442-798 IN COMPLEX WITH ZN(2+). RX PubMed=31793776; DOI=10.1021/acs.jmedchem.9b01540; RA Osko J.D., Porter N.J., Narayana Reddy P.A., Xiao Y.C., Rokka J., Jung M., RA Hooker J.M., Salvino J.M., Christianson D.W.; RT "Exploring Structural Determinants of Inhibitor Affinity and Selectivity in RT Complexes with Histone Deacetylase 6."; RL J. Med. Chem. 63:295-308(2020). RN [18] {ECO:0007829|PDB:6TCY} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=32815366; DOI=10.1021/acs.jmedchem.0c00567; RA Noonepalle S., Shen S., Ptacek J., Tavares M.T., Zhang G., Stransky J., RA Pavlicek J., Ferreira G.M., Hadley M., Pelaez G., Barinka C., RA Kozikowski A.P., Villagra A.; RT "Rational Design of Suprastat: A Novel Selective Histone Deacetylase 6 RT Inhibitor with the Ability to Potentiate Immunotherapy in Melanoma RT Models."; RL J. Med. Chem. 63:10246-10262(2020). RN [19] {ECO:0007829|PDB:6PYE} RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=32803970; DOI=10.1021/acs.jmedchem.9b01888; RA Ressing N., Sonnichsen M., Osko J.D., Scholer A., Schliehe-Diecks J., RA Skerhut A., Borkhardt A., Hauer J., Kassack M.U., Christianson D.W., RA Bhatia S., Hansen F.K.; RT "Multicomponent Synthesis, Binding Mode, and Structure-Activity RT Relationship of Selective Histone Deacetylase 6 (HDAC6) Inhibitors with RT Bifurcated Capping Groups."; RL J. Med. Chem. 63:10339-10351(2020). RN [20] {ECO:0007829|PDB:7O2P, ECO:0007829|PDB:7O2R} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=34795871; DOI=10.1021/acsmedchemlett.1c00425; RA Sandrone G., Cukier C.D., Zrubek K., Marchini M., Vergani B., Caprini G., RA Fossati G., Steinkuhler C., Stevenazzi A.; RT "Role of Fluorination in the Histone Deacetylase 6 (HDAC6) Selectivity of RT Benzohydroxamate-Based Inhibitors."; RL ACS Med. Chem. Lett. 12:1810-1817(2021). RN [21] {ECO:0007829|PDB:7JOM} RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=33576627; DOI=10.1021/acs.jmedchem.0c01922; RA Olaoye O.O., Watson P.R., Nawar N., Geletu M., Sedighi A., Bukhari S., RA Raouf Y.S., Manaswiyoungkul P., Erdogan F., Abdeldayem A., Cabral A.D., RA Hassan M.M., Toutah K., Shouksmith A.E., Gawel J.M., Israelian J., RA Radu T.B., Kachhiyapatel N., de Araujo E.D., Christianson D.W., RA Gunning P.T.; RT "Unique Molecular Interaction with the Histone Deacetylase 6 Catalytic RT Tunnel: Crystallographic and Biological Characterization of a Model RT Chemotype."; RL J. Med. Chem. 64:2691-2704(2021). RN [22] {ECO:0007829|PDB:6ZW1} RP X-RAY CRYSTALLOGRAPHY (1.13 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=33830764; DOI=10.1021/acs.jmedchem.0c02210; RA Shen S., Picci C., Ustinova K., Benoy V., Kutil Z., Zhang G., Tavares M.T., RA Pavlicek J., Zimprich C.A., Robers M.B., Van Den Bosch L., Barinka C., RA Langley B., Kozikowski A.P.; RT "Tetrahydroquinoline-Capped Histone Deacetylase 6 Inhibitor SW-101 RT Ameliorates Pathological Phenotypes in a Charcot-Marie-Tooth Type 2A Mouse RT Model."; RL J. Med. Chem. 64:4810-4840(2021). RN [23] {ECO:0007829|PDB:6V79} RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=34251197; DOI=10.1021/acs.jmedchem.1c00184; RA Campiani G., Cavella C., Osko J.D., Brindisi M., Relitti N., Brogi S., RA Saraswati A.P., Federico S., Chemi G., Maramai S., Carullo G., Jaeger B., RA Carleo A., Benedetti R., Sarno F., Lamponi S., Rottoli P., Bargagli E., RA Bertucci C., Tedesco D., Herp D., Senger J., Ruberti G., Saccoccia F., RA Saponara S., Gorelli B., Valoti M., Kennedy B., Sundaramurthi H., RA Butini S., Jung M., Roach K.M., Altucci L., Bradding P., Christianson D.W., RA Gemma S., Prasse A.; RT "Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, RT Synthesis, Structural Analysis, and Biological Evaluation of Potent RT Inhibitors."; RL J. Med. Chem. 64:9960-9988(2021). RN [24] {ECO:0007829|PDB:6WSJ} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=34099674; DOI=10.1038/s41467-021-23609-8; RA Hosseinzadeh P., Watson P.R., Craven T.W., Li X., Rettie S., RA Pardo-Avila F., Bera A.K., Mulligan V.K., Lu P., Ford A.S., Weitzner B.D., RA Stewart L.J., Moyer A.P., Di Piazza M., Whalen J.G., Greisen P.J., RA Christianson D.W., Baker D.; RT "Anchor extension: a structure-guided approach to design cyclic peptides RT targeting enzyme active sites."; RL Nat. Commun. 12:3384-3384(2021). RN [25] {ECO:0007829|PDB:8D98, ECO:0007829|PDB:8D99} RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=36073962; DOI=10.1021/acs.biochem.2c00332; RA Watson P.R., Bai P., Wang C., Cragin A.D., Hooker J.M., Christianson D.W.; RT "Aromatic Ring Fluorination Patterns Modulate Inhibitory Potency of RT Fluorophenylhydroxamates Complexed with Histone Deacetylase 6."; RL Biochemistry 61:1945-1954(2022). RN [26] {ECO:0007829|PDB:7U8Z} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=36351184; DOI=10.1021/acs.jmedchem.2c01418; RA Ressing N., Schliehe-Diecks J., Watson P.R., Sonnichsen M., Cragin A.D., RA Scholer A., Yang J., Schaker-Hubner L., Borkhardt A., Christianson D.W., RA Bhatia S., Hansen F.K.; RT "Development of Fluorinated Peptoid-Based Histone Deacetylase (HDAC) RT Inhibitors for Therapy-Resistant Acute Leukemia."; RL J. Med. Chem. 65:15457-15472(2022). RN [27] {ECO:0007829|PDB:7UK2} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 442-798 IN COMPLEX WITH ZN(2+). RX PubMed=36355493; DOI=10.3390/ph15111321; RA Garcha H.K., Nawar N., Sorger H., Erdogan F., Aung M.M.K., Sedighi A., RA Manaswiyoungkul P., Seo H.S., Schonefeldt S., Poloske D., Dhe-Paganon S., RA Neubauer H.A., Mustjoki S.M., Herling M., de Araujo E.D., Moriggl R., RA Gunning P.T.; RT "High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in RT Natural Killer (NK)/T-Cell Lymphoma."; RL Pharmaceuticals (Basel) 15:1321-1321(2022). RN [28] {ECO:0007829|PDB:8EQI} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=37027789; DOI=10.1021/acschembio.3c00113; RA Watson P.R., Gupta S., Hosseinzadeh P., Brown B.P., Baker D., RA Christianson D.W.; RT "Macrocyclic Octapeptide Binding and Inferences on Protein Substrate