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Protein

Asparagine synthetase [glutamine-hydrolyzing]

Gene

ASNS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

ATP + L-aspartate + L-glutamine + H2O = AMP + diphosphate + L-asparagine + L-glutamate.1 Publication

Pathwayi: L-asparagine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-asparagine from L-aspartate (L-Gln route).
Proteins known to be involved in this subpathway in this organism are:
  1. Asparagine synthetase [glutamine-hydrolyzing] (ASNS)
This subpathway is part of the pathway L-asparagine biosynthesis, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-asparagine from L-aspartate (L-Gln route), the pathway L-asparagine biosynthesis and in Amino-acid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2For GATase activity2 Publications1
Binding sitei97GlutamineBy similarity1
Binding sitei256ATP; via carbonyl oxygenBy similarity1
Binding sitei288ATP; via amide nitrogen and carbonyl oxygenBy similarity1
Sitei365Important for beta-aspartyl-AMP intermediate formationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi363 – 364ATPBy similarity2

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Amino-acid biosynthesis, Asparagine biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01002-MONOMER.
BRENDAi6.3.5.4. 2681.
ReactomeiR-HSA-380994. ATF4 activates genes.
R-HSA-70614. Amino acid synthesis and interconversion (transamination).
UniPathwayiUPA00134; UER00195.

Protein family/group databases

MEROPSiC44.974.

Names & Taxonomyi

Protein namesi
Recommended name:
Asparagine synthetase [glutamine-hydrolyzing] (EC:6.3.5.4)
Alternative name(s):
Cell cycle control protein TS11
Glutamine-dependent asparagine synthetase
Gene namesi
Name:ASNS
Synonyms:TS11
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:753. ASNS.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Asparagine synthetase deficiency (ASNSD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn inborn error of asparagine biosynthesis that results in a severe neurologic disorder characterized by microcephaly, severely delayed psychomotor development, progressive encephalopathy, cortical atrophy, and seizure or hyperekplexic activity.
See also OMIM:615574
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0708966A → E in ASNSD; dramatic reduction in protein abundance. 1 PublicationCorresponds to variant rs398122975dbSNPEnsembl.1
Natural variantiVAR_070897362F → V in ASNSD; dramatic reduction in protein abundance. 1 PublicationCorresponds to variant rs398122973dbSNPEnsembl.1
Natural variantiVAR_070898550R → C in ASNSD; increases level of protein abundance. 1 PublicationCorresponds to variant rs398122974dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2C → A: Loss of the glutamine-dependent asparagine synthetase activity, while the ammonia-dependent activity remained unaffected. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi440.
MalaCardsiASNS.
MIMi615574. phenotype.
OpenTargetsiENSG00000070669.
Orphaneti391376. Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome.
PharmGKBiPA25052.

Chemistry databases

ChEMBLiCHEMBL3120.
DrugBankiDB00171. Adenosine triphosphate.
DB00174. L-Asparagine.
DB00128. L-Aspartic Acid.
DB00130. L-Glutamine.

Polymorphism and mutation databases

BioMutaiASNS.
DMDMi13432102.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000569102 – 561Asparagine synthetase [glutamine-hydrolyzing]Add BLAST560

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei385N6-acetyllysineCombined sources1
Modified residuei545PhosphothreonineCombined sources1
Modified residuei557PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP08243.
MaxQBiP08243.
PaxDbiP08243.
PeptideAtlasiP08243.
PRIDEiP08243.

PTM databases

iPTMnetiP08243.
PhosphoSitePlusiP08243.
SwissPalmiP08243.

Expressioni

Gene expression databases

BgeeiENSG00000070669.
CleanExiHS_ASNS.
ExpressionAtlasiP08243. baseline and differential.
GenevisibleiP08243. HS.

Organism-specific databases

HPAiHPA029318.
HPA064737.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TRIM69Q86WT63EBI-722989,EBI-749955
WDR27A2RRH53EBI-722989,EBI-9476803

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106932. 82 interactors.
IntActiP08243. 9 interactors.
MINTiMINT-1371662.
STRINGi9606.ENSP00000175506.

