GLYR1_HUMAN
ID GLYR1_HUMAN Reviewed; 553 AA.
AC Q49A26; B4DL47; C9JJ40; C9JJ60; Q5U632; Q6P1Q2; Q6V3W7; Q9BTI1; Q9BXK2;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 4.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Cytokine-like nuclear factor N-PAC {ECO:0000305|PubMed:30970244};
DE Short=NPAC {ECO:0000303|PubMed:30970244};
DE AltName: Full=3-hydroxyisobutyrate dehydrogenase-like protein;
DE AltName: Full=Glyoxylate reductase 1 homolog;
DE AltName: Full=Nuclear protein NP60;
DE AltName: Full=Nuclear protein of 60 kDa;
DE AltName: Full=Nucleosome-destabilizing factor {ECO:0000303|PubMed:29759984};
DE Short=hNDF {ECO:0000303|PubMed:29759984};
DE AltName: Full=Putative oxidoreductase GLYR1 {ECO:0000305};
GN Name=GLYR1 {ECO:0000312|HGNC:HGNC:24434};
GN Synonyms=HIBDL, NDF {ECO:0000303|PubMed:29759984}, NP60,
GN NPAC {ECO:0000303|PubMed:30970244};
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP DOMAIN, AND INTERACTION WITH MAPK14.
RX PubMed=16352664; DOI=10.1242/jcs.02699;
RA Fu J., Yang Z., Wei J., Han J., Gu J.;
RT "Nuclear protein NP60 regulates p38 MAPK activity.";
RL J. Cell Sci. 119:115-123(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Watari Y., Tsujino T., Nonaka H., Shirai Y., Saito N., Yokoyama M.;
RT "Molecular characterization of a novel human PWWP domain containing protein
RT with homology to 3-hydroxyisobutyrate dehydrogenase.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA New L., Han J.;
RT "A novel cytokine-like nuclear factor, N-PAC.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Tongue;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 14-553 (ISOFORM 2).
RC TISSUE=Brain, Lymph, Placenta, and Testis;
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP DOMAIN PWWP, AND FUNCTION.
RX PubMed=20850016; DOI=10.1016/j.cell.2010.08.020;
RA Vermeulen M., Eberl H.C., Matarese F., Marks H., Denissov S., Butter F.,
RA Lee K.K., Olsen J.V., Hyman A.A., Stunnenberg H.G., Mann M.;
RT "Quantitative interaction proteomics and genome-wide profiling of
RT epigenetic histone marks and their readers.";
RL Cell 142:967-980(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130 AND SER-540, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167 AND SER-540, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130 AND SER-540, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-269, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [16]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-135; LYS-227; LYS-237 AND
RP LYS-269, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-135; LYS-176; LYS-179; LYS-201;
RP LYS-211; LYS-227; LYS-237; LYS-240; LYS-269 AND LYS-302, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [18]
RP FUNCTION, INTERACTION WITH NUCLEOSOMES, AND SUBCELLULAR LOCATION.
RX PubMed=29759984; DOI=10.1101/gad.313973.118;
RA Fei J., Ishii H., Hoeksema M.A., Meitinger F., Kassavetis G.A., Glass C.K.,
RA Ren B., Kadonaga J.T.;
RT "NDF, a nucleosome-destabilizing factor that facilitates transcription
RT through nucleosomes.";
RL Genes Dev. 32:682-694(2018).
RN [19]
RP SUBUNIT.
RX PubMed=31408337; DOI=10.1021/acs.jcim.9b00588;
RA Montefiori M., Pilotto S., Marabelli C., Moroni E., Ferraro M.,
RA Serapian S.A., Mattevi A., Colombo G.;
RT "Impact of Mutations on NPAC Structural Dynamics: Mechanistic Insights from
RT MD Simulations.";
RL J. Chem. Inf. Model. 59:3927-3937(2019).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 261-553 IN COMPLEX WITH NAD
RP ANALOG.
RA Tickle J., Pilka E.S., Bunkoczi G., Berridge G., Smee C., Kavanagh K.L.,
RA Hozjan V., Niesen F.H., Papagrigoriou E., Pike A.C.W., Turnbull A.,
RA Arrowsmith C.H., Edwards A., Sundstrom M., Weigelt J., Von Delft F.,
RA Oppermann U.;
RT "The structure of the cytokine-like nuclear factor N-PAC.";
RL Submitted (APR-2007) to the PDB data bank.
