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Protein

Glutamine-dependent NAD(+) synthetase

Gene

NADSYN1

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

Functioni

Catalytic activityi

ATP + deamido-NAD+ + L-glutamine + H2O = AMP + diphosphate + NAD+ + L-glutamate.

Kineticsi

  1. KM=0.49 mM for deamido-NAD+1 Publication
  2. KM=0.089 mM for ATP1 Publication
  3. KM=1.44 mM for glutamine1 Publication
  4. KM=13.1 mM for ammonium1 Publication
  1. Vmax=0.99 nmol/min/µg enzyme deamido-NAD+1 Publication
  2. Vmax=0.61 nmol/min/µg enzyme ATP1 Publication
  3. Vmax=0.70 nmol/min/µg enzyme glutamine1 Publication
  4. Vmax=1.04 nmol/min/µg enzyme ammonium1 Publication

Pathwayi: NAD(+) biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes NAD(+) from deamido-NAD(+) (L-Gln route).
Proteins known to be involved in this subpathway in this organism are:
  1. Glutamine-dependent NAD(+) synthetase (NADSYN1), Glutamine-dependent NAD(+) synthetase (nadE), Glutamine-dependent NAD(+) synthetase (nadE)
This subpathway is part of the pathway NAD(+) biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes NAD(+) from deamido-NAD(+) (L-Gln route), the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei45Proton acceptor; for glutaminase activityBy similarity1
Active sitei114For glutaminase activityBy similarity1
Active sitei175Nucleophile; for glutaminase activityBy similarity1
Active sitei357By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi355 – 362ATPBy similarity8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • glutaminase activity Source: GO_Central
  • NAD+ synthase (glutamine-hydrolyzing) activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionLigase
LigandATP-binding, NAD, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS10587-MONOMER
BRENDAi6.3.5.1 2681
ReactomeiR-HSA-196807 Nicotinate metabolism
UniPathwayi
UPA00253;UER00334

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamine-dependent NAD(+) synthetase (EC:6.3.5.1)
Alternative name(s):
NAD(+) synthase [glutamine-hydrolyzing]
NAD(+) synthetase
Gene namesi
Name:NADSYN1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000172890.11
HGNCiHGNC:29832 NADSYN1
MIMi608285 gene
neXtProtiNX_Q6IA69

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi175C → S: Eliminates glutamine-dependent NAD synthetase activity with the ammonia-dependent activity intact. 1 Publication1

Organism-specific databases

DisGeNETi55191
OpenTargetsiENSG00000172890
PharmGKBiPA142671299

Chemistry databases

DrugBankiDB00142 L-Glutamic Acid
DB00130 L-Glutamine

Polymorphism and mutation databases

BioMutaiNADSYN1
DMDMi257051045

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002375771 – 706Glutamine-dependent NAD(+) synthetaseAdd BLAST706

Proteomic databases

EPDiQ6IA69
MaxQBiQ6IA69
PaxDbiQ6IA69
PeptideAtlasiQ6IA69
PRIDEiQ6IA69
ProteomicsDBi66358

PTM databases

iPTMnetiQ6IA69
PhosphoSitePlusiQ6IA69

Expressioni

Gene expression databases

BgeeiENSG00000172890 Expressed in 200 organ(s), highest expression level in small intestine Peyer's patch
CleanExiHS_NADSYN1
ExpressionAtlasiQ6IA69 baseline and differential
GenevisibleiQ6IA69 HS

Organism-specific databases

HPAiCAB017798
HPA038523
HPA038524

Interactioni

Subunit structurei

Homohexamer.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi120488, 12 interactors
IntActiQ6IA69, 16 interactors
STRINGi9606.ENSP00000326424

Chemistry databases

BindingDBiQ6IA69

Structurei

3D structure databases

ProteinModelPortaliQ6IA69
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 275CN hydrolasePROSITE-ProRule annotationAdd BLAST271

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni325 – 706LigaseBy similarityAdd BLAST382

Sequence similaritiesi

In the C-terminal section; belongs to the NAD synthetase family.Curated

Phylogenomic databases

eggNOGiKOG2303 Eukaryota
COG0171 LUCA
COG0388 LUCA
GeneTreeiENSGT00390000010152
HOGENOMiHOG000160137
HOVERGENiHBG082007
InParanoidiQ6IA69
KOiK01950
OMAiARNRHKM
OrthoDBiEOG091G022X
PhylomeDBiQ6IA69
TreeFamiTF351426