RT Binding to Histone Deacetylase 6."; RL ACS Chem. Biol. 18:959-968(2023). RN [29] {ECO:0007829|PDB:8BJK} RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=37392419; DOI=10.1021/acschembio.3c00212; RA Motlova L., Snajdr I., Kutil Z., Andris E., Ptacek J., Novotna A., RA Novakova Z., Havlinova B., Tueckmantel W., Draberova H., Majer P., RA Schutkowski M., Kozikowski A., Rulisek L., Barinka C.; RT "Comprehensive Mechanistic View of the Hydrolysis of Oxadiazole-Based RT Inhibitors by Histone Deacetylase 6 (HDAC6)."; RL ACS Chem. Biol. 18:1594-1610(2023). RN [30] {ECO:0007829|PDB:8A8Z} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=36528061; DOI=10.1016/j.jbc.2022.102800; RA Cellupica E., Caprini G., Cordella P., Cukier C., Fossati G., Marchini M., RA Rocchio I., Sandrone G., Vanoni M.A., Vergani B., Zrubek K., Stevenazzi A., RA Steinkuhler C.; RT "Difluoromethyl-1,3,4-oxadiazoles are slow-binding substrate analog RT inhibitors of histone deacetylase 6 with unprecedented isotype RT selectivity."; RL J. Biol. Chem. 299:102800-102800(2023). RN [31] {ECO:0007829|PDB:8CJ7} RP X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) OF 440-798 IN COMPLEX WITH ZN(2+). RX PubMed=37797307; DOI=10.1021/acs.jmedchem.3c01269; RA Ripa L., Sandmark J., Hughes G., Shamovsky I., Gunnarsson A., Johansson J., RA Llinas A., Collins M., Jung B., Noven A., Pemberton N., Mogemark M., RA Xiong Y., Li Q., Tangefjord S., Ek M., Astrand A.; RT "Selective and Bioavailable HDAC6 2-(Difluoromethyl)-1,3,4-oxadiazole RT Substrate Inhibitors and Modeling of Their Bioactivation Mechanism."; RL J. Med. Chem. 66:14188-14207(2023). RN [32] {ECO:0007829|PDB:7QNO} RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 40-831 IN COMPLEX WITH ZN(2+). RX PubMed=36255643; DOI=10.1007/978-1-0716-2788-4_30; RA Langousis G., Sanchez J., Kempf G., Matthias P.; RT "Expression and Crystallization of HDAC6 Tandem Catalytic Domains."; RL Methods Mol. Biol. 2589:467-480(2023). RN [33] {ECO:0000313|RefSeq:XP_009302026.1, ECO:0000313|RefSeq:XP_009302027.1} RP IDENTIFICATION. RC STRAIN=Tuebingen {ECO:0000313|RefSeq:XP_009302026.1, RC ECO:0000313|RefSeq:XP_009302027.1}; RG RefSeq; RL Submitted (NOV-2023) to UniProtKB. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|ARBA:ARBA00004123}. 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; BX469901; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR RefSeq; XP_009302026.1; XM_009303751.3. DR RefSeq; XP_009302027.1; XM_009303752.2. DR PDB; 5EEF; X-ray; 2.15 A; A/B=60-419. DR PDB; 5EEI; X-ray; 1.32 A; A/B=440-798. DR PDB; 5EEK; X-ray; 1.59 A; A=440-798. DR PDB; 5EEM; X-ray; 2.00 A; A/B=440-798. DR PDB; 5EEN; X-ray; 1.86 A; A/B=440-798. DR PDB; 5EF7; X-ray; 1.90 A; A/B=440-798. DR PDB; 5EF8; X-ray; 2.60 A; A/B=440-798. DR PDB; 5EFB; X-ray; 2.54 A; D=440-798. DR PDB; 5EFG; X-ray; 2.25 A; A/D=440-798. DR PDB; 5EFH; X-ray; 2.16 A; A/D=440-798. DR PDB; 5EFJ; X-ray; 1.73 A; D=440-798. DR PDB; 5EFK; X-ray; 1.82 A; B=440-798. DR PDB; 5EFN; X-ray; 