O95865 (DDAH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2
Short name=DDAH-2
Short name=Dimethylarginine dimethylaminohydrolase 2
EC=3.5.3.18

Alternative name(s):
DDAHII
Dimethylargininase-2
Protein G6a
S-phase protein

Gene names

Name:	DDAH2
Synonyms:	DDAH, G6A, NG30

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	285 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation. Ref.1
Catalytic activity	N(omega),N(omega)-dimethyl-L-arginine + H2O = dimethylamine + L-citrulline. Ref.1
Subcellular location	Cytoplasm. Mitochondrion. Note: Translocates from cytosol to mitochondrion upon IL-1beta stimulation in chondrocytes. Ref.12
Tissue specificity	Detected in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas, and at very low levels in brain. Ref.1
Sequence similarities	Belongs to the DDAH family.

Ontologies

Keywords
Cellular component	Cytoplasm Mitochondrion
Molecular function	Hydrolase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	arginine catabolic process Traceable author statement Ref.1. Source: ProtInc citrulline metabolic process Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of apoptotic process Traceable author statement PubMed 16130169. Source: UniProtKB nitric oxide biosynthetic process Traceable author statement Ref.1. Source: ProtInc nitric oxide mediated signal transduction Traceable author statement Ref.1. Source: ProtInc positive regulation of nitric oxide biosynthetic process Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	amino acid binding Inferred from electronic annotation. Source: Compara dimethylargininase activity Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TRIP13	Q15645	3	EBI-749139,EBI-358993

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 285	285	N(G),N(G)-dimethylarginine dimethylaminohydrolase 2		PRO_0000171121
Sites
	Active site	171	1	Proton donor By similarity
	Active site	276	1	Nucleophile Potential