Family and domain databases

CDDicd00553 NAD_synthase, 1 hit
Gene3Di3.40.50.620, 1 hit
3.60.110.10, 1 hit
HAMAPiMF_02090 NadE_glutamine_dep, 1 hit
InterProiView protein in InterPro
IPR003010 C-N_Hydrolase
IPR036526 C-N_Hydrolase_sf
IPR014445 Gln-dep_NAD_synthase
IPR022310 NAD/GMP_synthase
IPR003694 NAD_synthase
IPR014729 Rossmann-like_a/b/a_fold
PANTHERiPTHR23090 PTHR23090, 1 hit
PfamiView protein in Pfam
PF00795 CN_hydrolase, 1 hit
PF02540 NAD_synthase, 1 hit
PIRSFiPIRSF006630 NADS_GAT, 1 hit
SUPFAMiSSF56317 SSF56317, 1 hit
TIGRFAMsiTIGR00552 nadE, 1 hit
PROSITEiView protein in PROSITE
PS50263 CN_HYDROLASE, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q6IA69-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGRKVTVATC ALNQWALDFE GNLQRILKSI EIAKNRGARY RLGPELEICG
60 70 80 90 100
YGCWDHYYES DTLLHSFQVL AALVESPVTQ DIICDVGMPV MHRNVRYNCR
110 120 130 140 150
VIFLNRKILL IRPKMALANE GNYRELRWFT PWSRSRHTEE YFLPRMIQDL
160 170 180 190 200
TKQETVPFGD AVLVTWDTCI GSEICEELWT PHSPHIDMGL DGVEIITNAS
210 220 230 240 250
GSHQVLRKAN TRVDLVTMVT SKNGGIYLLA NQKGCDGDRL YYDGCAMIAM
260 270 280 290 300
NGSVFAQGSQ FSLDDVEVLT ATLDLEDVRS YRAEISSRNL AASRASPYPR
310 320 330 340 350
VKVDFALSCH EDLLAPISEP IEWKYHSPEE EISLGPACWL WDFLRRSQQA
360 370 380 390 400
GFLLPLSGGV DSAATACLIY SMCCQVCEAV RSGNEEVLAD VRTIVNQISY
410 420 430 440 450
TPQDPRDLCG RILTTCYMAS KNSSQETCTR ARELAQQIGS HHISLNIDPA
460 470 480 490 500
VKAVMGIFSL VTGKSPLFAA HGGSSRENLA LQNVQARIRM VLAYLFAQLS
510 520 530 540 550
LWSRGVHGGL LVLGSANVDE SLLGYLTKYD CSSADINPIG GISKTDLRAF
560 570 580 590 600
VQFCIQRFQL PALQSILLAP ATAELEPLAD GQVSQTDEED MGMTYAELSV
610 620 630 640 650
YGKLRKVAKM GPYSMFCKLL GMWRHICTPR QVADKVKRFF SKYSMNRHKM
660 670 680 690 700
TTLTPAYHAE NYSPEDNRFD LRPFLYNTSW PWQFRCIENQ VLQLERAEPQ

SLDGVD
Length:706
Mass (Da):79,285
Last modified:September 1, 2009 - v3
Checksum:i9788B060F3A1D13B
GO
Isoform 2 (identifier: Q6IA69-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MGRKVT → MGISGQ
     7-266: Missing.

Note: No experimental confirmation available.
Show »
Length:446
Mass (Da):49,718
Checksum:i405425F9F53D8AC7
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YCQ6H0YCQ6_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
259Annotation score:
E9PKY6E9PKY6_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
294Annotation score:
E9PND0E9PND0_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
88Annotation score:
E9PNF5E9PNF5_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
149Annotation score:
H0YED2H0YED2_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
59Annotation score:
H0YDH3H0YDH3_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
111Annotation score:
A0A0B4J216A0A0B4J216_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
335Annotation score:
H0YCF9H0YCF9_HUMAN
Glutamine-dependent NAD(+) syntheta...
NADSYN1
127Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti102I → V in BAC65148 (PubMed:12547821).Curated1
Sequence conflicti207R → H in CAG33567 (Ref. 3) Curated1
Sequence conflicti623W → R in BAC65148 (PubMed:12547821).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02649774V → L3 PublicationsCorresponds to variant dbSNP:rs2276360Ensembl.1
Natural variantiVAR_058703204Q → H4 PublicationsCorresponds to variant dbSNP:rs7950441Ensembl.1
Natural variantiVAR_056204297P → L. Corresponds to variant dbSNP:rs7121106Ensembl.1
Natural variantiVAR_056205591M → I. Corresponds to variant dbSNP:rs35007971Ensembl.1
Natural variantiVAR_056206704G → S. Corresponds to variant dbSNP:rs12282060Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0565851 – 6MGRKVT → MGISGQ in isoform 2. 1 Publication6
Alternative sequenceiVSP_0565867 – 266Missing in isoform 2. 1 PublicationAdd BLAST260

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB091316 mRNA Translation: BAC65148.1
AK001493 mRNA Translation: BAA91722.1
AK022436 mRNA Translation: BAB14034.1
AK097946 mRNA Translation: BAG53556.1
CR457286 mRNA Translation: CAG33567.1
AP000867 Genomic DNA No translation available.
AP002387 Genomic DNA No translation available.
CH471076 Genomic DNA Translation: EAW74792.1
BC003638 mRNA Translation: AAH03638.1
BC003666 mRNA Translation: AAH03666.1
CCDSiCCDS8201.1 [Q6IA69-1]
RefSeqiNP_060631.2, NM_018161.4 [Q6IA69-1]
UniGeneiHs.556986

