ID   ENO4_HUMAN              Reviewed;         625 AA.
AC   A6NNW6; A0A087WZY6; A6NI74; B8ZZN9; J3KNX1;
DT   02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-DEC-2018, sequence version 4.
DT   24-JAN-2024, entry version 116.
DE   RecName: Full=Enolase 4 {ECO:0000305};
DE            EC=4.2.1.11 {ECO:0000250|UniProtKB:Q8C042};
DE   AltName: Full=2-phospho-D-glycerate hydro-lyase;
GN   Name=ENO4 {ECO:0000312|HGNC:HGNC:31670}; Synonyms=C10orf134;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
CC   -!- FUNCTION: May be required for sperm motility and function.
CC       {ECO:0000250|UniProtKB:Q8C042}.
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:0000250|UniProtKB:Q8C042};
CC   -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
CC       glyceraldehyde 3-phosphate: step 4/5. {ECO:0000250|UniProtKB:Q8C042}.
CC   -!- SUBUNIT: Interacts with ENO1 and AKAP4. {ECO:0000250|UniProtKB:Q8C042}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=3;
CC         IsoId=A6NNW6-3; Sequence=Displayed;
CC       Name=2;
CC         IsoId=A6NNW6-2; Sequence=VSP_059947, VSP_059948;
CC       Name=4;
CC         IsoId=A6NNW6-4; Sequence=VSP_059949, VSP_059951, VSP_059950;
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.
CC       {ECO:0000250|UniProtKB:Q8C042}.
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}.
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DR   EMBL; BX647301; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC023283; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS73206.1; -. [A6NNW6-3]
DR   RefSeq; NP_001229628.1; NM_001242699.1. [A6NNW6-3]
DR   AlphaFoldDB; A6NNW6; -.
DR   SMR; A6NNW6; -.
DR   IntAct; A6NNW6; 2.
DR   STRING; 9606.ENSP00000345555; -.
DR   iPTMnet; A6NNW6; -.
DR   PhosphoSitePlus; A6NNW6; -.
DR   BioMuta; ENO4; -.
DR   EPD; A6NNW6; -.
DR   MassIVE; A6NNW6; -.
DR   PaxDb; 9606-ENSP00000345555; -.
DR   PeptideAtlas; A6NNW6; -.
DR   ProteomicsDB; 1254; -.
DR   ProteomicsDB; 1644; -. [A6NNW6-2]
DR   Antibodypedia; 49029; 98 antibodies from 14 providers.
DR   DNASU; 387712; -.
DR   Ensembl; ENST00000341276.11; ENSP00000345555.6; ENSG00000188316.15. [A6NNW6-3]
DR   Ensembl; ENST00000409522.5; ENSP00000387194.1; ENSG00000188316.15. [A6NNW6-2]
DR   GeneID; 387712; -.
DR   KEGG; hsa:387712; -.
DR   MANE-Select; ENST00000341276.11; ENSP00000345555.6; NM_001242699.2; NP_001229628.1.
DR   UCSC; uc001lcw.4; human. [A6NNW6-3]
DR   UCSC; uc057wfb.1; human.
DR   UCSC; uc057wfd.1; human.
DR   AGR; HGNC:31670; -.
DR   CTD; 387712; -.
DR   DisGeNET; 387712; -.
DR   GeneCards; ENO4; -.
DR   HGNC; HGNC:31670; ENO4.
DR   HPA; ENSG00000188316; Tissue enhanced (choroid plexus, fallopian tube).
DR   MIM; 131375; gene.
DR   neXtProt; NX_A6NNW6; -.
DR   OpenTargets; ENSG00000188316; -.
DR   VEuPathDB; HostDB:ENSG00000188316; -.
DR   eggNOG; KOG2670; Eukaryota.
DR   GeneTree; ENSGT00950000182805; -.
DR   HOGENOM; CLU_1079780_0_0_1; -.
DR   InParanoid; A6NNW6; -.
DR   OMA; MKELICI; -.
DR   OrthoDB; 2908712at2759; -.
DR   PhylomeDB; A6NNW6; -.
DR   TreeFam; TF354238; -.
DR   PathwayCommons; A6NNW6; -.
DR   Reactome; R-HSA-70171; Glycolysis.
DR   Reactome; R-HSA-70263; Gluconeogenesis.
DR   SignaLink; A6NNW6; -.
DR   UniPathway; UPA00109; UER00187.
DR   BioGRID-ORCS; 387712; 9 hits in 354 CRISPR screens.
DR   ChiTaRS; ENO4; human.
DR   GenomeRNAi; 387712; -.
DR   Pharos; A6NNW6; Tbio.
DR   PRO; PR:A6NNW6; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; A6NNW6; Protein.
DR   Bgee; ENSG00000188316; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 87 other cell types or tissues.
DR   ExpressionAtlas; A6NNW6; baseline and differential.
DR   GO; GO:0000015; C:phosphopyruvate hydratase complex; IBA:GO_Central.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0004634; F:phosphopyruvate hydratase activity; IBA:GO_Central.
DR   GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
DR   CDD; cd22974; DD_ENO4; 1.
DR   Gene3D; 3.20.20.120; Enolase-like C-terminal domain; 1.
DR   Gene3D; 3.30.390.10; Enolase-like, N-terminal domain; 1.
DR   InterPro; IPR047500; DD_ENO4.
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; ENOLASE; 1.
DR   PANTHER; PTHR11902:SF30; ENOLASE 4; 1.
DR   Pfam; PF00113; Enolase_C; 1.
DR   SMART; SM01192; Enolase_C; 1.
DR   SMART; SM01193; Enolase_N; 1.
DR   SUPFAM; SSF51604; Enolase C-terminal domain-like; 1.
DR   SUPFAM; SSF54826; Enolase N-terminal domain-like; 1.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Glycolysis; Lyase; Reference proteome.
FT   CHAIN           1..625
FT                   /note="Enolase 4"
FT                   /id="PRO_0000348454"
FT   REGION          184..226
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          331..350
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          604..625
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        188..206
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         300
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         548
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..235
FT                   /note="Missing (in isoform 4)"
FT                   /id="VSP_059949"
FT   VAR_SEQ         56..330
FT                   /note="Missing (in isoform 2)"
FT                   /id="VSP_059947"
FT   VAR_SEQ         406..448
FT                   /note="NKGKYEVIMGTYKNAAEMVDLYVDLINKYPSIIALIDPFRKED -> D (in
FT                   isoform 2)"
FT                   /id="VSP_059948"
FT   VAR_SEQ         575..598
FT                   /note="GFKEEHTFFYFNEEAEKAAEALEA -> ATSSSSCDARIGGQEQETMTLVKV
FT                   (in isoform 4)"
FT                   /id="VSP_059951"
FT   VAR_SEQ         599..625
FT                   /note="Missing (in isoform 4)"
FT                   /id="VSP_059950"
FT   CONFLICT        32
FT                   /note="V -> I (in Ref. 1; BX647301)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   625 AA;  68465 MW;  3FE6180EE2D83CE5 CRC64;
     MEEEGGGRSC GTTRELQKLK QQAMEYYREN DVPRRLEELL NSTFYLQPAD VYGHLANCFS
     KLAKPPTICK IVGKDVLDGL GLPTLQVDIF CTIQNFPKNV CSVVISTHFE VHENALPELA
     KAEEAERASA VSTAVQWVNS TITHELQGMA PSDQAEVDHL LRIFFASKVQ EDKGRKELEK
     SLEYSTVPTP LPPVPPPPPP PPPTKKKGQK PGRKDTITEK PIAPAEPVEP VLSGSMAIGA
     VSLAVAKACA MLLNKPLYLN IALLKHNQEQ PTTLSMPLLM VSLVSCGKSS SGKLNLMKEV
     ICIPHPELTT KQGVEMLMEM QKHINKIIEM PSPPKAETKK GHDGSKRGQQ QITGKMSHLG
     CLTINCDSIE QPLLLIQEIC ANLGLELGTN LHLAINCAGH ELMDYNKGKY EVIMGTYKNA
     AEMVDLYVDL INKYPSIIAL IDPFRKEDSE QWDSIYHALG SRCYIIAGTA SKSISKLLEQ
     GNISIPKSNG LIIKHTNQTT MSDLVEITNL IDSKKHITVF GSTEGESSDD SLVDLAVGLG
     VRFIKLGGLS RGERVTKYNR LLTIEEELVQ NGTLGFKEEH TFFYFNEEAE KAAEALEAAA
     AREPLVPTFP TQGVEESAET GASSG
//