Chemistry databases

BindingDBiP08243.

Structurei

3D structure databases

ProteinModelPortaliP08243.
SMRiP08243.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 191Glutamine amidotransferase type-2PROSITE-ProRule annotationAdd BLAST190
Domaini213 – 536Asparagine synthetaseAdd BLAST324

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni49 – 53Glutamine bindingBy similarity5
Regioni75 – 77Glutamine bindingBy similarity3

Sequence similaritiesi

Contains 1 asparagine synthetase domain.Curated
Contains 1 glutamine amidotransferase type-2 domain.PROSITE-ProRule annotation

Keywords - Domaini

Glutamine amidotransferase

Phylogenomic databases

eggNOGiKOG0571. Eukaryota.
COG0367. LUCA.
GeneTreeiENSGT00390000001994.
HOGENOMiHOG000027493.
HOVERGENiHBG003103.
InParanoidiP08243.
KOiK01953.
OMAiDWSGIYS.
OrthoDBiEOG091G13BD.
PhylomeDBiP08243.
TreeFamiTF300603.

Family and domain databases

CDDicd01991. Asn_Synthase_B_C. 1 hit.
cd00712. AsnB. 1 hit.
Gene3Di3.40.50.620. 1 hit.
3.60.20.10. 1 hit.
InterProiIPR006426. Asn_synth_AEB.
IPR001962. Asn_synthase.
IPR033738. AsnB_N.
IPR017932. GATase_2_dom.
IPR029055. Ntn_hydrolases_N.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamiPF00733. Asn_synthase. 1 hit.
PF13537. GATase_7. 1 hit.
[Graphical view]
SUPFAMiSSF56235. SSF56235. 1 hit.
TIGRFAMsiTIGR01536. asn_synth_AEB. 1 hit.
PROSITEiPS51278. GATASE_TYPE_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P08243-1) [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
MCGIWALFGS DDCLSVQCLS AMKIAHRGPD AFRFENVNGY TNCCFGFHRL
60 70 80 90 100
AVVDPLFGMQ PIRVKKYPYL WLCYNGEIYN HKKMQQHFEF EYQTKVDGEI
110 120 130 140 150
ILHLYDKGGI EQTICMLDGV FAFVLLDTAN KKVFLGRDTY GVRPLFKAMT
160 170 180 190 200
EDGFLAVCSE AKGLVTLKHS ATPFLKVEPF LPGHYEVLDL KPNGKVASVE
210 220 230 240 250
MVKYHHCRDV PLHALYDNVE KLFPGFEIET VKNNLRILFN NAVKKRLMTD
260 270 280 290 300
RRIGCLLSGG LDSSLVAATL LKQLKEAQVQ YPLQTFAIGM EDSPDLLAAR
310 320 330 340 350
KVADHIGSEH YEVLFNSEEG IQALDEVIFS LETYDITTVR ASVGMYLISK
360 370 380 390 400
YIRKNTDSVV IFSGEGSDEL TQGYIYFHKA PSPEKAEEES ERLLRELYLF
410 420 430 440 450
DVLRADRTTA AHGLELRVPF LDHRFSSYYL SLPPEMRIPK NGIEKHLLRE
460 470 480 490 500
TFEDSNLIPK EILWRPKEAF SDGITSVKNS WFKILQEYVE HQVDDAMMAN
510 520 530 540 550
AAQKFPFNTP KTKEGYYYRQ VFERHYPGRA DWLSHYWMPK WINATDPSAR
560
TLTHYKSAVK A
Length:561
Mass (Da):64,370
Last modified:January 23, 2007 - v4
Checksum:i3E9B75E21D799FBE
GO
Isoform 2 (identifier: P08243-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Note: No experimental confirmation available.
Show »
Length:540
Mass (Da):62,168
Checksum:i7531F53E232D5AB0
GO
Isoform 3 (identifier: P08243-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-83: Missing.

