GLYR1_MOUSE
ID GLYR1_MOUSE Reviewed; 546 AA.
AC Q922P9; Q3TX02; Q9CYQ1;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Cytokine-like nuclear factor N-PAC;
DE Short=NPAC;
DE AltName: Full=Glyoxylate reductase 1 homolog;
DE AltName: Full=Nuclear protein NP60;
DE AltName: Full=Putative oxidoreductase GLYR1;
GN Name=Glyr1 {ECO:0000312|MGI:MGI:1921272}; Synonyms=Np60;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
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 [6]
RP FUNCTION, AND MUTAGENESIS OF PRO-489.
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:29759984). Acts as a nucleosome-destabilizing factor
CC that is recruited to genes during transcriptional activation.
CC Recognizes and binds histone H3 without a preference for specific
CC epigenetic markers and also binds DNA. Interacts with KDM1B and
CC promotes its histone demethylase activity by facilitating the capture
CC of H3 tails, they form a multifunctional enzyme complex that modifies
CC transcribed chromatin and facilitates Pol II transcription through
CC nucleosomes. Stimulates the acetylation of 'Lys-56' of nucleosomal
CC histone H3 (H3K56ac) by EP300 (By similarity). 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. Indirectly promotes
CC phosphorylation of MAPK14 and activation of ATF2. The phosphorylation
CC of MAPK14 requires upstream activity of MAP2K4 and MAP2K6 (By
CC similarity). {ECO:0000250|UniProtKB:Q49A26,
CC ECO:0000269|PubMed:29759984, ECO:0000269|PubMed:35182466}.
CC -!- SUBUNIT: Homotetramere. Interacts with MAPK14. Interacts with KDM1B at
CC nucleosomes; this interaction stimulates H3K4me1 and H3K4me2
CC demethylation. Binds to mononucleosomes. Interacts with GATA4; the
CC interaction is required for a synergistic activation of GATA4 target
CC genes transcription. {ECO:0000250|UniProtKB:Q49A26}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q49A26}.
CC Chromosome {ECO:0000250|UniProtKB:Q49A26}. Note=Found in actively
CC RNAPolII-transcribed gene bodies. {ECO:0000250|UniProtKB:Q49A26}.
CC -!- DOMAIN: The A.T hook DNA-binding domain is required for the interaction
CC with MAPK14. {ECO:0000250|UniProtKB:Q49A26}.
CC -!- DOMAIN: The PWWP domain is a H3 reader and strongly binds DNA.
CC {ECO:0000250|UniProtKB:Q49A26}.
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. However, since the active
CC site is not conserved, the dehydrogenase domain seems to serve as a
CC catalytically inert oligomerization module.
CC {ECO:0000250|UniProtKB:Q49A26}.
CC -!- SIMILARITY: Belongs to the HIBADH-related family. NP60 subfamily.
CC {ECO:0000305}.
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; AK014456; BAB29363.1; -; mRNA.
DR EMBL; AK150349; BAE29486.1; -; mRNA.
DR EMBL; AK152887; BAE31570.1; -; mRNA.
DR EMBL; AK159476; BAE35114.1; -; mRNA.
DR EMBL; BC006893; AAH06893.1; -; mRNA.
DR CCDS; CCDS27930.1; -.
DR RefSeq; NP_082996.2; NM_028720.2.
DR AlphaFoldDB; Q922P9; -.
DR SMR; Q922P9; -.
DR BioGRID; 216431; 7.
DR IntAct; Q922P9; 3.
DR MINT; Q922P9; -.
DR STRING; 10090.ENSMUSP00000111510; -.
DR iPTMnet; Q922P9; -.
DR PhosphoSitePlus; Q922P9; -.
DR EPD; Q922P9; -.
DR MaxQB; Q922P9; -.
DR PaxDb; Q922P9; -.
DR PeptideAtlas; Q922P9; -.
DR PRIDE; Q922P9; -.
DR ProteomicsDB; 263378; -.
DR Antibodypedia; 24437; 112 antibodies from 21 providers.
