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Protein

Alpha-enolase

Gene

ENO1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Multifunctional enzyme that, as well as its role in glycolysis, plays a part in various processes such as growth control, hypoxia tolerance and allergic responses. May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons. Stimulates immunoglobulin production.
MBP1 binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor.

Miscellaneous

Used as a diagnostic marker for many tumors and, in the heterodimeric form, alpha/gamma, as a marker for hypoxic brain injury after cardiac arrest. Also marker for endometriosis. Antibodies against alpha-enolase are present in sera from patients with cancer-associated retinopathy syndrome (CAR), a progressive blinding disease which occurs in the presence of systemic tumor growth, primarily small-cell carcinoma of the lung and other malignancies. Is identified as an autoantigen in Hashimoto encephalopathy (HE) a rare autoimmune disease associated with Hashimoto thyroiditis (HT). HT is a disorder in which destructive processes overcome the potential capacity of thyroid replacement leading to hypothyroidism.

Catalytic activityi

2-phospho-D-glycerate = phosphoenolpyruvate + H2O.1 Publication

Cofactori

Mg2+1 PublicationNote: Binds two Mg2+ per subunit. Required for catalysis and for stabilizing the dimer.1 Publication

pH dependencei

Enolase activity is lost above pH 9.0. Immunoglobulin production stimulating activity is retained at pH 13.0.1 Publication

Pathwayi: glycolysis

This protein is involved in step 4 of the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate.
Proteins known to be involved in the 5 steps of the subpathway in this organism are:
  1. Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase (HEL-S-162eP), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase (HEL-S-278), Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (GAPDHS)
  2. Phosphoglycerate kinase 2 (PGK2), Phosphoglycerate kinase, Phosphoglycerate kinase, Phosphoglycerate kinase (HEL-S-68p), Phosphoglycerate kinase (HEL-S-272), Phosphoglycerate kinase, Phosphoglycerate kinase, Phosphoglycerate kinase 1 (PGK1), Phosphoglycerate kinase
  3. no protein annotated in this organism
  4. Alpha-enolase (ENO1), Beta-enolase (ENO3), Enolase 4 (ENO4), Gamma-enolase (ENO2)
  5. Pyruvate kinase, Pyruvate kinase PKM (PKM), Pyruvate kinase (PKM2), Pyruvate kinase (PKM), Pyruvate kinase (PKM2), Pyruvate kinase (PKM), Pyruvate kinase, Pyruvate kinase (PKM), Pyruvate kinase, Pyruvate kinase PKLR (PKLR), Pyruvate kinase, Pyruvate kinase (PKM2), Pyruvate kinase (PKM), Pyruvate kinase (HEL-S-30), Pyruvate kinase (PKM2)
This subpathway is part of the pathway glycolysis, which is itself part of Carbohydrate degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate, the pathway glycolysis and in Carbohydrate degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi40Magnesium 11
Binding sitei158SubstrateBy similarity1
Binding sitei167SubstrateBy similarity1
Active sitei210Proton donorBy similarity1
Metal bindingi245Magnesium 21
Metal bindingi293Magnesium 21
Binding sitei293SubstrateBy similarity1
Metal bindingi318Magnesium 21
Binding sitei318SubstrateBy similarity1
Active sitei343Proton acceptorBy similarity1
Binding sitei394SubstrateBy similarity1

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • GTPase binding Source: UniProtKB
  • magnesium ion binding Source: InterPro
  • phosphopyruvate hydratase activity Source: CAFA
  • protein homodimerization activity Source: CAFA
  • RNA binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: CAFA
  • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB

GO - Biological processi

  • canonical glycolysis Source: CAFA
  • gluconeogenesis Source: Reactome
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway Source: CAFA
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: CAFA
  • positive regulation of ATP biosynthetic process Source: CAFA
  • positive regulation of muscle contraction Source: CAFA
  • positive regulation of plasminogen activation Source: CAFA
  • response to virus Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding, Lyase, Repressor
Biological processGlycolysis, Plasminogen activation, Transcription, Transcription regulation
LigandMagnesium, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000074800-MONOMER
BRENDAi4.2.1.11 2681
ReactomeiR-HSA-70171 Glycolysis
R-HSA-70263 Gluconeogenesis
SABIO-RKiP06733
SIGNORiP06733
UniPathwayiUPA00109; UER00187

Protein family/group databases

MoonProtiP06733

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-enolase (EC:4.2.1.11)
Alternative name(s):
2-phospho-D-glycerate hydro-lyase
C-myc promoter-binding protein
Enolase 1
MBP-1
MPB-1
Non-neural enolase
Short name:
NNE
Phosphopyruvate hydratase
Plasminogen-binding protein
Gene namesi
Name:ENO1
Synonyms:ENO1L1, MBPB1, MPB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000074800.13
HGNCiHGNC:3350 ENO1
MIMi172430 gene
neXtProtiNX_P06733

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi94M → I: MBP1 protein production. No MBP1 protein production; when associated with I-97. 1 Publication1
Mutagenesisi97M → I: MBP1 protein production. No MBP1 protein production; when associated with I-94. 1 Publication1
Mutagenesisi384L → A: Loss of transcriptional repression and cell growth inhibition; when associated with A-388. 1 Publication1
Mutagenesisi388L → A: Loss of transcriptional repression and cell growth inhibition; when associated with A-384. 1 Publication1

Organism-specific databases

DisGeNETi2023
OpenTargetsiENSG00000074800
PharmGKBiPA27786

Chemistry databases

ChEMBLiCHEMBL3298

Polymorphism and mutation databases

BioMutaiENO1
DMDMi119339

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001340972 – 434Alpha-enolaseAdd BLAST433

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei5N6-acetyllysineCombined sources1
Modified residuei27PhosphoserineCombined sources1
Modified residuei44PhosphotyrosineCombined sources1
Modified residuei60N6-acetyllysine; alternateBy similarity1
Modified residuei60N6-succinyllysine; alternateBy similarity1
Modified residuei64N6-acetyllysineCombined sources1
Modified residuei71N6-acetyllysineCombined sources1
Modified residuei89N6-acetyllysine; alternateCombined sources1
Modified residuei89N6-succinyllysine; alternateBy similarity1
Modified residuei92N6-acetyllysineBy similarity1
Modified residuei126N6-acetyllysineCombined sources1
Modified residuei193N6-acetyllysineCombined sources1
Modified residuei199N6-acetyllysineCombined sources1
Modified residuei202N6-acetyllysine; alternateBy similarity1
Cross-linki202Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei228N6-acetyllysine; alternateCombined sources1
Modified residuei228N6-succinyllysine; alternateBy similarity1
Modified residuei233N6-acetyllysine; alternateCombined sources1
Modified residuei233N6-malonyllysine; alternate1 Publication1
Modified residuei254PhosphoserineCombined sources1
Modified residuei256N6-acetyllysineCombined sources1
Modified residuei263PhosphoserineCombined sources1
Modified residuei272PhosphoserineCombined sources1
Modified residuei281N6-acetyllysineCombined sources1
Modified residuei285N6-acetyllysineCombined sources1
Modified residuei287PhosphotyrosineCombined sources1
Modified residuei291PhosphoserineCombined sources1
Modified residuei335N6-acetyllysineBy similarity1
Modified residuei343N6-acetyllysineBy similarity1
Modified residuei406N6-acetyllysineBy similarity1
Modified residuei420N6-acetyllysine; alternateCombined sources1
Modified residuei420N6-malonyllysine; alternate1 Publication1
Modified residuei420N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

ISGylated.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP06733
MaxQBiP06733
PaxDbiP06733
PeptideAtlasiP06733
PRIDEiP06733
TopDownProteomicsiP06733-1 [P06733-1]
P06733-2 [P06733-2]

2D gel databases

DOSAC-COBS-2DPAGEiP06733
OGPiP06733
REPRODUCTION-2DPAGEiIPI00465248
P06733
SWISS-2DPAGEiP06733
UCD-2DPAGEiP06733

PTM databases

iPTMnetiP06733
PhosphoSitePlusiP06733
SwissPalmiP06733

Miscellaneous databases

PMAP-CutDBiP06733

Expressioni

Tissue specificityi

The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons.

Developmental stagei

During ontogenesis, there is a transition from the alpha/alpha homodimer to the alpha/beta heterodimer in striated muscle cells, and to the alpha/gamma heterodimer in nerve cells.

Inductioni

Induced in diffuse large cell lymphoma (DLCL) after treatment with the natural biological agent, Bryo1. Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000074800
ExpressionAtlasiP06733 baseline and differential
GenevisibleiP06733 HS

Organism-specific databases

HPAiCAB018614
CAB069394
HPA068284

Interactioni

Subunit structurei

Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific (PubMed:18560153). ENO1 interacts with PLG in the neuronal plasma membrane and promotes its activation. The C-terminal lysine is required for this binding (PubMed:9308760). Isoform MBP-1 interacts with TRAPPC2B (PubMed:11134351). Interacts with ENO4 and PGAM2 (By similarity). Interacts with CMTM6 (PubMed:28813417).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • GTPase binding Source: UniProtKB
  • protein homodimerization activity Source: CAFA

Protein-protein interaction databases

BioGridi108338, 292 interactors
IntActiP06733, 90 interactors
MINTiP06733
STRINGi9606.ENSP00000234590

Chemistry databases

BindingDBiP06733

Structurei

Secondary structure

1434
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 12Combined sources8
Beta strandi18 – 26Combined sources9
Beta strandi29 – 34Combined sources6
Helixi57 – 59Combined sources3
Helixi63 – 71Combined sources9
Helixi73 – 79Combined sources7
Helixi87 – 98Combined sources12
Turni104 – 106Combined sources3
Helixi108 – 125Combined sources18
Helixi130 – 138Combined sources9
Beta strandi147 – 154Combined sources8
Helixi156 – 158Combined sources3
Beta strandi159 – 162Combined sources4
Beta strandi167 – 171Combined sources5
Helixi178 – 200Combined sources23
Helixi202 – 204Combined sources3
Helixi220 – 233Combined sources14
Turni237 – 239Combined sources3
Beta strandi241 – 245Combined sources5
Helixi248 – 250Combined sources3
Turni259 – 262Combined sources4
Helixi267 – 269Combined sources3
Helixi273 – 286Combined sources14
Beta strandi289 – 293Combined sources5
Helixi301 – 311Combined sources11
Beta strandi313 – 318Combined sources6
Turni319 – 323Combined sources5
Helixi325 – 334Combined sources10
Beta strandi338 – 342Combined sources5
Helixi344 – 347Combined sources4
Helixi350 – 362Combined sources13
Beta strandi366 – 370Combined sources5
Helixi380 – 387Combined sources8
Beta strandi391 – 394Combined sources4
Helixi401 – 417Combined sources17
Helixi418 – 420Combined sources3
Helixi425 – 427Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PSNX-ray2.20A/B/C/D1-434[»]
3B97X-ray2.20A/B/C/D2-434[»]
5JLZX-ray1.99E/F26-40[»]
5LAXX-ray2.60E/F26-40[»]
ProteinModelPortaliP06733
SMRiP06733
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06733

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni31 – 38Epitope recognized by CAR and healthy patient antibodies8
Regioni56 – 63Epitope recognized by CAR antibodies8
Regioni97 – 237Required for repression of c-myc promoter activityAdd BLAST141
Regioni370 – 373Substrate bindingBy similarity4
Regioni405 – 434Required for interaction with PLGBy similarityAdd BLAST30

Sequence similaritiesi

Belongs to the enolase family.Curated

Phylogenomic databases

eggNOGiKOG2670 Eukaryota
COG0148 LUCA
GeneTreeiENSGT00910000144064
HOVERGENiHBG000067
InParanoidiP06733
KOiK01689
OMAiEFMIIPV
OrthoDBiEOG091G07NH
PhylomeDBiP06733
TreeFamiTF300391

Family and domain databases

CDDicd03313 enolase, 1 hit
Gene3Di3.20.20.120, 1 hit
3.30.390.10, 1 hit
HAMAPiMF_00318 Enolase, 1 hit
InterProiView protein in InterPro
IPR000941 Enolase
IPR036849 Enolase-like_C_sf
IPR029017 Enolase-like_N
IPR034390 Enolase-like_superfamily
IPR020810 Enolase_C
IPR020809 Enolase_CS
IPR020811 Enolase_N
PANTHERiPTHR11902 PTHR11902, 1 hit
PfamiView protein in Pfam
PF00113 Enolase_C, 1 hit
PF03952 Enolase_N, 1 hit
PIRSFiPIRSF001400 Enolase, 1 hit
PRINTSiPR00148 ENOLASE
SFLDiSFLDG00178 enolase, 1 hit
SFLDS00001 Enolase, 1 hit
SMARTiView protein in SMART
SM01192 Enolase_C, 1 hit
SM01193 Enolase_N, 1 hit
SUPFAMiSSF51604 SSF51604, 1 hit
TIGRFAMsiTIGR01060 eno, 1 hit
PROSITEiView protein in PROSITE
PS00164 ENOLASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform alpha-enolase (identifier: P06733-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSILKIHARE IFDSRGNPTV EVDLFTSKGL FRAAVPSGAS TGIYEALELR
60 70 80 90 100
DNDKTRYMGK GVSKAVEHIN KTIAPALVSK KLNVTEQEKI DKLMIEMDGT
110 120 130 140 150
ENKSKFGANA ILGVSLAVCK AGAVEKGVPL YRHIADLAGN SEVILPVPAF
160 170 180 190 200
NVINGGSHAG NKLAMQEFMI LPVGAANFRE AMRIGAEVYH NLKNVIKEKY
210 220 230 240 250
GKDATNVGDE GGFAPNILEN KEGLELLKTA IGKAGYTDKV VIGMDVAASE
260 270 280 290 300
FFRSGKYDLD FKSPDDPSRY ISPDQLADLY KSFIKDYPVV SIEDPFDQDD
310 320 330 340 350
WGAWQKFTAS AGIQVVGDDL TVTNPKRIAK AVNEKSCNCL LLKVNQIGSV
360 370 380 390 400
TESLQACKLA QANGWGVMVS HRSGETEDTF IADLVVGLCT GQIKTGAPCR
410 420 430
SERLAKYNQL LRIEEELGSK AKFAGRNFRN PLAK
Length:434
Mass (Da):47,169
Last modified:January 23, 2007 - v2
Checksum:iA0ED663FCC15ADA5
GO
Isoform MBP-1 (identifier: P06733-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: Missing.

Note: It is uncertain whether the alternative initiation site is at Met-94 or at Met-97.
Show »
Length:341
Mass (Da):36,928
Checksum:i96D437CF21772928
GO

Sequence cautioni

The sequence AAA35698 differs from that shown. Sequencing errors.Curated
The sequence AAA35698 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55T → A in CAD97642 (PubMed:17974005).Curated1
Sequence conflicti78V → A in BAD96237 (Ref. 7) Curated1
Sequence conflicti187E → G in CAD97642 (PubMed:17974005).Curated1
Sequence conflicti199K → R in BAD96912 (Ref. 7) Curated1
Sequence conflicti252F → S in CAA59331 (PubMed:8824716).Curated1
Sequence conflicti310S → I in CAD97642 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025172177N → K1 PublicationCorresponds to variant dbSNP:rs11544513Ensembl.1
Natural variantiVAR_048936325P → Q. Corresponds to variant dbSNP:rs11544514Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0187251 – 93Missing in isoform MBP-1. 1 PublicationAdd BLAST93

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14328 mRNA Translation: AAA52387.1
X16288, X16289, X16290 Genomic DNA Translation: CAA34360.1
M55914 mRNA Translation: AAA35698.1 Frameshift.
X84907 mRNA Translation: CAA59331.1
BT007163 mRNA Translation: AAP35827.1
AK315417 mRNA Translation: BAG37806.1
AL833741 mRNA Translation: CAH56247.1
BX537400 mRNA Translation: CAD97642.1
AK222517 mRNA Translation: BAD96237.1
AK223192 mRNA Translation: BAD96912.1
DQ056744 Genomic DNA Translation: AAY43128.1
AL139415 Genomic DNA Translation: CAC42425.1
CH471130 Genomic DNA Translation: EAW71604.1
BC001810 mRNA Translation: AAH01810.1
BC004325 mRNA Translation: AAH04325.1
BC004458 mRNA Translation: AAH04458.1
BC009218 mRNA Translation: AAH09218.2
BC009912 mRNA Translation: AAH09912.1
BC011130 mRNA Translation: AAH11130.1
BC015641 mRNA Translation: AAH15641.1
BC021166 mRNA Translation: AAH21166.2
BC022545 mRNA Translation: AAH22545.1
BC027725 mRNA Translation: AAH27725.1
BC050642 mRNA Translation: AAH50642.1
U88968 mRNA Translation: AAC39935.1
AF035286 mRNA Translation: AAB88178.1
CCDSiCCDS97.1 [P06733-1]
PIRiA39579
S11696 A29170
RefSeqiNP_001188412.1, NM_001201483.1 [P06733-2]
NP_001419.1, NM_001428.3 [P06733-1]
UniGeneiHs.517145

Genome annotation databases

EnsembliENST00000234590; ENSP00000234590; ENSG00000074800 [P06733-1]
GeneIDi2023
KEGGihsa:2023
UCSCiuc001apj.3 human [P06733-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiENOA_HUMAN
AccessioniPrimary (citable) accession number: P06733
Secondary accession number(s): B2RD59
, P22712, Q16704, Q4TUS4, Q53FT9, Q53HR3, Q658M5, Q6GMP2, Q71V37, Q7Z3V6, Q8WU71, Q96GV1, Q9BT62, Q9UCH6, Q9UM55
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 223 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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