NMRL1_MOUSE
ID NMRL1_MOUSE Reviewed; 309 AA.
AC Q8K2T1; Q8BVF0; Q9CZP2;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=NmrA-like family domain-containing protein 1;
GN Name=Nmral1;
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] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 PROTEIN SEQUENCE OF 6-22 AND 114-128, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
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).
CC -!- FUNCTION: Redox sensor protein. Undergoes restructuring and subcellular
CC redistribution in response to changes in intracellular NADPH/NADP(+)
CC levels. At low NADPH concentrations the protein is found mainly as a
CC monomer, and binds argininosuccinate synthase (ASS1), the enzyme
CC involved in nitric oxide synthesis. Association with ASS1 impairs its
CC activity and reduces the production of nitric oxide, which subsecuently
CC prevents apoptosis. Under normal NADPH concentrations, the protein is
CC found as a dimer and hides the binding site for ASS1. The homodimer
CC binds one molecule of NADPH. Has higher affinity for NADPH than for
CC NADP(+). Binding to NADPH is necessary to form a stable dimer (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with ASS1. Interaction is enhanced by low
CC NADPH/NADP(+) ratios, which results in inhibition of ASS1 activity (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region.
CC Nucleus. Note=Under normal redox growth conditions localizes in the
CC cytoplasm and perinuclear region. Nuclear localization is promoted by
CC increased intracellular nitric oxide and reduced NADPH/NADP(+) ratios
CC (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8K2T1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K2T1-2; Sequence=VSP_023151, VSP_023153, VSP_023154;
CC Name=3;
CC IsoId=Q8K2T1-3; Sequence=VSP_023151, VSP_027873, VSP_027874;
CC -!- SIMILARITY: Belongs to the NmrA-type oxidoreductase family.
CC {ECO:0000305}.
CC -!- CAUTION: Lacks the conserved Tyr residue in the active site triad of
CC Ser-Tyr-Lys necessary for dehydrogenase activity, suggesting that it
CC has no oxidoreductase activity. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB28172.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK012340; BAB28172.1; ALT_FRAME; mRNA.
DR EMBL; AK078389; BAC37249.1; -; mRNA.
DR EMBL; BC030039; AAH30039.1; -; mRNA.
DR CCDS; CCDS27923.1; -. [Q8K2T1-1]
DR CCDS; CCDS70680.1; -. [Q8K2T1-2]
DR RefSeq; NP_001277690.1; NM_001290761.1.
DR RefSeq; NP_001277691.1; NM_001290762.1.
DR RefSeq; NP_001277692.1; NM_001290763.1. [Q8K2T1-2]
DR RefSeq; NP_080669.1; NM_026393.2. [Q8K2T1-1]
DR AlphaFoldDB; Q8K2T1; -.
DR SMR; Q8K2T1; -.
DR BioGRID; 212461; 3.
DR IntAct; Q8K2T1; 2.
DR STRING; 10090.ENSMUSP00000078132; -.
DR iPTMnet; Q8K2T1; -.
DR PhosphoSitePlus; Q8K2T1; -.
DR REPRODUCTION-2DPAGE; IPI00169979; -.
DR REPRODUCTION-2DPAGE; Q8K2T1; -.
DR UCD-2DPAGE; Q8K2T1; -.
DR EPD; Q8K2T1; -.
DR MaxQB; Q8K2T1; -.
DR PaxDb; Q8K2T1; -.
DR PeptideAtlas; Q8K2T1; -.
DR PRIDE; Q8K2T1; -.
DR ProteomicsDB; 293584; -. [Q8K2T1-1]
DR ProteomicsDB; 293585; -. [Q8K2T1-2]
DR ProteomicsDB; 293586; -. [Q8K2T1-3]
DR Antibodypedia; 24328; 108 antibodies from 25 providers.
DR DNASU; 67824; -.
DR Ensembl; ENSMUST00000074970; ENSMUSP00000074500; ENSMUSG00000063445. [Q8K2T1-2]
DR Ensembl; ENSMUST00000079130; ENSMUSP00000078132; ENSMUSG00000063445. [Q8K2T1-1]
DR GeneID; 67824; -.
DR KEGG; mmu:67824; -.
DR UCSC; uc007yae.2; mouse. [Q8K2T1-1]
DR UCSC; uc056zav.1; mouse. [Q8K2T1-2]
DR CTD; 57407; -.
DR MGI; MGI:1915074; Nmral1.
DR VEuPathDB; HostDB:ENSMUSG00000063445; -.
DR eggNOG; ENOG502RG69; Eukaryota.
DR GeneTree; ENSGT00940000160872; -.
DR HOGENOM; CLU_007383_8_2_1; -.
DR InParanoid; Q8K2T1; -.
DR OrthoDB; 707551at2759; -.
DR PhylomeDB; Q8K2T1; -.
DR TreeFam; TF335532; -.
DR Reactome; R-MMU-70635; Urea cycle.
DR BioGRID-ORCS; 67824; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Nmral1; mouse.
DR PRO; PR:Q8K2T1; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8K2T1; protein.
DR Bgee; ENSMUSG00000063445; Expressed in manus and 208 other tissues.
DR ExpressionAtlas; Q8K2T1; baseline and differential.
DR Genevisible; Q8K2T1; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR008030; NmrA-like.
DR Pfam; PF05368; NmrA; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Direct protein sequencing; NADP; Nucleus;
KW Reference proteome.
FT CHAIN 1..309
FT /note="NmrA-like family domain-containing protein 1"
FT /id="PRO_0000278205"
FT REGION 163..199
FT /note="Interaction with ASS1"
FT /evidence="ECO:0000250"
FT BINDING 11..16
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 37..41
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 58..59
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 79..81
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 102
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250"
FT BINDING 143
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT BINDING 165..168
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250"
FT VAR_SEQ 93..102
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023151"
FT VAR_SEQ 188..192
FT /note="LPMGD -> RLAHG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027873"
FT VAR_SEQ 193..309
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_027874"
FT VAR_SEQ 251..253
FT /note="TTP -> PVH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023153"
FT VAR_SEQ 254..309
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023154"
FT CONFLICT 188
FT /note="L -> M (in Ref. 1; BAB28172)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 309 AA; 34376 MW; 0DA109085DF25142 CRC64;
MADRKLVVVF GATGAQGGSV ARALLEDGTF RIRVVTRNPE QRAAKELKQQ GAEVVRGDQD
DAASMELALA GAHATFIVTN YWETCSQDRE VQQPHQWDQV FKQGKLLADL AKRLGLHYVV
YSGLENIRKL TAGKLAAGHF DGKGEVEEYF RDIGVPMTSV RLPCYFENLL SYFLPQKAAD
GKSFLLDLPM GDVPMDGMSV SDLGPVVLSL LKKPEEYVGQ NIGLSTCRHT AEEYAALLSK
HTGKAVHHAK TTPEDYEKLG FQGAQDLANM FRFYTLKPDR NIHLTLRLNP KAQTLDQWLE
QHKGDFAQL
