P32189 (GLPK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycerol kinase
Short name=GK
Short name=Glycerokinase
EC=2.7.1.30

Alternative name(s):
ATP:glycerol 3-phosphotransferase

Gene names

Name:

GK

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

General annotation (Comments)

Function	Key enzyme in the regulation of glycerol uptake and metabolism.
Catalytic activity	ATP + glycerol = ADP + sn-glycerol 3-phosphate.
Pathway	Polyol metabolism; glycerol degradation via glycerol kinase pathway; sn-glycerol 3-phosphate from glycerol: step 1/1.
Subcellular location	Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm. Note: In sperm and fetal tissues, the majority of the enzyme is bound to mitochondria, but in adult tissues, such as liver found in the cytoplasm.
Tissue specificity	Highly expressed in the liver, kidney and testis. Isoform 2 and isoform 3 are expressed specifically in testis and fetal liver, but not in the adult liver.
Involvement in disease	Defects in GK are the cause of GK deficiency (GKD) [MIM:307030]. This disease can be either symptomatic with episodic metabolic and CNS decompensation or asymptomatic with hyperglycerolemia and hyperglyceroluria only. Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the FGGY kinase family.
Sequence caution	The sequence CAA48346.1 differs from that shown. Reason: Frameshift at positions 201, 210 and 459.

Ontologies

Keywords
Biological process	Glycerol metabolism
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane
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	glycerol-3-phosphate biosynthetic process Inferred from mutant phenotype Ref.8. Source: BHF-UCL triglyceride biosynthetic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome mitochondrial outer membrane Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW glycerol kinase activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NR4A1	P22736	3	EBI-3926629,EBI-721550

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 3 (identifier: P32189-3)

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 1 (identifier: P32189-1)

The sequence of this isoform differs from the canonical sequence as follows:
     245-250: Missing.
     528-556: Missing.

Isoform 2 (identifier: P32189-2)

