P51570 (GALK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Galactokinase
EC=2.7.1.6

Alternative name(s):
Galactose kinase

Gene names

Name:	GALK1
Synonyms:	GALK

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

General annotation (Comments)

Function	Major enzyme for galactose metabolism.
Catalytic activity	ATP + D-galactose = ADP + alpha-D-galactose 1-phosphate.
Pathway	Carbohydrate metabolism; galactose metabolism.
Subunit structure	Homodimer Probable. Ref.9
Involvement in disease	Galactosemia II (GALCT2) [MIM:230200]: Autosomal recessive deficiency characterized by congenital cataracts during infancy and presenile cataracts in the adult population. The cataracts are secondary to accumulation of galactitol in the lenses. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16
Sequence similarities	Belongs to the GHMP kinase family. GalK subfamily.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Galactose metabolism
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	galactose catabolic process Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from direct assay Ref.14. Source: UniProtKB galactokinase activity Inferred from direct assay Ref.14Ref.7. Source: UniProtKB galactose binding Inferred from direct assay PubMed 14596685. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 392

392

Galactokinase

PRO_0000184645

Regions

Nucleotide binding

134 – 144

11

ATP

Region

43 – 46

4

Substrate binding

Region

183 – 186

4

Substrate binding

Sites

Active site

186

1

Proton acceptor By similarity

Binding site

236

1

Substrate

Site

37

1

Transition state stabilizer Probable

Natural variations

Natural variant

28

1

P → T in GALCT2; founder Romani mutation. Ref.10 Ref.11 Ref.14

VAR_008514

Natural variant

32

1

V → M in GALCT2. Ref.1 Ref.14 Ref.16

VAR_002547

Natural variant

36

1

G → R in GALCT2. Ref.11 Ref.14

VAR_023486

Natural variant

44

1

H → Y in GALCT2. Ref.11 Ref.14

VAR_023487

Natural variant

68

1

R → C in GALCT2. Ref.13 Ref.14

VAR_023488

Natural variant

184

1

I → M. Ref.15

VAR_023489

Natural variant

198

1

A → V in GALCT2; mild deficiency; Osaka. Ref.12 Ref.14

VAR_015746

Natural variant

239

1

R → Q in GALCT2. Ref.16

VAR_023490

Natural variant

274

1

G → D. Ref.15

VAR_023491

Natural variant

288

1

T → M in GALCT2. Ref.13 Ref.14

VAR_023492

Natural variant

338

1

V → A. Ref.15

VAR_023493

Natural variant

346

1

G → S in GALCT2. Ref.11 Ref.14

VAR_023494

Natural variant

349

1

G → S in GALCT2. Ref.11 Ref.14

VAR_023495

Natural variant

384

1

A → P in GALCT2. Ref.13 Ref.14

VAR_023496

Secondary structure

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392

Helix Strand Turn

Details...

Helix

9 – 24

16

Beta strand

29 – 41

13

Helix

46 – 48

3

Beta strand

51 – 68

18

Beta strand

72 – 77

6

Beta strand

80 – 82

3

Beta strand

86 – 91

6

Helix

105 – 107

3

Helix

108 – 116

9

Beta strand

118 – 120

3

Beta strand

124 – 131

8

Beta strand

137 – 139

3

Helix

141 – 156

16

Helix

163 – 176

14

Helix

185 – 192

8

Beta strand

197 – 202

6

Turn

203 – 205

3

Beta strand

208 – 212

5

Beta strand

216 – 228

13

Turn

233 – 235

3

Helix

236 – 249

14

Helix

260 – 263

4

Helix

266 – 269

4

Helix

272 – 296

25

Helix

300 – 316

17

Helix

323 – 333

11

Beta strand

338 – 343

6

Beta strand

348 – 357

10

Helix

358 – 360

3

Helix

361 – 371

11

Beta strand

377 – 381

5

Beta strand

387 – 389

3

Sequences

	Sequence		Length	Mass (Da)
	P51570 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 8D7CFF8FDB0E4718	FASTA	392	42,272
	10 20 30 40 50 60 MAALRQPQVA ELLAEARRAF REEFGAEPEL AVSAPGRVNL IGEHTDYNQG LVLPMALELM 70 80 90 100 110 120 TVLVGSPRKD GLVSLLTTSE GADEPQRLQF PLPTAQRSLE PGTPRWANYV KGVIQYYPAA 130 140 150 160 170 180 PLPGFSAVVV SSVPLGGGLS SSASLEVATY TFLQQLCPDS GTIAARAQVC QQAEHSFAGM 190 200 210 220 230 240 PCGIMDQFIS LMGQKGHALL IDCRSLETSL VPLSDPKLAV LITNSNVRHS LASSEYPVRR 250 260 270 280 290 300 RQCEEVARAL GKESLREVQL EELEAARDLV SKEGFRRARH VVGEIRRTAQ AAAALRRGDY 310 320 330 340 350 360 RAFGRLMVES HRSLRDDYEV SCPELDQLVE AALAVPGVYG SRMTGGGFGG CTVTLLEASA 370 380 390 APHAMRHIQE HYGGTATFYL SQAADGAKVL CL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the galactokinase cDNA and identification of mutations in two families with cataracts." Stambolian D., Ai Y., Sidjanin D., Nesburn K., Sathe G., Rosenberg M., Bergsma D.J. Nat. Genet. 10:307-312(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT II GALACTOSEMIA MET-32.
[2]	"Fine structure of the human galactokinase GALK1 gene." Bergsma D.J., Ai Y., Skach W.R., Nesburn K., Anoia E., van Horn S., Stambolian D. Genome Res. 6:980-985(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 6-17; 22-37; 70-97; 205-239; 257-267; 288-296 AND 343-388, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[7]	"Comparison of the enzymatic activities of human galactokinase GALK1 and a related human galactokinase protein GK2." Ai Y., Basu M., Bergsma D.J., Stambolian D. Biochem. Biophys. Res. Commun. 212:687-691(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"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].
[9]	"Molecular structure of human galactokinase: implications for type II galactosemia." Thoden J.B., Timson D.J., Reece R.J., Holden H.M. J. Biol. Chem. 280:9662-9670(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-392 IN COMPLEX WITH D-GALACTOSE AND ATP ANALOG, SUBUNIT, SUBSTRATE-BINDING SITES.
[10]	"A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies)." Kalaydjieva L., Perez-Lezaun A., Angelicheva D., Onengut S., Dye D., Bosshard N.U., Jordanova A., Savov A., Yanakiev P., Kremensky I., Radeva B., Hallmayer J., Markov A., Nedkova V., Tournev I., Aneva L., Gitzelmann R. Am. J. Hum. Genet. 65:1299-1307(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GALCT2 THR-28.
[11]	"Novel mutations in 13 probands with galactokinase deficiency." Kolosha V., Anoia E., de Cespedes C., Gitzelmann R., Shih L., Casco T., Saborio M., Trejos R., Buist N., Tedesco T., Skach W., Mitelmann O., Ledee D., Huang K., Stambolian D. Hum. Mutat. 15:447-453(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GALCT2 THR-28; ARG-36; TYR-44; SER-346 AND SER-349.
[12]	"A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, 'Osaka,' in Asians." Okano Y., Asada M., Fujimoto A., Ohtake A., Murayama K., Hsiao K.-J., Choeh K., Yang Y., Cao Q., Reichardt J.K.V., Niihira S., Imamura T., Yamano T. Am. J. Hum. Genet. 68:1036-1042(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GALCT2 VAL-198.
[13]	"Novel mutations in the GALK1 gene in patients with galactokinase deficiency." Hunter M., Angelicheva D., Levy H.L., Pueschel S.M., Kalaydjieva L. Hum. Mutat. 17:77-78(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GALCT2 CYS-68; MET-288 AND PRO-384.
[14]	"Functional analysis of disease-causing mutations in human galactokinase." Timson D.J., Reece R.J. Eur. J. Biochem. 270:1767-1774(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS GALCT2 THR-28; MET-32; ARG-36; TYR-44; CYS-68; VAL-198; MET-288; SER-346; SER-349 AND PRO-384.
[15]	"Galactokinase gene mutations and age-related cataract. Lack of association in an Italian population." Maraini G., Hejtmancik J.F., Shiels A., Mackay D.S., Aldigeri R., Jiao X.D., Williams S.L., Sperduto R.D., Reed G. Mol. Vis. 9:397-400(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MET-184; ASP-274 AND ALA-338.
[16]	"Biochemical characterization of two GALK1 mutations in patients with galactokinase deficiency." Sangiuolo F., Magnani M., Stambolian D., Novelli G. Hum. Mutat. 23:396-396(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GALCT2 MET-32 AND GLN-239.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U26401 mRNA. Translation: AAA96147.1.
L76927 Genomic DNA. Translation: AAB51607.1.
AK314890 mRNA. Translation: BAG37404.1.
BT007005 mRNA. Translation: AAP35651.1.
BC001166 mRNA. Translation: AAH01166.1.

IPI

IPI00940264.

RefSeq

NP_000145.1. NM_000154.1.

UniGene

Hs.407966.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WUU	X-ray	2.50	A/B/C/D	2-392	[»]
1YH7	model	-	A	1-392	[»]

ProteinModelPortal

P51570.

ModBase

Search...

Protein-protein interaction databases

IntAct

P51570. 3 interactions.

STRING

9606.ENSP00000225614.

PTM databases

PhosphoSite

P51570.

Polymorphism databases

DMDM

1730187.

2D gel databases

OGP

P51570.

REPRODUCTION-2DPAGE

IPI00019383.

Proteomic databases

PaxDb

P51570.

PRIDE

P51570.

Protocols and materials databases

DNASU

2584.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225614; ENSP00000225614; ENSG00000108479.
ENST00000588479; ENSP00000465930; ENSG00000108479.

GeneID

2584.

KEGG

hsa:2584.

UCSC

uc002jpk.3. human.

Organism-specific databases

CTD

2584.

GeneCards

GC17M073730.

HGNC

HGNC:4118. GALK1.

HPA

HPA007094.
HPA016960.

MIM

230200. phenotype.
604313. gene.

neXtProt

NX_P51570.

Orphanet

79237. Galactokinase deficiency.

PharmGKB

PA28533.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0153.

HOGENOM

HOG000241100.

HOVERGEN

HBG051695.

KO

K00849.

OrthoDB

EOG44MXSH.

PhylomeDB

P51570.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P51570.

UniPathway

UPA00214.

Gene expression databases

ArrayExpress

P51570.

Bgee

P51570.

CleanEx

HS_GALK1.

Genevestigator

P51570.

GermOnline

ENSG00000108479. Homo sapiens.

Family and domain databases

Gene3D

3.30.230.10. 1 hit.

InterPro

IPR000705. Galactokinase.
IPR019741. Galactokinase_CS.
IPR019539. GalKase_gal-bd.
IPR013750. GHMP_kinase_C_dom.
IPR006204. GHMP_kinase_N_dom.
IPR006203. GHMP_knse_ATP-bd_CS.
IPR006206. Mevalonate/galactokinase.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
[Graphical view]

Pfam

PF10509. GalKase_gal_bdg. 1 hit.
PF08544. GHMP_kinases_C. 1 hit.
PF00288. GHMP_kinases_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000530. Galactokinase. 1 hit.

PRINTS

PR00473. GALCTOKINASE.
PR00959. MEVGALKINASE.

SUPFAM

SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.

TIGRFAMs

TIGR00131. gal_kin. 1 hit.

PROSITE

PS00106. GALACTOKINASE. 1 hit.
PS00627. GHMP_KINASES_ATP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1293257.

EvolutionaryTrace

P51570.

GenomeRNAi

2584.

NextBio

10223.

SOURCE

Search...

Entry information

Entry name

GALK1_HUMAN

Accession

Primary (citable) accession number: P51570
Secondary accession number(s): B2RC07

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 133 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.