DR Ensembl; ENSMUST00000023189; ENSMUSP00000023189; ENSMUSG00000022536.
DR GeneID; 74022; -.
DR KEGG; mmu:74022; -.
DR UCSC; uc007ybm.1; mouse.
DR CTD; 84656; -.
DR MGI; MGI:1921272; Glyr1.
DR VEuPathDB; HostDB:ENSMUSG00000022536; -.
DR eggNOG; KOG0409; Eukaryota.
DR eggNOG; KOG1904; Eukaryota.
DR GeneTree; ENSGT00940000156435; -.
DR InParanoid; Q922P9; -.
DR BioGRID-ORCS; 74022; 9 hits in 75 CRISPR screens.
DR ChiTaRS; Glyr1; mouse.
DR PRO; PR:Q922P9; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q922P9; protein.
DR Bgee; ENSMUSG00000022536; Expressed in ear vesicle and 255 other tissues.
DR ExpressionAtlas; Q922P9; baseline and differential.
DR Genevisible; Q922P9; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000786; C:nucleosome; ISS: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; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISS: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; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0035066; P:positive regulation of histone acetylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
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 Chromosome; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..546
FT /note="Cytokine-like nuclear factor N-PAC"
FT /id="PRO_0000312122"
FT DOMAIN 8..66
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT DNA_BIND 167..179
FT /note="A.T hook"
FT /evidence="ECO:0000305"
FT REGION 91..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..216
FT /note="Interaction with histone H3"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT REGION 215..224
FT /note="Interaction with KDM1B"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT REGION 260..546
FT /note="Dehydrogenase domain"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT COMPBIAS 91..183
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 270..284
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT BINDING 355
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT BINDING 498
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT SITE 216
FT /note="Required to promote KDM1B demethylase activity
FT toward histone H3K4me1 and H3K4me2"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 135
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 175
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 178
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 200
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 210
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 226
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 236
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 239
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 268
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT CROSSLNK 301
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q49A26"
FT MUTAGEN 489
FT /note="P->L: Mutant animals are born at expected Mendelian
FT ratios. 54% mutants display postnatal lethality between
FT days 0 and 1. They show centricular septal defects."
FT /evidence="ECO:0000269|PubMed:35182466"
FT CONFLICT 50..51
FT /note="ED -> KN (in Ref. 1; BAB29363)"
FT /evidence="ECO:0000305"
FT CONFLICT 109..110
FT /note="NR -> DW (in Ref. 1; BAB29363)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="N -> S (in Ref. 1; BAE35114)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="N -> S (in Ref. 1; BAE35114)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 546 AA; 59716 MW; F5D2090DE1F64723 CRC64;
MAAVSLRLGD LVWGKLGRYP PWPGKIVNPP KDLKKPRGKK CFFVKFFGTE DHAWIKVEQL
KPYHAHKEEM IKINKGKRFQ QAVDAVEEFL RRAKGKDQTS SHTSADDKNR RNSSEERSRP
NSGDEKRKLS LSEGKVKKNM GEGKKRVTSG SADRGSKCLK RAQEQSPRKR GRPPKDEKDL
TIPESSTVKG MMAGPMAAFK WQPTATEPVK DADPHFHHFL LSQTEKPAVC YQAITKKLKI
CEEETGSTSI QAADSTAVNG SITPTDKKIG FLGLGLMGSG IVSNLLKMGH TVTVWNRTAE
KEGARLGRTP AEVVSTCDIT FACVSDPKAA KDLVLGPSGV LQGIRPGKCY VDMSTVDADT
VTELAQVIVS RGGRFLEAPV SGNQQLSNDG MLVILAAGDR GLYEDCSSCF QAMGKTSFFL
GEVGNAAKMM LIVNMVQGSF MATIAEGLTL AQVTGQSQQT LLDILNQGQL ASIFLDQKCQ
NILQGNFKPD FYLKYIQKDL RLAIALGDAV NHPTPMAAAA NEVYKRAKAL DQSDNDMSAV
YRAYIH