KAT2B_HUMAN
ID KAT2B_HUMAN Reviewed; 832 AA.
AC Q92831; Q6NSK1;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 3.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Histone acetyltransferase KAT2B;
DE EC=2.3.1.48 {ECO:0000269|PubMed:8945521};
DE AltName: Full=Histone acetyltransferase PCAF {ECO:0000303|PubMed:12486002};
DE Short=Histone acetylase PCAF {ECO:0000303|PubMed:12486002};
DE AltName: Full=Lysine acetyltransferase 2B {ECO:0000303|PubMed:27796307};
DE AltName: Full=P300/CBP-associated factor {ECO:0000303|PubMed:12486002};
DE Short=P/CAF {ECO:0000303|PubMed:12486002};
DE AltName: Full=Spermidine acetyltransferase KAT2B;
DE EC=2.3.1.57 {ECO:0000269|PubMed:27389534};
GN Name=KAT2B {ECO:0000303|PubMed:27796307, ECO:0000312|HGNC:HGNC:8638};
GN Synonyms=PCAF {ECO:0000303|PubMed:12486002};
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 {ECO:0000312|EMBL:AAC50890.2};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, TISSUE SPECIFICITY, AND
RP INTERACTION WITH EP300 AND CREBBP.
RC TISSUE=Liver;
RX PubMed=8684459; DOI=10.1038/382319a0;
RA Yang X.-J., Ogryzko V.V., Nishikawa J., Howard B.H., Nakatani Y.;
RT "A p300/CBP-associated factor that competes with the adenoviral oncoprotein
RT E1A.";
RL Nature 382:319-324(1996).
RN [2] {ECO:0000305}
RP SEQUENCE REVISION.
RC TISSUE=Liver;
RA Nakatani Y.;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8945521; DOI=10.1016/s0092-8674(00)82001-2;
RA Ogryzko V.V., Schiltz R.L., Russanova V., Howard B.H., Nakatani Y.;
RT "The transcriptional coactivators p300 and CBP are histone
RT acetyltransferases.";
RL Cell 87:953-959(1996).
RN [5]
RP INTERACTION WITH NCOA3.
RX PubMed=9346901; DOI=10.1074/jbc.272.44.27629;
RA Takeshita A., Cardona G.R., Koibuchi N., Suen C.-S., Chin W.W.;
RT "TRAM-1, a novel 160-kDa thyroid hormone receptor activator molecule,
RT exhibits distinct properties from steroid receptor coactivator-1.";
RL J. Biol. Chem. 272:27629-27634(1997).
RN [6]
RP INTERACTION WITH NCOA1.
RX PubMed=9296499; DOI=10.1038/38304;
RA Spencer T.E., Jenster G., Burcin M.M., Allis C.D., Zhou J., Mizzen C.A.,
RA McKenna N.J., Onate S.A., Tsai S.Y., Tsai M.-J., O'Malley B.W.;
RT "Steroid receptor coactivator-1 is a histone acetyltransferase.";
RL Nature 389:194-198(1997).
RN [7]
RP INTERACTION WITH KLF1, AND FUNCTION.
RX PubMed=9707565; DOI=10.1073/pnas.95.17.9855;
RA Zhang W., Bieker J.J.;
RT "Acetylation and modulation of erythroid Krueppel-like factor (EKLF)
RT activity by interaction with histone acetyltransferases.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9855-9860(1998).
RN [8]
RP INTERACTION WITH E2F1, AND FUNCTION.
RX PubMed=10675335; DOI=10.1093/emboj/19.4.662;
RA Martinez-Balbas M.A., Bauer U.M., Nielsen S.J., Brehm A., Kouzarides T.;
RT "Regulation of E2F1 activity by acetylation.";
RL EMBO J. 19:662-671(2000).
RN [9]
RP INTERACTION WITH HTLV-1 TAX (MICROBIAL INFECTION).
RX PubMed=10766811; DOI=10.1074/jbc.275.16.11852;
RA Harrod R., Kuo Y.-L., Tang Y., Yao Y., Vassilev A., Nakatani Y.,
RA Giam C.-Z.;
RT "p300 and p300/cAMP-responsive element-binding protein associated factor
RT interact with human T-cell lymphotropic virus type-1 Tax in a multi-histone
RT acetyltransferase/activator-enhancer complex.";
RL J. Biol. Chem. 275:11852-11857(2000).
RN [10]
RP INTERACTION WITH MECOM.
RX PubMed=11568182; DOI=10.1074/jbc.m106733200;
RA Chakraborty S., Senyuk V., Sitailo S., Chi Y., Nucifora G.;
RT "Interaction of EVI1 with cAMP-responsive element-binding protein-binding
RT protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible
RT acetylation of EVI1 and in co-localization in nuclear speckles.";
RL J. Biol. Chem. 276:44936-44943(2001).
RN [11]
RP INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION).