The sequence of this isoform differs from the canonical sequence as follows:
     245-250: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 559	559	Glycerol kinase		PRO_0000059535
Regions
	Nucleotide binding	433 – 437	5	ATP By similarity
Sites
	Binding site	20	1	Substrate By similarity
	Binding site	24	1	ATP By similarity
	Binding site	94	1	Substrate By similarity
	Binding site	148	1	Substrate By similarity
	Binding site	265	1	Substrate By similarity
	Binding site	287	1	ATP By similarity
	Binding site	332	1	ATP; via carbonyl oxygen By similarity
Natural variations
	Alternative sequence	245 – 250	6	Missing in isoform 1 and isoform 2.		VSP_000770
	Alternative sequence	528 – 556	29	Missing in isoform 1.		VSP_000771
	Natural variant	185	1	S → N.		VAR_001374
	Natural variant	232	1	N → H.		VAR_001375
	Natural variant	294	1	N → D in GKD. Ref.10		VAR_015433
	Natural variant	382	1	A → T.		VAR_001376
	Natural variant	446	1	D → V in GKD. Ref.8		VAR_001377
	Natural variant	509	1	W → R in GKD. Ref.9		VAR_010138
Experimental info
	Sequence conflict	79	1	N → K in AAH42421. Ref.5
	Sequence conflict	131	1	P → T in AAH42421. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 [UniParc]. Last modified July 22, 2008. Version 3. Checksum: 18268B7A4C6A09F3	FASTA	559	61,245
	10 20 30 40 50 60 MAASKKAVLG PLVGAVDQGT SSTRFLVFNS KTAELLSHHQ VEIKQEFPRE GWVEQDPKEI 70 80 90 100 110 120 LHSVYECIEK TCEKLGQLNI DISNIKAIGV SNQRETTVVW DKITGEPLYN AVVWLDLRTQ 130 140 150 160 170 180 STVESLSKRI PGNNNFVKSK TGLPLSTYFS AVKLRWLLDN VRKVQKAVEE KRALFGTIDS 190 200 210 220 230 240 WLIWSLTGGV NGGVHCTDVT NASRTMLFNI HSLEWDKQLC EFFGIPMEIL PNVRSSSEIY 250 260 270 280 290 300 GLMKISHSVK AGALEGVPIS GCLGDQSAAL VGQMCFQIGQ AKNTYGTGCF LLCNTGHKCV 310 320 330 340 350 360 FSDHGLLTTV AYKLGRDKPV YYALEGSVAI AGAVIRWLRD NLGIIKTSEE IEKLAKEVGT 370 380 390 400 410 420 SYGCYFVPAF SGLYAPYWEP SARGIICGLT QFTNKCHIAF AALEAVCFQT REILDAMNRD 430 440 450 460 470 480 CGIPLSHLQV DGGMTSNKIL MQLQADILYI PVVKPSMPET TALGAAMAAG AAEGVGVWSL 490 500 510 520 530 540 EPEDLSAVTM ERFEPQINAE ESEIRYSTWK KAVMKSMGWV TTQSPESGDP SIFCSLPLGF 550 FIVSSMVMLI GARYISGIP
	Isoform 1 [UniParc]. Checksum: 0FAA29ADC6054154	FASTA	524	57,489
	10 20 30 40 50 60 MAASKKAVLG PLVGAVDQGT SSTRFLVFNS KTAELLSHHQ VEIKQEFPRE GWVEQDPKEI 70 80 90 100 110 120 LHSVYECIEK TCEKLGQLNI DISNIKAIGV SNQRETTVVW DKITGEPLYN AVVWLDLRTQ 130 140 150 160 170 180 STVESLSKRI PGNNNFVKSK TGLPLSTYFS AVKLRWLLDN VRKVQKAVEE KRALFGTIDS 190 200 210 220 230 240 WLIWSLTGGV NGGVHCTDVT NASRTMLFNI HSLEWDKQLC EFFGIPMEIL PNVRSSSEIY 250 260 270 280 290 300 GLMKAGALEG VPISGCLGDQ SAALVGQMCF QIGQAKNTYG TGCFLLCNTG HKCVFSDHGL 310 320 330 340 350 360 LTTVAYKLGR DKPVYYALEG SVAIAGAVIR WLRDNLGIIK TSEEIEKLAK EVGTSYGCYF 370 380 390 400 410 420 VPAFSGLYAP YWEPSARGII CGLTQFTNKC HIAFAALEAV CFQTREILDA MNRDCGIPLS 430 440 450 460 470 480 HLQVDGGMTS NKILMQLQAD ILYIPVVKPS MPETTALGAA MAAGAAEGVG VWSLEPEDLS 490 500 510 520 AVTMERFEPQ INAEESEIRY STWKKAVMKS MGWVTTQSPE SGIP
	Isoform 2 [UniParc]. Checksum: 145FA42A6BEA104F	FASTA	553	60,593
	10 20 30 40 50 60 MAASKKAVLG PLVGAVDQGT SSTRFLVFNS KTAELLSHHQ VEIKQEFPRE GWVEQDPKEI 70 80 90 100 110 120 LHSVYECIEK TCEKLGQLNI DISNIKAIGV SNQRETTVVW DKITGEPLYN AVVWLDLRTQ 130 140 150 160 170 180 STVESLSKRI PGNNNFVKSK TGLPLSTYFS AVKLRWLLDN VRKVQKAVEE KRALFGTIDS 190 200 210 220 230 240 WLIWSLTGGV NGGVHCTDVT NASRTMLFNI HSLEWDKQLC EFFGIPMEIL PNVRSSSEIY 250 260 270 280 290 300 GLMKAGALEG VPISGCLGDQ SAALVGQMCF QIGQAKNTYG TGCFLLCNTG HKCVFSDHGL 310 320 330 340 350 360 LTTVAYKLGR DKPVYYALEG SVAIAGAVIR WLRDNLGIIK TSEEIEKLAK EVGTSYGCYF 370 380 390 400 410 420 VPAFSGLYAP YWEPSARGII CGLTQFTNKC HIAFAALEAV CFQTREILDA MNRDCGIPLS 430 440 450 460 470 480 HLQVDGGMTS NKILMQLQAD ILYIPVVKPS MPETTALGAA MAAGAAEGVG VWSLEPEDLS 490 500 510 520 530 540 AVTMERFEPQ INAEESEIRY STWKKAVMKS MGWVTTQSPE SGDPSIFCSL PLGFFIVSSM 550 VMLIGARYIS GIP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genomic scanning for expressed sequences in Xp21 identifies the glycerol kinase gene." Guo W., Worley K.C., Adams V., Mason J., Sylvester-Jackson D.E., Zhang Y.-H., Towbin J.A., Fogt D.D., Madu S., Wheeler D.A., McCabe E.R.B. Nat. Genet. 4:367-372(1993) [PubMed: 8401584] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"The glycerol kinase gene family: structure of the Xp gene, and related intronless retroposons." Sargent C.A., Young C., Marsh S., Ferguson-Smith M.A., Affara N.A. Hum. Mol. Genet. 3:1317-1324(1994) [PubMed: 7987308] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2). Tissue: Fetal brain.
[3]	"Five cases of isolated glycerol kinase deficiency, including two families: failure to find genotype:phenotype correlation." Sargent C.A., Kidd A., Moore S., Dean J., Besley G.T.N., Affara N.A. J. Med. Genet. 37:434-441(2000) [PubMed: 10851254] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3).