Genome annotation databases

EnsembliENST00000319023; ENSP00000326424; ENSG00000172890 [Q6IA69-1]
GeneIDi55191
KEGGihsa:55191
UCSCiuc001oqn.4 human [Q6IA69-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB091316 mRNA Translation: BAC65148.1
AK001493 mRNA Translation: BAA91722.1
AK022436 mRNA Translation: BAB14034.1
AK097946 mRNA Translation: BAG53556.1
CR457286 mRNA Translation: CAG33567.1
AP000867 Genomic DNA No translation available.
AP002387 Genomic DNA No translation available.
CH471076 Genomic DNA Translation: EAW74792.1
BC003638 mRNA Translation: AAH03638.1
BC003666 mRNA Translation: AAH03666.1
CCDSiCCDS8201.1 [Q6IA69-1]
RefSeqiNP_060631.2, NM_018161.4 [Q6IA69-1]
UniGeneiHs.556986

3D structure databases

ProteinModelPortaliQ6IA69
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120488, 12 interactors
IntActiQ6IA69, 16 interactors
STRINGi9606.ENSP00000326424

Chemistry databases

BindingDBiQ6IA69
DrugBankiDB00142 L-Glutamic Acid
DB00130 L-Glutamine

PTM databases

iPTMnetiQ6IA69
PhosphoSitePlusiQ6IA69

Polymorphism and mutation databases

BioMutaiNADSYN1
DMDMi257051045

Proteomic databases

EPDiQ6IA69
MaxQBiQ6IA69
PaxDbiQ6IA69
PeptideAtlasiQ6IA69
PRIDEiQ6IA69
ProteomicsDBi66358

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000319023; ENSP00000326424; ENSG00000172890 [Q6IA69-1]
GeneIDi55191
KEGGihsa:55191
UCSCiuc001oqn.4 human [Q6IA69-1]

Organism-specific databases

CTDi55191
DisGeNETi55191
EuPathDBiHostDB:ENSG00000172890.11
GeneCardsiNADSYN1
H-InvDBiHIX0035837
HGNCiHGNC:29832 NADSYN1
HPAiCAB017798
HPA038523
HPA038524
MIMi608285 gene
neXtProtiNX_Q6IA69
OpenTargetsiENSG00000172890
PharmGKBiPA142671299
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2303 Eukaryota
COG0171 LUCA
COG0388 LUCA
GeneTreeiENSGT00390000010152
HOGENOMiHOG000160137
HOVERGENiHBG082007
InParanoidiQ6IA69
KOiK01950
OMAiARNRHKM
OrthoDBiEOG091G022X
PhylomeDBiQ6IA69
TreeFamiTF351426

Enzyme and pathway databases

UniPathwayi
UPA00253;UER00334

BioCyciMetaCyc:HS10587-MONOMER
BRENDAi6.3.5.1 2681
ReactomeiR-HSA-196807 Nicotinate metabolism

Miscellaneous databases

ChiTaRSiNADSYN1 human
GeneWikiiNADSYN1
GenomeRNAii55191
PROiPR:Q6IA69
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172890 Expressed in 200 organ(s), highest expression level in small intestine Peyer's patch
CleanExiHS_NADSYN1
ExpressionAtlasiQ6IA69 baseline and differential
GenevisibleiQ6IA69 HS

Family and domain databases

CDDicd00553 NAD_synthase, 1 hit
Gene3Di3.40.50.620, 1 hit
3.60.110.10, 1 hit
HAMAPiMF_02090 NadE_glutamine_dep, 1 hit
InterProiView protein in InterPro
IPR003010 C-N_Hydrolase
IPR036526 C-N_Hydrolase_sf
IPR014445 Gln-dep_NAD_synthase
IPR022310 NAD/GMP_synthase
IPR003694 NAD_synthase
IPR014729 Rossmann-like_a/b/a_fold
PANTHERiPTHR23090 PTHR23090, 1 hit
PfamiView protein in Pfam
PF00795 CN_hydrolase, 1 hit
PF02540 NAD_synthase, 1 hit
PIRSFiPIRSF006630 NADS_GAT, 1 hit
SUPFAMiSSF56317 SSF56317, 1 hit
TIGRFAMsiTIGR00552 nadE, 1 hit
PROSITEiView protein in PROSITE
PS50263 CN_HYDROLASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNADE_HUMAN
AccessioniPrimary (citable) accession number: Q6IA69
Secondary accession number(s): B3KUU4
, Q86SN2, Q9HA25, Q9NVM8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: September 1, 2009
Last modified: September 12, 2018
This is version 125 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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