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Reviewed, UniProtKB/Swiss-Prot P05089 (ARGI1_HUMAN)

Last modified July 7, 2009. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Arginase-1
    EC=3.5.3.1
Alternative name(s):
    Type I arginase
    Liver-type arginase
Gene names
Name: ARG1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length322 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

L-arginine + H2O = L-ornithine + urea.

Cofactor

Binds 2 manganese ions per subunit.

Pathway

Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1.

Subunit structure

Homotrimer. Ref.9 Ref.11

Subcellular location

Cytoplasm. Ref.9

Induction

By arginine or homoarginine.

Involvement in disease

Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:207800]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia. Ref.13 Ref.15

Sequence similarities

Belongs to the arginase family.

Ontologies

Keywords
   Biological processArginine metabolism
Urea cycle
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandManganese
Metal-binding
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processarginine catabolic process Ref.1

Traceable author statement. Source: ProtInc

urea cycle

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentcytoplasm Ref.1

Traceable author statement. Source: ProtInc

   Molecular functionarginase activity Ref.1

Traceable author statement. Source: ProtInc

manganese ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P05089-1)

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: P05089-2)

Also known as: Erythroid variant;

The sequence of this isoform differs from the canonical sequence as follows:
     43-43: Q → QVTQNFLIL
Note: May be due to a competing acceptor splice site. No experimental confirmation available.
Isoform 3 (identifier: P05089-3)

The sequence of this isoform differs from the canonical sequence as follows:
     204-289: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 322322Arginase-1
PRO_0000173693

Regions

Region126 – 1305Substrate binding
Region137 – 1393Substrate binding

Sites

Metal binding1011Manganese 1
Metal binding1241Manganese 1
Metal binding1241Manganese 2
Metal binding1261Manganese 2
Metal binding1281Manganese 1
Metal binding2321Manganese 1
Metal binding2321Manganese 2
Metal binding2341Manganese 2
Binding site1831Substrate

Amino acid modifications

Modified residue2301Phosphoserine By similarity

Natural variations

Alternative sequence431Q → QVTQNFLIL in isoform 2.
VSP_009330
Alternative sequence204 – 28986Missing in isoform 3.
VSP_009331
Natural variant111I → T in ARGIN; 12% of wild-type activity.
VAR_015594
Natural variant1381G → V in ARGIN.
VAR_015595
Natural variant2351G → R in ARGIN.
VAR_000674
Natural variant2901T → S Could be a polymorphism. Ref.14
VAR_000675

Experimental info

Sequence conflict481K → E in AAL71547. Ref.3
Sequence conflict861E → Q in AAA51776. Ref.1
Sequence conflict2021E → K in AAL71547. Ref.3

Secondary structure

...................................................... 322
Helix Strand Turn

Details...

Sequences

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

Last modified January 11, 2001. Version 2.
Checksum: 8F3BE2652243F622

FASTA32234,735
        10         20         30         40         50         60 
MSAKSRTIGI IGAPFSKGQP RGGVEEGPTV LRKAGLLEKL KEQECDVKDY GDLPFADIPN 

        70         80         90        100        110        120 
DSPFQIVKNP RSVGKASEQL AGKVAEVKKN GRISLVLGGD HSLAIGSISG HARVHPDLGV 

       130        140        150        160        170        180 
IWVDAHTDIN TPLTTTSGNL HGQPVSFLLK ELKGKIPDVP GFSWVTPCIS AKDIVYIGLR 

       190        200        210        220        230        240 
DVDPGEHYIL KTLGIKYFSM TEVDRLGIGK VMEETLSYLL GRKKRPIHLS FDVDGLDPSF 

       250        260        270        280        290        300 
TPATGTPVVG GLTYREGLYI TEEIYKTGLL SGLDIMEVNP SLGKTPEEVT RTVNTAVAIT 

       310        320 
LACFGLAREG NHKPIDYLNP PK 

« Hide

Isoform 2 (Erythroid variant).

Checksum: 3547D8B6C254179B
Show »

FASTA33035,664
Isoform 3.

Checksum: 79F02C69B700AB67
Show »

