Q8IVS8 (GLCTK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycerate kinase
EC=2.7.1.31

Alternative name(s):
HBeAg-binding protein 4

Gene names

Name:	GLYCTK
Synonyms:	HBEBP4
ORF Names:	LP5910

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	523 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + (R)-glycerate = ADP + 3-phospho-(R)-glycerate.
Subcellular location	Isoform 1: Cytoplasm Ref.1. Isoform 2: Cytoplasm. Mitochondrion Ref.1.
Tissue specificity	Widely expressed. Ref.1
Involvement in disease	Defects in GLYCTK are the cause of D-glyceric aciduria (D-GA) [MIM:220120]. D-GA is a rare metabolic disease characterized by chronic metabolic acidosis and a highly variable clinical phenotype. Clinical features range from an encephalopathic presentation with seizures, microcephaly, severe mental retardation and early death, to milder manifestations with only speech delay or even normal development. Ref.7
Sequence similarities	Belongs to the glycerate kinase type-2 family.
Biophysicochemical properties	Kinetic parameters: KM=0.1 mM for D-glycerate Ref.7
Sequence caution	The sequence AAH36862.1 differs from that shown. Reason: Frameshift at position 177.

Ontologies

Keywords
Cellular component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein phosphorylation Inferred from direct assay Ref.1. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW glycerate kinase activity Inferred from direct assay Ref.1. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TRIP13	Q15645	3	EBI-748515,EBI-358993

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IVS8-1)

Also known as: Glycerate kinase 1; GLYCTK1;

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: Q8IVS8-2)

Also known as: Glycerate kinase 2; GLYCTK2;

The sequence of this isoform differs from the canonical sequence as follows:
     179-234: GSALLPAPIP...GGLAQAAYPA → EPHPVRCGGG...CEDCAVSGRL
     235-523: Missing.

Isoform 3 (identifier: Q8IVS8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     119-184: Missing.

Isoform 4 (identifier: Q8IVS8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     340-367: DVKSMAQFYGLLAHVARTRLTPSMAGAS → WGTPAAHRDDRYQCHGHPPLVPAASVMA
     368-523: Missing.

Isoform 5 (identifier: Q8IVS8-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.
     340-367: DVKSMAQFYGLLAHVARTRLTPSMAGAS → WGTPAAHRDDRYQCHGHPPIVPAASVMA
     368-523: Missing.

Isoform 6 (identifier: Q8IVS8-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-336: Missing.

Isoform 7 (identifier: Q8IVS8-7)

The sequence of this isoform differs from the canonical sequence as follows:
     178-205: GGSALLPAPIPPVTLEEKQTLTRLLAAR → WGTPAAHRDDRYQCHGHPPLVPAASVMA
     206-523: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 523	523	Glycerate kinase		PRO_0000287192
Regions
	Compositional bias	94 – 97	4	Poly-Ala
Natural variations
	Alternative sequence	1 – 336	336	Missing in isoform 6.		VSP_025356
	Alternative sequence	1 – 127	127	Missing in isoform 5.		VSP_025357
	Alternative sequence	119 – 184	66	Missing in isoform 3.		VSP_025358
	Alternative sequence	178 – 205	28	GGSAL…LLAAR → WGTPAAHRDDRYQCHGHPPL VPAASVMA in isoform 7.		VSP_025359
	Alternative sequence	179 – 234	56	GSALL…AAYPA → EPHPVRCGGGPCGGDCQWPH RGQFPQCARLPAYPQSLRPP CSPATFCEDCAVSGRL in isoform 2.		VSP_025360
	Alternative sequence	206 – 523	318	Missing in isoform 7.		VSP_025361
	Alternative sequence	235 – 523	289	Missing in isoform 2.		VSP_025362
	Alternative sequence	340 – 367	28	DVKSM…MAGAS → WGTPAAHRDDRYQCHGHPPL VPAASVMA in isoform 4.		VSP_025363
	Alternative sequence	340 – 367	28	DVKSM…MAGAS → WGTPAAHRDDRYQCHGHPPI VPAASVMA in isoform 5.		VSP_025364
	Alternative sequence	368 – 523	156	Missing in isoform 4 and isoform 5.		VSP_025365
	Natural variant	27	1	R → C. Corresponds to variant rs34502608 [ dbSNP | Ensembl ].		VAR_061205
	Natural variant	170	1	L → V. Corresponds to variant rs35130772 [ dbSNP | Ensembl ].		VAR_032285
	Natural variant	394	1	T → I. Corresponds to variant rs9813489 [ dbSNP | Ensembl ].		VAR_032286
	Natural variant	493	1	F → C in D-GA; the mutant protein is not expressed and has no enzymatic activity. Ref.7		VAR_065909
Experimental info
	Sequence conflict	144	1	D → Y in AAP51132. Ref.1
	Sequence conflict	245	1	V → E in BAB85018. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Glycerate kinase 1) (GLYCTK1) [UniParc]. Last modified March 1, 2003. Version 1. Checksum: CCBEC88E8850FC11	FASTA	523	55,253
	10 20 30 40 50 60 MAAALQVLPR LARAPLHPLL WRGSVARLAS SMALAEQARQ LFESAVGAVL PGPMLHRALS 70 80 90 100 110 120 LDPGGRQLKV RDRNFQLRQN LYLVGFGKAV LGMAAAAEEL LGQHLVQGVI SVPKGIRAAM 130 140 150 160 170 180 ERAGKQEMLL KPHSRVQVFE GAEDNLPDRD ALRAALAIQQ LAEGLTADDL LLVLISGGGS 190 200 210 220 230 240 ALLPAPIPPV TLEEKQTLTR LLAARGATIQ ELNTIRKALS QLKGGGLAQA AYPAQVVSLI 250 260 270 280 290 300 LSDVVGDPVE VIASGPTVAS SHNVQDCLHI LNRYGLRAAL PRSVKTVLSR ADSDPHGPHT 310 320 330 340 350 360 CGHVLNVIIG SNVLALAEAQ RQAEALGYQA VVLSAAMQGD VKSMAQFYGL LAHVARTRLT 370 380 390 400 410 420 PSMAGASVEE DAQLHELAAE LQIPDLQLEE ALETMAWGRG PVCLLAGGEP TVQLQGSGRG 430 440 450 460 470 480 GRNQELALRV GAELRRWPLG PIDVLFLSGG TDGQDGPTEA AGAWVTPELA SQAAAEGLDI 490 500 510 520 ATFLAHNDSH TFFCCLQGGA HLLHTGMTGT NVMDTHLLFL RPR
	Isoform 2 (Glycerate kinase 2) (GLYCTK2) [UniParc]. Checksum: FC94283B39472157	FASTA	234	25,037
	10 20 30 40 50 60 MAAALQVLPR LARAPLHPLL WRGSVARLAS SMALAEQARQ LFESAVGAVL PGPMLHRALS 70 80 90 100 110 120 LDPGGRQLKV RDRNFQLRQN LYLVGFGKAV LGMAAAAEEL LGQHLVQGVI SVPKGIRAAM 130 140 150 160 170 180 ERAGKQEMLL KPHSRVQVFE GAEDNLPDRD ALRAALAIQQ LAEGLTADDL LLVLISGGEP 190 200 210 220 230 HPVRCGGGPC GGDCQWPHRG QFPQCARLPA YPQSLRPPCS PATFCEDCAV SGRL
