P49448 (DHE4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate dehydrogenase 2, mitochondrial
Short name=GDH 2
EC=1.4.1.3

Gene names

Name:	GLUD2
Synonyms:	GLUDP1

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	558 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	Important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission.
Catalytic activity	L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H.
Subunit structure	Homohexamer By similarity.
Subcellular location	Mitochondrion matrix Ref.7.
Tissue specificity	Expressed in retina, testis and, at a lower level, brain.
Post-translational modification	Stoichiometry shows that ADP-ribosylation occurs in one subunit per catalytically active homohexamer.
Sequence similarities	Belongs to the Glu/Leu/Phe/Val dehydrogenases family.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	NADP
Molecular function	Oxidoreductase
PTM	ADP-ribosylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glutamate biosynthetic process Inferred from direct assay PubMed 11032875. Source: BHF-UCL glutamate catabolic process Inferred from direct assay PubMed 11032875. Source: BHF-UCL
Cellular_component	mitochondrion Inferred from direct assay PubMed 18688271. Source: BHF-UCL
Molecular_function	ADP binding Inferred from direct assay PubMed 12742085. Source: BHF-UCL GTP binding Inferred from direct assay PubMed 11032875. Source: BHF-UCL glutamate dehydrogenase (NAD+) activity Inferred from direct assay PubMed 15578726Ref.1. Source: UniProtKB glutamate dehydrogenase [NAD(P)+] activity Inferred from direct assay PubMed 11032875. Source: BHF-UCL leucine binding Inferred from direct assay PubMed 12742085. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 53	53	Mitochondrion
	Chain	54 – 558	505	Glutamate dehydrogenase 2, mitochondrial		PRO_0000007208
Sites
	Active site	183	1	By similarity
	Binding site	84	1	Substrate By similarity
Amino acid modifications
	Modified residue	172	1	ADP-ribosylcysteine
Natural variations
	Natural variant	498	1	S → A. Corresponds to variant rs9697983 [ dbSNP | Ensembl ].		VAR_048867
Experimental info
	Sequence conflict	286	1	E → Q in CAA46995. Ref.1
	Sequence conflict	286	1	E → Q in AAA20969. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P49448 [UniParc]. Last modified April 27, 2001. Version 2. Checksum: F222B1B2CB74A6EA	FASTA	558	61,434
	10 20 30 40 50 60 MYRYLAKALL PSRAGPAALG SAANHSAALL GRGRGQPAAA SQPGLALAAR RHYSELVADR 70 80 90 100 110 120 EDDPNFFKMV EGFFDRGASI VEDKLVKDLR TQESEEQKRN RVRGILRIIK PCNHVLSLSF 130 140 150 160 170 180 PIRRDDGSWE VIEGYRAQHS QHRTPCKGGI RYSTDVSVDE VKALASLMTY KCAVVDVPFG 190 200 210 220 230 240 GAKAGVKINP KNYTENELEK ITRRFTMELA KKGFIGPGVD VPAPDMNTGE REMSWIADTY 250 260 270 280 290 300 ASTIGHYDIN AHACVTGKPI SQGGIHGRIS ATGRGVFHGI ENFINEASYM SILGMTPGFR 310 320 330 340 350 360 DKTFVVQGFG NVGLHSMRYL HRFGAKCIAV GESDGSIWNP DGIDPKELED FKLQHGSILG 370 380 390 400 410 420 FPKAKPYEGS ILEVDCDILI PAATEKQLTK SNAPRVKAKI IAEGANGPTT PEADKIFLER 430 440 450 460 470 480 NILVIPDLYL NAGGVTVSYF EWLKNLNHVS YGRLTFKYER DSNYHLLLSV QESLERKFGK 490 500 510 520 530 540 HGGTIPIVPT AEFQDSISGA SEKDIVHSAL AYTMERSARQ IMHTAMKYNL GLDLRTAAYV 550 NAIEKVFKVY SEAGVTFT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel human glutamate dehydrogenase expressed in neural and testicular tissues and encoded by an X-linked intronless gene." Shashidharan P., Michaelidis T.M., Robakis N.K., Kresovali A., Papamatheakis J., Plaitakis A. J. Biol. Chem. 269:16971-16976(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Retina.
[2]	"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]. Tissue: Testis.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Skin.
[5]	"Identification of ADP-ribosylation site in human glutamate dehydrogenase isozymes." Choi M.M., Huh J.W., Yang S.J., Cho E.H., Choi S.Y., Cho S.W. FEBS Lett. 579:4125-4130(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ADP-RIBOSYLATION AT CYS-172.
[6]	"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].
[7]	"Alpha helical structures in the leader sequence of human GLUD2 glutamate dehydrogenase responsible for mitochondrial import." Kotzamani D., Plaitakis A. Neurochem. Int. 61:463-469(2012) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSIT PEPTIDE, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X66310 Genomic DNA. Translation: CAA46995.1. U08997 Genomic DNA. Translation: AAA20969.1. AK313356 mRNA. Translation: BAG36157.1. AC006144 Genomic DNA. Translation: AAD05030.1. BC050732 mRNA. Translation: AAH50732.1.
IPI	IPI00027146.
PIR	A53719.
RefSeq	NP_036216.2. NM_012084.3.
UniGene	Hs.368538.
3D structure databases
ProteinModelPortal	P49448.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49448. 4 interactions.
MINT	MINT-1411373.
STRING	9606.ENSP00000327589.
PTM databases
PhosphoSite	P49448.
Polymorphism databases
DMDM	13432152.
2D gel databases
REPRODUCTION-2DPAGE	IPI00027146.
Proteomic databases
PaxDb	P49448.
PeptideAtlas	P49448.
PRIDE	P49448.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000328078; ENSP00000327589; ENSG00000182890.
GeneID	2747.
KEGG	hsa:2747.
UCSC	uc004eto.3. human.
Organism-specific databases
CTD	2747.
GeneCards	GC0XP120181.
HGNC	HGNC:4336. GLUD2.
HPA	HPA042492. HPA044839.
MIM	300144. gene.
neXtProt	NX_P49448.
PharmGKB	PA28738.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0334.
HOGENOM	HOG000243801.
HOVERGEN	HBG005479.
InParanoid	P49448.
KO	K00261.
OMA	MNTGERE.
OrthoDB	EOG41NTKQ.
PhylomeDB	P49448.
Enzyme and pathway databases
BioCyc	MetaCyc:HS00018-MONOMER.
BRENDA	1.4.1.3. 2681.
SABIO-RK	P49448.
Gene expression databases
ArrayExpress	P49448.
Bgee	P49448.
Genevestigator	P49448.
GermOnline	ENSG00000182890. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR006095. Glu/Leu/Phe/Val_DH. IPR006096. Glu/Leu/Phe/Val_DH_C. IPR006097. Glu/Leu/Phe/Val_DH_dimer_dom. IPR016040. NAD(P)-bd_dom. [Graphical view]
Pfam	PF00208. ELFV_dehydrog. 1 hit. PF02812. ELFV_dehydrog_N. 1 hit. [Graphical view]
PRINTS	PR00082. GLFDHDRGNASE.
SMART	SM00839. ELFV_dehydrog. 1 hit. [Graphical view]
PROSITE	PS00074. GLFV_DEHYDROGENASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00142. L-Glutamic Acid. DB00157. NADH.
GenomeRNAi	2747.
NextBio	10828.
SOURCE	Search...

Entry information

Entry name

DHE4_HUMAN

Accession

Primary (citable) accession number: P49448
Secondary accession number(s): B2R8G0, Q9UDQ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	April 27, 2001
Last modified:	May 1, 2013
This is version 117 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.