Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q7L266 (ASGL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Isoaspartyl peptidase/L-asparaginase

EC=3.4.19.5
EC=3.5.1.1
Alternative name(s):
Asparaginase-like protein 1
Beta-aspartyl-peptidase
Isoaspartyl dipeptidase
L-asparagine amidohydrolase
Gene names
Name:ASRGL1
Synonyms:ALP, CRASH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length308 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine. Ref.7

Catalytic activity

L-asparagine + H2O = L-aspartate + NH3. Ref.7 Ref.9

Cleavage of a beta-linked Asp residue from the N-terminus of a polypeptide. Ref.7 Ref.9

Enzyme regulation

Glycine accelerates autocleavage into an alpha and beta chain. Ref.8

Subunit structure

Heterodimer of an alpha and beta chain produced by autocleavage. This heterodimer may then dimerize in turn, giving rise to a heterotetramer. Ref.8 Ref.9

Subcellular location

Cytoplasm. Note: Midpiece of sperm tail. Ref.1

Tissue specificity

Expressed in brain, kidney, testis and tissues of the gastrointestinal tract. Present in sperm (at protein level). Over-expressed in uterine, mammary, prostatic and ovarian carcinoma. Ref.1 Ref.2

Induction

By 5-alpha-di-hydrotestosterone and progesterone. Ref.2 Ref.8

Post-translational modification

Cleaved into an alpha and beta chain by autocatalysis; this activates the enzyme. The N-terminal residue of the beta subunit is responsible for the nucleophile hydrolase activity.

Sequence similarities

Belongs to the Ntn-hydrolase family.

Biophysicochemical properties

Kinetic parameters:

KM=3.4 mM for L-asparagine (L-Asn) Ref.7

KM=0.4 mM for L-aspartic acid beta-methyl ester

KM=0.4 mM for L-Asp-L-Phe

KM=1.0 mM for L-Asp-L-Ala

Sequence caution

The sequence BAB15302.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAB15302.1 differs from that shown. Reason: Contaminating sequence.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7L266-1)

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.
Isoform 2 (identifier: Q7L266-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-128: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 167167Isoaspartyl peptidase/L-asparaginase alpha chain
PRO_0000305204
Chain168 – 308141Isoaspartyl peptidase/L-asparaginase beta chain
PRO_0000420556

Regions

Region196 – 1994Substrate binding
Region219 – 2224Substrate binding

Sites

Active site1681Nucleophile Ref.7 Ref.8

Amino acid modifications

Modified residue11N-acetylmethionine Ref.6

Natural variations

Alternative sequence1 – 128128Missing in isoform 2.
VSP_028287

Experimental info

Mutagenesis1681T → A or C: Abolishes activation by autocleavage. Abolishes enzyme activity. Ref.7 Ref.9
Mutagenesis1681T → S: Strongly reduced enzyme activity. Ref.7 Ref.9
Sequence conflict1811A → T in AAM28434. Ref.1

Secondary structure

................................................ 308
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 3, 2007. Version 2.
Checksum: 84E3D6C2D1555B32

FASTA30832,055
        10         20         30         40         50         60 
MNPIVVVHGG GAGPISKDRK ERVHQGMVRA ATVGYGILRE GGSAVDAVEG AVVALEDDPE 

        70         80         90        100        110        120 
FNAGCGSVLN TNGEVEMDAS IMDGKDLSAG AVSAVQCIAN PIKLARLVME KTPHCFLTDQ 

       130        140        150        160        170        180 
GAAQFAAAMG VPEIPGEKLV TERNKKRLEK EKHEKGAQKT DCQKNLGTVG AVALDCKGNV 

       190        200        210        220        230        240 
AYATSTGGIV NKMVGRVGDS PCLGAGGYAD NDIGAVSTTG HGESILKVNL ARLTLFHIEQ 

       250        260        270        280        290        300 
GKTVEEAADL SLGYMKSRVK GLGGLIVVSK TGDWVAKWTS TSMPWAAAKD GKLHFGIDPD 


DTTITDLP 

« Hide

Isoform 2 [UniParc].

