GLPK2_HUMAN
ID GLPK2_HUMAN Reviewed; 553 AA.
AC Q14410; A8K876; Q6PD73; Q86XV8;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Glycerol kinase 2;
DE Short=GK 2;
DE Short=Glycerokinase 2;
DE EC=2.7.1.30;
DE AltName: Full=ATP:glycerol 3-phosphotransferase 2;
DE AltName: Full=Glycerol kinase, testis specific 2;
GN Name=GK2; Synonyms=GKP2, GKTA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=7987308; DOI=10.1093/hmg/3.8.1317;
RA Sargent C.A., Young C., Marsh S., Ferguson-Smith M.A., Affara N.A.;
RT "The glycerol kinase gene family: structure of the Xp gene, and related
RT intronless retroposons.";
RL Hum. Mol. Genet. 3:1317-1324(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, INTERACTION WITH PLD6, AND TISSUE SPECIFICITY.
RX PubMed=28852571; DOI=10.1038/celldisc.2017.30;
RA Chen Y., Liang P., Huang Y., Li M., Zhang X., Ding C., Feng J., Zhang Z.,
RA Zhang X., Gao Y., Zhang Q., Cao S., Zheng H., Liu D., Songyang Z.,
RA Huang J.;
RT "Glycerol kinase-like proteins cooperate with Pld6 in regulating sperm
RT mitochondrial sheath formation and male fertility.";
RL Cell Discov. 3:17030-17030(2017).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=33536340; DOI=10.1073/pnas.2018355118;
RA Shimada K., Park S., Miyata H., Yu Z., Morohoshi A., Oura S., Matzuk M.M.,
RA Ikawa M.;
RT "ARMC12 regulates spatiotemporal mitochondrial dynamics during
RT spermiogenesis and is required for male fertility.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC -!- FUNCTION: Key enzyme in the regulation of glycerol uptake and
CC metabolism. Essential for male fertility and sperm mitochondrial sheath
CC formation (By similarity). Required for proper arrangement of crescent-
CC like mitochondria to form the mitochondrial sheath during
CC spermatogenesis (By similarity). Can induce mitochondrial clustering
CC through interactions with PLD6 and up-regulation of phosphatidic acid
CC synthesis in the mitochondria (PubMed:28852571).
CC {ECO:0000250|UniProtKB:Q9WU65, ECO:0000269|PubMed:28852571}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glycerol = ADP + H(+) + sn-glycerol 3-phosphate;
CC Xref=Rhea:RHEA:21644, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57597, ChEBI:CHEBI:456216;
CC EC=2.7.1.30;
CC -!- PATHWAY: Polyol metabolism; glycerol degradation via glycerol kinase
CC pathway; sn-glycerol 3-phosphate from glycerol: step 1/1.
CC -!- SUBUNIT: Interacts with ARMC12 (By similarity). Interacts with PLD6
CC (PubMed:28852571). {ECO:0000250|UniProtKB:Q9WU65,
CC ECO:0000269|PubMed:28852571}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q9WU65}; Single-pass type IV membrane protein
CC {ECO:0000250|UniProtKB:Q9WU65}. Cytoplasm {ECO:0000250}. Note=In sperm
CC the majority of the enzyme is bound to mitochondria.
CC {ECO:0000250|UniProtKB:Q9WU65}.
CC -!- TISSUE SPECIFICITY: Testis-specific (PubMed:33536340). Expressed in the
CC midpiece of spermatozoa (PubMed:28852571).
CC {ECO:0000269|PubMed:28852571, ECO:0000269|PubMed:33536340}.
CC -!- SIMILARITY: Belongs to the FGGY kinase family. {ECO:0000305}.
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DR EMBL; X78712; CAA55365.1; -; mRNA.
DR EMBL; AK292241; BAF84930.1; -; mRNA.
DR EMBL; CH471057; EAX05842.1; -; Genomic_DNA.
DR EMBL; BC029820; AAH29820.1; -; mRNA.
DR EMBL; BC048274; AAH48274.2; -; mRNA.
DR EMBL; BC058888; AAH58888.1; -; mRNA.
DR CCDS; CCDS3585.1; -.
DR PIR; I37417; I37417.
DR RefSeq; NP_149991.2; NM_033214.2.
DR AlphaFoldDB; Q14410; -.
DR SMR; Q14410; -.
DR BioGRID; 108977; 13.
DR IntAct; Q14410; 2.
DR STRING; 9606.ENSP00000351706; -.
DR iPTMnet; Q14410; -.
DR PhosphoSitePlus; Q14410; -.
DR BioMuta; GK2; -.
DR DMDM; 212286188; -.
DR EPD; Q14410; -.
DR jPOST; Q14410; -.
DR MassIVE; Q14410; -.
DR MaxQB; Q14410; -.
DR PaxDb; Q14410; -.
DR PeptideAtlas; Q14410; -.
DR PRIDE; Q14410; -.
DR ProteomicsDB; 59985; -.
DR Antibodypedia; 24966; 277 antibodies from 31 providers.
DR DNASU; 2712; -.
DR Ensembl; ENST00000358842.5; ENSP00000351706.3; ENSG00000196475.6.
DR GeneID; 2712; -.
DR KEGG; hsa:2712; -.
DR MANE-Select; ENST00000358842.5; ENSP00000351706.3; NM_033214.3; NP_149991.2.
DR UCSC; uc003hlu.4; human.
DR CTD; 2712; -.
DR DisGeNET; 2712; -.
DR GeneCards; GK2; -.
DR HGNC; HGNC:4291; GK2.
DR HPA; ENSG00000196475; Tissue enriched (testis).
DR MIM; 600148; gene.
DR neXtProt; NX_Q14410; -.
DR OpenTargets; ENSG00000196475; -.
DR PharmGKB; PA28702; -.
DR VEuPathDB; HostDB:ENSG00000196475; -.
DR eggNOG; KOG2517; Eukaryota.
DR GeneTree; ENSGT01000000214434; -.
DR HOGENOM; CLU_009281_2_3_1; -.
DR InParanoid; Q14410; -.
DR OMA; VQWMRDQ; -.
DR OrthoDB; 519426at2759; -.
DR PhylomeDB; Q14410; -.
DR TreeFam; TF321504; -.
DR PathwayCommons; Q14410; -.
DR Reactome; R-HSA-75109; Triglyceride biosynthesis.
DR SignaLink; Q14410; -.
DR UniPathway; UPA00618; UER00672.
DR BioGRID-ORCS; 2712; 7 hits in 1061 CRISPR screens.
DR GenomeRNAi; 2712; -.
DR Pharos; Q14410; Tbio.
DR PRO; PR:Q14410; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q14410; protein.
DR Bgee; ENSG00000196475; Expressed in sperm and 35 other tissues.
DR ExpressionAtlas; Q14410; baseline and differential.
DR Genevisible; Q14410; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0097226; C:sperm mitochondrial sheath; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004370; F:glycerol kinase activity; IBA:GO_Central.
DR GO; GO:0016773; F:phosphotransferase activity, alcohol group as acceptor; IBA:GO_Central.
DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:0019563; P:glycerol catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006071; P:glycerol metabolic process; IBA:GO_Central.
DR GO; GO:0046167; P:glycerol-3-phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IBA:GO_Central.
DR GO; GO:0120317; P:sperm mitochondrial sheath assembly; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0006641; P:triglyceride metabolic process; IBA:GO_Central.
DR CDD; cd07792; FGGY_GK1-3_metazoa; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR000577; Carb_kinase_FGGY.
DR InterPro; IPR018485; Carb_kinase_FGGY_C.
DR InterPro; IPR018483; Carb_kinase_FGGY_CS.
DR InterPro; IPR018484; Carb_kinase_FGGY_N.
DR InterPro; IPR042018; GK1-3_metazoa.
DR InterPro; IPR005999; Glycerol_kin.
DR Pfam; PF02782; FGGY_C; 1.
DR Pfam; PF00370; FGGY_N; 1.
DR PIRSF; PIRSF000538; GlpK; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR TIGRFAMs; TIGR01311; glycerol_kin; 1.
DR PROSITE; PS00933; FGGY_KINASES_1; 1.
DR PROSITE; PS00445; FGGY_KINASES_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Differentiation; Glycerol metabolism; Kinase;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Reference proteome; Spermatogenesis; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..553
FT /note="Glycerol kinase 2"
FT /id="PRO_0000059536"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 20
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 24
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 148
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 259
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 281
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 326
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 427..431
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT CONFLICT 238
FT /note="E -> G (in Ref. 2; BAF84930)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="A -> T (in Ref. 2; BAF84930)"
FT /evidence="ECO:0000305"
FT CONFLICT 499
FT /note="R -> C (in Ref. 2; BAF84930)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="S -> C (in Ref. 1; CAA55365)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 60594 MW; 8CE43A0686BC4AD6 CRC64;
MAAPKTAAVG PLVGAVVQGT NSTRFLVFNS KTAELLSHHK VELTQEFPKE GWVEQDPKEI
LQSVYECIAR TCEKLDELNI DISNIKAVGV SNQRETTVIW DKLTGEPLYN AVVWLDLRTQ
TTVEDLSKKI PGNSNFVKSK TGLPLSTYFS AVKLRWMLDN VRNVQKAVEE GRALFGTIDS
WLIWSLTGGV NGGVHCTDVT NASRTMLFNI HSLEWDKELC DFFEIPMDLL PNVFSSSEIY
GLIKTGALEG VPISGCLGDQ CAALVGQMCF QEGQAKNTYG TGCFLLCNTG RKCVFSEHGL
LTTVAYKLGR EKPAYYALEG SVAIAGAVIR WLRDNLGIIE TSGDIERLAK EVGTSYGCYF
VPAFSGLYAP YWEPSARGIL CGLTQFTNKC HIAFAALEAV CFQTREILEA MNRDCGIPLR
HLQVDGGMTN NKVLMQLQAD ILHIPVIKPF MPETTALGAA MAAGAAEGVS VWSLEPQALS
VLRMERFEPQ IQATESEIRY ATWKKAVMKS MGWVTSQSPE GGDPSIFSSL PLGFFIVSSM
VMLIGARYIS GVP
