Q6IA69 (NADE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamine-dependent NAD(+) synthetase
EC=6.3.5.1

Alternative name(s):
NAD(+) synthase [glutamine-hydrolyzing]
NAD(+) synthetase

Gene names

Name:

NADSYN1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	706 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + deamido-NAD+ + L-glutamine + H2O = AMP + diphosphate + NAD+ + L-glutamate.
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from deamido-NAD(+) (L-Gln route): step 1/1.
Subunit structure	Homohexamer. Ref.1
Sequence similarities	In the C-terminal section; belongs to the NAD synthetase family. Contains 1 CN hydrolase domain.
Biophysicochemical properties	Kinetic parameters: KM=0.49 mM for deamido-NAD+ Ref.1 KM=0.089 mM for ATP KM=1.44 mM for glutamine KM=13.1 mM for ammonium Vmax=0.99 nmol/min/µg enzyme deamido-NAD+ Vmax=0.61 nmol/min/µg enzyme ATP Vmax=0.70 nmol/min/µg enzyme glutamine Vmax=1.04 nmol/min/µg enzyme ammonium

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	ATP-binding NAD Nucleotide-binding
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	NAD biosynthetic process Inferred from electronic annotation. Source: InterPro water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW NAD+ synthase (glutamine-hydrolyzing) activity Traceable author statement. Source: Reactome hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
UPF1	Q92900	1	EBI-748610,EBI-373471