Checksum: E21C4620A2261D0C
Show »

FASTA18018,981

References

« Hide 'large scale' references
[1]"A novel asparaginase-like protein is a sperm autoantigen in rats."
Bush L.A., Herr J.C., Wolkowicz M., Sherman N.E., Shore A., Flickinger C.J.
Mol. Reprod. Dev. 62:233-247(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
Tissue: Testis.
[2]"Identification of CRASH, a gene deregulated in gynecological tumors."
Evtimova V., Zeillinger R., Kaul S., Weidle U.H.
Int. J. Oncol. 24:33-41(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION.
[3]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Corpus callosum.
[4]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. expand/collapse author list , 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].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Eye, Lung and Skin.
[6]"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] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"The human asparaginase-like protein 1 hASRGL1 is an Ntn hydrolase with beta-aspartyl peptidase activity."
Cantor J.R., Stone E.M., Chantranupong L., Georgiou G.
Biochemistry 48:11026-11031(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, MUTAGENESIS OF THR-168, MASS SPECTROMETRY, AUTOCATALYTIC CLEAVAGE.
[8]"Structures of apo and product-bound human L-asparaginase: insights into the mechanism of autoproteolysis and substrate hydrolysis."
Nomme J., Su Y., Konrad M., Lavie A.
Biochemistry 51:6816-6826(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEXES WITH ASPARTATE, ACTIVE SITE, SUBUNIT, ENZYME REGULATION, AUTOCATALYTIC CLEAVAGE.
[9]"Uncoupling intramolecular processing and substrate hydrolysis in the N-terminal nucleophile hydrolase hASRGL1 by circular permutation."
Li W., Cantor J.R., Yogesha S.D., Yang S., Chantranupong L., Liu J.Q., Agnello G., Georgiou G., Stone E.M., Zhang Y.
ACS Chem. Biol. 7:1840-1847(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS), CATALYTIC ACTIVITY, MUTAGENESIS OF THR-168, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF411076 mRNA. Translation: AAM28434.1.
AK025969 mRNA. Translation: BAB15302.1. Different initiation.
AK091894 mRNA. Translation: BAG52437.1.
AK313069 mRNA. Translation: BAG35897.1.
CH471076 Genomic DNA. Translation: EAW74012.1.
BC021295 mRNA. Translation: AAH21295.3.
BC064963 mRNA. Translation: AAH64963.1.
BC093070 mRNA. Translation: AAH93070.1.
RefSeqNP_001077395.1. NM_001083926.1.
NP_079356.3. NM_025080.3.
XP_005274362.1. XM_005274305.1.
XP_005274363.1. XM_005274306.1.
UniGeneHs.535326.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3TKJX-ray2.30A/B2-308[»]
4ET0X-ray3.30A/B2-308[»]
4GDTX-ray1.85A/B1-308[»]
4GDUX-ray2.13A/B1-308[»]
4GDVX-ray1.75A/B1-308[»]
4GDWX-ray1.84A/B1-308[»]
4HLOX-ray1.95A/B1-308[»]
4HLPX-ray1.91A/B1-308[»]
ProteinModelPortalQ7L266.
SMRQ7L266. Positions 1-308.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123142. 5 interactions.
IntActQ7L266. 4 interactions.
STRING9606.ENSP00000301776.

Chemistry

DrugBankDB00174. L-Asparagine.
DB00128. L-Aspartic Acid.

Protein family/group databases

MEROPST02.002.

PTM databases

PhosphoSiteQ7L266.

Polymorphism databases

DMDM158706477.

2D gel databases

UCD-2DPAGEQ7L266.

Proteomic databases

PaxDbQ7L266.
PRIDEQ7L266.

Protocols and materials databases

DNASU80150.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301776; ENSP00000301776; ENSG00000162174. [Q7L266-1]
ENST00000415229; ENSP00000400057; ENSG00000162174. [Q7L266-1]
GeneID80150.
KEGGhsa:80150.
UCSCuc001nte.4. human. [Q7L266-1]

Organism-specific databases

CTD80150.
GeneCardsGC11P062104.
HGNCHGNC:16448. ASRGL1.
HPAHPA029725.
MIM609212. gene.
neXtProtNX_Q7L266.
PharmGKBPA25059.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1446.
HOGENOMHOG000174613.
HOVERGENHBG101662.
InParanoidQ7L266.
KOK13051.
OMADECLAAK.
OrthoDBEOG7TBC2N.
PhylomeDBQ7L266.
TreeFamTF323960.

Gene expression databases

ArrayExpressQ7L266.
BgeeQ7L266.
CleanExHS_ASRGL1.
GenevestigatorQ7L266.

Family and domain databases

InterProIPR000246. Peptidase_T2.
[Graphical view]
PANTHERPTHR10188. PTHR10188. 1 hit.
PfamPF01112. Asparaginase_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSASRGL1. human.
GeneWikiASRGL1.
GenomeRNAi80150.
NextBio70434.
PROQ7L266.
SOURCESearch...

Entry information

Entry nameASGL1_HUMAN
AccessionPrimary (citable) accession number: Q7L266
Secondary accession number(s): B2R7Q0 expand/collapse secondary AC list , Q567Q4, Q6P1P0, Q8NI34, Q9H6F7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: April 3, 2007
Last modified: March 19, 2014
This is version 92 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM