Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Glutamine-dependent NAD(+) synthetase

Gene

NADSYN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)
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

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.
UniPathwayiUPA00253; 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

HGNCiHGNC:29832. NADSYN1.

Subcellular locationi

GO - Cellular componenti

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.

PTM databases

iPTMnetiQ6IA69.
PhosphoSitePlusiQ6IA69.

Expressioni

Gene expression databases

BgeeiENSG00000172890.
CleanExiHS_NADSYN1.
ExpressionAtlasiQ6IA69. baseline and differential.
GenevisibleiQ6IA69. HS.

Organism-specific databases

HPAiCAB017798.
HPA038523.
HPA038524.

Interactioni

Subunit structurei

Homohexamer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Q9H6143EBI-748610,EBI-10249899

Protein-protein interaction databases

BioGridi120488. 7 interactors.
IntActiQ6IA69. 15 interactors.
MINTiMINT-1450170.
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.
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

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

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

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.

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: June 7, 2017
This is version 118 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. Human chromosome 11
    Human chromosome 11: 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. 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. SIMILARITY comments
    Index of protein domains and families