1.80 A; A/B=440-798. DR PDB; 5G0F; X-ray; 1.90 A; A=974-1081. DR PDB; 5G0G; X-ray; 1.50 A; A=41-418. DR PDB; 5G0H; X-ray; 1.60 A; A=40-831. DR PDB; 5G0I; X-ray; 1.99 A; A/B=25-831. DR PDB; 5G0J; X-ray; 2.88 A; A=40-831. DR PDB; 5W5K; X-ray; 2.70 A; A/B/C=440-798. DR PDB; 5WGI; X-ray; 1.05 A; A=440-798. DR PDB; 5WGK; X-ray; 1.82 A; A=440-798. DR PDB; 5WGL; X-ray; 1.70 A; A/B=440-798. DR PDB; 5WGM; X-ray; 1.75 A; A/B/C=440-798. DR PDB; 6CSP; X-ray; 1.24 A; A/B=440-798. DR PDB; 6CSQ; X-ray; 2.03 A; A/B=440-798. DR PDB; 6CSR; X-ray; 1.62 A; A/B=440-798. DR PDB; 6CSS; X-ray; 1.70 A; A/B=440-798. DR PDB; 6CW8; X-ray; 1.90 A; A/B=440-798. DR PDB; 6DVL; X-ray; 2.10 A; A/B=440-798. DR PDB; 6DVM; X-ray; 1.47 A; A/B/C/D=440-798. DR PDB; 6DVN; X-ray; 2.20 A; A/B/C/D=440-798. DR PDB; 6DVO; X-ray; 1.98 A; A=440-798. DR PDB; 6MR5; X-ray; 1.85 A; A/B=440-798. DR PDB; 6PYE; X-ray; 1.48 A; A/B=440-798. DR PDB; 6PZO; X-ray; 1.50 A; A/B=442-798. DR PDB; 6PZR; X-ray; 2.30 A; A/B=441-798. DR PDB; 6PZS; X-ray; 1.79 A; A=442-798. DR PDB; 6PZU; X-ray; 1.74 A; A/B=442-798. DR PDB; 6Q0Z; X-ray; 1.75 A; A/B=442-798. DR PDB; 6R0K; X-ray; 1.15 A; A=440-798. DR PDB; 6TCY; X-ray; 1.60 A; AAA/BBB=440-798. DR PDB; 6THV; X-ray; 1.10 A; A=440-798. DR PDB; 6UO2; X-ray; 1.65 A; A/B=60-419. DR PDB; 6UO3; X-ray; 1.09 A; A=60-419. DR PDB; 6UO4; X-ray; 1.27 A; A/B=60-419. DR PDB; 6UO5; X-ray; 1.44 A; A=60-419. DR PDB; 6UO7; X-ray; 1.40 A; A=60-419. DR PDB; 6UOB; X-ray; 1.58 A; A/B=60-419. DR PDB; 6UOC; X-ray; 1.40 A; A=60-419. DR PDB; 6V79; X-ray; 2.04 A; A/B=440-798. DR PDB; 6V7A; X-ray; 2.09 A; A=440-798. DR PDB; 6VNR; X-ray; 1.94 A; A/B=440-798. DR PDB; 6WSJ; X-ray; 1.70 A; A=440-798. DR PDB; 6WYO; X-ray; 2.30 A; A/B=61-419. DR PDB; 6WYP; X-ray; 2.40 A; A=61-419. DR PDB; 6WYQ; X-ray; 1.90 A; A/B=61-419. DR PDB; 6ZW1; X-ray; 1.13 A; A=440-798. DR PDB; 7JOM; X-ray; 1.84 A; A/B=440-798. DR PDB; 7O2P; X-ray; 1.90 A; A/B=440-798. DR PDB; 7O2R; X-ray; 2.30 A; A=440-798. DR PDB; 7QNO; X-ray; 2.38 A; A=40-831. DR PDB; 7U8Z; X-ray; 1.85 A; A/B/C/D=440-798. DR PDB; 7UK2; X-ray; 1.60 A; A=442-798. DR PDB; 8A8Z; X-ray; 1.60 A; A/B=440-798. DR PDB; 8BJK; X-ray; 1.35 A; A=440-798. DR PDB; 8CJ7; X-ray; 1.51 A; A/B/C=440-798. DR PDB; 8D98; X-ray; 1.66 A; A/B=440-798. DR PDB; 8D99; X-ray; 1.79 A; A/B=440-798. DR PDB; 8D9A; X-ray; 1.75 A; A/B=440-798. DR PDB; 8D9B; X-ray; 1.63 A; A/B=440-798. DR PDB; 8D9C; X-ray; 1.82 A; A/B=440-798. DR PDB; 8EQI; X-ray; 2.00 A; A/B=440-798. DR PDBsum; 5EEF; -. DR PDBsum; 5EEI; -. DR PDBsum; 5EEK; -. DR PDBsum; 5EEM; -. DR PDBsum; 5EEN; -. DR PDBsum; 5EF7; -. DR PDBsum; 5EF8; -. DR PDBsum; 5EFB; -. DR PDBsum; 5EFG; -. DR PDBsum; 5EFH; -. DR PDBsum; 5EFJ; -. DR PDBsum; 5EFK; -. DR PDBsum; 5EFN; -. DR PDBsum; 5G0F; -. DR PDBsum; 5G0G; -. DR PDBsum; 5G0H; -. DR PDBsum; 5G0I; -. DR PDBsum; 5G0J; -. DR PDBsum; 5W5K; -. DR PDBsum; 5WGI; -. DR PDBsum; 5WGK; -. DR PDBsum; 5WGL; -. DR PDBsum; 5WGM; -. DR PDBsum; 6CSP; -. DR PDBsum; 6CSQ; -. DR PDBsum; 6CSR; -. DR PDBsum; 6CSS; -. DR