[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 1).
[5]	"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: Blood and Brain.
[6]	"Cloning of the X-linked glycerol kinase deficiency gene and its identification by sequence comparison to the Bacillus subtilis homologue." Sargent C.A., Affara N.A., Bentley E., Pelmear A., Bailey D.M.D., Davey P., Dow D., Leversha M., Aplin H., Besley G.T.N., Ferguson-Smith M.A. Hum. Mol. Genet. 2:97-106(1993) [PubMed: 8499912] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 77-559 (ISOFORM 3). Tissue: Fetal brain.
[7]	"Isolation of the human Xp21 glycerol kinase gene by positional cloning." Walker A.P., Muscatelli F., Monaco A.P. Hum. Mol. Genet. 2:107-114(1993) [PubMed: 8499898] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 130-559 (ISOFORM 1). Tissue: Fetal liver.
[8]	"Mutations and phenotype in isolated glycerol kinase deficiency." Walker A.P., Muscatelli F., Stafford A.N., Chelly J., Dahl N., Blomquist H.K., Delanghe J., Willems P.J., Steinmann B., Monaco A.P. Am. J. Hum. Genet. 58:1205-1211(1996) [PubMed: 8651297] [Abstract] Cited for: VARIANT GKD VAL-446.
[9]	"Clinical heterogeneity and novel mutations in the glycerol kinase gene in three families with isolated glycerol kinase deficiency." Sjarif D.R., Sinke R.J., Duran M., Beemer F.A., Kleijer W.J., Ploos van Amstel J.K., Poll-The B.T. J. Med. Genet. 35:650-656(1998) [PubMed: 9719371] [Abstract] Cited for: VARIANT GKD ARG-509.
[10]	"Glycerol as a correlate of impaired glucose tolerance: dissection of a complex system by use of a simple genetic trait." Gaudet D., Arsenault S., Perusse L., Vohl M.C., St Pierre J., Bergeron J., Despres J.P., Dewar K., Daly M.J., Hudson T., Rioux J.D. Am. J. Hum. Genet. 66:1558-1568(2000) [PubMed: 10736265] [Abstract] Cited for: VARIANT GKD ASP-294.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	L13943 mRNA. Translation: AAA52576.1. X78211 Genomic DNA. No translation available. AJ252550 , AJ252551, AJ252552, AJ252553, AJ252554, AJ252555, AJ252556, AJ252557, AJ252558, AJ252559, AJ252560, AJ252561, AJ252562, AJ252563, AJ252564, AJ252565, AJ252566, AJ252567, AJ252568, AJ252569, AJ252570 Genomic DNA. Translation: CAB54859.1. AJ252550 , AJ252551, AJ252552, AJ252553, AJ252554, AJ252555, AJ252556, AJ252557, AJ252559, AJ252560, AJ252561, AJ252562, AJ252563, AJ252564, AJ252565, AJ252566, AJ252567, AJ252568, AJ252569, AJ252570 Genomic DNA. Translation: CAB54858.1. AJ252550 , AJ252551, AJ252552, AJ252553, AJ252554, AJ252555, AJ252556, AJ252557, AJ252559, AJ252560, AJ252561, AJ252562, AJ252563, AJ252564, AJ252565, AJ252566, AJ252567, AJ252568, AJ252570 Genomic DNA. Translation: CAB54857.1. AK313215 mRNA. Translation: BAG36030.1. BC037549 mRNA. Translation: AAH37549.1. BC042421 mRNA. Translation: AAH42421.1. X68285 mRNA. Translation: CAA48346.1. Frameshift. X69886 mRNA. Translation: CAA49512.1.
IPI	IPI00027424. IPI00216066. IPI00216067.
PIR	S36175. I37427.
RefSeq	NP_000158.1. NM_000167.5. NP_001121599.1. NM_001128127.2. NP_001191948.1. NM_001205019.1. NP_976325.1. NM_203391.3.
UniGene	Hs.1466. Hs.670599.
3D structure databases
ProteinModelPortal	P32189.
SMR	P32189. Positions 11-523.
ModBase	Search...
Protein-protein interaction databases
IntAct	P32189. 11 interactions.
STRING	P32189.
Polymorphism databases
DMDM	205830913.
Proteomic databases
PRIDE	P32189.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378948; ENSP00000368231; ENSG00000198814.
GeneID	2710.
KEGG	hsa:2710.
UCSC	uc004dci.2. human. uc010ngj.1. human.
Organism-specific databases
CTD	2710.
GeneCards	GC0XP030671.
HGNC	HGNC:4289. GK.
MIM	300474. gene. 307030. phenotype.
neXtProt	NX_P32189.
Orphanet	408. Hyperglycerolemia.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07530.
GeneTree	ENSGT00530000063143.
HOGENOM	HBG511469.
HOVERGEN	HBG002451.
InParanoid	P32189.
OMA	FEPQINP.
PhylomeDB	P32189.
Enzyme and pathway databases
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P32189.
CleanEx	HS_GK.
Genevestigator	P32189.
Family and domain databases
InterPro	IPR000577. Carb_kinase_FGGY. IPR018485. Carb_kinase_FGGY_C. IPR018483. Carb_kinase_FGGY_CS. IPR018484. Carb_kinase_FGGY_N. IPR005999. Glycerol_kin. [Graphical view]
KO	K00864.
PANTHER	PTHR10196. FGGY_kin. 1 hit. PTHR10196:SF9. Glycerol_kin. 1 hit.
Pfam	PF02782. FGGY_C. 1 hit. PF00370. FGGY_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR01311. Glycerol_kin. 1 hit.
PROSITE	PS00933. FGGY_KINASES_1. 1 hit. PS00445. FGGY_KINASES_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

GLPK_HUMAN

Accession

Primary (citable) accession number: P32189
Secondary accession number(s): B2R833 , Q8IVR5, Q9UMP0, Q9UMP1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	July 22, 2008
Last modified:	January 25, 2012
This is version 123 of the entry and version 3 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.