RX PubMed=12486002; DOI=10.1093/emboj/cdf669;
RA Bres V., Tagami H., Peloponese J.-M., Loret E., Jeang K.-T., Nakatani Y.,
RA Emiliani S., Benkirane M., Kiernan R.E.;
RT "Differential acetylation of Tat coordinates its interaction with the co-
RT activators cyclin T1 and PCAF.";
RL EMBO J. 21:6811-6819(2002).
RN [12]
RP FUNCTION, AND INTERACTION WITH NPAS2; ARNTL/BMAL1 AND CLOCK.
RX PubMed=14645221; DOI=10.1074/jbc.m311973200;
RA Curtis A.M., Seo S.B., Westgate E.J., Rudic R.D., Smyth E.M.,
RA Chakravarti D., FitzGerald G.A., McNamara P.;
RT "Histone acetyltransferase-dependent chromatin remodeling and the vascular
RT clock.";
RL J. Biol. Chem. 279:7091-7097(2004).
RN [13]
RP INTERACTION WITH NFE4.
RX PubMed=15273251; DOI=10.1074/jbc.m405129200;
RA Zhao Q., Cumming H., Cerruti L., Cunningham J.M., Jane S.M.;
RT "Site-specific acetylation of the fetal globin activator NF-E4 prevents its
RT ubiquitination and regulates its interaction with the histone deacetylase,
RT HDAC1.";
RL J. Biol. Chem. 279:41477-41486(2004).
RN [14]
RP INTERACTION WITH TACC1; TACC2 AND TACC3.
RX PubMed=14767476; DOI=10.1038/sj.onc.1207424;
RA Gangisetty O., Lauffart B., Sondarva G.V., Chelsea D.M., Still I.H.;
RT "The transforming acidic coiled coil proteins interact with nuclear histone
RT acetyltransferases.";
RL Oncogene 23:2559-2563(2004).
RN [15]
RP INTERACTION WITH NR2C2.
RX PubMed=16887930; DOI=10.1074/mcp.m600180-mcp200;
RA Huq M.D., Gupta P., Tsai N.P., Wei L.N.;
RT "Modulation of testicular receptor 4 activity by mitogen-activated protein
RT kinase-mediated phosphorylation.";
RL Mol. Cell. Proteomics 5:2072-2082(2006).
RN [16]
RP INTERACTION WITH DDX17.
RX PubMed=17226766; DOI=10.1002/jcb.21250;
RA Shin S., Janknecht R.;
RT "Concerted activation of the Mdm2 promoter by p72 RNA helicase and the
RT coactivators p300 and P/CAF.";
RL J. Cell. Biochem. 101:1252-1265(2007).
RN [17]
RP INTERACTION WITH CEBPB.
RX PubMed=17301242; DOI=10.1073/pnas.0607378104;
RA Wiper-Bergeron N., Salem H.A., Tomlinson J.J., Wu D., Hache R.J.;
RT "Glucocorticoid-stimulated preadipocyte differentiation is mediated through
RT acetylation of C/EBPbeta by GCN5.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2703-2708(2007).
RN [18]
RP IDENTIFICATION IN A LARGE CHROMATIN REMODELING COMPLEX.
RX PubMed=17707232; DOI=10.1016/j.molcel.2007.07.024;
RA Zhu P., Zhou W., Wang J., Puc J., Ohgi K.A., Erdjument-Bromage H.,
RA Tempst P., Glass C.K., Rosenfeld M.G.;
RT "A histone H2A deubiquitinase complex coordinating histone acetylation and
RT H1 dissociation in transcriptional regulation.";
RL Mol. Cell 27:609-621(2007).
RN [19]
RP INTERACTION WITH BCAS3.
RX PubMed=17505058; DOI=10.1210/me.2006-0514;
RA Gururaj A.E., Peng S., Vadlamudi R.K., Kumar R.;
RT "Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha
RT coactivator, through proline-, glutamic acid-, and leucine-rich protein-1
RT (PELP1).";
RL Mol. Endocrinol. 21:1847-1860(2007).
RN [20]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=20940255; DOI=10.1242/jcs.068924;
RA Pickard A., Wong P.P., McCance D.J.;
RT "Acetylation of Rb by PCAF is required for nuclear localization and
RT keratinocyte differentiation.";
RL J. Cell Sci. 123:3718-3726(2010).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=27389534; DOI=10.1080/14756366.2016.1205045;
RA Burgio G., Corona D.F., Nicotra C.M., Carruba G., Taibi G.;
RT "P/CAF-mediated spermidine acetylation regulates histone acetyltransferase
RT activity.";
RL J. Enzym. Inhib. Med. Chem. 31:75-82(2016).
RN [22]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23001180; DOI=10.1073/pnas.1202639109;
RA Xia P., Wang Z., Liu X., Wu B., Wang J., Ward T., Zhang L., Ding X.,
RA Gibbons G., Shi Y., Yao X.;
RT "EB1 acetylation by P300/CBP-associated factor (PCAF) ensures accurate
RT kinetochore-microtubule interactions in mitosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:16564-16569(2012).
RN [23]
RP FUNCTION.
RX PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002;
RA Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.;
RT "Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and
RT tumor growth.";
RL Mol. Cell 51:506-518(2013).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PLK4.
RX PubMed=27796307; DOI=10.1038/ncomms13227;
RA Fournier M., Orpinell M., Grauffel C., Scheer E., Garnier J.M., Ye T.,
RA Chavant V., Joint M., Esashi F., Dejaegere A., Goenczy P., Tora L.;
RT "KAT2A/KAT2B-targeted acetylome reveals a role for PLK4 acetylation in
RT preventing centrosome amplification.";
RL Nat. Commun. 7:13227-13227(2016).
RN [25]
RP FUNCTION.
RX PubMed=26867678; DOI=10.1038/ncomms10734;
RA Chen S., Blank M.F., Iyer A., Huang B., Wang L., Grummt I., Voit R.;
RT "SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA
RT processing.";
RL Nat. Commun. 7:10734-10734(2016).
RN [26]
RP FUNCTION, AND INTERACTION WITH TBX5.
RX PubMed=29174768; DOI=10.1016/j.yjmcc.2017.11.013;
RA Ghosh T.K., Aparicio-Sanchez J.J., Buxton S., Ketley A., Mohamed T.,
RA Rutland C.S., Loughna S., Brook J.D.;
RT "Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb
RT development.";
RL J. Mol. Cell. Cardiol. 114:185-198(2017).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 493-658 IN COMPLEX WITH COENZYME
RP A, AND ACTIVE SITE.
RX PubMed=10393169; DOI=10.1093/emboj/18.13.3521;
RA Clements A., Rojas J.R., Trievel R.C., Wang L., Berger S.L.,
RA Marmorstein R.;
RT "Crystal structure of the histone acetyltransferase domain of the human
RT PCAF transcriptional regulator bound to coenzyme A.";
RL EMBO J. 18:3521-3532(1999).
RN [28]
RP STRUCTURE BY NMR OF 715-832, AND MUTAGENESIS OF VAL-752; TYR-760; TYR-802
RP AND TYR-809.
RC TISSUE=Liver;
RX PubMed=10365964; DOI=10.1038/20974;
RA Dhalluin C., Carlson J.E., Zeng L., He C., Aggarwal A.K., Zhou M.-M.;
RT "Structure and ligand of a histone acetyltransferase bromodomain.";
RL Nature 399:491-496(1999).
RN [29]
RP STRUCTURE BY NMR OF 719-832 IN COMPLEX WITH HIV-1 TAT.
RX PubMed=11931765; DOI=10.1016/s1097-2765(02)00483-5;
RA Mujtaba S., He Y., Zeng L., Farooq A., Carlson J.E., Ott M., Verdin E.,
RA Zhou M.-M.;
RT "Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF
RT bromodomain.";
RL Mol. Cell 9:575-586(2002).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 715-831.
RX PubMed=22464331; DOI=10.1016/j.cell.2012.02.013;
RA Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P.,
RA Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T.,
RA Gingras A.C., Arrowsmith C.H., Knapp S.;
RT "Histone recognition and large-scale structural analysis of the human
RT bromodomain family.";
RL Cell 149:214-231(2012).
RN [31]
RP VARIANT GLY-130.
RX PubMed=28493397; DOI=10.1002/humu.23246;
RG UK10K;
RA Rainger J., Williamson K.A., Soares D.C., Truch J., Kurian D.,
RA Gillessen-Kaesbach G., Seawright A., Prendergast J., Halachev M.,
RA Wheeler A., McTeir L., Gill A.C., van Heyningen V., Davey M.G.,
RA FitzPatrick D.R.;
RT "A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma.";
RL Hum. Mutat. 38:942-946(2017).
CC -!- FUNCTION: Functions as a histone acetyltransferase (HAT) to promote
CC transcriptional activation (PubMed:8945521). Has significant histone
CC acetyltransferase activity with core histones (H3 and H4), and also
CC with nucleosome core particles (PubMed:8945521). Also acetylates non-
CC histone proteins, such as ACLY, MAPRE1/EB1, PLK4, RRP9/U3-55K and TBX5
CC (PubMed:9707565, PubMed:10675335, PubMed:23001180, PubMed:27796307,
CC PubMed:23932781, PubMed:26867678, PubMed:29174768). Inhibits cell-cycle
CC progression and counteracts the mitogenic activity of the adenoviral
CC oncoprotein E1A (PubMed:8684459). Acts as a circadian transcriptional
CC coactivator which enhances the activity of the circadian
CC transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1
CC heterodimers (PubMed:14645221). Involved in heart and limb development
CC by mediating acetylation of TBX5, acetylation regulating
CC nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a
CC negative regulator of centrosome amplification by mediating acetylation
CC of PLK4 (PubMed:27796307). Acetylates RRP9/U3-55K, a core subunit of
CC the U3 snoRNP complex, impairing pre-rRNA processing (PubMed:26867678).
CC Acetylates MAPRE1/EB1, promoting dynamic kinetochore-microtubule
CC interactions in early mitosis (PubMed:23001180). Also acetylates
CC spermidine (PubMed:27389534). {ECO:0000269|PubMed:10675335,
CC ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:23001180,
CC ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:26867678,
CC ECO:0000269|PubMed:27389534, ECO:0000269|PubMed:27796307,
CC ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:8684459,
CC ECO:0000269|PubMed:8945521, ECO:0000269|PubMed:9707565}.
CC -!- FUNCTION: (Microbial infection) In case of HIV-1 infection, it is
CC recruited by the viral protein Tat. Regulates Tat's transactivating
CC activity and may help inducing chromatin remodeling of proviral genes.
CC {ECO:0000269|PubMed:12486002}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-
CC lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48;
CC Evidence={ECO:0000269|PubMed:23001180, ECO:0000269|PubMed:27389534,
CC ECO:0000269|PubMed:8945521};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45949;
CC Evidence={ECO:0000269|PubMed:23001180, ECO:0000305|PubMed:27389534};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + spermidine = CoA + H(+) + N(8)-acetylspermidine;
CC Xref=Rhea:RHEA:28270, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57834, ChEBI:CHEBI:58535; EC=2.3.1.57;
CC Evidence={ECO:0000269|PubMed:27389534};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28271;
CC Evidence={ECO:0000305|PubMed:27389534};
CC -!- ACTIVITY REGULATION: Activated in vitro by very low concentrations of
CC spermidine, but inhibited at spermidine concentrations higher than 4
CC uM. The activating effect of low spermidine concentrations may be
CC mediated by N(8)-acetylspermidine produced by KAT2B/P/CAF itself acting
CC as a positive feedback loop. {ECO:0000269|PubMed:27389534}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.74 uM for acetyl-CoA {ECO:0000269|PubMed:27389534};
CC KM=2.29 uM for spermidine {ECO:0000269|PubMed:27389534};
CC -!- SUBUNIT: Interacts with SIRT1. Interacts (unsumoylated form) with
CC NR2C1; the interaction promotes transactivation activity (By
CC similarity). Interacts with EP300, CREBBP and DDX17. Interacts with
CC NCOA1 and NCOA3. Component of a large chromatin remodeling complex, at
CC least composed of MYSM1, KAT2B/PCAF, RBM10 and KIF11/TRIP5. Interacts
CC with NR2C2 (hypophosphorylated and unsumoylated form); the interaction
CC promotes the transactivation activity of NR2C2. Interacts with KLF1;
CC the interaction does not acetylate KLF1 and there is no enhancement of
CC its transactivational activity. Interacts with NFE4. Interacts with
CC MECOM. Interacts with E2F1; the interaction acetylates E2F1 augmenting
CC its DNA-binding and transcriptional activity. Interacts with NPAS2,
CC ARNTL/BMAL1 and CLOCK. Interacts with BCAS3. Interacts with CEBPB
CC (PubMed:17301242). Interacts with NR4A3 (By similarity). Interacts with
CC NFATC2 (By similarity). Interacts with TBX5 (PubMed:29174768).
CC Interacts with PLK4 (PubMed:27796307). Interacts with RB1; this
CC interaction leads to RB1 acetylation (By similarity).
CC {ECO:0000250|UniProtKB:Q9JHD1, ECO:0000269|PubMed:10675335,
CC ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:11931765,
CC ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:14767476,
CC ECO:0000269|PubMed:15273251, ECO:0000269|PubMed:16887930,
CC ECO:0000269|PubMed:17226766, ECO:0000269|PubMed:17301242,
CC ECO:0000269|PubMed:17505058, ECO:0000269|PubMed:17707232,
CC ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768,
CC ECO:0000269|PubMed:8684459, ECO:0000269|PubMed:9296499,
CC ECO:0000269|PubMed:9346901, ECO:0000269|PubMed:9707565}.
CC -!- SUBUNIT: (Microbial infection) Interacts with and acetylates HIV-1 Tat.
CC {ECO:0000269|PubMed:12486002}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HTLV-1 Tax.
CC {ECO:0000269|PubMed:10766811}.
CC -!- INTERACTION:
CC Q92831; O60566: BUB1B; NbExp=14; IntAct=EBI-477430, EBI-1001438;
CC Q92831; Q92793: CREBBP; NbExp=4; IntAct=EBI-477430, EBI-81215;
CC Q92831; Q96KQ7: EHMT2; NbExp=3; IntAct=EBI-477430, EBI-744366;
CC Q92831; Q09472: EP300; NbExp=2; IntAct=EBI-477430, EBI-447295;
CC Q92831; Q16665: HIF1A; NbExp=2; IntAct=EBI-477430, EBI-447269;
CC Q92831; Q9Y5W3: KLF2; NbExp=2; IntAct=EBI-477430, EBI-9846663;
CC Q92831; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-477430, EBI-1802965;
CC Q92831; Q8IXJ6: SIRT2; NbExp=4; IntAct=EBI-477430, EBI-477232;
CC Q92831; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-477430, EBI-5235340;
CC Q92831; Q16594: TAF9; NbExp=3; IntAct=EBI-477430, EBI-712521;
CC Q92831; Q15672: TWIST1; NbExp=2; IntAct=EBI-477430, EBI-1797287;
CC Q92831; P22415: USF1; NbExp=5; IntAct=EBI-477430, EBI-1054489;
CC Q92831; P28033: Cebpb; Xeno; NbExp=2; IntAct=EBI-477430, EBI-1029979;
CC Q92831; P03129: E7; Xeno; NbExp=3; IntAct=EBI-477430, EBI-866453;
CC Q92831; P02299: His3:CG33854; Xeno; NbExp=2; IntAct=EBI-477430, EBI-522090;
CC Q92831; P84040: His4:CG33909; Xeno; NbExp=2; IntAct=EBI-477430, EBI-185028;
CC Q92831; P0DTC9: N; Xeno; NbExp=2; IntAct=EBI-477430, EBI-25475856;
CC Q92831; P59595: N; Xeno; NbExp=2; IntAct=EBI-477430, EBI-7602718;
CC Q92831; O88898-2: Tp63; Xeno; NbExp=3; IntAct=EBI-477430, EBI-2338228;
CC Q92831; P03255; Xeno; NbExp=3; IntAct=EBI-477430, EBI-2603114;
CC Q92831; P03255-2; Xeno; NbExp=3; IntAct=EBI-477430, EBI-6859460;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20940255,
CC ECO:0000269|PubMed:29174768}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:29174768}. Cytoplasm
CC {ECO:0000269|PubMed:20940255}. Note=Mainly localizes to the nucleus.
CC Also localizes to centrosomes in late G1 and around the G1/S
CC transition, coinciding with the onset of centriole formation.
CC Subcellular location may vary depending upon cell differentiation
CC state. Cytoplasmic at the very stages of keratinocyte differentiation,
CC becomes nuclear at later differentiation stages. Cytoplasmic in basal
CC epithelial cells (undifferentiated cells) and nuclear in parabasal
CC cells (differentiated cells) (PubMed:20940255).
CC {ECO:0000269|PubMed:20940255, ECO:0000269|PubMed:29174768}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed but most abundant in heart
CC and skeletal muscle. Also expressed in the skin, in keratinocytes (at
CC protein level) (PubMed:20940255). {ECO:0000269|PubMed:20940255,
CC ECO:0000269|PubMed:8684459}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during keratinocyte differentiation
CC (at protein level). {ECO:0000269|PubMed:20940255}.
CC -!- DOMAIN: (Microbial infection) The bromodomain mediates binding to HIV-1
CC Tat. {ECO:0000269|PubMed:11931765}.
CC -!- DISEASE: Note=Defects in KAT2B has been found in a patient with
CC isolated coloboma, a defect of the eye characterized by the absence of
CC ocular structures due to abnormal morphogenesis of the optic cup and
CC stalk, and the fusion of the fetal fissure (optic fissure). Isolated
CC colobomas may be associated with an abnormally small eye
CC (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. GCN5 subfamily.
CC {ECO:0000305}.
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DR EMBL; U57317; AAC50890.2; -; mRNA.
DR EMBL; BC060823; AAH60823.1; -; mRNA.
DR EMBL; BC070075; AAH70075.1; -; mRNA.
DR CCDS; CCDS2634.1; -.
DR PIR; S71788; S71788.
DR RefSeq; NP_003875.3; NM_003884.4.
DR PDB; 1CM0; X-ray; 2.30 A; A/B=493-658.
DR PDB; 1JM4; NMR; -; B=719-832.
DR PDB; 1N72; NMR; -; A=719-832.
DR PDB; 1WUG; NMR; -; A=719-832.
DR PDB; 1WUM; NMR; -; A=719-832.
DR PDB; 1ZS5; NMR; -; A=719-832.
DR PDB; 2RNW; NMR; -; A=719-832.
DR PDB; 2RNX; NMR; -; A=719-832.
DR PDB; 3GG3; X-ray; 2.25 A; A/B=715-831.
DR PDB; 4NSQ; X-ray; 2.31 A; A/B/C/D=493-658.
DR PDB; 5FDZ; X-ray; 2.40 A; A/B=715-831.
DR PDB; 5FE0; X-ray; 2.30 A; A/B=715-831.
DR PDB; 5FE1; X-ray; 2.22 A; A/B=715-831.
DR PDB; 5FE2; X-ray; 2.25 A; A/B=715-831.
DR PDB; 5FE3; X-ray; 2.12 A; A/B=715-831.
DR PDB; 5FE4; X-ray; 2.15 A; A/B=715-831.
