ID GRL1A_HUMAN Reviewed; 368 AA. AC P0CAP2; Q6EER8; Q6EES2; Q6EEV3; Q6EF00; Q6EF01; Q6EF02; Q6EF46; Q6EFN8; AC Q6EM48; Q6K046; Q6K050; Q6K051; Q6ZQZ3; Q8NC58; Q8NCF3; Q96DI5; Q96JB7; AC Q96NF5; Q9Y3V6; DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot. DT 26-MAY-2009, sequence version 1. DT 27-MAR-2024, entry version 109. DE RecName: Full=DNA-directed RNA polymerase II subunit GRINL1A; DE AltName: Full=DNA-directed RNA polymerase II subunit M; DE AltName: Full=Glutamate receptor-like protein 1A; GN Name=POLR2M; Synonyms=GRINL1A; 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). RC TISSUE=Brain; RX PubMed=11474202; DOI=10.1159/000056971; RA Roginski R.S., Mohan Raj B.K., Finkernagel S.W., Sciorra L.J.; RT "Assignment of an ionotropic glutamate receptor-like gene (GRINL1A) to RT human chromosome 15q22.1 by in situ hybridization."; RL Cytogenet. Cell Genet. 93:143-144(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 11), AND TISSUE SPECIFICITY. RC TISSUE=Brain, and Lung; RX PubMed=15233991; DOI=10.1016/j.ygeno.2004.04.004; RA Roginski R.S., Mohan Raj B.K., Birditt B., Rowen L.; RT "The human GRINL1A gene defines a complex transcription unit, an unusual RT form of gene organization in eukaryotes."; RL Genomics 84:265-276(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Heart; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [5] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain cortex; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 171-368. RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [9] RP FUNCTION (ISOFORM I), AND RECONSTITUTION OF THE POL II(G) COMPLEX (ISOFORM RP I). RX PubMed=16769904; DOI=10.1073/pnas.0603702103; RA Hu X., Malik S., Negroiu C.C., Hubbard K., Velalar C.N., Hampton B., RA Grosu D., Catalano J., Roeder R.G., Gnatt A.; RT "A Mediator-responsive form of metazoan RNA polymerase II."; RL Proc. Natl. Acad. Sci. U.S.A. 103:9506-9511(2006). RN [10] RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 300-316, REGION, RP FUNCTION (ISOFORM I), AND MUTAGENESIS OF 29-LYS-ARG-30; GLU-32; ARG-33; RP 49-LYS-LYS-50; ASP-53; 66-GLU-GLU-67 AND 303-LEU-LEU-304. RX PubMed=30190596; DOI=10.1038/s41594-018-0118-5; RA Jishage M., Yu X., Shi Y., Ganesan S.J., Chen W.Y., Sali A., Chait B.T., RA Asturias F.J., Roeder R.G.; RT "Architecture of Pol II(G) and molecular mechanism of transcription RT regulation by Gdown1."; RL Nat. Struct. Mol. Biol. 25:859-867(2018). CC -!- FUNCTION: [Isoform 1]: Appears to be a stable component of the Pol CC II(G) complex form of RNA polymerase II (Pol II). Pol II synthesizes CC mRNA precursors and many functional non-coding RNAs and is the central CC component of the basal RNA polymerase II transcription machinery. May CC play a role in the Mediator complex-dependent regulation of CC transcription activation. Acts as a negative regulator of CC transcriptional activation; this repression is relieved by the Mediator CC complex, which restores Pol II(G) activator-dependent transcription to CC a level equivalent to that of Pol II. {ECO:0000269|PubMed:16769904, CC ECO:0000269|PubMed:30190596}. CC -!- SUBUNIT: [Isoform 1]: Component of the Pol II(G) complex, which CC contains the RNA polymerase II (Pol II) core complex subunits and CC POLR2M isoform 1. Pol II(G) appears to be an abundant form of Pol II. CC {ECO:0000269|PubMed:16769904, ECO:0000269|PubMed:30190596}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Comment=Additional isoforms seem to exist.; CC Name=1; Synonyms=Gdown1; CC IsoId=P0CAP2-1; Sequence=Displayed; CC Name=2; Synonyms=Gdown6; CC IsoId=P0CAP2-2; Sequence=VSP_037387; CC Name=3; CC IsoId=P0CAP2-3; Sequence=VSP_037388; CC Name=4; Synonyms=Gdown4; CC IsoId=Q6EEV4-1; Sequence=External; CC Name=5; Synonyms=Gdown3; CC IsoId=Q6EEV4-2; Sequence=External; CC Name=11; Synonyms=Gcom1, GRINL1A complex locus protein 1; CC IsoId=P0CAP1-11; Sequence=External; CC -!- TISSUE SPECIFICITY: Detected in adult an fetal brain. Detected in CC heart, kidney, skeletal muscle, small intestine, lung, prostate and CC testis. {ECO:0000269|PubMed:15233991}. CC -!- MISCELLANEOUS: The adjacent MYZAP and POLR2M genes are part of a CC complex transcription unit. The respective transcripts derive from CC different promoters and are alternatively spliced. In human, some CC transcripts of the upstream promoter of MYZAP use exons of the CC downstream POLR2M gene. CC -!- SIMILARITY: Belongs to the GRINL1 family. {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; AF326773; AAK92284.2; -; mRNA. DR EMBL; AY207007; AAO39707.1; -; mRNA. DR EMBL; AY353061; AAQ76837.1; -; mRNA. DR EMBL; AK074767; BAC11193.1; -; mRNA. DR EMBL; AK074955; BAC11313.1; -; mRNA. DR EMBL; AK128618; BAC87533.1; -; mRNA. DR EMBL; AC090651; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471082; EAW77525.1; -; Genomic_DNA. DR EMBL; BC001510; AAH01510.1; -; mRNA. DR EMBL; AL050091; CAB43263.1; -; mRNA. DR CCDS; CCDS32252.1; -. [P0CAP2-1] DR CCDS; CCDS42045.1; -. [P0CAP2-2] DR PIR; T08740; T08740. DR RefSeq; NP_001018112.1; NM_001018102.2. [P0CAP2-2] DR RefSeq; NP_056347.1; NM_015532.4. [P0CAP2-1] DR PDB; 6DRD; EM; 3.90 A; M=300-316. DR PDBsum; 6DRD; -. DR AlphaFoldDB; P0CAP2; -. DR EMDB; EMD-7997; -. DR SMR; P0CAP2; -. DR BioGRID; 123498; 137. DR ComplexPortal; CPX-2387; DNA-directed RNA polymerase II complex, Pol II(G) variant. DR DIP; DIP-61933N; -. DR IntAct; P0CAP2; 61. DR MINT; P0CAP2; -. DR STRING; 9606.ENSP00000299638; -. DR GlyGen; P0CAP2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P0CAP2; -. DR PhosphoSitePlus; P0CAP2; -. DR BioMuta; POLR2M; -. DR DMDM; 238064986; -. DR EPD; P0CAP2; -. DR jPOST; P0CAP2; -. DR MassIVE; P0CAP2; -. DR MaxQB; P0CAP2; -. DR PaxDb; 9606-ENSP00000299638; -. DR PeptideAtlas; P0CAP2; -. DR ProteomicsDB; 52428; -. [P0CAP2-1] DR ProteomicsDB; 52429; -. [P0CAP2-2] DR ProteomicsDB; 52430; -. [P0CAP2-3] DR Pumba; P0CAP2; -. DR Antibodypedia; 57855; 122 antibodies from 16 providers. DR DNASU; 81488; -. DR Ensembl; ENST00000299638.8; ENSP00000299638.3; ENSG00000255529.9. [P0CAP2-1] DR Ensembl; ENST00000380557.4; ENSP00000369930.4; ENSG00000255529.9. [P0CAP2-2] DR Ensembl; ENST00000482852.5; ENSP00000432615.1; ENSG00000255529.9. [P0CAP2-3] DR GeneID; 81488; -. DR KEGG; hsa:81488; -. DR MANE-Select; ENST00000299638.8; ENSP00000299638.3; NM_015532.5; NP_056347.1. DR UCSC; uc002aet.6; human. [P0CAP2-1] DR AGR; HGNC:14862; -. DR CTD; 81488; -. DR DisGeNET; 81488; -. DR GeneCards; POLR2M; -. DR HGNC; HGNC:14862; POLR2M. DR HPA; ENSG00000255529; Low tissue specificity. DR MIM; 606485; gene. DR neXtProt; NX_P0CAP2; -. DR OpenTargets; ENSG00000255529; -. DR PharmGKB; PA28986; -. DR VEuPathDB; HostDB:ENSG00000255529; -. DR eggNOG; ENOG502S3HI; Eukaryota. DR GeneTree; ENSGT00950000183065; -. DR HOGENOM; CLU_051512_0_0_1; -. DR InParanoid; P0CAP2; -. DR OMA; YQQAFAH; -. DR OrthoDB; 5360787at2759; -. DR PhylomeDB; P0CAP2; -. DR TreeFam; TF332945; -. DR PathwayCommons; P0CAP2; -. DR SignaLink; P0CAP2; -. DR SIGNOR; P0CAP2; -. DR BioGRID-ORCS; 81488; 155 hits in 1107 CRISPR screens. DR ChiTaRS; POLR2M; human. DR GenomeRNAi; 81488; -. DR Pharos; P0CAP2; Tbio. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P0CAP2; Protein. DR Bgee; ENSG00000255529; Expressed in germinal epithelium of ovary and 207 other cell types or tissues. DR ExpressionAtlas; P0CAP2; baseline and differential. DR GO; GO:0031674; C:I band; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005635; C:nuclear envelope; IDA:LIFEdb. DR GO; GO:0005665; C:RNA polymerase II, core complex; IPI:FlyBase. DR GO; GO:0016591; C:RNA polymerase II, holoenzyme; IBA:GO_Central. DR GO; GO:0097550; C:transcription preinitiation complex; IDA:UniProtKB. DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:UniProtKB. DR GO; GO:0003711; F:transcription elongation factor activity; IEA:InterPro. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0051685; P:maintenance of ER location; IBA:GO_Central. DR GO; GO:0006368; P:transcription elongation by RNA polymerase II; IEA:InterPro. DR InterPro; IPR026213; GRINL1. DR PANTHER; PTHR23171:SF5; DNA-DIRECTED RNA POLYMERASE II SUBUNIT GRINL1A; 1. DR PANTHER; PTHR23171; GDOWN1; 1. DR Pfam; PF15328; GCOM2; 1. DR PRINTS; PR02085; POLR2GRINL1. DR Genevisible; P0CAP2; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; KW DNA-directed RNA polymerase; Nucleus; Reference proteome; Transcription. FT CHAIN 1..368 FT /note="DNA-directed RNA polymerase II subunit GRINL1A" FT /id="PRO_5000089546" FT REGION 29..68 FT /note="Important for transcription repressor activity" FT /evidence="ECO:0000269|PubMed:30190596" FT REGION 116..186 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 203..227 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 227..298 FT /note="Interaction with Pol II" FT /evidence="ECO:0000269|PubMed:30190596" FT REGION 255..282 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 299..314 FT /note="Important for transcription repressor activity" FT /evidence="ECO:0000269|PubMed:30190596" FT REGION 315..340 FT /note="Interaction with Pol II" FT /evidence="ECO:0000269|PubMed:30190596" FT REGION 339..368 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 301..335 FT /evidence="ECO:0000255" FT COMPBIAS 116..134 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 149..163 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 164..179 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 203..224 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 255..270 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 39..195 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15233991" FT /id="VSP_037387" FT VAR_SEQ 323..368 FT /note="MQAKLAAQKLAERLNIKMRSYNPEGESSGRYREVRDEDDDWSSDEF -> RP FT FYSPQYRSSMNLLSLAAAAKDTRGSKSGKMGSLALLTKL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037388" FT MUTAGEN 29..30 FT /note="KR->DD: Abolishes the interaction with Pol II." FT /evidence="ECO:0000269|PubMed:30190596" FT MUTAGEN 32 FT /note="E->K: Stabilizes the interaction with Pol II." FT /evidence="ECO:0000269|PubMed:30190596" FT MUTAGEN 33 FT /note="R->D: Markedly reduces the interaction with Pol II." FT /evidence="ECO:0000269|PubMed:30190596" FT MUTAGEN 49..50 FT /note="KK->DD: Markedly reduces the interaction with Pol FT II." FT /evidence="ECO:0000269|PubMed:30190596" FT MUTAGEN 53 FT /note="D->K: Stabilizes the interaction with Pol II." FT /evidence="ECO:0000269|PubMed:30190596" FT MUTAGEN 66..67 FT /note="EE->KK: Stabilizes the interaction with Pol II." FT /evidence="ECO:0000269|PubMed:30190596" FT MUTAGEN 303..304 FT /note="LL->AA: Loss of transcription repressor activity. FT Abolishes the interaction with Pol II." FT /evidence="ECO:0000269|PubMed:30190596" FT CONFLICT 171 FT /note="H -> D (in Ref. 7; CAB43263)" FT /evidence="ECO:0000305" SQ SEQUENCE 368 AA; 41740 MW; B2F3ADAC21793D1E CRC64; MCSLPRGFEP QAPEDLAQRS LVELREMLKR QERLLRNEKF ICKLPDKGKK IFDSFAKLKA AIAECEEVRR KSELFNPVSL DCKLRQKAIA EVDVGTDKAQ NSDPILDTSS LVPGCSSVDN IKSSQTSQNQ GLGRPTLEGD EETSEVEYTV NKGPASSNRD RVPPSSEASE HHPRHRVSSQ AEDTSSSFDN LFIDRLQRIT IADQGEQQSE ENASTKNLTG LSSGTEKKPH YMEVLEMRAK NPVPQLRKFK TNVLPFRQND SSSHCQKSGS PISSEERRRR DKQHLDDITA ARLLPLHHMP TQLLSIEESL ALQKQQKQNY EEMQAKLAAQ KLAERLNIKM RSYNPEGESS GRYREVRDED DDWSSDEF //