Sequences

	Sequence		Length	Mass (Da)
	O95865 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: B3D9B00F29492548	FASTA	285	29,644
	10 20 30 40 50 60 MGTPGEGLGR CSHALIRGVP ESLASGEGAG AGLPALDLAK AQREHGVLGG KLRQRLGLQL 70 80 90 100 110 120 LELPPEESLP LGPLLGDTAV IQGDTALITR PWSPARRPEV DGVRKALQDL GLRIVEIGDE 130 140 150 160 170 180 NATLDGTDVL FTGREFFVGL SKWTNHRGAE IVADTFRDFA VSTVPVSGPS HLRGLCGMGG 190 200 210 220 230 240 PRTVVAGSSD AAQKAVRAMA VLTDHPYASL TLPDDAAADC LFLRPGLPGV PPFLLHRGGG 250 260 270 280 DLPNSQEALQ KLSDVTLVPV SCSELEKAGA GLSSLCLVLS TRPHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases." Leiper J.M., Santa Maria J., Chubb A., MacAllister R.J., Charles I.G., Whitley G.S., Vallance P. Biochem. J. 343:209-214(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY.
[2]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[3]	"Genes encoding three new members of the leukocyte antigen 6 superfamily and a novel member of Ig superfamily, together with genes encoding the regulatory nuclear chloride ion channel protein (hRNCC) and an N omega-N omega-dimethylarginine dimethylaminohydrolase homologue, are found in a 30-kb segment of the MHC class III region." Ribas G., Neville M., Wixon J.L., Cheng J., Campbell R.D. J. Immunol. 163:278-287(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	Yu L. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse." Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L. Genome Res. 13:2621-2636(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region." Shiina S., Tamiya G., Oka A., Inoko H. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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. , 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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]. Tissue: Placenta.
[10]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 18-40; 113-134; 148-173 AND 268-285, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[11]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Dimethylarginine dimethylaminohydrolase 2, a newly identified mitochondrial protein modulating nitric oxide synthesis in normal human chondrocytes." Cillero-Pastor B., Mateos J., Fernandez-Lopez C., Oreiro N., Ruiz-Romero C., Blanco F.J. Arthritis Rheum. 64:204-212(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF070667 mRNA. Translation: AAD20973.1. AJ012008 Genomic DNA. Translation: CAB46079.1. AF087894 mRNA. Translation: AAP97193.1. AF129756 Genomic DNA. Translation: AAD18074.1. BA000025 Genomic DNA. Translation: BAB63377.1. AL662899 Genomic DNA. Translation: CAI18413.1. AL670886 Genomic DNA. Translation: CAI17820.1. AL844216 Genomic DNA. Translation: CAM45772.1. BX248244 Genomic DNA. Translation: CAM26098.1. CR354443 Genomic DNA. Translation: CAQ07022.1. CR759787 Genomic DNA. Translation: CAQ10110.1. CR936239 Genomic DNA. Translation: CAQ08895.1. CH471081 Genomic DNA. Translation: EAX03500.1. BC001435 mRNA. Translation: AAH01435.1.
IPI	IPI00000760.
RefSeq	NP_039268.1. NM_013974.1.
UniGene	Hs.247362.
3D structure databases
ProteinModelPortal	O95865.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95865. 1 interaction.
MINT	MINT-5000845.
STRING	9606.ENSP00000372901.
PTM databases
PhosphoSite	O95865.
2D gel databases
REPRODUCTION-2DPAGE	IPI00000760. O95865.
Proteomic databases
PaxDb	O95865.
PeptideAtlas	O95865.
PRIDE	O95865.
Protocols and materials databases
DNASU	23564.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375787; ENSP00000364943; ENSG00000213722. ENST00000375789; ENSP00000364945; ENSG00000213722. ENST00000375792; ENSP00000364949; ENSG00000213722. ENST00000383409; ENSP00000372901; ENSG00000206395. ENST00000400062; ENSP00000382935; ENSG00000206395. ENST00000400063; ENSP00000382936; ENSG00000206395. ENST00000411456; ENSP00000409396; ENSG00000226634. ENST00000413532; ENSP00000402594; ENSG00000226634. ENST00000413655; ENSP00000412800; ENSG00000233076. ENST00000414455; ENSP00000404342; ENSG00000225635. ENST00000424790; ENSP00000391632; ENSG00000233076. ENST00000426149; ENSP00000412327; ENSG00000228128. ENST00000427126; ENSP00000395372; ENSG00000228128. ENST00000430482; ENSP00000408148; ENSG00000227317. ENST00000434464; ENSP00000391833; ENSG00000228128. ENST00000437889; ENSP00000399023; ENSG00000227317. ENST00000443533; ENSP00000389552; ENSG00000226634. ENST00000444699; ENSP00000404851; ENSG00000225635. ENST00000447101; ENSP00000405515; ENSG00000233076. ENST00000451411; ENSP00000403154; ENSG00000227317. ENST00000454138; ENSP00000399357; ENSG00000225635.
GeneID	23564.
KEGG	hsa:23564.
UCSC	uc003nwp.3. human.
Organism-specific databases
CTD	23564.
GeneCards	GC06M031694.
HGNC	HGNC:2716. DDAH2.
HPA	HPA012509.
MIM	604744. gene.
neXtProt	NX_O95865.
PharmGKB	PA27186.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG86337.
HOGENOM	HOG000161035.
HOVERGEN	HBG055937.
InParanoid	O95865.
KO	K01482.
OMA	MGDENAT.
OrthoDB	EOG4QJRP2.
PhylomeDB	O95865.
Gene expression databases
ArrayExpress	O95865.
Bgee	O95865.
CleanEx	HS_DDAH2.
Genevestigator	O95865.
GermOnline	ENSG00000204418. Homo sapiens.
Family and domain databases
InterPro	IPR003198. Amidino_trans. [Graphical view]
Pfam	PF02274. Amidinotransf. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	DDAH2. human.
DrugBank	DB00155. L-Citrulline.
GenomeRNAi	23564.
NextBio	46156.
SOURCE	Search...

Entry information

Entry name

DDAH2_HUMAN

Accession

Primary (citable) accession number: O95865
Secondary accession number(s): A2BEZ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 112 of the entry and version 1 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.