DR PDB; 5FE5; X-ray; 2.12 A; A/B=715-831.
DR PDB; 5FE6; X-ray; 1.77 A; A/B=715-831.
DR PDB; 5FE7; X-ray; 2.08 A; A/B=715-831.
DR PDB; 5FE8; X-ray; 2.10 A; A/B=715-831.
DR PDB; 5FE9; X-ray; 2.35 A; A/B=715-831.
DR PDB; 5LVQ; X-ray; 2.05 A; A/B=715-831.
DR PDB; 5LVR; X-ray; 2.05 A; A/B=715-831.
DR PDB; 5MKX; X-ray; 1.68 A; A/B=715-831.
DR PDB; 6J3O; X-ray; 2.11 A; A/B=715-831.
DR PDBsum; 1CM0; -.
DR PDBsum; 1JM4; -.
DR PDBsum; 1N72; -.
DR PDBsum; 1WUG; -.
DR PDBsum; 1WUM; -.
DR PDBsum; 1ZS5; -.
DR PDBsum; 2RNW; -.
DR PDBsum; 2RNX; -.
DR PDBsum; 3GG3; -.
DR PDBsum; 4NSQ; -.
DR PDBsum; 5FDZ; -.
DR PDBsum; 5FE0; -.
DR PDBsum; 5FE1; -.
DR PDBsum; 5FE2; -.
DR PDBsum; 5FE3; -.
DR PDBsum; 5FE4; -.
DR PDBsum; 5FE5; -.
DR PDBsum; 5FE6; -.
DR PDBsum; 5FE7; -.
DR PDBsum; 5FE8; -.
DR PDBsum; 5FE9; -.
DR PDBsum; 5LVQ; -.
DR PDBsum; 5LVR; -.
DR PDBsum; 5MKX; -.
DR PDBsum; 6J3O; -.
DR AlphaFoldDB; Q92831; -.
DR BMRB; Q92831; -.
DR SMR; Q92831; -.
DR BioGRID; 114375; 235.
DR ComplexPortal; CPX-1004; PCAF-containing ATAC complex.
DR ComplexPortal; CPX-6802; SAGA complex, KAT2B variant.
DR ComplexPortal; CPX-989; PCAF histone acetylase complex.
DR CORUM; Q92831; -.
DR DIP; DIP-29778N; -.
DR IntAct; Q92831; 64.
DR MINT; Q92831; -.
DR STRING; 9606.ENSP00000263754; -.
DR BindingDB; Q92831; -.
DR ChEMBL; CHEMBL5500; -.
DR DrugBank; DB08186; (3E)-4-(1-METHYL-1H-INDOL-3-YL)BUT-3-EN-2-ONE.
DR DrugBank; DB01992; Coenzyme A.
DR DrugBank; DB08291; N-(3-AMINOPROPYL)-2-NITROBENZENAMINE.
DR GuidetoPHARMACOLOGY; 2737; -.
DR CarbonylDB; Q92831; -.
DR iPTMnet; Q92831; -.
DR PhosphoSitePlus; Q92831; -.
DR BioMuta; KAT2B; -.
DR DMDM; 83287776; -.
DR REPRODUCTION-2DPAGE; Q92831; -.
DR EPD; Q92831; -.
DR jPOST; Q92831; -.
DR MassIVE; Q92831; -.
DR MaxQB; Q92831; -.
DR PaxDb; Q92831; -.
DR PeptideAtlas; Q92831; -.
DR PRIDE; Q92831; -.
DR ProteomicsDB; 75508; -.
DR Antibodypedia; 3865; 463 antibodies from 39 providers.
DR DNASU; 8850; -.
DR Ensembl; ENST00000263754.5; ENSP00000263754.4; ENSG00000114166.8.
DR GeneID; 8850; -.
DR KEGG; hsa:8850; -.
DR MANE-Select; ENST00000263754.5; ENSP00000263754.4; NM_003884.5; NP_003875.3.
DR UCSC; uc003cbq.4; human.
DR CTD; 8850; -.
DR DisGeNET; 8850; -.
DR GeneCards; KAT2B; -.
DR HGNC; HGNC:8638; KAT2B.
DR HPA; ENSG00000114166; Low tissue specificity.
DR MIM; 602303; gene.
DR neXtProt; NX_Q92831; -.
DR OpenTargets; ENSG00000114166; -.
DR PharmGKB; PA162392705; -.
DR VEuPathDB; HostDB:ENSG00000114166; -.
DR eggNOG; KOG1472; Eukaryota.
DR GeneTree; ENSGT00940000154995; -.
DR HOGENOM; CLU_015901_0_0_1; -.
DR InParanoid; Q92831; -.
DR OMA; DFAIGYF; -.
DR OrthoDB; 349249at2759; -.
DR PhylomeDB; Q92831; -.
DR TreeFam; TF105399; -.
DR BRENDA; 2.3.1.48; 2681.
DR PathwayCommons; Q92831; -.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
DR Reactome; R-HSA-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-HSA-5578768; Physiological factors.
