P08243 (ASNS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Asparagine synthetase [glutamine-hydrolyzing]
EC=6.3.5.4

Alternative name(s):
Cell cycle control protein TS11
Glutamine-dependent asparagine synthetase

Gene names

Name:	ASNS
Synonyms:	TS11

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	561 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + L-aspartate + L-glutamine + H2O = AMP + diphosphate + L-asparagine + L-glutamate.
Pathway	Amino-acid biosynthesis; L-asparagine biosynthesis; L-asparagine from L-aspartate (L-Gln route): step 1/1.
Sequence similarities	Contains 1 asparagine synthetase domain. Contains 1 glutamine amidotransferase type-2 domain.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Asparagine biosynthesis
Coding sequence diversity	Polymorphism
Domain	Glutamine amidotransferase
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	asparagine biosynthetic process Inferred by curator Ref.10. Source: UniProtKB cellular response to glucose starvation Inferred from direct assay. Source: UniProtKB glutamine metabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptotic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from direct assay Ref.9. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome soluble fraction Inferred from direct assay Ref.10. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW asparagine synthase (glutamine-hydrolyzing) activity Inferred from direct assay Ref.10Ref.9Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 561	560	Asparagine synthetase [glutamine-hydrolyzing]		PRO_0000056910
Regions
	Domain	2 – 191	190	Glutamine amidotransferase type-2
	Domain	213 – 536	324	Asparagine synthetase
Sites
	Active site	2	1	For GATase activity Ref.10
Amino acid modifications
	Modified residue	385	1	N6-acetyllysine Ref.13
	Modified residue	471	1	Phosphoserine Ref.12
Natural variations
	Natural variant	210	1	V → E. Ref.4 Ref.5 Ref.6 Ref.7 Corresponds to variant rs1049674 [ dbSNP | Ensembl ].		VAR_023443
Experimental info
	Mutagenesis	2	1	C → A: Loss of the glutamine-dependent asparagine synthetase activity, while the ammonia-dependent activity remained unaffected. Ref.11
	Sequence conflict	333 – 343	11	TYDITTVRASV → LMTLQQFVLRI in AAA36781. Ref.8
	Sequence conflict	353 – 360	8	RKNTDSVV → GRTQIAWL in AAA36781. Ref.8
	Sequence conflict	426	1	S → F Ref.1
	Sequence conflict	426	1	S → F Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P08243 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 3E9B75E21D799FBE	FASTA	561	64,370
	10 20 30 40 50 60 MCGIWALFGS DDCLSVQCLS AMKIAHRGPD AFRFENVNGY TNCCFGFHRL AVVDPLFGMQ 70 80 90 100 110 120 PIRVKKYPYL WLCYNGEIYN HKKMQQHFEF EYQTKVDGEI ILHLYDKGGI EQTICMLDGV 130 140 150 160 170 180 FAFVLLDTAN KKVFLGRDTY GVRPLFKAMT EDGFLAVCSE AKGLVTLKHS ATPFLKVEPF 190 200 210 220 230 240 LPGHYEVLDL KPNGKVASVE MVKYHHCRDV PLHALYDNVE KLFPGFEIET VKNNLRILFN 250 260 270 280 290 300 NAVKKRLMTD RRIGCLLSGG LDSSLVAATL LKQLKEAQVQ YPLQTFAIGM EDSPDLLAAR 310 320 330 340 350 360 KVADHIGSEH YEVLFNSEEG IQALDEVIFS LETYDITTVR ASVGMYLISK YIRKNTDSVV 370 380 390 400 410 420 IFSGEGSDEL TQGYIYFHKA PSPEKAEEES ERLLRELYLF DVLRADRTTA AHGLELRVPF 430 440 450 460 470 480 LDHRFSSYYL SLPPEMRIPK NGIEKHLLRE TFEDSNLIPK EILWRPKEAF SDGITSVKNS 490 500 510 520 530 540 WFKILQEYVE HQVDDAMMAN AAQKFPFNTP KTKEGYYYRQ VFERHYPGRA DWLSHYWMPK 550 560 WINATDPSAR TLTHYKSAVK A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of human cDNAs for asparagine synthetase and expression in Jensen rat sarcoma cells." Andrulis I.L., Chen J., Ray P.N. Mol. Cell. Biol. 7:2435-2443(1987) [PubMed: 2886907] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular structure of the human asparagine synthetase gene." Zhang Y.P., Lambert M.A., Cairney A.E., Wills D., Ray P.N., Andrulis I.L. Genomics 4:259-265(1989) [PubMed: 2565875] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-210.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-210.
[6]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-210.
[7]	"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], VARIANT GLU-210. Tissue: Muscle.
[8]	"Molecular cloning of a gene that is necessary for G1 progression in mammalian cells." Greco A., Ittmann M., Basilico C. Proc. Natl. Acad. Sci. U.S.A. 84:1565-1569(1987) [PubMed: 3470743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-561.
[9]	"Organization and expression of the cell cycle gene, ts11, that encodes asparagine synthetase." Greco A., Gong S.S., Ittmann M., Basilico C. Mol. Cell. Biol. 9:2350-2359(1989) [PubMed: 2569668] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-83.
[10]	"Expression of human asparagine synthetase in Escherichia coli." van Heeke G., Schuster S.M. J. Biol. Chem. 264:5503-5509(1989) [PubMed: 2564390] [Abstract] Cited for: ACTIVE SITE.
[11]	"The N-terminal cysteine of human asparagine synthetase is essential for glutamine-dependent activity." van Heeke G., Schuster S.M. J. Biol. Chem. 264:19475-19477(1989) [PubMed: 2573597] [Abstract] Cited for: MUTAGENESIS OF CYS-2.
[12]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-385, MASS SPECTROMETRY.
[14]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	M27396 mRNA. Translation: AAA51789.1. L35946 , L35936, L35937, L35938, L35939, L35940, L35941, L35942, L35943, L35944, L35945 Genomic DNA. Translation: AAA52756.1. BT007113 mRNA. Translation: AAP35777.1. AC079781 Genomic DNA. Translation: AAQ96856.1. CH236949 Genomic DNA. Translation: EAL24115.1. CH471091 Genomic DNA. Translation: EAW76730.1. CH471091 Genomic DNA. Translation: EAW76723.1. CH471091 Genomic DNA. Translation: EAW76731.1. CH471091 Genomic DNA. Translation: EAW76732.1. CH471091 Genomic DNA. Translation: EAW76733.1. BC008723 mRNA. Translation: AAH08723.1. BC014621 mRNA. Translation: AAH14621.1. M15798 mRNA. Translation: AAA36781.1. M27054 Genomic DNA. Translation: AAA63266.1.
IPI	IPI00554777.
PIR	AJHUN1. A27062.
RefSeq	NP_001171546.1. NM_001178075.1. NP_001171547.1. NM_001178076.1. NP_001171548.1. NM_001178077.1. NP_001664.3. NM_001673.4. NP_597680.2. NM_133436.3. NP_899199.2. NM_183356.3.
UniGene	Hs.489207.
3D structure databases
ProteinModelPortal	P08243.
SMR	P08243. Positions 2-531.
ModBase	Search...
Protein-protein interaction databases
IntAct	P08243. 3 interactions.
MINT	MINT-1371662.
STRING	P08243.
Protein family/group databases
MEROPS	C44.974.
PTM databases
PhosphoSite	P08243.
Polymorphism databases
DMDM	13432102.
Proteomic databases
PeptideAtlas	P08243.
PRIDE	P08243.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000175506; ENSP00000175506; ENSG00000070669. ENST00000394308; ENSP00000377845; ENSG00000070669. ENST00000394309; ENSP00000377846; ENSG00000070669.
GeneID	440.
KEGG	hsa:440.
UCSC	uc003uot.2. human.
Organism-specific databases
CTD	440.
GeneCards	GC07M097481.
H-InvDB	HIX0006875.
HGNC	HGNC:753. ASNS.
HPA	HPA029318.
MIM	108370. gene.
neXtProt	NX_P08243.
PharmGKB	PA25052.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000001994.
HOGENOM	HBG752912.
HOVERGEN	HBG003103.
InParanoid	P08243.
OMA	NYYVASE.
OrthoDB	EOG4RV2R2.
PhylomeDB	P08243.
Enzyme and pathway databases
BRENDA	6.3.5.4. 2681.
Reactome	REACT_111217. Metabolism. REACT_15380. Diabetes pathways.
Gene expression databases
ArrayExpress	P08243.
Bgee	P08243.
CleanEx	HS_ASNS.
Genevestigator	P08243.
GermOnline	ENSG00000070669. Homo sapiens.
Family and domain databases
InterPro	IPR006426. Asn_synth_AEB. IPR001962. Asn_synthase. IPR000583. GATase_2. IPR017932. GATase_II. IPR014729. Rossmann-like_a/b/a_fold. [Graphical view]
Gene3D	G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.
KO	K01953.
Pfam	PF00733. Asn_synthase. 1 hit. PF00310. GATase_2. 1 hit. [Graphical view]
PIRSF	PIRSF001589. Asn_synthetase_glu-h. 1 hit.
TIGRFAMs	TIGR01536. Asn_synth_AEB. 1 hit.
PROSITE	PS51278. GATASE_TYPE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00171. Adenosine triphosphate. DB00174. L-Asparagine. DB00128. L-Aspartic Acid. DB00142. L-Glutamic Acid. DB00130. L-Glutamine.
NextBio	1843.
SOURCE	Search...

Entry information

Entry name

ASNS_HUMAN

Accession

Primary (citable) accession number: P08243
Secondary accession number(s): A4D1I8 , D6W5R3, P08184, Q15666, Q549T9, Q96HD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 135 of the entry and version 4 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.