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 152-268.
RX PubMed=23357850; DOI=10.1038/cr.2013.17;
RA Chen F., Yang H., Dong Z., Fang J., Wang P., Zhu T., Gong W., Fang R.,
RA Shi Y.G., Li Z., Xu Y.;
RT "Structural insight into substrate recognition by histone demethylase
RT LSD2/KDM1b.";
RL Cell Res. 23:306-309(2013).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 152-268 IN COMPLEX WITH KDM1B AND
RP HISTONE H3 PEPTIDE, FUNCTION, INTERACTION WITH KDM1B, AND MUTAGENESIS OF
RP ASP-214; HIS-216; PHE-217; HIS-219; 220-PHE--LEU-222 AND SER-223.
RX PubMed=23260659; DOI=10.1016/j.molcel.2012.11.019;
RA Fang R., Chen F., Dong Z., Hu D., Barbera A.J., Clark E.A., Fang J.,
RA Yang Y., Mei P., Rutenberg M., Li Z., Zhang Y., Xu Y., Yang H., Wang P.,
RA Simon M.D., Zhou Q., Li J., Marynick M.P., Li X., Lu H., Kaiser U.B.,
RA Kingston R.E., Xu Y., Shi Y.G.;
RT "LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular
RT model for regulation of H3K4 demethylation.";
RL Mol. Cell 49:558-570(2013).
RN [23] {ECO:0007744|PDB:6R1U, ECO:0007744|PDB:6R25}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.36 ANGSTROMS) OF 152-268 IN COMPLEX
RP WITH NUCLEOSOMES AND KDM1B, FUNCTION, INTERACTION WITH KDM1B, SUBCELLULAR
RP LOCATION, SUBUNIT, NADPH-BINDING, AND MUTAGENESIS OF MET-437.
RX PubMed=30970244; DOI=10.1016/j.celrep.2019.03.061;
RA Marabelli C., Marrocco B., Pilotto S., Chittori S., Picaud S., Marchese S.,
RA Ciossani G., Forneris F., Filippakopoulos P., Schoehn G., Rhodes D.,
RA Subramaniam S., Mattevi A.;
RT "A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC
RT Multimeric Complex.";
RL Cell Rep. 27:387-399.e7(2019).
RN [24]
RP FUNCTION, INTERACTION WITH GATA4, VARIANT LEU-496, AND CHARACTERIZATION OF
RP VARIANT LEU-496.
RX PubMed=35182466; DOI=10.1016/j.cell.2022.01.021;
RA Gonzalez-Teran B., Pittman M., Felix F., Thomas R., Richmond-Buccola D.,
RA Huettenhain R., Choudhary K., Moroni E., Costa M.W., Huang Y.,
RA Padmanabhan A., Alexanian M., Lee C.Y., Maven B.E.J., Samse-Knapp K.,
RA Morton S.U., McGregor M., Gifford C.A., Seidman J.G., Seidman C.E.,
RA Gelb B.D., Colombo G., Conklin B.R., Black B.L., Bruneau B.G., Krogan N.J.,
RA Pollard K.S., Srivastava D.;
RT "Transcription factor protein interactomes reveal genetic determinants in
RT heart disease.";
RL Cell 0:0-0(2022).
CC -!- FUNCTION: Cytokine-like nuclear factor with chromatin gene reader
CC activity involved in chromatin modification and regulation of gene
CC expression (PubMed:23260659, PubMed:30970244). Acts as a nucleosome-
CC destabilizing factor that is recruited to genes during transcriptional
CC activation (PubMed:30970244, PubMed:29759984). Recognizes and binds
CC histone H3 without a preference for specific epigenetic markers and
CC also binds DNA (PubMed:20850016, PubMed:30970244). Interacts with KDM1B
CC and promotes its histone demethylase activity by facilitating the
CC capture of H3 tails, they form a multifunctional enzyme complex that
CC modifies transcribed chromatin and facilitates Pol II transcription
CC through nucleosomes (PubMed:23260659, PubMed:30970244,
CC PubMed:29759984). Stimulates the acetylation of 'Lys-56' of nucleosomal
CC histone H3 (H3K56ac) by EP300 (PubMed:29759984). With GATA4, co-binds a
CC defined set of heart development genes and coregulates their expression
CC during cardiomyocyte differentiation (PubMed:35182466). Regulates p38
CC MAP kinase activity by mediating stress activation of MAPK14/p38alpha
CC and specifically regulating MAPK14 signaling (PubMed:16352664).
CC Indirectly promotes phosphorylation of MAPK14 and activation of ATF2
CC (PubMed:16352664). The phosphorylation of MAPK14 requires upstream
CC activity of MAP2K4 and MAP2K6 (PubMed:16352664).
CC {ECO:0000269|PubMed:16352664, ECO:0000269|PubMed:20850016,
CC ECO:0000269|PubMed:23260659, ECO:0000269|PubMed:29759984,
CC ECO:0000269|PubMed:30970244, ECO:0000269|PubMed:35182466}.
CC -!- SUBUNIT: Homotetramere (PubMed:31408337, PubMed:30970244). Interacts
CC with MAPK14 (PubMed:16352664). Interacts with KDM1B at nucleosomes;
CC this interaction stimulates H3K4me1 and H3K4me2 demethylation
CC (PubMed:23260659). Binds to mononucleosomes (PubMed:29759984).
CC Interacts with GATA4; the interaction is required for a synergistic
CC activation of GATA4 target genes transcription (PubMed:35182466).
CC {ECO:0000269|PubMed:16352664, ECO:0000269|PubMed:23260659,
CC ECO:0000269|PubMed:29759984, ECO:0000269|PubMed:30970244,
CC ECO:0000269|PubMed:31408337, ECO:0000269|PubMed:35182466}.
CC -!- INTERACTION:
CC Q49A26; P24863: CCNC; NbExp=3; IntAct=EBI-2804292, EBI-395261;
CC Q49A26; Q8IYR0: CFAP206; NbExp=3; IntAct=EBI-2804292, EBI-749051;
CC Q49A26; Q8N9N8: EIF1AD; NbExp=4; IntAct=EBI-2804292, EBI-750700;
CC Q49A26; Q14192: FHL2; NbExp=4; IntAct=EBI-2804292, EBI-701903;
CC Q49A26-4; Q0P5N6: ARL16; NbExp=3; IntAct=EBI-12143817, EBI-10186132;
CC Q49A26-4; P55212: CASP6; NbExp=3; IntAct=EBI-12143817, EBI-718729;
CC Q49A26-4; P55273: CDKN2D; NbExp=3; IntAct=EBI-12143817, EBI-745859;
CC Q49A26-4; O95833: CLIC3; NbExp=3; IntAct=EBI-12143817, EBI-10192241;
CC Q49A26-4; P22607: FGFR3; NbExp=3; IntAct=EBI-12143817, EBI-348399;
CC Q49A26-4; Q14192: FHL2; NbExp=3; IntAct=EBI-12143817, EBI-701903;
CC Q49A26-4; Q14957: GRIN2C; NbExp=3; IntAct=EBI-12143817, EBI-8285963;
CC Q49A26-4; O00291: HIP1; NbExp=3; IntAct=EBI-12143817, EBI-473886;
CC Q49A26-4; P13473-2: LAMP2; NbExp=3; IntAct=EBI-12143817, EBI-21591415;
CC Q49A26-4; Q9BV86: NTMT1; NbExp=3; IntAct=EBI-12143817, EBI-373016;
CC Q49A26-4; Q96CV9: OPTN; NbExp=3; IntAct=EBI-12143817, EBI-748974;
CC Q49A26-4; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-12143817, EBI-5280197;
CC Q49A26-4; P62826: RAN; NbExp=3; IntAct=EBI-12143817, EBI-286642;
CC Q49A26-4; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-12143817, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16352664}. Chromosome
CC {ECO:0000269|PubMed:29759984, ECO:0000269|PubMed:30970244}. Note=Found
CC in actively RNAPolII-transcribed gene bodies.
CC {ECO:0000269|PubMed:30970244, ECO:0000269|PubMed:31408337}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q49A26-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q49A26-2; Sequence=VSP_029707;
CC Name=5;
CC IsoId=Q49A26-5; Sequence=VSP_038222;
CC Name=3;
CC IsoId=Q49A26-3; Sequence=VSP_029708;
CC Name=4;
CC IsoId=Q49A26-4; Sequence=VSP_029706;
CC -!- DOMAIN: The A.T hook DNA-binding domain is required for the interaction
CC with MAPK14. {ECO:0000269|PubMed:16352664, ECO:0000305}.
CC -!- DOMAIN: The PWWP domain is a H3 reader and strongly binds DNA.
CC {ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:30970244}.
CC -!- DOMAIN: In the dehydrogenase domain, the conserved NAD(P)H-binding
CC sites and sequence similarity to plant dehydrogenases suggest that this
CC protein may have oxidoreductase activity (PubMed:23260659,
CC PubMed:30970244). However, since the active site is not conserved, the
CC dehydrogenase domain seems to serve as a catalytically inert
CC oligomerization module (PubMed:30970244). {ECO:0000269|PubMed:23260659,
CC ECO:0000269|PubMed:30970244}.
CC -!- SIMILARITY: Belongs to the HIBADH-related family. NP60 subfamily.
CC {ECO:0000305}.
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DR EMBL; AY352585; AAQ57265.1; -; mRNA.
DR EMBL; AF244907; AAQ14242.1; -; mRNA.
DR EMBL; AF326966; AAK15524.1; -; mRNA.
DR EMBL; AK296842; BAG59409.1; -; mRNA.
DR EMBL; AC020663; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85252.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85257.1; -; Genomic_DNA.
DR EMBL; BC003693; AAH03693.1; -; mRNA.
DR EMBL; BC032855; AAH32855.1; -; mRNA.
DR EMBL; BC047223; AAH47223.1; -; mRNA.
DR EMBL; BC064940; AAH64940.1; -; mRNA.
DR CCDS; CCDS10524.1; -. [Q49A26-1]
DR CCDS; CCDS81945.1; -. [Q49A26-3]
DR RefSeq; NP_001295025.1; NM_001308096.1. [Q49A26-3]
DR RefSeq; NP_001311026.1; NM_001324097.1. [Q49A26-5]
DR RefSeq; NP_115958.2; NM_032569.3. [Q49A26-1]
DR RefSeq; XP_011521019.1; XM_011522717.1. [Q49A26-4]
DR PDB; 2UYY; X-ray; 2.50 A; A/B/C/D=261-553.
DR PDB; 4GUR; X-ray; 2.51 A; B=152-268.
DR PDB; 4GUS; X-ray; 2.23 A; B=152-268.
DR PDB; 4GUT; X-ray; 2.00 A; B=152-268.
DR PDB; 4GUU; X-ray; 2.30 A; B=152-268.
DR PDB; 4HSU; X-ray; 1.99 A; B=152-268.
DR PDB; 6R1U; EM; 4.36 A; L=152-268.
DR PDB; 6R25; EM; 4.61 A; L=214-225.
DR PDBsum; 2UYY; -.
DR PDBsum; 4GUR; -.
DR PDBsum; 4GUS; -.
DR PDBsum; 4GUT; -.
DR PDBsum; 4GUU; -.
DR PDBsum; 4HSU; -.
DR PDBsum; 6R1U; -.
DR PDBsum; 6R25; -.
DR AlphaFoldDB; Q49A26; -.
DR SASBDB; Q49A26; -.
DR SMR; Q49A26; -.
DR BioGRID; 124176; 218.
DR IntAct; Q49A26; 107.
DR MINT; Q49A26; -.
DR STRING; 9606.ENSP00000322716; -.
DR GlyGen; Q49A26; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q49A26; -.
DR PhosphoSitePlus; Q49A26; -.
DR SwissPalm; Q49A26; -.
DR BioMuta; GLYR1; -.
DR DMDM; 269849681; -.
DR CPTAC; CPTAC-1348; -.
DR EPD; Q49A26; -.
DR jPOST; Q49A26; -.
DR MassIVE; Q49A26; -.
DR PaxDb; Q49A26; -.
DR PeptideAtlas; Q49A26; -.
DR PRIDE; Q49A26; -.
DR ProteomicsDB; 62016; -. [Q49A26-1]
DR ProteomicsDB; 62017; -. [Q49A26-2]
DR ProteomicsDB; 62018; -. [Q49A26-3]
DR ProteomicsDB; 62019; -. [Q49A26-4]
DR ProteomicsDB; 62020; -. [Q49A26-5]
DR TopDownProteomics; Q49A26-2; -. [Q49A26-2]
DR Antibodypedia; 24437; 112 antibodies from 21 providers.
DR DNASU; 84656; -.
DR Ensembl; ENST00000321919.14; ENSP00000322716.6; ENSG00000140632.17. [Q49A26-1]
DR Ensembl; ENST00000436648.9; ENSP00000390276.4; ENSG00000140632.17. [Q49A26-5]
DR Ensembl; ENST00000591451.5; ENSP00000468328.1; ENSG00000140632.17. [Q49A26-3]
DR GeneID; 84656; -.
DR KEGG; hsa:84656; -.
DR MANE-Select; ENST00000321919.14; ENSP00000322716.6; NM_032569.4; NP_115958.2.
DR UCSC; uc002cxx.5; human. [Q49A26-1]
DR CTD; 84656; -.
DR DisGeNET; 84656; -.
DR GeneCards; GLYR1; -.
DR HGNC; HGNC:24434; GLYR1.
DR HPA; ENSG00000140632; Low tissue specificity.
DR MIM; 610660; gene.
DR neXtProt; NX_Q49A26; -.
DR OpenTargets; ENSG00000140632; -.
DR PharmGKB; PA165450093; -.
DR VEuPathDB; HostDB:ENSG00000140632; -.
DR eggNOG; KOG0409; Eukaryota.
DR eggNOG; KOG1904; Eukaryota.
DR GeneTree; ENSGT00940000156435; -.
DR HOGENOM; CLU_018075_0_0_1; -.
DR InParanoid; Q49A26; -.
DR OMA; DNIMSKN; -.
DR OrthoDB; 885724at2759; -.
DR PhylomeDB; Q49A26; -.
DR TreeFam; TF324195; -.
DR PathwayCommons; Q49A26; -.
DR SignaLink; Q49A26; -.
DR BioGRID-ORCS; 84656; 21 hits in 1088 CRISPR screens.
DR ChiTaRS; GLYR1; human.
DR EvolutionaryTrace; Q49A26; -.
DR GenomeRNAi; 84656; -.
DR Pharos; Q49A26; Tbio.
DR PRO; PR:Q49A26; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q49A26; protein.
DR Bgee; ENSG00000140632; Expressed in monocyte and 196 other tissues.
DR ExpressionAtlas; Q49A26; baseline and differential.
DR Genevisible; Q49A26; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0000786; C:nucleosome; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0031491; F:nucleosome binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR CDD; cd05836; N_Pac_NP60; 1.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR006115; 6PGDH_NADP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR029154; NADP-bd.
DR InterPro; IPR035501; NP60_PWWP.
DR InterPro; IPR000313; PWWP_dom.
DR Pfam; PF14833; NAD_binding_11; 1.
DR Pfam; PF03446; NAD_binding_2; 1.
DR Pfam; PF00855; PWWP; 1.
DR SMART; SM00293; PWWP; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS50812; PWWP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..553
FT /note="Cytokine-like nuclear factor N-PAC"
FT /id="PRO_0000312121"
FT DOMAIN 8..66
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT DNA_BIND 168..180
FT /note="A.T hook"
FT /evidence="ECO:0000305|PubMed:30970244"
FT REGION 92..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 214..217
FT /note="Interaction with histone H3"
FT /evidence="ECO:0000269|PubMed:23260659"
FT REGION 216..225
FT /note="Interaction with KDM1B"
FT /evidence="ECO:0000269|PubMed:23260659,
FT ECO:0007744|PDB:4GUR, ECO:0007744|PDB:4GUS,
FT ECO:0007744|PDB:4GUT, ECO:0007744|PDB:4GUU"
FT REGION 261..553
FT /note="Dehydrogenase domain"
FT /evidence="ECO:0000305|PubMed:30970244"
FT COMPBIAS 92..151
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 271..285
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.20, ECO:0007744|PDB:2UYY"
FT BINDING 362
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.20, ECO:0007744|PDB:2UYY"
FT BINDING 505
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.20, ECO:0007744|PDB:2UYY"
FT SITE 217
FT /note="Required to promote KDM1B demethylase activity
FT toward histone H3K4me1 and H3K4me2"
FT /evidence="ECO:0000269|PubMed:23260659"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT CROSSLNK 135
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 176
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 179
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 201
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 211
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 227
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 237
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 240
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 269
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..69
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029706"
FT VAR_SEQ 99..179
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038222"
FT VAR_SEQ 228..244
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029707"
FT VAR_SEQ 303..308
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_029708"
FT VARIANT 103
FT /note="N -> D (in dbSNP:rs34176249)"
FT /id="VAR_037403"
FT VARIANT 459
FT /note="Q -> H (in dbSNP:rs2085329)"
FT /id="VAR_037404"
FT VARIANT 496
FT /note="P -> L (decreased interaction with GATA4; decreased
FT synergistic activation of GATA4 target genes transcription;
FT detrimental effect on cardiomyocyte differentiation)"
FT /evidence="ECO:0000269|PubMed:35182466"
FT /id="VAR_086184"
FT VARIANT 531
FT /note="Y -> C (in dbSNP:rs17703111)"
FT /id="VAR_037405"
FT MUTAGEN 214
FT /note="D->A: Slightly reduced stimulation of KDM1B
FT demethylase activity, but normal KDM1B-binding."
FT /evidence="ECO:0000269|PubMed:23260659"
FT MUTAGEN 216
FT /note="H->A: Slightly reduced stimulation of KDM1B
FT demethylase activity, but normal KDM1B-binding."
FT /evidence="ECO:0000269|PubMed:23260659"
FT MUTAGEN 217
FT /note="F->A: Abolished stimulation of KDM1B demethylase
FT activity, reduced affinity for histone H3 of the dimer with
FT KDM1B, but normal KDM1B-binding."
FT /evidence="ECO:0000269|PubMed:23260659"
FT MUTAGEN 219
FT /note="H->A: Impaired KDM1B-binding and abolished
FT stimulation of KDM1B demethylase activity; when associated
FT with A-223."
FT /evidence="ECO:0000269|PubMed:23260659"
FT MUTAGEN 220..222
FT /note="FLL->AAA: Impaired KDM1B-binding and abolished
FT stimulation of KDM1B demethylase activity."
FT /evidence="ECO:0000269|PubMed:23260659"
FT MUTAGEN 223
FT /note="S->A: Impaired KDM1B-binding and abolished
FT stimulation of KDM1B demethylase activity; when associated
FT with A-219."
FT /evidence="ECO:0000269|PubMed:23260659"
FT MUTAGEN 437
FT /note="M->K: Loss of tetramerization and protein
FT stability."
FT /evidence="ECO:0000269|PubMed:30970244"
FT MUTAGEN 437
FT /note="M->N: No effect on tetramerization or protein
FT stability."
FT /evidence="ECO:0000269|PubMed:30970244"
FT CONFLICT 40
FT /note="K -> E (in Ref. 7; AAH32855)"
FT /evidence="ECO:0000305"
FT CONFLICT 419
FT /note="A -> T (in Ref. 7; AAH47223)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="Q -> R (in Ref. 7; AAH47223)"
FT /evidence="ECO:0000305"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:4HSU"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4HSU"
FT STRAND 270..273
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 277..288
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 304..308
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 317..323
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 334..342
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 365..377
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 391..396
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 407..412
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 414..420
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 421..426
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 432..460
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 465..474
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 480..491
FT /evidence="ECO:0007829|PDB:2UYY"
FT STRAND 497..499
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 500..516
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 522..536
FT /evidence="ECO:0007829|PDB:2UYY"
FT HELIX 544..550
FT /evidence="ECO:0007829|PDB:2UYY"
SQ SEQUENCE 553 AA; 60547 MW; 2327FC8164B338B7 CRC64;
MAAVSLRLGD LVWGKLGRYP PWPGKIVNPP KDLKKPRGKK CFFVKFFGTE DHAWIKVEQL
KPYHAHKEEM IKINKGKRFQ QAVDAVEEFL RRAKGKDQTS SHNSSDDKNR RNSSEERSRP
NSGDEKRKLS LSEGKVKKNM GEGKKRVSSG SSERGSKSPL KRAQEQSPRK RGRPPKDEKD
LTIPESSTVK GMMAGPMAAF KWQPTASEPV KDADPHFHHF LLSQTEKPAV CYQAITKKLK
ICEEETGSTS IQAADSTAVN GSITPTDKKI GFLGLGLMGS GIVSNLLKMG HTVTVWNRTA
EKCDLFIQEG ARLGRTPAEV VSTCDITFAC VSDPKAAKDL VLGPSGVLQG IRPGKCYVDM
STVDADTVTE LAQVIVSRGG RFLEAPVSGN QQLSNDGMLV ILAAGDRGLY EDCSSCFQAM
GKTSFFLGEV GNAAKMMLIV NMVQGSFMAT IAEGLTLAQV TGQSQQTLLD ILNQGQLASI
FLDQKCQNIL QGNFKPDFYL KYIQKDLRLA IALGDAVNHP TPMAAAANEV YKRAKALDQS
DNDMSAVYRA YIH