Note: No experimental confirmation available.
Show »
Length:478
Mass (Da):54,818
Checksum:iF8AE4D4375F38522
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti333 – 343TYDITTVRASV → LMTLQQFVLRI in AAA36781 (PubMed:3470743).CuratedAdd BLAST11
Sequence conflicti353 – 360RKNTDSVV → GRTQIAWL in AAA36781 (PubMed:3470743).Curated8
Sequence conflicti426S → F (PubMed:2886907).Curated1
Sequence conflicti426S → F (PubMed:2565875).Curated1
Sequence conflicti462I → V in BAG63553 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0708966A → E in ASNSD; dramatic reduction in protein abundance. 1 PublicationCorresponds to variant rs398122975dbSNPEnsembl.1
Natural variantiVAR_023443210V → E.5 PublicationsCorresponds to variant rs1049674dbSNPEnsembl.1
Natural variantiVAR_070897362F → V in ASNSD; dramatic reduction in protein abundance. 1 PublicationCorresponds to variant rs398122973dbSNPEnsembl.1
Natural variantiVAR_070898550R → C in ASNSD; increases level of protein abundance. 1 PublicationCorresponds to variant rs398122974dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0458171 – 83Missing in isoform 3. 1 PublicationAdd BLAST83
Alternative sequenceiVSP_0458181 – 21Missing in isoform 2. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK302189 mRNA. Translation: BAG63553.1.
AK316224 mRNA. Translation: BAH14595.1.
AC005326 Genomic DNA. No translation available.
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.
CCDSiCCDS55131.1. [P08243-3]
CCDS55132.1. [P08243-2]
CCDS5652.1. [P08243-1]
PIRiA27062. AJHUN1.
RefSeqiNP_001171546.1. NM_001178075.1. [P08243-2]
NP_001171547.1. NM_001178076.1. [P08243-3]
NP_001171548.1. NM_001178077.1. [P08243-3]
NP_001664.3. NM_001673.4. [P08243-1]
NP_597680.2. NM_133436.3. [P08243-1]
NP_899199.2. NM_183356.3. [P08243-1]
UniGeneiHs.489207.

Genome annotation databases

EnsembliENST00000175506; ENSP00000175506; ENSG00000070669. [P08243-1]
ENST00000394308; ENSP00000377845; ENSG00000070669. [P08243-1]
ENST00000394309; ENSP00000377846; ENSG00000070669. [P08243-1]
ENST00000422745; ENSP00000414901; ENSG00000070669. [P08243-2]
ENST00000437628; ENSP00000414379; ENSG00000070669. [P08243-3]
ENST00000444334; ENSP00000406994; ENSG00000070669. [P08243-2]
ENST00000455086; ENSP00000408472; ENSG00000070669. [P08243-3]
GeneIDi440.
KEGGihsa:440.
UCSCiuc003uot.5. human. [P08243-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AK302189 mRNA. Translation: BAG63553.1.
AK316224 mRNA. Translation: BAH14595.1.
AC005326 Genomic DNA. No translation available.
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.
CCDSiCCDS55131.1. [P08243-3]
CCDS55132.1. [P08243-2]
CCDS5652.1. [P08243-1]
PIRiA27062. AJHUN1.
RefSeqiNP_001171546.1. NM_001178075.1. [P08243-2]
NP_001171547.1. NM_001178076.1. [P08243-3]
NP_001171548.1. NM_001178077.1. [P08243-3]
NP_001664.3. NM_001673.4. [P08243-1]
NP_597680.2. NM_133436.3. [P08243-1]
NP_899199.2. NM_183356.3. [P08243-1]
UniGeneiHs.489207.

3D structure databases

ProteinModelPortaliP08243.
SMRiP08243.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106932. 82 interactors.
IntActiP08243. 9 interactors.
MINTiMINT-1371662.
STRINGi9606.ENSP00000175506.

