GLPK2_MOUSE
ID GLPK2_MOUSE Reviewed; 554 AA.
AC Q9WU65;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 139.
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=Gk-rs2, Gkrs2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv; TISSUE=Testis;
RX PubMed=10444329; DOI=10.1006/geno.1999.5874;
RA Pan Y., Decker W.K., Huq A.H., Craigen W.J.;
RT "Retrotransposition of glycerol kinase-related genes from the X chromosome
RT to autosomes: functional and evolutionary aspects.";
RL Genomics 59:282-290(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TOPOLOGY, INTERACTION
RP 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 [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=30662012; DOI=10.1262/jrd.2018-136;
RA Shimada K., Kato H., Miyata H., Ikawa M.;
RT "Glycerol kinase 2 is essential for proper arrangement of crescent-like
RT mitochondria to form the mitochondrial sheath during mouse
RT spermatogenesis.";
RL J. Reprod. Dev. 65:155-162(2019).
RN [6]
RP INTERACTION WITH ARMC12, AND 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 (PubMed:28852571, PubMed:30662012). Required for proper
CC arrangement of crescent-like mitochondria to form the mitochondrial
CC sheath during spermatogenesis.(PubMed:30662012). Can induce
CC mitochondrial clustering through interactions with PLD6 and up-
CC regulation of phosphatidic acid synthesis in the mitochondria
CC (PubMed:28852571). {ECO:0000269|PubMed:28852571,
CC ECO:0000269|PubMed:30662012}.
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 PLD6 (PubMed:28852571). Interacts with ARMC12
CC (PubMed:33536340). {ECO:0000269|PubMed:28852571,
CC ECO:0000269|PubMed:33536340}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:28852571}; Single-pass type IV membrane protein
CC {ECO:0000305|PubMed:28852571}. Cytoplasm {ECO:0000250}. Note=In sperm
CC the majority of the enzyme is bound to mitochondria.
CC {ECO:0000269|PubMed:28852571}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:28852571,
CC ECO:0000269|PubMed:30662012, ECO:0000269|PubMed:33536340}.
CC -!- DISRUPTION PHENOTYPE: Male mice are infertile due to dysfunctional
CC spermatozoa, which exhibit unregulated ATP production, disordered
CC mitochondrial sheath formation, abnormal mitochondrial morphology, and
CC defective sperm tail (PubMed:30662012, PubMed:33536340). Spermatozoa
CC cannot transit the uterotubal junction due to reduced motility leading
CC to male infertility (PubMed:33536340). Spermatids exhibit abnormal
CC arrangement of crescent-like mitochondria, which causes a
CC disorganization of the mitochondrial sheath (PubMed:33536340).
CC {ECO:0000269|PubMed:30662012, ECO:0000269|PubMed:33536340}.
CC -!- SIMILARITY: Belongs to the FGGY kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF117734; AAD24551.1; -; mRNA.
DR EMBL; BC050764; AAH50764.1; -; mRNA.
DR EMBL; BC061147; AAH61147.1; -; mRNA.
DR CCDS; CCDS19454.1; -.
DR RefSeq; NP_034424.1; NM_010294.1.
DR AlphaFoldDB; Q9WU65; -.
DR SMR; Q9WU65; -.
DR STRING; 10090.ENSMUSP00000052226; -.
DR iPTMnet; Q9WU65; -.
DR PhosphoSitePlus; Q9WU65; -.
DR jPOST; Q9WU65; -.
DR MaxQB; Q9WU65; -.
DR PaxDb; Q9WU65; -.
DR PRIDE; Q9WU65; -.
DR ProteomicsDB; 270996; -.
DR Antibodypedia; 24966; 277 antibodies from 31 providers.
DR DNASU; 14626; -.
DR Ensembl; ENSMUST00000059657; ENSMUSP00000052226; ENSMUSG00000050553.
DR GeneID; 14626; -.
DR KEGG; mmu:14626; -.
DR UCSC; uc008yfz.1; mouse.
DR CTD; 2712; -.
DR MGI; MGI:1329027; Gk2.
DR VEuPathDB; HostDB:ENSMUSG00000050553; -.
DR eggNOG; KOG2517; Eukaryota.
DR GeneTree; ENSGT01000000214434; -.
DR HOGENOM; CLU_009281_2_3_1; -.
DR InParanoid; Q9WU65; -.
DR OMA; VQWMRDQ; -.
DR OrthoDB; 519426at2759; -.
DR PhylomeDB; Q9WU65; -.
DR TreeFam; TF321504; -.
DR BRENDA; 2.7.1.30; 3474.
DR Reactome; R-MMU-75109; Triglyceride biosynthesis.
DR UniPathway; UPA00618; UER00672.
DR BioGRID-ORCS; 14626; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q9WU65; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9WU65; protein.
DR Bgee; ENSMUSG00000050553; Expressed in spermatid and 8 other tissues.
DR Genevisible; Q9WU65; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0097226; C:sperm mitochondrial sheath; IDA: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; IMP: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; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP: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..554
FT /note="Glycerol kinase 2"
FT /id="PRO_0000343678"
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"
SQ SEQUENCE 554 AA; 60630 MW; 8DFD5E85E74F5198 CRC64;
MAASKQTSAG PLVGAVVQGT NSTRFLVFNS KTAELVCSHQ VELTQEYPKE GWVEQDPKEI
LKSVYECIAK ACEKLAEVNI DISNIKAIGV SNQRETTVVW DKFTGDPLYN AVVWLDLRTQ
STVETLTKKI PGNSNFVKSK TGLPLSTYFS AVKLRWMLDN LRPIQKAVEE GRAMFGTIDS
WLIWCMTGGV NGGIHCTDVT NACRTMLFNI HSLEWDKDLC DFFEIPMSIL PNVCSSSEIY
GLMTSGALEG VPISGCLGDQ SAALVGQMCF HEGQAKNTYG TGCFLLCNTG QKCVFSEHGL
LTTLAYKLGK NKPVFYALEG SVAIAGAVIR WLRDNFEIIT TSGEVENLAR EVGTSYGCYF
VPAFSGLYAP YWEPSARGII CGLTQFTNKC HIAFAALEAV CFQTREILDA MNRDCGIPLS
HLQVDGGMTN NRILMQLQAD ILHIPVVKSV MPETTALGAA MAAGAAEGVN VWSLEPEDLS
TILMERYEPQ IQATESEIRF STWKRAVMKS MGWVTAKDPE NGDNPVFSCL PLGFFIVSSM
TLLIGARCVS TAEE