PDBsum; 6CW8; -. DR PDBsum; 6DVL; -. DR PDBsum; 6DVM; -. DR PDBsum; 6DVN; -. DR PDBsum; 6DVO; -. DR PDBsum; 6MR5; -. DR PDBsum; 6R0K; -. DR PDBsum; 6UO2; -. DR PDBsum; 6UO3; -. DR PDBsum; 6UO4; -. DR PDBsum; 6UO5; -. DR PDBsum; 6UO7; -. DR PDBsum; 6UOB; -. DR PDBsum; 6UOC; -. DR DIP; DIP-62085N; -. DR STRING; 7955.ENSDARP00000124246; -. DR PaxDb; 7955-ENSDARP00000124246; -. DR Ensembl; ENSDART00000148993.3; ENSDARP00000124246.1; ENSDARG00000008384.10. DR Ensembl; ENSDART00000180659.1; ENSDARP00000153983.1; ENSDARG00000008384.10. DR GeneID; 565482; -. DR KEGG; dre:565482; -. DR AGR; ZFIN:ZDB-GENE-030131-3232; -. DR CTD; 10013; -. DR ZFIN; ZDB-GENE-030131-3232; hdac6. DR eggNOG; KOG1343; Eukaryota. DR HOGENOM; CLU_007727_2_1_1; -. DR OMA; MCHLEEL; -. DR OrthoDB; 124800at2759; -. DR TreeFam; TF106173; -. DR Reactome; R-DRE-3371511; HSF1 activation. DR Reactome; R-DRE-350054; Notch-HLH transcription pathway. DR Reactome; R-DRE-9646399; Aggrephagy. DR Proteomes; UP000000437; Chromosome 8. DR Bgee; ENSDARG00000008384; Expressed in testis and 24 other cell types or tissues. DR GO; GO:0000118; C:histone deacetylase complex; IBA:GO_Central. DR GO; GO:0004407; F:histone deacetylase activity; IBA:GO_Central. DR GO; GO:0030955; F:potassium ion binding; IDA:ZFIN. DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:ZFIN. DR GO; GO:0042903; F:tubulin deacetylase activity; IDA:ZFIN. DR GO; GO:0008270; F:zinc ion binding; IDA:ZFIN. DR GO; GO:0001525; P:angiogenesis; IMP:ZFIN. DR GO; GO:0060216; P:definitive hemopoiesis; IMP:ZFIN. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IMP:ZFIN. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0090043; P:regulation of tubulin deacetylation; IMP:ZFIN. DR GO; GO:0036269; P:swimming behavior; IGI:ZFIN. DR CDD; cd11682; HDAC6-dom1; 1. DR CDD; cd10003; HDAC6-dom2; 1. DR Gene3D; 3.40.800.20; Histone deacetylase domain; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR000286; His_deacetylse. DR InterPro; IPR023801; His_deacetylse_dom. DR InterPro; IPR037138; His_deacetylse_dom_sf. DR InterPro; IPR023696; Ureohydrolase_dom_sf. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR001607; Znf_UBP. DR PANTHER; PTHR10625:SF22; HISTONE DEACETYLASE 6; 1. DR PANTHER; PTHR10625; HISTONE DEACETYLASE HDAC1-RELATED; 1. DR Pfam; PF00850; Hist_deacetyl; 2. DR Pfam; PF02148; zf-UBP; 1. DR PRINTS; PR01270; HDASUPER. DR SMART; SM00290; ZnF_UBP; 1. DR SUPFAM; SSF52768; Arginase/deacetylase; 2. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50271; ZF_UBP; 1. PE 1: Evidence at protein level; KW 3D-structure {ECO:0007829|PDB:5EEF, ECO:0007829|PDB:5EEI}; KW Metal-binding {ECO:0007829|PDB:5EEF, ECO:0007829|PDB:5EEI}; KW Proteomics identification {ECO:0007829|PeptideAtlas:F8W4B7}; KW Reference proteome {ECO:0000313|Proteomes:UP000000437}; KW Zinc {ECO:0007829|PDB:5EEF, ECO:0007829|PDB:5EEI}; KW Zinc-finger {ECO:0000256|PROSITE-ProRule:PRU00502}. FT DOMAIN 977..1077 FT /note="UBP-type" FT /evidence="ECO:0000259|PROSITE:PS50271" FT REGION 