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 706	706	Glutamine-dependent NAD(+) synthetase		PRO_0000237577
Regions
	Domain	5 – 299	295	CN hydrolase
	Nucleotide binding	355 – 362	8	ATP By similarity
	Region	325 – 706	382	Ligase By similarity
Sites
	Active site	357	1	By similarity
Natural variations
	Natural variant	74	1	V → L. Ref.2 Ref.3 Ref.5 Corresponds to variant rs2276360 [ dbSNP | Ensembl ].		VAR_026497
	Natural variant	204	1	Q → H. Ref.1 Ref.2 Ref.3 Ref.5 Corresponds to variant rs7950441 [ dbSNP | Ensembl ].		VAR_058703
	Natural variant	297	1	P → L. Corresponds to variant rs7121106 [ dbSNP | Ensembl ].		VAR_056204
	Natural variant	591	1	M → I. Corresponds to variant rs35007971 [ dbSNP | Ensembl ].		VAR_056205
	Natural variant	704	1	G → S. Corresponds to variant rs12282060 [ dbSNP | Ensembl ].		VAR_056206
Experimental info
	Mutagenesis	175	1	C → S: Eliminates glutamine-dependent NAD synthetase activity with the ammonia-dependent activity intact. Ref.1
	Sequence conflict	102	1	I → V in BAC65148. Ref.1
	Sequence conflict	207	1	R → H in CAG33567. Ref.3
	Sequence conflict	623	1	W → R in BAC65148. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q6IA69 [UniParc]. Last modified September 1, 2009. Version 3. Checksum: 9788B060F3A1D13B	FASTA	706	79,285
	10 20 30 40 50 60 MGRKVTVATC ALNQWALDFE GNLQRILKSI EIAKNRGARY RLGPELEICG YGCWDHYYES 70 80 90 100 110 120 DTLLHSFQVL AALVESPVTQ DIICDVGMPV MHRNVRYNCR VIFLNRKILL IRPKMALANE 130 140 150 160 170 180 GNYRELRWFT PWSRSRHTEE YFLPRMIQDL TKQETVPFGD AVLVTWDTCI GSEICEELWT 190 200 210 220 230 240 PHSPHIDMGL DGVEIITNAS GSHQVLRKAN TRVDLVTMVT SKNGGIYLLA NQKGCDGDRL 250 260 270 280 290 300 YYDGCAMIAM NGSVFAQGSQ FSLDDVEVLT ATLDLEDVRS YRAEISSRNL AASRASPYPR 310 320 330 340 350 360 VKVDFALSCH EDLLAPISEP IEWKYHSPEE EISLGPACWL WDFLRRSQQA GFLLPLSGGV 370 380 390 400 410 420 DSAATACLIY SMCCQVCEAV RSGNEEVLAD VRTIVNQISY TPQDPRDLCG RILTTCYMAS 430 440 450 460 470 480 KNSSQETCTR ARELAQQIGS HHISLNIDPA VKAVMGIFSL VTGKSPLFAA HGGSSRENLA 490 500 510 520 530 540 LQNVQARIRM VLAYLFAQLS LWSRGVHGGL LVLGSANVDE SLLGYLTKYD CSSADINPIG 550 560 570 580 590 600 GISKTDLRAF VQFCIQRFQL PALQSILLAP ATAELEPLAD GQVSQTDEED MGMTYAELSV 610 620 630 640 650 660 YGKLRKVAKM GPYSMFCKLL GMWRHICTPR QVADKVKRFF SKYSMNRHKM TTLTPAYHAE 670 680 690 700 NYSPEDNRFD LRPFLYNTSW PWQFRCIENQ VLQLERAEPQ SLDGVD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular identification of human glutamine- and ammonia-dependent NAD synthetases. Carbon-nitrogen hydrolase domain confers glutamine dependency." Hara N., Yamada K., Terashima M., Osago H., Shimoyama M., Tsuchiya M. J. Biol. Chem. 278:10914-10921(2003) [PubMed: 12547821] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, MUTAGENESIS OF CYS-175, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT HIS-204. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-74 AND HIS-204. Tissue: Mammary gland.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-74 AND HIS-204.
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-74 AND HIS-204. Tissue: Lymph.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB091316 mRNA. Translation: BAC65148.1. AK001493 mRNA. Translation: BAA91722.1. AK022436 mRNA. Translation: BAB14034.1. CR457286 mRNA. Translation: CAG33567.1. AP000867 Genomic DNA. No translation available. AP002387 Genomic DNA. No translation available. BC003638 mRNA. Translation: AAH03638.1. BC003666 mRNA. Translation: AAH03666.1.
IPI	IPI00306689.
RefSeq	NP_060631.2. NM_018161.4.
UniGene	Hs.556986.
3D structure databases
ProteinModelPortal	Q6IA69.
SMR	Q6IA69. Positions 4-689.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6IA69. 1 interaction.
MINT	MINT-1450170.
STRING	Q6IA69.
Polymorphism databases
DMDM	257051045.
Proteomic databases
PRIDE	Q6IA69.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000319023; ENSP00000326424; ENSG00000172890.
GeneID	55191.
KEGG	hsa:55191.
UCSC	uc001oqn.1. human.
Organism-specific databases
CTD	55191.
GeneCards	GC11P071164.
H-InvDB	HIX0009900.
HGNC	HGNC:29832. NADSYN1.
HPA	CAB017798.
MIM	608285. gene.
neXtProt	NX_Q6IA69.
PharmGKB	PA142671299.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11690.
GeneTree	ENSGT00390000010152.
HOGENOM	HBG334087.
HOVERGEN	HBG082007.
InParanoid	Q6IA69.
OMA	TCEELFT.
OrthoDB	EOG45X7VK.
PhylomeDB	Q6IA69.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q6IA69.
Bgee	Q6IA69.
CleanEx	HS_NADSYN1.
Genevestigator	Q6IA69.
GermOnline	ENSG00000172890. Homo sapiens.
Family and domain databases
InterPro	IPR014445. Gln-dep_NAD_synthase. IPR022310. NAD/GMP_synthase. IPR003694. NAD_synthase. IPR003010. Ntlse/CNhydtse. IPR014729. Rossmann-like_a/b/a_fold. [Graphical view]
Gene3D	G3DSA:3.60.110.10. Ntlse/CNhydtse. 1 hit. G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.
KO	K01950.
Pfam	PF00795. CN_hydrolase. 1 hit. PF02540. NAD_synthase. 1 hit. [Graphical view]
PIRSF	PIRSF006630. NADS_GAT. 1 hit.
SUPFAM	SSF56317. Ntlse/CNhydtse. 1 hit.
TIGRFAMs	TIGR00552. NadE. 1 hit.
PROSITE	PS50263. CN_HYDROLASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00142. L-Glutamic Acid. DB00130. L-Glutamine.
NextBio	59043.
SOURCE	Search...

Entry information

Entry name

NADE_HUMAN

Accession

Primary (citable) accession number: Q6IA69
Secondary accession number(s): Q86SN2, Q9HA25, Q9NVM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	September 1, 2009
Last modified:	January 25, 2012
This is version 71 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.