	Isoform 3 [UniParc]. Checksum: F14D0F0F05086422	FASTA	457	48,276
	10 20 30 40 50 60 MAAALQVLPR LARAPLHPLL WRGSVARLAS SMALAEQARQ LFESAVGAVL PGPMLHRALS 70 80 90 100 110 120 LDPGGRQLKV RDRNFQLRQN LYLVGFGKAV LGMAAAAEEL LGQHLVQGVI SVPKGIRAAP 130 140 150 160 170 180 IPPVTLEEKQ TLTRLLAARG ATIQELNTIR KALSQLKGGG LAQAAYPAQV VSLILSDVVG 190 200 210 220 230 240 DPVEVIASGP TVASSHNVQD CLHILNRYGL RAALPRSVKT VLSRADSDPH GPHTCGHVLN 250 260 270 280 290 300 VIIGSNVLAL AEAQRQAEAL GYQAVVLSAA MQGDVKSMAQ FYGLLAHVAR TRLTPSMAGA 310 320 330 340 350 360 SVEEDAQLHE LAAELQIPDL QLEEALETMA WGRGPVCLLA GGEPTVQLQG SGRGGRNQEL 370 380 390 400 410 420 ALRVGAELRR WPLGPIDVLF LSGGTDGQDG PTEAAGAWVT PELASQAAAE GLDIATFLAH 430 440 450 NDSHTFFCCL QGGAHLLHTG MTGTNVMDTH LLFLRPR
	Isoform 4 [UniParc]. Checksum: BD1676AC40F6A128	FASTA	367	38,743
	10 20 30 40 50 60 MAAALQVLPR LARAPLHPLL WRGSVARLAS SMALAEQARQ LFESAVGAVL PGPMLHRALS 70 80 90 100 110 120 LDPGGRQLKV RDRNFQLRQN LYLVGFGKAV LGMAAAAEEL LGQHLVQGVI SVPKGIRAAM 130 140 150 160 170 180 ERAGKQEMLL KPHSRVQVFE GAEDNLPDRD ALRAALAIQQ LAEGLTADDL LLVLISGGGS 190 200 210 220 230 240 ALLPAPIPPV TLEEKQTLTR LLAARGATIQ ELNTIRKALS QLKGGGLAQA AYPAQVVSLI 250 260 270 280 290 300 LSDVVGDPVE VIASGPTVAS SHNVQDCLHI LNRYGLRAAL PRSVKTVLSR ADSDPHGPHT 310 320 330 340 350 360 CGHVLNVIIG SNVLALAEAQ RQAEALGYQA VVLSAAMQGW GTPAAHRDDR YQCHGHPPLV PAASVMA
	Isoform 5 [UniParc]. Checksum: 2D3CC412413553BF	FASTA	240	25,138
	10 20 30 40 50 60 MLLKPHSRVQ VFEGAEDNLP DRDALRAALA IQQLAEGLTA DDLLLVLISG GGSALLPAPI 70 80 90 100 110 120 PPVTLEEKQT LTRLLAARGA TIQELNTIRK ALSQLKGGGL AQAAYPAQVV SLILSDVVGD 130 140 150 160 170 180 PVEVIASGPT VASSHNVQDC LHILNRYGLR AALPRSVKTV LSRADSDPHG PHTCGHVLNV 190 200 210 220 230 240 IIGSNVLALA EAQRQAEALG YQAVVLSAAM QGWGTPAAHR DDRYQCHGHP PIVPAASVMA
	Isoform 6 [UniParc]. Checksum: A0D08595835AABD5	FASTA	187	19,867
	10 20 30 40 50 60 MQGDVKSMAQ FYGLLAHVAR TRLTPSMAGA SVEEDAQLHE LAAELQIPDL QLEEALETMA 70 80 90 100 110 120 WGRGPVCLLA GGEPTVQLQG SGRGGRNQEL ALRVGAELRR WPLGPIDVLF LSGGTDGQDG 130 140 150 160 170 180 PTEAAGAWVT PELASQAAAE GLDIATFLAH NDSHTFFCCL QGGAHLLHTG MTGTNVMDTH LLFLRPR
	Isoform 7 [UniParc]. Checksum: 44BEE76722C8F7A8	FASTA	205	22,027
	10 20 30 40 50 60 MAAALQVLPR LARAPLHPLL WRGSVARLAS SMALAEQARQ LFESAVGAVL PGPMLHRALS 70 80 90 100 110 120 LDPGGRQLKV RDRNFQLRQN LYLVGFGKAV LGMAAAAEEL LGQHLVQGVI SVPKGIRAAM 130 140 150 160 170 180 ERAGKQEMLL KPHSRVQVFE GAEDNLPDRD ALRAALAIQQ LAEGLTADDL LLVLISGWGT 190 200 PAAHRDDRYQ CHGHPPLVPA ASVMA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the human D-glyceric acidemia related glycerate kinase gene GLYCTK1 and its alternatively splicing variant GLYCTK2." Guo J.-H., Hexige S., Chen L., Zhou G.-J., Wang X., Jiang J.-M., Kong Y.-H., Ji G.-Q., Wu C.-Q., Zhao S.-Y., Yu L. DNA Seq. 17:1-7(2006) [PubMed: 16753811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"Cloning of HCG9886S gene and identification of a novel domain." Guo J.H. Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). Tissue: Lung.
[3]	"Large-scale cDNA transfection screening for genes related to cancer development and progression." Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J. Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed: 15498874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
