Reviewed, UniProtKB/Swiss-Prot Q9H936 (GHC1_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitochondrial glutamate carrier 1
      Short name=GC-1
Alternative name(s):
    Glutamate/H(+) symporter 1
    Solute carrier family 25 member 22

Gene names

Name:	SLC25A22
Synonyms:	GC1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in the transport of glutamate across the inner mitochondrial membrane. Glutamate is cotransported with H+. Ref.1
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein Potential.
Tissue specificity	Highly expressed in most tissues.
Involvement in disease	Defects in SLC25A22 are the cause of epileptic encephalopathy early infantile type 3 (EIEE3) [MIM:609304]; also known as early myoclonic encephalopathy (EME) or neonatal epilepsy with suppression-burst pattern. Severe neonatal epilepsies with suppression-burst pattern are early-onset epileptic syndromes characterized by a typical EEG pattern. The suppression-burst pattern of the EEG is characterized by higher-voltage bursts of slow waves mixed with multifocal spikes alternating with isoelectric suppression phases. EME is characterized by a very early onset, erratic and fragmentary myoclonus, massive myoclonus, partial motor seizures and late tonic spasms. The prognosis of EME is poor, with no effective treatment, and children with the condition either die within 1 to 2 years after birth or survive in a persistent vegetative state. EME inheritance is autosomal recessive.
Sequence similarities	Belongs to the mitochondrial carrier family. Contains 3 Solcar repeats.

Ontologies

Keywords
Biological process	Symport Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Disease	Disease mutation Epilepsy
Domain	Repeat Transmembrane
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	L-glutamate transport Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	L-glutamate transmembrane transporter activity Ref.1 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP4	P49662	1	EBI-1050588,EBI-1057327
TSC22D1	Q15714	1	EBI-1050588,EBI-712609

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 323	323	Mitochondrial glutamate carrier 1		PRO_0000090619
Regions
	Transmembrane	12 – 32	21	1 Potential
	Transmembrane	62 – 82	21	2 Potential
	Transmembrane	107 – 127	21	3 Potential
	Transmembrane	189 – 209	21	4 Potential
	Transmembrane	223 – 243	21	5 Potential
	Transmembrane	292 – 312	21	6 Potential
	Repeat	6 – 93	88	Solcar 1
	Repeat	101 – 214	114	Solcar 2
	Repeat	223 – 312	90	Solcar 3
Natural variations
	Natural variant	206	1	P → L in EIEE3. Ref.5		VAR_022737

Sequences

	Sequence		Length	Mass (Da)
	Q9H936-1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: D0E06FD88E5A3198	FASTA	323	34,470
	10 20 30 40 50 60 MADKQISLPA KLINGGIAGL IGVTCVFPID LAKTRLQNQQ NGQRVYTSMS DCLIKTVRSE 70 80 90 100 110 120 GYFGMYRGAA VNLTLVTPEK AIKLAANDFF RHQLSKDGQK LTLLKEMLAG CGAGTCQVIV 130 140 150 160 170 180 TTPMEMLKIQ LQDAGRIAAQ RKILAAQGQL SAQGGAQPSV EAPAAPRPTA TQLTRDLLRS 190 200 210 220 230 240 RGIAGLYKGL GATLLRDVPF SVVYFPLFAN LNQLGRPASE EKSPFYVSFL AGCVAGSAAA 250 260 270 280 290 300 VAVNPCDVVK TRLQSLQRGV NEDTYSGILD CARKILRHEG PSAFLKGAYC RALVIAPLFG 310 320 IAQVVYFLGI AESLLGLLQD PQA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms." Fiermonte G., Palmieri L., Todisco S., Agrimi G., Palmieri F., Walker J.E. J. Biol. Chem. 277:19289-19294(2002) [PubMed: 11897791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Brain.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"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]. Tissue: Lung, Muscle and Skin.
[4]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[5]	"Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy." Molinari F., Raas-Rothschild A., Rio M., Fiermonte G., Encha-Razavi F., Palmieri L., Palmieri F., Ben-Neriah Z., Kadhom N., Vekemans M., Attie-Bitach T., Munnich A., Rustin P., Colleaux L. Am. J. Hum. Genet. 76:334-339(2005) [PubMed: 15592994] [Abstract] Cited for: VARIANT EIEE3 LEU-206.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ428202 mRNA. Translation: CAD21007.1. AK023106 mRNA. Translation: BAB14407.1. AK290481 mRNA. Translation: BAF83170.1. BC019033 mRNA. Translation: AAH19033.1. BC023545 mRNA. Translation: AAH23545.1. BC024212 mRNA. Translation: AAH24212.2. Different initiation.
IPI	IPI00003004.
RefSeq	NP_078974.1.
UniGene	Hs.99486
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H936. 5 interactions.
Protein family/group databases
TCDB	2.A.29.14.3. mitochondrial carrier (MC) family.
Proteomic databases
PeptideAtlas	Q9H936.
PRIDE	Q9H936.
Genome annotation databases
Ensembl	ENSG00000177542. Homo sapiens. [Contig view]
GeneID	79751.
KEGG	hsa:79751.
UCSC	uc001lri.1. human.
Organism-specific databases
GeneCards	GC11M000785.
H-InvDB	HIX0019448.
HGNC	HGNC:19954. SLC25A22.
MIM	609302. gene. 609304. phenotype.
Orphanet	1934. Early infantile epileptic encephalopathy. 1935. Early myoclonic encephalopathy.
PharmGKB	PA134955826.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9H936.
HOVERGEN	Q9H936.
OMA	Q9H936. KSPTAMQ.
Gene expression databases
ArrayExpress	Q9H936.
Bgee	Q9H936.
CleanEx	HS_SLC25A22.
GermOnline	ENSG00000177542. Homo sapiens.
Family and domain databases
InterPro	IPR002113. Aden_trnslctor. IPR002067. Mit_carrier. IPR001993. Mitochondria_substrate_carrier. IPR018108. Mitochondrial_sb/sol_carrier. [Graphical view]
PANTHER	PTHR11896. Mitoch_carrier. 1 hit.
Pfam	PF00153. Mito_carr. 3 hits. [Graphical view]
PRINTS	PR00927. ADPTRNSLCASE. PR00926. MITOCARRIER.
PROSITE	PS50920. SOLCAR. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00142. L-Glutamic Acid.
NextBio	69195.
SOURCE	Search...

Entry information

Entry name

GHC1_HUMAN

Accession

Primary (citable) accession number: Q9H936
Secondary accession number(s): A8K366, Q8TBU8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 22, 2003
Last sequence update:	March 1, 2001
Last modified:	July 7, 2009
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)