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Protein

NmrA-like family domain-containing protein 1

Gene

NMRAL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Redox sensor protein. Undergoes restructuring and subcellular redistribution in response to changes in intracellular NADPH/NADP+ levels. At low NADPH concentrations the protein is found mainly as a monomer, and binds argininosuccinate synthase (ASS1), the enzyme involved in nitric oxide synthesis. Association with ASS1 impairs its activity and reduces the production of nitric oxide, which subsecuently prevents apoptosis. Under normal NADPH concentrations, the protein is found as a dimer and hides the binding site for ASS1. The homodimer binds one molecule of NADPH. Has higher affinity for NADPH than for NADP+. Binding to NADPH is necessary to form a stable dimer.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei62 – 621NADP; shared with dimeric partner1 Publication
Binding sitei92 – 921NADP; shared with dimeric partner1 Publication
Binding sitei133 – 1331NADP1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi11 – 166NADP1 Publication
Nucleotide bindingi37 – 415NADP1 Publication
Nucleotide bindingi58 – 592NADP1 Publication
Nucleotide bindingi79 – 813NADP1 Publication
Nucleotide bindingi155 – 1584NADP1 Publication

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000153406-MONOMER.
ReactomeiR-HSA-70635. Urea cycle.

Names & Taxonomyi

Protein namesi
Recommended name:
NmrA-like family domain-containing protein 1
Gene namesi
Name:NMRAL1
Synonyms:HSCARG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:24987. NMRAL1.

Subcellular locationi

  • Cytoplasm
  • Cytoplasmperinuclear region
  • Nucleus

  • Note: Under normal redox growth conditions localizes in the cytoplasm and perinuclear region. Nuclear localization is promoted by increased intracellular nitric oxide and reduced NADPH/NADP+ ratios.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi37 – 371R → A: Impairs binding to NADPH; abolishes the ability to dimerize; enhances binding to ASS1; reduces perinuclear localization. 1 Publication
Mutagenesisi41 – 411K → S: Does not impair binding to NADPH; maintains the dimerization properties as the wild type; does not affect binding to ASS1; does not affect perinuclear localization. 1 Publication
Mutagenesisi81 – 811Y → A: Impairs binding to NADPH; abolishes the ability to dimerize; enhances binding to ASS1; reduces perinuclear localization. 1 Publication
Mutagenesisi133 – 1331K → A: Impairs binding to NADPH; enhances binding to ASS1; reduces perinuclear localization. 1 Publication

Organism-specific databases

PharmGKBiPA145007922.

Polymorphism and mutation databases

BioMutaiNMRAL1.
DMDMi74734255.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 299299NmrA-like family domain-containing protein 1PRO_0000278204Add
BLAST

Proteomic databases

EPDiQ9HBL8.
MaxQBiQ9HBL8.
PaxDbiQ9HBL8.
PeptideAtlasiQ9HBL8.
PRIDEiQ9HBL8.

PTM databases

iPTMnetiQ9HBL8.
PhosphoSiteiQ9HBL8.

Expressioni

Inductioni

By nitric oxide, cGMP and proinflammatory cytokines.1 Publication

Gene expression databases

BgeeiQ9HBL8.
CleanExiHS_NMRAL1.
ExpressionAtlasiQ9HBL8. baseline and differential.
GenevisibleiQ9HBL8. HS.

Organism-specific databases

HPAiHPA041353.
HPA062287.

Interactioni

Subunit structurei

Homodimer. Interacts with ASS1. Interaction is enhanced by low NADPH/NADP+ ratios, which results in inhibition of ASS1 activity.4 Publications

Protein-protein interaction databases

BioGridi121509. 12 interactions.
DIPiDIP-60944N.
IntActiQ9HBL8. 3 interactions.
MINTiMINT-5003586.
STRINGi9606.ENSP00000283429.

Structurei

Secondary structure

1
299
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 105Combined sources
Turni11 – 133Combined sources
Helixi15 – 2713Combined sources
Beta strandi29 – 379Combined sources
Helixi42 – 498Combined sources
Beta strandi53 – 564Combined sources
Helixi62 – 698Combined sources
Beta strandi73 – 775Combined sources
Helixi81 – 833Combined sources
Helixi87 – 10418Combined sources
Beta strandi107 – 1115Combined sources
Helixi117 – 1204Combined sources
Turni121 – 1233Combined sources
Helixi128 – 14316Combined sources
Beta strandi147 – 1515Combined sources
Helixi156 – 1605Combined sources
Turni161 – 1633Combined sources
Beta strandi171 – 1766Combined sources
Beta strandi185 – 1884Combined sources
Helixi190 – 1923Combined sources
Helixi193 – 20210Combined sources
Helixi204 – 2074Combined sources
Beta strandi211 – 2133Combined sources
Beta strandi216 – 2194Combined sources
Helixi221 – 23212Combined sources
Beta strandi236 – 2383Combined sources
Helixi244 – 2474Combined sources
Helixi254 – 26411Combined sources
Helixi272 – 2787Combined sources
Helixi285 – 2928Combined sources
Helixi293 – 2953Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EXXX-ray2.40A/B1-299[»]
2WM3X-ray1.85A1-298[»]
2WMDX-ray2.00A1-298[»]
3DXFX-ray2.20A/B1-299[»]
3E5MX-ray2.70A/B1-299[»]
ProteinModelPortaliQ9HBL8.
SMRiQ9HBL8. Positions 3-298.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HBL8.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni153 – 18937Interaction with ASS1Add
BLAST

Sequence similaritiesi

Belongs to the NmrA-type oxidoreductase family.Curated

Phylogenomic databases

eggNOGiENOG410IVQ5. Eukaryota.
COG0702. LUCA.
GeneTreeiENSGT00390000016395.
HOGENOMiHOG000035269.
HOVERGENiHBG082032.
InParanoidiQ9HBL8.
OMAiPATFMEL.
OrthoDBiEOG7W154P.
PhylomeDBiQ9HBL8.
TreeFamiTF335532.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR008030. NmrA-like.
[Graphical view]
PfamiPF05368. NmrA. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9HBL8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVDKKLVVVF GGTGAQGGSV ARTLLEDGTF KVRVVTRNPR KKAAKELRLQ
60 70 80 90 100
GAEVVQGDQD DQVIMELALN GAYATFIVTN YWESCSQEQE VKQGKLLADL
110 120 130 140 150
ARRLGLHYVV YSGLENIKKL TAGRLAAAHF DGKGEVEEYF RDIGVPMTSV
160 170 180 190 200
RLPCYFENLL SHFLPQKAPD GKSYLLSLPT GDVPMDGMSV SDLGPVVLSL
210 220 230 240 250
LKMPEKYVGQ NIGLSTCRHT AEEYAALLTK HTRKVVHDAK MTPEDYEKLG
260 270 280 290
FPGARDLANM FRFYALRPDR DIELTLRLNP KALTLDQWLE QHKGDFNLL
Length:299
Mass (Da):33,344
Last modified:March 1, 2001 - v1
Checksum:iD740334F8F8D4E1E
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti23 – 231T → I.
Corresponds to variant rs11557236 [ dbSNP | Ensembl ].
VAR_030689
Natural varianti252 – 2521P → L.
Corresponds to variant rs3747582 [ dbSNP | Ensembl ].
VAR_030690

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF225419 mRNA. Translation: AAG09721.1.
AC012676 Genomic DNA. No translation available.
AC007606 Genomic DNA. No translation available.
BC002927 mRNA. Translation: AAH02927.1.
BC007364 mRNA. Translation: AAH07364.1.
CCDSiCCDS10516.1.
RefSeqiNP_001292070.1. NM_001305141.1.
NP_001292071.1. NM_001305142.1.
NP_065728.1. NM_020677.4.
UniGeneiHs.288969.

Genome annotation databases

EnsembliENST00000283429; ENSP00000283429; ENSG00000153406.
ENST00000404295; ENSP00000383962; ENSG00000153406.
ENST00000574425; ENSP00000460263; ENSG00000153406.
ENST00000574733; ENSP00000458762; ENSG00000153406.
ENST00000616587; ENSP00000479569; ENSG00000274684.
ENST00000621810; ENSP00000478990; ENSG00000274684.
ENST00000632013; ENSP00000488692; ENSG00000274684.
ENST00000633085; ENSP00000488644; ENSG00000274684.
GeneIDi57407.
KEGGihsa:57407.
UCSCiuc002cwm.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF225419 mRNA. Translation: AAG09721.1.
AC012676 Genomic DNA. No translation available.
AC007606 Genomic DNA. No translation available.
BC002927 mRNA. Translation: AAH02927.1.
BC007364 mRNA. Translation: AAH07364.1.
CCDSiCCDS10516.1.
RefSeqiNP_001292070.1. NM_001305141.1.
NP_001292071.1. NM_001305142.1.
NP_065728.1. NM_020677.4.
UniGeneiHs.288969.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2EXXX-ray2.40A/B1-299[»]
2WM3X-ray1.85A1-298[»]
2WMDX-ray2.00A1-298[»]
3DXFX-ray2.20A/B1-299[»]
3E5MX-ray2.70A/B1-299[»]
ProteinModelPortaliQ9HBL8.
SMRiQ9HBL8. Positions 3-298.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121509. 12 interactions.
DIPiDIP-60944N.
IntActiQ9HBL8. 3 interactions.
MINTiMINT-5003586.
STRINGi9606.ENSP00000283429.

