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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)DescriptionActionsGraphical viewLength
Binding sitei62NADP; shared with dimeric partner1 Publication1
Binding sitei92NADP; shared with dimeric partner1 Publication1
Binding sitei133NADP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi11 – 16NADP1 Publication6
Nucleotide bindingi37 – 41NADP1 Publication5
Nucleotide bindingi58 – 59NADP1 Publication2
Nucleotide bindingi79 – 81NADP1 Publication3
Nucleotide bindingi155 – 158NADP1 Publication4

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000153406-MONOMER.
ZFISH: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)DescriptionActionsGraphical viewLength
Mutagenesisi37R → A: Impairs binding to NADPH; abolishes the ability to dimerize; enhances binding to ASS1; reduces perinuclear localization. 1 Publication1
Mutagenesisi41K → 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 Publication1
Mutagenesisi81Y → A: Impairs binding to NADPH; abolishes the ability to dimerize; enhances binding to ASS1; reduces perinuclear localization. 1 Publication1
Mutagenesisi133K → A: Impairs binding to NADPH; enhances binding to ASS1; reduces perinuclear localization. 1 Publication1

Organism-specific databases

DisGeNETi57407.
OpenTargetsiENSG00000153406.
ENSG00000274684.
PharmGKBiPA145007922.

Polymorphism and mutation databases

BioMutaiNMRAL1.
DMDMi74734255.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002782041 – 299NmrA-like family domain-containing protein 1Add BLAST299

Proteomic databases

EPDiQ9HBL8.
MaxQBiQ9HBL8.
PaxDbiQ9HBL8.
PeptideAtlasiQ9HBL8.
PRIDEiQ9HBL8.

PTM databases

iPTMnetiQ9HBL8.
PhosphoSitePlusiQ9HBL8.

Expressioni

Inductioni

By nitric oxide, cGMP and proinflammatory cytokines.1 Publication

Gene expression databases

BgeeiENSG00000153406.
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 interactors.
DIPiDIP-60944N.
IntActiQ9HBL8. 3 interactors.
MINTiMINT-5003586.
STRINGi9606.ENSP00000283429.

Structurei

Secondary structure

1299
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 10Combined sources5
Turni11 – 13Combined sources3
Helixi15 – 27Combined sources13
Beta strandi29 – 37Combined sources9
Helixi42 – 49Combined sources8
Beta strandi53 – 56Combined sources4
Helixi62 – 69Combined sources8
Beta strandi73 – 77Combined sources5
Helixi81 – 83Combined sources3
Helixi87 – 104Combined sources18
Beta strandi107 – 111Combined sources5
Helixi117 – 120Combined sources4
Turni121 – 123Combined sources3
Helixi128 – 143Combined sources16
Beta strandi147 – 151Combined sources5
Helixi156 – 160Combined sources5
Turni161 – 163Combined sources3
Beta strandi171 – 176Combined sources6
Beta strandi185 – 188Combined sources4
Helixi190 – 192Combined sources3
Helixi193 – 202Combined sources10
Helixi204 – 207Combined sources4
Beta strandi211 – 213Combined sources3
Beta strandi216 – 219Combined sources4
Helixi221 – 232Combined sources12
Beta strandi236 – 238Combined sources3
Helixi244 – 247Combined sources4
Helixi254 – 264Combined sources11
Helixi272 – 278Combined sources7
Helixi285 – 292Combined sources8
Helixi293 – 295Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HBL8.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni153 – 189Interaction with ASS1Add BLAST37

Sequence similaritiesi

Belongs to the NmrA-type oxidoreductase family.Curated

Phylogenomic databases

eggNOGiENOG410IVQ5. Eukaryota.
COG0702. LUCA.
GeneTreeiENSGT00390000016395.
HOGENOMiHOG000035269.
HOVERGENiHBG082032.
InParanoidiQ9HBL8.
OMAiPATFMEL.
OrthoDBiEOG091G0E3T.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_03068923T → I.Corresponds to variant rs11557236dbSNPEnsembl.1
Natural variantiVAR_030690252P → L.Corresponds to variant rs3747582dbSNPEnsembl.1

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
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ9HBL8.
PhosphoSitePlusiQ9HBL8.

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.
DisGeNETi57407.
GeneCardsiNMRAL1.
HGNCiHGNC:24987. NMRAL1.
HPAiHPA041353.
HPA062287.
neXtProtiNX_Q9HBL8.
OpenTargetsiENSG00000153406.
ENSG00000274684.
PharmGKBiPA145007922.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVQ5. Eukaryota.
COG0702. LUCA.
GeneTreeiENSGT00390000016395.
HOGENOMiHOG000035269.
HOVERGENiHBG082032.
InParanoidiQ9HBL8.
OMAiPATFMEL.
OrthoDBiEOG091G0E3T.
PhylomeDBiQ9HBL8.
TreeFamiTF335532.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiNMRAL1. human.
EvolutionaryTraceiQ9HBL8.
GenomeRNAii57407.
PROiQ9HBL8.

Gene expression databases

BgeeiENSG00000153406.
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...

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: November 2, 2016
This is version 117 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.