Q7L266 (ASGL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Cleaved into the following 2 chains:

1. Isoaspartyl peptidase/L-asparaginase alpha chain
2. Isoaspartyl peptidase/L-asparaginase beta chain

Gene names

Name:	ASRGL1
Synonyms:	ALP, CRASH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	308 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)

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.6
Catalytic activity	L-asparagine + H2O = L-aspartate + NH3. Ref.6 Ref.8 Cleavage of a beta-linked Asp residue from the N-terminus of a polypeptide. Ref.6 Ref.8
Enzyme regulation	Glycine accelerates autocleavage into an alpha and beta chain. Ref.7
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.7 Ref.8
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.7
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.6 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease
PTM	Autocatalytic cleavage
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	asparagine catabolic process via L-aspartate Inferred from direct assay Ref.6. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB microtubule cytoskeleton Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	asparaginase activity Inferred from direct assay Ref.6. Source: UniProtKB beta-aspartyl-peptidase activity Inferred from direct assay Ref.6. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 167

167

Isoaspartyl peptidase/L-asparaginase alpha chain

PRO_0000305204

Chain

168 – 308

141

Isoaspartyl peptidase/L-asparaginase beta chain

PRO_0000420556

Regions

Region

196 – 199

4

Substrate binding

Region

219 – 222

4

Substrate binding

Sites

Active site

168

1

Nucleophile Ref.6 Ref.7

Natural variations

Alternative sequence

1 – 128

128

Missing in isoform 2.

VSP_028287

Experimental info

Mutagenesis

168

1

T → A or C: Abolishes activation by autocleavage. Abolishes enzyme activity. Ref.6 Ref.8

Mutagenesis

168

1

T → S: Strongly reduced enzyme activity. Ref.6 Ref.8

Sequence conflict

181

1

A → T in AAM28434. Ref.1

Secondary structure

1

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308

Helix Strand Turn

Details...

Beta strand

4 – 8

5

Helix

17 – 38

22

Turn

39 – 41

3

Helix

44 – 57

14

Beta strand

61 – 64

4

Beta strand

77 – 83

7

Turn

84 – 87

4

Beta strand

88 – 95

8

Helix

101 – 111

11

Beta strand

115 – 118

4

Helix

119 – 128

10

Helix

136 – 138

3

Helix

142 – 151

10

Beta strand

169 – 174

6

Beta strand

180 – 186

7

Turn

203 – 205

3

Beta strand

206 – 210

5

Turn

211 – 213

3

Beta strand

214 – 220

7

Helix

222 – 228

7

Helix

230 – 239

10

Helix

244 – 259

16

Beta strand

263 – 269

7

Beta strand

274 – 282

9

Beta strand

285 – 289

5

Beta strand

292 – 298

7

Beta strand

303 – 306

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: 84E3D6C2D1555B32	FASTA	308	32,055
	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
	Isoform 2 [UniParc]. Checksum: E21C4620A2261D0C	FASTA	180	18,981
	10 20 30 40 50 60 MGVPEIPGEK LVTERNKKRL EKEKHEKGAQ KTDCQKNLGT VGAVALDCKG NVAYATSTGG 70 80 90 100 110 120 IVNKMVGRVG DSPCLGAGGY ADNDIGAVST TGHGESILKV NLARLTLFHI EQGKTVEEAA 130 140 150 160 170 180 DLSLGYMKSR VKGLGGLIVV SKTGDWVAKW TSTSMPWAAA KDGKLHFGID PDDTTITDLP

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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, AUTOCLEAVAGE.
[7]	"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, AUTOCLEAVAGE.
[8]	"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.

IPI

IPI00555734.
IPI00867663.

RefSeq

NP_001077395.1. NM_001083926.1.
NP_079356.3. NM_025080.3.

UniGene

Hs.535326.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3TKJ	X-ray	2.30	A/B	2-308	[»]
4ET0	X-ray	3.30	A/B	2-308	[»]
4GDT	X-ray	1.85	A/B	1-308	[»]
4GDU	X-ray	2.13	A/B	1-308	[»]
4GDV	X-ray	1.75	A/B	1-308	[»]
4GDW	X-ray	1.84	A/B	1-308	[»]

ProteinModelPortal

Q7L266.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000301776.

Protein family/group databases

MEROPS

T02.002.

PTM databases

PhosphoSite

Q7L266.

Polymorphism databases

DMDM

158706477.

2D gel databases

UCD-2DPAGE

Q7L266.

Proteomic databases

PaxDb

Q7L266.

PRIDE

Q7L266.

Protocols and materials databases

DNASU

80150.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301776; ENSP00000301776; ENSG00000162174.
ENST00000415229; ENSP00000400057; ENSG00000162174.

GeneID

80150.

KEGG

hsa:80150.

UCSC

uc001nte.4. human.

Organism-specific databases

CTD

80150.

GeneCards

GC11P062104.

HGNC

HGNC:16448. ASRGL1.

HPA

HPA029725.

MIM

609212. gene.

neXtProt

NX_Q7L266.

PharmGKB

PA25059.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1446.

HOGENOM

HOG000174613.

HOVERGEN

HBG101662.

InParanoid

Q7L266.

KO

K13051.

OMA

AVVRGCQ.

OrthoDB

EOG4ZS93Q.

PhylomeDB

Q7L266.

Gene expression databases

ArrayExpress

Q7L266.

Bgee

Q7L266.

CleanEx

HS_ASRGL1.

Genevestigator

Q7L266.

Family and domain databases

InterPro

IPR000246. Peptidase_T2.
[Graphical view]

PANTHER

PTHR10188. PTHR10188. 1 hit.

Pfam

PF01112. Asparaginase_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ASRGL1. human.

DrugBank

DB00174. L-Asparagine.
DB00128. L-Aspartic Acid.

GenomeRNAi

80150.

NextBio

70434.

SOURCE

Search...

Entry information

Entry name

ASGL1_HUMAN

Accession

Primary (citable) accession number: Q7L266
Secondary accession number(s): B2R7Q0 , Q567Q4, Q6P1P0, Q8NI34, Q9H6F7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	April 3, 2007
Last modified:	May 1, 2013
This is version 83 of the entry and version 2 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.