FASTA23625,356

References

« Hide 'large scale' references
[1]"Molecular cloning and nucleotide sequence of cDNA for human liver arginase."
Haraguchi Y., Takiguchi M., Amaya Y., Kawamoto S., Matsuda I., Mori M.
Proc. Natl. Acad. Sci. U.S.A. 84:412-415(1987) [PubMed: 3540966] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"Human liver-type arginase gene: structure of the gene and analysis of the promoter region."
Takiguchi M., Haraguchi Y., Mori M.
Nucleic Acids Res. 16:8789-8802(1988) [PubMed: 3174433] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Blood.
[3]Lee Y.T., Miller J.L.
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Erythroblast.
[4]"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] (ISOFORM 3).
[5]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed: 14574404] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 1 AND 3).
Tissue: Liver and Skeletal muscle.
[7]"Expression of human liver arginase in Escherichia coli. Purification and properties of the product."
Ikemoto M., Tabata M., Miyake T., Kono T., Mori M., Totani M., Murachi T.
Biochem. J. 270:697-703(1990) [PubMed: 2241902] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 1-13, CHARACTERIZATION.
Tissue: Liver.
[8]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]"Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response."
Di Costanzo L., Sabio G., Mora A., Rodriguez P.C., Ochoa A.C., Centeno F., Christianson D.W.
Proc. Natl. Acad. Sci. U.S.A. 102:13058-13063(2005) [PubMed: 16141327] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.29 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THE SYNTHETIC INHIBITOR 2(S)-AMINO-6-BORONOHEXANOIC ACID, SUBCELLULAR LOCATION, SUBUNIT.
[10]"Expression, purification, assay, and crystal structure of perdeuterated human arginase I."
Di Costanzo L., Moulin M., Haertlein M., Meilleur F., Christianson D.W.
Arch. Biochem. Biophys. 465:82-89(2007) [PubMed: 17562323] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THE SYNTHETIC INHIBITOR 2(S)-AMINO-6-BORONOHEXANOIC ACID, MASS SPECTROMETRY.
[11]"Crystal structure of human arginase I complexed with thiosemicarbazide reveals an unusual thiocarbonyl mu-sulfide ligand in the binuclear manganese cluster."
Di Costanzo L., Pique M.E., Christianson D.W.
J. Am. Chem. Soc. 129:6388-6389(2007) [PubMed: 17469833] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THIOSEMICARBAZIDE, SUBUNIT.
[12]"Synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid and structure of its metal-bridging complex with human arginase I."
Zakharian T.Y., Di Costanzo L., Christianson D.W.
Org. Biomol. Chem. 6:3240-3243(2008) [PubMed: 18802628] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS AND THE SYNTHETIC INHIBITOR (2S)-2-AMINO-7,8-EPOXYOCTANOIC ACID.
[13]"Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia."
Uchino T., Haraguchi Y., Aparicio J.M., Mizutani N., Higashikawa M., Naitoh H., Mori M., Matsuda I.
Am. J. Hum. Genet. 51:1406-1412(1992) [PubMed: 1463019] [Abstract]
Cited for: VARIANT ARGIN ARG-235.
[14]"Molecular genetic study of human arginase deficiency."
Grody W.W., Klein D., Dodson A.E., Kern R.M., Wissmann P.B., Goodman B.K., Bassand P., Marescau B., Kang S.-S., Leonard J.V., Cederbaum S.D.
Am. J. Hum. Genet. 50:1281-1290(1992) [PubMed: 1598908] [Abstract]
Cited for: VARIANT SER-290.
[15]"Molecular basis of phenotypic variation in patients with argininemia."
Uchino T., Snyderman S.E., Lambert M., Qureshi I.A., Shapira S.K., Sansaricq C., Smit L.M.E., Jakobs C., Matsuda I.
Hum. Genet. 96:255-260(1995) [PubMed: 7649538] [Abstract]
Cited for: VARIANTS ARGIN THR-11 AND VAL-138.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

M14502 mRNA. Translation: AAA51776.1.
X12662 expand/collapse EMBL AC list , X12663, X12664, X12665, X12666, X12667, X12668, X12669 Genomic DNA. Translation: CAA31188.1.
AY074488 mRNA. Translation: AAL71547.1.
BT006741 mRNA. Translation: AAP35387.1.
AL121575 Genomic DNA. Translation: CAB92071.1.
AL121575 Genomic DNA. Translation: CAI23317.1.
AL121575 Genomic DNA. Translation: CAI23318.1.
BC005321 mRNA. Translation: AAH05321.1.
BC020653 mRNA. Translation: AAH20653.1.
IPIIPI00038356.
IPI00291560.
IPI00398768.
PIRA26370. S02132.
RefSeqNP_000036.2.
UniGeneHs.440934

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1WVAX-ray1.94A/B1-322[»]
1WVBX-ray2.30A/B1-322[»]
2AEBX-ray1.29A/B1-322[»]
2PHAX-ray1.90A/B1-322[»]
2PHOX-ray1.95A/B1-322[»]
2PLLX-ray1.90A/B1-322[»]
2ZAVX-ray1.70A/B1-322[»]
3DJ8X-ray1.51A/B1-322[»]
3E6KX-ray2.10A/B1-322[»]
3E6VX-ray1.72A/B1-322[»]
3F80X-ray1.60A/B1-322[»]
ModBaseSearch...

PTM databases

PhosphoSiteP05089.

Proteomic databases

PRIDEP05089.

Genome annotation databases

EnsemblENSG00000118520. Homo sapiens. [Contig view]
GeneID383.
KEGGhsa:383.
UCSCuc003qcp.1. human.
uc010kfm.1. human.

Organism-specific databases

GeneCardsGC06P131936.
H-InvDBHIX0006220.
HGNCHGNC:663. ARG1.
HPACAB009434.
HPA003595.
MIM207800. phenotype.
608313. gene.
Orphanet90. Argininemia.
PharmGKBPA24947.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP05089.
OMAP05089. QIVKNPR.

Enzyme and pathway databases

BioCycMetaCyc:MON-11284.
BRENDA3.5.3.1. 247.
Pathway_Interaction_DBil4_2pathway. IL4-mediated signaling events.
ReactomeREACT_13. Metabolism of amino acids.

Gene expression databases

ArrayExpressP05089.
BgeeP05089.
CleanExHS_ARG1.
GermOnlineENSG00000118520. Homo sapiens.

Family and domain databases

InterProIPR005924. Arginase.
IPR014033. Arginase_sub.
IPR006035. Ureohydrolase.
[Graphical view]
Gene3DG3DSA:3.40.800.10. Ureohydrolase. 1 hit.
PANTHERPTHR11358:SF2. Arginase_sub. 1 hit.
PTHR11358. Ureohydrolase. 1 hit.
PfamPF00491. Arginase. 1 hit.
[Graphical view]
PRINTSPR00116. ARGINASE.
TIGRFAMsTIGR01229. rocF_arginase. 1 hit.
PROSITEPS01053. ARGINASE_1. 1 hit.
PS51409. ARGINASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00129. L-Ornithine.
NextBio1603.
SOURCESearch...

Entry information

Entry nameARGI1_HUMAN
AccessionPrimary (citable) accession number: P05089
Secondary accession number(s): A6NEA0 expand/collapse secondary AC list , Q5JWT5, Q5JWT6, Q8TE72, Q9BS50
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 11, 2001
Last modified: July 7, 2009
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents