ENO4_MOUSE
ID ENO4_MOUSE Reviewed; 619 AA.
AC Q8C042; E9QLA7; Q8BVS9; Q8CFL9;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Enolase 4 {ECO:0000303|PubMed:23446454};
DE EC=4.2.1.11 {ECO:0000305|PubMed:23446454};
DE AltName: Full=2-phospho-D-glycerate hydro-lyase;
GN Name=Eno4;
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 [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 265-619 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 177-619 (ISOFORM 3).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP INTERACTION WITH ENO1 AND AKAP4, AND ALTERNATIVE SPLICING (ISOFORMS 4 AND
RP 5).
RX PubMed=23446454; DOI=10.1095/biolreprod.112.107128;
RA Nakamura N., Dai Q., Williams J., Goulding E.H., Willis W.D., Brown P.R.,
RA Eddy E.M.;
RT "Disruption of a spermatogenic cell-specific mouse enolase 4 (eno4) gene
RT causes sperm structural defects and male infertility.";
RL Biol. Reprod. 88:90-90(2013).
RN [6]
RP TISSUE SPECIFICITY, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=32248064; DOI=10.1016/j.isci.2020.100992;
RA Narita K., Nagatomo H., Kozuka-Hata H., Oyama M., Takeda S.;
RT "Discovery of a Vertebrate-Specific Factor that Processes Flagellar
RT Glycolytic Enolase during Motile Ciliogenesis.";
RL IScience 23:100992-100992(2020).
CC -!- FUNCTION: Required for sperm motility, function and male fertility. May
CC be involved in the normal assembly of the sperm fibrous sheath and
CC provides most of the enolase activity in sperm (PubMed:23446454).
CC {ECO:0000269|PubMed:23446454}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2-phosphoglycerate = H2O + phosphoenolpyruvate;
CC Xref=Rhea:RHEA:10164, ChEBI:CHEBI:15377, ChEBI:CHEBI:58289,
CC ChEBI:CHEBI:58702; EC=4.2.1.11;
CC Evidence={ECO:0000305|PubMed:23446454};
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
CC glyceraldehyde 3-phosphate: step 4/5. {ECO:0000305|PubMed:23446454}.
CC -!- SUBUNIT: Interacts with ENO1 (PubMed:23446454). Isoform 1 and isoform 4
CC interact with AKAP4 (PubMed:23446454). {ECO:0000269|PubMed:23446454}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8C042-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C042-2; Sequence=VSP_035167;
CC Name=3;
CC IsoId=Q8C042-3; Sequence=VSP_035168, VSP_035169;
CC Name=4;
CC IsoId=Q8C042-4; Sequence=VSP_058230;
CC Name=5;
CC IsoId=Q8C042-5; Sequence=VSP_058229;
CC -!- TISSUE SPECIFICITY: Testis-specific (PubMed:23446454, PubMed:32248064).
CC Expressed in spermatids and ependyma (at protein level)
CC (PubMed:32248064). {ECO:0000269|PubMed:23446454,
CC ECO:0000269|PubMed:32248064}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Expressed at higher levels in late
CC spermatids than in pachytene spermatocytes.
CC {ECO:0000269|PubMed:23446454}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Expressed at higher levels in
CC pachytene spermatocytes than in late spermatids.
CC {ECO:0000269|PubMed:23446454}.
CC -!- PTM: Synthesized as an approximately 70-kDa precursor, which then
CC undergoes proteolytic cleavage to an approximately 60-kDa enzyme; HOATZ
CC associates directly or indirectly with ENO4 to mediate this process
CC before its transport to mature flagella. {ECO:0000269|PubMed:32248064}.
CC -!- DISRUPTION PHENOTYPE: Male mice are infertile and the sperm have
CC significantly reduced motility, ATP levels, and enolase enzymatic
CC activity as well as a structurally abnormal sperm fibrous sheath.
CC {ECO:0000269|PubMed:23446454}.
CC -!- SIMILARITY: Belongs to the enolase family. {ECO:0000305}.
CC -!- CAUTION: Although it belongs to the enolase family, Leu-362 is present
CC instead of the conserved Glu which is expected to be an active site
CC residue. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH23285.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC36444.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK032395; BAC27851.1; -; mRNA.
DR EMBL; AK076682; BAC36444.1; ALT_INIT; mRNA.
DR EMBL; AC102604; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023285; AAH23285.1; ALT_INIT; mRNA.
DR RefSeq; NP_848804.2; NM_178689.4.
DR AlphaFoldDB; Q8C042; -.
DR SMR; Q8C042; -.
DR STRING; 10090.ENSMUSP00000062584; -.
DR iPTMnet; Q8C042; -.
DR PhosphoSitePlus; Q8C042; -.
DR MaxQB; Q8C042; -.
DR PaxDb; Q8C042; -.
DR PRIDE; Q8C042; -.
DR ProteomicsDB; 275662; -. [Q8C042-1]
DR ProteomicsDB; 275663; -. [Q8C042-2]
DR ProteomicsDB; 275664; -. [Q8C042-3]
DR ProteomicsDB; 275665; -. [Q8C042-4]
DR ProteomicsDB; 275666; -. [Q8C042-5]
DR Antibodypedia; 49029; 81 antibodies from 14 providers.
DR DNASU; 226265; -.
DR Ensembl; ENSMUST00000054280; ENSMUSP00000062584; ENSMUSG00000048029. [Q8C042-1]
DR GeneID; 226265; -.
DR KEGG; mmu:226265; -.
DR UCSC; uc012bob.1; mouse. [Q8C042-1]
DR CTD; 387712; -.
DR MGI; MGI:2441717; Eno4.
DR VEuPathDB; HostDB:ENSMUSG00000048029; -.
DR eggNOG; KOG2670; Eukaryota.
DR GeneTree; ENSGT00950000182805; -.
DR HOGENOM; CLU_493979_0_0_1; -.
DR InParanoid; Q8C042; -.
DR OrthoDB; 1097401at2759; -.
DR PhylomeDB; Q8C042; -.
DR TreeFam; TF354238; -.
DR UniPathway; UPA00109; UER00187.
DR BioGRID-ORCS; 226265; 1 hit in 65 CRISPR screens.
DR PRO; PR:Q8C042; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8C042; protein.
DR Bgee; ENSMUSG00000048029; Expressed in ventricular system choroidal fissure and 84 other tissues.
DR ExpressionAtlas; Q8C042; baseline and differential.
DR Genevisible; Q8C042; MM.
DR GO; GO:0000015; C:phosphopyruvate hydratase complex; IBA:GO_Central.
DR GO; GO:0097228; C:sperm principal piece; IDA:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004634; F:phosphopyruvate hydratase activity; IMP:MGI.
DR GO; GO:0044782; P:cilium organization; IMP:MGI.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0006096; P:glycolytic process; IMP:MGI.
DR Gene3D; 3.20.20.120; -; 1.
DR Gene3D; 3.30.390.10; -; 1.
DR InterPro; IPR000941; Enolase.
DR InterPro; IPR036849; Enolase-like_C_sf.
DR InterPro; IPR029017; Enolase-like_N.
DR InterPro; IPR020810; Enolase_C.
DR InterPro; IPR020811; Enolase_N.
DR PANTHER; PTHR11902; PTHR11902; 1.
DR Pfam; PF00113; Enolase_C; 1.
DR SMART; SM01192; Enolase_C; 1.
DR SMART; SM01193; Enolase_N; 1.
DR SUPFAM; SSF51604; SSF51604; 1.
DR SUPFAM; SSF54826; SSF54826; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycolysis; Lyase; Reference proteome.
FT CHAIN 1..619
FT /note="Enolase 4"
FT /id="PRO_0000348455"
FT REGION 173..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..354
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..209
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 497
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 548
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..238
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:23446454"
FT /id="VSP_058229"
FT VAR_SEQ 539..619
FT /note="AVGFGARFIKLGGLSRGERMTKYNRLLAIEEELIQRGVWGFSEEHNFSFFQE
FT DATATMAEETLGLLDSIFPTEVIEESAKT -> VSVKNTIFLSFKRMLLPQWLRKLLGS
FT WTPSSPQR (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:23446454"
FT /id="VSP_058230"
FT VAR_SEQ 578..589
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_035167"
FT VAR_SEQ 579..584
FT /note="FSEEHN -> CYCHNG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035168"
FT VAR_SEQ 585..619
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035169"
FT CONFLICT 161
FT /note="R -> W (in Ref. 1; BAC27851)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 619 AA; 67853 MW; 9EE6C085A3438AFC CRC64;
MGDEDGGRRG GITRDLQKLK QQAMAYYQEN DVPRKLEDLL NSTFYLQPAD VYGHLKANYF
SKLAKPPSIC KIVGKTILDG LGLPTLQVEI SCTIQNFPKY ICAVAIPTHF EVVENALPEA
LDAEDSERAQ AVNTAVQWIN QSITEELWGL VPSNQAEVDH RLRTFFEHKV QEDKERKELE
KSQEELVPAP PPVTLPPPPP PPPPPPSKKK GQKAGRRDTL LEKPVSPPEP PEPVLHGSMA
IGAVSLAVAK ASATLASDPL YLTLASLKHD QEQPSTFSMP LLMGSVLSCG KSSPGKLHLM
KEVICIPSPG LTAKQSVELL LEIQKQVNRA METLPPPKQE TKKGHNGSKR AQPPITGKVS
HLGCLTINYD AIEQPLLLLQ GICSNLGLEL GVNFHLAINC AGHELMDYSK GKYEVMVGTH
KSAAEMVELY VDLINKYPSI IALIDPFRKE DAEQWDSLYA ALASRCYLIA GAASGSVSKL
LECRNISTLK SHGLIIKHTN QTTMSDLVEI THLINGKKLL AVFGSTDSES SDDSLVDLAV
GFGARFIKLG GLSRGERMTK YNRLLAIEEE LIQRGVWGFS EEHNFSFFQE DATATMAEET
LGLLDSIFPT EVIEESAKT