1..50 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 806..848 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 860..930 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 22..47 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 825..843 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 860..874 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 230 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007829|PDB:5EEF, ECO:0007829|PDB:5G0G" FT BINDING 232 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007829|PDB:5EEF, ECO:0007829|PDB:5G0G" FT BINDING 323 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0007829|PDB:5EEF, ECO:0007829|PDB:5G0G" FT BINDING 612 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007829|PDB:5EEI, ECO:0007829|PDB:5EEK" FT BINDING 614 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007829|PDB:5EEI, ECO:0007829|PDB:5EEK" FT BINDING 705 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0007829|PDB:5EEI, ECO:0007829|PDB:5EEK" FT BINDING 979 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 981 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 999 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1002 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1011 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1014 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1019 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1026 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1030 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1036 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1049 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0007829|PDB:5G0F" FT BINDING 1052 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0007829|PDB:5G0F" SQ SEQUENCE 1081 AA; 118375 MW; 8807F58CDD0AEFB0 CRC64; MDAVPDTKGS SGPPRGTPET KNNKKNLQEA RRKGRMDRSK AEEEMSNELQ NLDVQGKSKA TGTGLVYVDA FTRFHCLWDA SHPECPARVS TVMEMLETEG LLGRCVQVEA RAVTEDELLL VHTKEYVELM KSTQNMTEEE LKTLAEKYDS VYLHPGFFSS ACLSVGSVLQ LVDKVMTSQL RNGFSINRPP GHHAQADKMN GFCMFNNLAI AARYAQKRHR VQRVLIVDWD VHHGQGIQYI FEEDPSVLYF SVHRYEDGSF WPHLKESDSS SVGSGAGQGY NINLPWNKVG MESGDYITAF QQLLLPVAYE FQPQLVLVAA GFDAVIGDPK GGMQVSPECF SILTHMLKGV AQGRLVLALE GGYNLQSTAE GVCASMRSLL GDPCPHLPSS GAPCESALKS ISKTISDLYP FWKSLQTFEG GPLSEVSPLP APVCAEVKVS SPITGLVYDQ RMMLHHNMWD SHHPELPQRI SRIFSRHEEL RLLSRCHRIP ARLATEEELA LCHSSKHISI IKSSEHMKPR DLNRLGDEYN SIFISNESYT CALLAAGSCF NSAQAILTGQ VRNAVAIVRP PGHHAEKDTA CGFCFFNTAA LTARYAQSIT RESLRVLIVD WDVHHGNGTQ HIFEEDDSVL YISLHRYEDG AFFPNSEDAN YDKVGLGKGR GYNVNIPWNG GKMGDPEYMA AFHHLVMPIA REFAPELVLV SAGFDAARGD PLGGFQVTPE GYAHLTHQLM SLAAGRVLII LEGGYNLTSI SESMSMCTSM LLGDSPPSLD HLTPLKTSAT VSINNVLRAH APFWSSLRVN IPESLRLSLP SPKPKGKCTP GGKGKKSPRQ STPSQSPGQA THRPDQSGFD ELTADLLSLN LNTSTSSNTS PESVAVGGAR RKVKPNTHRV SAGLESESPL KLNPEKAGAG DDTDVKAETP NRSISEPVVT CDSSAVKDQE SLVLEAAGGN TVQSVLERVF GAQATDVDTM YVVDPLPWCP HLESVRPVPA GGIDVFQPCE ECGGEAENWI CLFCYKVLCG RYVNQHMVTH GQESGHPVVL SFADLSVWCY ACESYVHNKV LHEAKNAAHL VKFGEGIHPF N //