PTM databases

iPTMnetiQ9HBL8.
PhosphoSiteiQ9HBL8.

Polymorphism and mutation databases

BioMutaiNMRAL1.
DMDMi74734255.

Proteomic databases

EPDiQ9HBL8.
MaxQBiQ9HBL8.
PaxDbiQ9HBL8.
PeptideAtlasiQ9HBL8.
PRIDEiQ9HBL8.

Protocols and materials databases

DNASUi57407.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000283429; ENSP00000283429; ENSG00000153406.
ENST00000404295; ENSP00000383962; ENSG00000153406.
ENST00000574425; ENSP00000460263; ENSG00000153406.
ENST00000574733; ENSP00000458762; ENSG00000153406.
ENST00000616587; ENSP00000479569; ENSG00000274684.
ENST00000621810; ENSP00000478990; ENSG00000274684.
ENST00000632013; ENSP00000488692; ENSG00000274684.
ENST00000633085; ENSP00000488644; ENSG00000274684.
GeneIDi57407.
KEGGihsa:57407.
UCSCiuc002cwm.4. human.

Organism-specific databases

CTDi57407.
GeneCardsiNMRAL1.
HGNCiHGNC:24987. NMRAL1.
HPAiHPA041353.
HPA062287.
neXtProtiNX_Q9HBL8.
PharmGKBiPA145007922.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVQ5. Eukaryota.
COG0702. LUCA.
GeneTreeiENSGT00390000016395.
HOGENOMiHOG000035269.
HOVERGENiHBG082032.
InParanoidiQ9HBL8.
OMAiPATFMEL.
OrthoDBiEOG7W154P.
PhylomeDBiQ9HBL8.
TreeFamiTF335532.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000153406-MONOMER.
ReactomeiR-HSA-70635. Urea cycle.

Miscellaneous databases

ChiTaRSiNMRAL1. human.
EvolutionaryTraceiQ9HBL8.
GenomeRNAii57407.
PROiQ9HBL8.

Gene expression databases

BgeeiQ9HBL8.
CleanExiHS_NMRAL1.
ExpressionAtlasiQ9HBL8. baseline and differential.
GenevisibleiQ9HBL8. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR008030. NmrA-like.
[Graphical view]
PfamiPF05368. NmrA. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Xiao H., Song H., Gao G., Ren S., Chen Z., Han Z.
    Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Adrenal gland.
  2. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Skin and Uterus.
  4. "An NADPH sensor protein (HSCARG) down-regulates nitric oxide synthesis by association with argininosuccinate synthetase and is essential for epithelial cell viability."
    Zhao Y., Zhang J., Li H., Li Y., Ren J., Luo M., Zheng X.
    J. Biol. Chem. 283:11004-11013(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ASS1, SUBCELLULAR LOCATION, INDUCTION, REGION.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "Restructuring of the dinucleotide-binding fold in an NADP(H) sensor protein."
    Zheng X., Dai X., Zhao Y., Chen Q., Lu F., Yao D., Yu Q., Liu X., Zhang C., Gu X., Luo M.
    Proc. Natl. Acad. Sci. U.S.A. 104:8809-8814(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NADP, FUNCTION, HOMODIMERIZATION, INTERACTION WITH ASS1, SUBCELLULAR LOCATION.
  7. Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ALA-37, X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF MUTANT ALA-81, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-37; LYS-41; TYR-81 AND LYS-133.
  8. "Crystal structure of NMRA-like family domain containing protein 1 in complex with niflumic acid."
    Structural genomics consortium (SGC)
    Submitted (AUG-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH NIFLUMIC ACID.

Entry informationi

Entry nameiNMRL1_HUMAN
AccessioniPrimary (citable) accession number: Q9HBL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: March 1, 2001
Last modified: July 6, 2016
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Reduced levels of NMRAL1 by RNAi increases nitric oxide production and reduces cell viability. Overexpression of NMRAL1 increases cell viability.

Caution

Lacks the conserved Tyr residue in the active site triad of Ser-Tyr-Lys necessary for dehydrogenase activity, suggesting that it has no oxidoreductase activity.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.