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Protein

NmrA-like family domain-containing protein 1

Gene

NMRAL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

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 - Molecular functioni

  • identical protein binding Source: IntAct

Keywordsi

LigandNADP

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

EuPathDBiHostDB:ENSG00000153406.13
HGNCiHGNC:24987 NMRAL1
neXtProtiNX_Q9HBL8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
PharmGKBiPA145007922

Chemistry databases

DrugBankiDB08784 2-(4-CHLORO-PHENYLAMINO)-NICOTINIC ACID

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
ProteomicsDBi81572

PTM databases

iPTMnetiQ9HBL8
PhosphoSitePlusiQ9HBL8

Expressioni

Inductioni

By nitric oxide, cGMP and proinflammatory cytokines.1 Publication

Gene expression databases

BgeeiENSG00000153406 Expressed in 196 organ(s), highest expression level in prostate gland
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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121509, 14 interactors
DIPiDIP-60944N
IntActiQ9HBL8, 4 interactors
STRINGi9606.ENSP00000283429

Structurei

Secondary structure

1299
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiQDDEASM
OrthoDBiEOG091G0E3T
PhylomeDBiQ9HBL8
TreeFamiTF335532

Family and domain databases

InterProiView protein in InterPro
IPR036291 NAD(P)-bd_dom_sf
IPR008030 NmrA-like
PfamiView protein in Pfam
PF05368 NmrA, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L1Y8I3L1Y8_HUMAN
NmrA-like family domain-containing ...
NMRAL1
190Annotation score:
I3L0Y6I3L0Y6_HUMAN
NmrA-like family domain-containing ...
NMRAL1
188Annotation score:
I3L3Z0I3L3Z0_HUMAN
NmrA-like family domain-containing ...
NMRAL1
124Annotation score:
I3L543I3L543_HUMAN
NmrA-like family domain-containing ...
NMRAL1
159Annotation score:
I3L3I6I3L3I6_HUMAN
NmrA-like family domain-containing ...
NMRAL1
224Annotation score:
I3L2U0I3L2U0_HUMAN
NmrA-like family domain-containing ...
NMRAL1
41Annotation score:
I3L1Q7I3L1Q7_HUMAN
NmrA-like family domain-containing ...
NMRAL1
57Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03068923T → I. Corresponds to variant dbSNP:rs11557236Ensembl.1
Natural variantiVAR_030690252P → L. Corresponds to variant dbSNP:rs3747582Ensembl.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

Similar proteinsi

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, 14 interactors
DIPiDIP-60944N
IntActiQ9HBL8, 4 interactors
STRINGi9606.ENSP00000283429

Chemistry databases

DrugBankiDB08784 2-(4-CHLORO-PHENYLAMINO)-NICOTINIC ACID

PTM databases

iPTMnetiQ9HBL8
PhosphoSitePlusiQ9HBL8

Polymorphism and mutation databases

BioMutaiNMRAL1
DMDMi74734255

Proteomic databases

EPDiQ9HBL8
MaxQBiQ9HBL8
PaxDbiQ9HBL8
PeptideAtlasiQ9HBL8
PRIDEiQ9HBL8
ProteomicsDBi81572

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
EuPathDBiHostDB:ENSG00000153406.13
GeneCardsiNMRAL1
HGNCiHGNC:24987 NMRAL1
HPAiHPA041353
HPA062287
neXtProtiNX_Q9HBL8
OpenTargetsiENSG00000153406
PharmGKBiPA145007922
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVQ5 Eukaryota
COG0702 LUCA
GeneTreeiENSGT00390000016395
HOGENOMiHOG000035269
HOVERGENiHBG082032
InParanoidiQ9HBL8
OMAiQDDEASM
OrthoDBiEOG091G0E3T
PhylomeDBiQ9HBL8
TreeFamiTF335532

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiNMRAL1 human
EvolutionaryTraceiQ9HBL8
GenomeRNAii57407
PROiPR:Q9HBL8

Gene expression databases

BgeeiENSG00000153406 Expressed in 196 organ(s), highest expression level in prostate gland
CleanExiHS_NMRAL1
ExpressionAtlasiQ9HBL8 baseline and differential
GenevisibleiQ9HBL8 HS

Family and domain databases

InterProiView protein in InterPro
IPR036291 NAD(P)-bd_dom_sf
IPR008030 NmrA-like
PfamiView protein in Pfam
PF05368 NmrA, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNMRL1_HUMAN
AccessioniPrimary (citable) accession number: Q9HBL8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: March 1, 2001
Last modified: October 10, 2018
This is version 129 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

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