DR Reactome; R-HSA-5689901; Metalloprotease DUBs.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-HSA-8941856; RUNX3 regulates NOTCH signaling.
DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR SignaLink; Q92831; -.
DR SIGNOR; Q92831; -.
DR BioGRID-ORCS; 8850; 11 hits in 1101 CRISPR screens.
DR ChiTaRS; KAT2B; human.
DR EvolutionaryTrace; Q92831; -.
DR GeneWiki; PCAF; -.
DR GenomeRNAi; 8850; -.
DR Pharos; Q92831; Tchem.
DR PRO; PR:Q92831; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q92831; protein.
DR Bgee; ENSG00000114166; Expressed in lateral globus pallidus and 205 other tissues.
DR Genevisible; Q92831; HS.
DR GO; GO:0031672; C:A band; IEA:Ensembl.
DR GO; GO:0042641; C:actomyosin; IEA:Ensembl.
DR GO; GO:0140672; C:ATAC complex; IDA:BHF-UCL.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0000123; C:histone acetyltransferase complex; IBA:GO_Central.
DR GO; GO:0031674; C:I band; IEA:Ensembl.
DR GO; GO:0000776; C:kinetochore; IEA:Ensembl.
DR GO; GO:0072686; C:mitotic spindle; IC:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0000124; C:SAGA complex; NAS:UniProtKB.
DR GO; GO:0016407; F:acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0004145; F:diamine N-acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0004402; F:histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0004468; F:lysine N-acetyltransferase activity, acting on acetyl phosphate as donor; IDA:UniProtKB.
DR GO; GO:0061733; F:peptide-lysine-N-acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IPI:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL.
DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; TAS:Reactome.
DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0016573; P:histone acetylation; IC:ComplexPortal.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:BHF-UCL.
DR GO; GO:0043970; P:histone H3-K9 acetylation; IEA:Ensembl.
DR GO; GO:0018393; P:internal peptidyl-lysine acetylation; IDA:UniProtKB.
DR GO; GO:0060173; P:limb development; ISS:UniProtKB.
DR GO; GO:0018076; P:N-terminal peptidyl-lysine acetylation; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0046600; P:negative regulation of centriole replication; IDA:UniProtKB.
DR GO; GO:2000233; P:negative regulation of rRNA processing; IDA:UniProtKB.
DR GO; GO:0018394; P:peptidyl-lysine acetylation; IDA:BHF-UCL.
DR GO; GO:1902425; P:positive regulation of attachment of mitotic spindle microtubules to kinetochore; IDA:UniProtKB.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IC:ComplexPortal.
DR GO; GO:0006473; P:protein acetylation; IDA:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:ProtInc.
DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal.
DR GO; GO:0045995; P:regulation of embryonic development; IC:ComplexPortal.
DR GO; GO:0010835; P:regulation of protein ADP-ribosylation; IDA:BHF-UCL.
DR GO; GO:0043484; P:regulation of RNA splicing; IC:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IC:ComplexPortal.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR Gene3D; 1.20.920.10; -; 1.
DR IDEAL; IID00390; -.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR037800; GCN5.
DR InterPro; IPR016376; GCN5/PCAF.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR009464; PCAF_N.
DR PANTHER; PTHR45750; PTHR45750; 1.
DR Pfam; PF00583; Acetyltransf_1; 1.
DR Pfam; PF00439; Bromodomain; 1.
DR Pfam; PF06466; PCAF_N; 1.
DR PIRSF; PIRSF003048; Histone_acetylase_PCAF; 1.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00297; BROMO; 1.
DR SUPFAM; SSF47370; SSF47370; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS00633; BROMODOMAIN_1; 1.
DR PROSITE; PS50014; BROMODOMAIN_2; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Acyltransferase; Biological rhythms; Bromodomain;
KW Cell cycle; Cytoplasm; Cytoskeleton; Disease variant;
KW Host-virus interaction; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..832
FT /note="Histone acetyltransferase KAT2B"
FT /id="PRO_0000211208"
FT DOMAIN 503..651
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000250|UniProtKB:Q92830,
FT ECO:0000255|PROSITE-ProRule:PRU00532"
FT DOMAIN 740..810
FT /note="Bromo"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035,
FT ECO:0000305"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 706..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..40
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 711..725
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 570
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000303|PubMed:10393169"
FT BINDING 574..576
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:10393169"
FT BINDING 581..587
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:10393169"
FT BINDING 612..615
FT /ligand="acetyl-CoA"
FT /ligand_id="ChEBI:CHEBI:57288"
FT /evidence="ECO:0000269|PubMed:10393169"
FT VARIANT 130
FT /note="V -> G (found in a patient with isolated coloboma;
FT unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:28493397"
FT /id="VAR_079852"
FT VARIANT 386
FT /note="N -> S (in dbSNP:rs17006625)"
FT /id="VAR_034372"
FT MUTAGEN 752
FT /note="V->A: Reduced acetyl-lysine binding."