[4]	"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] (ISOFORM 5).
[5]	"Screening and cloning of HBeAg binding protein 4." Zhang J.-K., Cheng J., Lan X.-Y., Guo J., Zhang L.-Y. Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 6).
[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: Lung and Skin.
[7]	"D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK)." Sass J.O., Fischer K., Wang R., Christensen E., Scholl-Burgi S., Chang R., Kapelari K., Walter M. Hum. Mutat. 31:1280-1285(2010) [PubMed: 20949620] [Abstract] Cited for: KINETIC PARAMETERS, VARIANT D-GA CYS-493, CHARACTERIZATION OF VARIANT D-GA CYS-493.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY295075 mRNA. Translation: AAP51132.1. AF448855 mRNA. Translation: AAP41923.1. AY172690 mRNA. Translation: AAO17719.1. AY189286 mRNA. Translation: AAO86730.1. AK074215 mRNA. Translation: BAB85018.1. AY134474 mRNA. Translation: AAM95456.1. DQ352863 mRNA. Translation: ABD22985.1. BC021896 mRNA. Translation: AAH21896.1. BC036862 mRNA. Translation: AAH36862.1. Frameshift. BC042151 mRNA. Translation: AAH42151.1.
IPI	IPI00217117. IPI00332462. IPI00384753. IPI00385408. IPI00735631. IPI00845254. IPI00845451.
RefSeq	NP_001138423.1. NM_001144951.1. NP_660305.2. NM_145262.3.
UniGene	Hs.415312.
3D structure databases
HSSP	HSSP built from PDB template 1X3L based on UniProtKB O58231.
ProteinModelPortal	Q8IVS8.
SMR	Q8IVS8. Positions 33-520.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IVS8. 3 interactions.
MINT	MINT-1440661.
STRING	Q8IVS8.
PTM databases
PhosphoSite	Q8IVS8.
Polymorphism databases
DMDM	74728080.
Proteomic databases
PRIDE	Q8IVS8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000436784; ENSP00000389175; ENSG00000168237.
GeneID	132158.
KEGG	hsa:132158.
UCSC	uc003ddo.1. human. uc003ddp.1. human. uc003ddq.1. human. uc003ddr.1. human.
Organism-specific databases
CTD	132158.
GeneCards	GC03P052296.
H-InvDB	HIX0003350.
HGNC	HGNC:24247. GLYCTK.
HPA	HPA006913.
MIM	220120. phenotype. 610516. gene.
neXtProt	NX_Q8IVS8.
Orphanet	941. D-glycericacidemia.
PharmGKB	PA162389865.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16207.
GeneTree	ENSGT00390000014365.
HOVERGEN	HBG098351.
InParanoid	Q8IVS8.
OMA	LAHNDSH.
PhylomeDB	Q8IVS8.
Enzyme and pathway databases
BRENDA	2.7.1.31. 2681.
Gene expression databases
ArrayExpress	Q8IVS8.
Bgee	Q8IVS8.
CleanEx	HS_GLYCTK.
Genevestigator	Q8IVS8.
Family and domain databases
InterPro	IPR007835. MOFRL. [Graphical view]
Gene3D	G3DSA:3.40.1480.10. G3DSA:3.40.1480.10. 2 hits.
KO	K00865.
Pfam	PF05161. MOFRL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	83022.
SOURCE	Search...

Entry information

Entry name

GLCTK_HUMAN

Accession

Primary (citable) accession number: Q8IVS8
Secondary accession number(s): Q0P630 , Q2EZ43, Q6Y2K6, Q7Z6G5, Q86YR8, Q8TED2, Q8WTY2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	March 1, 2003
Last modified:	December 14, 2011
This is version 70 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.