Chemistry databases

BindingDBiP08243.
ChEMBLiCHEMBL3120.
DrugBankiDB00171. Adenosine triphosphate.
DB00174. L-Asparagine.
DB00128. L-Aspartic Acid.
DB00130. L-Glutamine.

Protein family/group databases

MEROPSiC44.974.

PTM databases

iPTMnetiP08243.
PhosphoSitePlusiP08243.
SwissPalmiP08243.

Polymorphism and mutation databases

BioMutaiASNS.
DMDMi13432102.

Proteomic databases

EPDiP08243.
MaxQBiP08243.
PaxDbiP08243.
PeptideAtlasiP08243.
PRIDEiP08243.

Protocols and materials databases

DNASUi440.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000175506; ENSP00000175506; ENSG00000070669. [P08243-1]
ENST00000394308; ENSP00000377845; ENSG00000070669. [P08243-1]
ENST00000394309; ENSP00000377846; ENSG00000070669. [P08243-1]
ENST00000422745; ENSP00000414901; ENSG00000070669. [P08243-2]
ENST00000437628; ENSP00000414379; ENSG00000070669. [P08243-3]
ENST00000444334; ENSP00000406994; ENSG00000070669. [P08243-2]
ENST00000455086; ENSP00000408472; ENSG00000070669. [P08243-3]
GeneIDi440.
KEGGihsa:440.
UCSCiuc003uot.5. human. [P08243-1]

Organism-specific databases

CTDi440.
DisGeNETi440.
GeneCardsiASNS.
HGNCiHGNC:753. ASNS.
HPAiHPA029318.
HPA064737.
MalaCardsiASNS.
MIMi108370. gene.
615574. phenotype.
neXtProtiNX_P08243.
OpenTargetsiENSG00000070669.
Orphaneti391376. Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome.
PharmGKBiPA25052.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0571. Eukaryota.
COG0367. LUCA.
GeneTreeiENSGT00390000001994.
HOGENOMiHOG000027493.
HOVERGENiHBG003103.
InParanoidiP08243.
KOiK01953.
OMAiDWSGIYS.
OrthoDBiEOG091G13BD.
PhylomeDBiP08243.
TreeFamiTF300603.

Enzyme and pathway databases

UniPathwayiUPA00134; UER00195.
BioCyciZFISH:HS01002-MONOMER.
BRENDAi6.3.5.4. 2681.
ReactomeiR-HSA-380994. ATF4 activates genes.
R-HSA-70614. Amino acid synthesis and interconversion (transamination).

Miscellaneous databases

GenomeRNAii440.
PROiP08243.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000070669.
CleanExiHS_ASNS.
ExpressionAtlasiP08243. baseline and differential.
GenevisibleiP08243. HS.

Family and domain databases

CDDicd01991. Asn_Synthase_B_C. 1 hit.
cd00712. AsnB. 1 hit.
Gene3Di3.40.50.620. 1 hit.
3.60.20.10. 1 hit.
InterProiIPR006426. Asn_synth_AEB.
IPR001962. Asn_synthase.
IPR033738. AsnB_N.
IPR017932. GATase_2_dom.
IPR029055. Ntn_hydrolases_N.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PfamiPF00733. Asn_synthase. 1 hit.
PF13537. GATase_7. 1 hit.
[Graphical view]
SUPFAMiSSF56235. SSF56235. 1 hit.
TIGRFAMsiTIGR01536. asn_synth_AEB. 1 hit.
PROSITEiPS51278. GATASE_TYPE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiASNS_HUMAN
AccessioniPrimary (citable) accession number: P08243
Secondary accession number(s): A4D1I8
, B4DXZ1, B7ZAA9, D6W5R3, E9PCI3, E9PCX6, P08184, Q15666, Q549T9, Q96HD0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 188 of the entry and version 4 of the sequence. [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 7
    Human chromosome 7: 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

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.