FT /evidence="ECO:0000269|PubMed:10365964"
FT MUTAGEN 760
FT /note="Y->A: Reduced acetyl-lysine binding."
FT /evidence="ECO:0000269|PubMed:10365964"
FT MUTAGEN 802
FT /note="Y->A: Reduced acetyl-lysine binding."
FT /evidence="ECO:0000269|PubMed:10365964"
FT MUTAGEN 809
FT /note="Y->A: Complete loss of acetyl-lysine binding."
FT /evidence="ECO:0000269|PubMed:10365964"
FT CONFLICT 804..805
FT /note="PP -> AA (in Ref. 1; AAC50890)"
FT /evidence="ECO:0000305"
FT STRAND 494..499
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:1CM0"
FT HELIX 509..525
FT /evidence="ECO:0007829|PDB:1CM0"
FT HELIX 531..538
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 543..550
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 553..563
FT /evidence="ECO:0007829|PDB:1CM0"
FT TURN 564..567
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 568..576
FT /evidence="ECO:0007829|PDB:1CM0"
FT HELIX 578..580
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:1CM0"
FT HELIX 585..599
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 604..609
FT /evidence="ECO:0007829|PDB:1CM0"
FT TURN 611..613
FT /evidence="ECO:0007829|PDB:1CM0"
FT HELIX 614..618
FT /evidence="ECO:0007829|PDB:1CM0"
FT TURN 619..621
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 623..625
FT /evidence="ECO:0007829|PDB:1CM0"
FT HELIX 630..633
FT /evidence="ECO:0007829|PDB:1CM0"
FT STRAND 644..649
FT /evidence="ECO:0007829|PDB:1CM0"
FT HELIX 727..741
FT /evidence="ECO:0007829|PDB:5MKX"
FT STRAND 742..744
FT /evidence="ECO:0007829|PDB:1WUM"
FT HELIX 746..748
FT /evidence="ECO:0007829|PDB:5MKX"
FT TURN 754..756
FT /evidence="ECO:0007829|PDB:5MKX"
FT STRAND 757..759
FT /evidence="ECO:0007829|PDB:1ZS5"
FT HELIX 760..763
FT /evidence="ECO:0007829|PDB:5MKX"
FT STRAND 764..766
FT /evidence="ECO:0007829|PDB:1JM4"
FT HELIX 770..778
FT /evidence="ECO:0007829|PDB:5MKX"
FT HELIX 785..802
FT /evidence="ECO:0007829|PDB:5MKX"
FT STRAND 805..807
FT /evidence="ECO:0007829|PDB:1WUG"
FT HELIX 808..827
FT /evidence="ECO:0007829|PDB:5MKX"
FT STRAND 828..830
FT /evidence="ECO:0007829|PDB:1N72"
SQ SEQUENCE 832 AA; 93013 MW; 72F516E8BC00CC0C CRC64;
MSEAGGAGPG GCGAGAGAGA GPGALPPQPA ALPPAPPQGS PCAAAAGGSG ACGPATAVAA
AGTAEGPGGG GSARIAVKKA QLRSAPRAKK LEKLGVYSAC KAEESCKCNG WKNPNPSPTP
PRADLQQIIV SLTESCRSCS HALAAHVSHL ENVSEEEMNR LLGIVLDVEY LFTCVHKEED
ADTKQVYFYL FKLLRKSILQ RGKPVVEGSL EKKPPFEKPS IEQGVNNFVQ YKFSHLPAKE
RQTIVELAKM FLNRINYWHL EAPSQRRLRS PNDDISGYKE NYTRWLCYCN VPQFCDSLPR
YETTQVFGRT LLRSVFTVMR RQLLEQARQE KDKLPLEKRT LILTHFPKFL SMLEEEVYSQ
NSPIWDQDFL SASSRTSQLG IQTVINPPPV AGTISYNSTS SSLEQPNAGS SSPACKASSG
LEANPGEKRK MTDSHVLEEA KKPRVMGDIP MELINEVMST ITDPAAMLGP ETNFLSAHSA
RDEAARLEER RGVIEFHVVG NSLNQKPNKK ILMWLVGLQN VFSHQLPRMP KEYITRLVFD
PKHKTLALIK DGRVIGGICF RMFPSQGFTE IVFCAVTSNE QVKGYGTHLM NHLKEYHIKH
DILNFLTYAD EYAIGYFKKQ GFSKEIKIPK TKYVGYIKDY EGATLMGCEL NPRIPYTEFS
VIIKKQKEII KKLIERKQAQ IRKVYPGLSC FKDGVRQIPI ESIPGIRETG WKPSGKEKSK
EPRDPDQLYS TLKSILQQVK SHQSAWPFME PVKRTEAPGY YEVIRFPMDL KTMSERLKNR
YYVSKKLFMA DLQRVFTNCK EYNPPESEYY KCANILEKFF FSKIKEAGLI DK
