ENO1
Alpha-enolase
Also known as: ENO1L1, ENOA_HUMAN, MBP-1, MPB1, PPH
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P06733
- Gene
- ENO1
- Ensembl
- ENSG00000074800
- Chromosome
- 1
- Canonical length
- 434 aa
- Protein class
- Cancer-related genes, Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Plasma membrane,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes alpha-enolase, one of three enolase isoenzymes found in mammals. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase in addition, functions as a structural lens protein (tau-crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy. [provided by RefSeq, Jan 2011]
Canonical amino-acid sequenceUniProt
434 residues, UniProt reviewed canonical sequence.
>P06733|ENO1
1 MSILKIHARE IFDSRGNPTV EVDLFTSKGL FRAAVPSGAS TGIYEALELR DNDKTRYMGK
61 GVSKAVEHIN KTIAPALVSK KLNVTEQEKI DKLMIEMDGT ENKSKFGANA ILGVSLAVCK
121 AGAVEKGVPL YRHIADLAGN SEVILPVPAF NVINGGSHAG NKLAMQEFMI LPVGAANFRE
181 AMRIGAEVYH NLKNVIKEKY GKDATNVGDE GGFAPNILEN KEGLELLKTA IGKAGYTDKV
241 VIGMDVAASE FFRSGKYDLD FKSPDDPSRY ISPDQLADLY KSFIKDYPVV SIEDPFDQDD
301 WGAWQKFTAS AGIQVVGDDL TVTNPKRIAK AVNEKSCNCL LLKVNQIGSV TESLQACKLA
361 QANGWGVMVS HRSGETEDTF IADLVVGLCT GQIKTGAPCR SERLAKYNQL LRIEEELGSK
421 AKFAGRNFRN PLAKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ENO1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.19
- Highest tissue expression
- 1,003 nTPM
Expression across tissuesHPA
Tissue
- esophagus: 1,003 nTPM
- kidney: 950 nTPM
- choroid plexus: 840 nTPM
- basal ganglia: 794 nTPM
- bone marrow: 749 nTPM
- cerebral cortex: 746 nTPM
Single-cell type
- esophageal basal cells: 2,586 nCPM
- extravillous trophoblasts: 2,439 nCPM
- esophageal suprabasal cells: 2,329 nCPM
- müller glia: 2,323 nCPM
- esophageal apical cells: 2,123 nCPM
- migrating cytotrophoblasts: 2,045 nCPM
Immune cell
- total PBMC: 2,170 nTPM
- myeloid DC: 1,217 nTPM
- classical monocyte: 1,200 nTPM
- non-classical monocyte: 834 nTPM
- intermediate monocyte: 823 nTPM
- T-reg: 702 nTPM
Brain region
- cerebellum: 692 nTPM
- hippocampal formation: 599 nTPM
- medulla oblongata: 573 nTPM
- midbrain: 552 nTPM
- pons: 536 nTPM
- hypothalamus: 524 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about ENO1.
Disease | ImmuneIEDB
Conditions an epitope on ENO1 was assayed in.
- rheumatoid arthritis B and T cell
- multiple sclerosis B cell
- autoimmune thyroiditis B cell
- systemic lupus erythematosus B cell
- autoimmune disease of skin and connective tissue B cell
- Sjogren's syndrome B cell
- narcolepsy B cell
- peripheral nervous system disease B cell
- Timothy grass allergy T cell
- allergic disease T cell
- ovarian cancer T cell
- periodontal disease B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against ENO1 are reported. Each links to that disease's full target list.
- Hashimoto Disease 9
- Lupus Erythematosus, Systemic 9
- Encephalitis 8
- Lung Neoplasms 7
- Glomerulonephritis, Membranous 6
- Behcet Syndrome 5
- Brain Diseases 5
- Arthritis, Rheumatoid 4
- Lupus Nephritis 4
- Scleroderma, Systemic 4
- Cerebellar Ataxia 3
- Cryoglobulinemia 3
- Vasculitis 3
Showing 13 of 14 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for ENO1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
92 publications
- Alpha-Enolase: Emerging Tumor-Associated Antigen, Cancer Biomarker, and Oncotherapeutic Target.
2020 · Front Genet · RCR 4.6 · 70 citations - Human alpha-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Behçet's disease.
2003 · Arthritis Rheum · RCR 4.3 · 162 citations - Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis.
1993 · Kidney Int · RCR 3.2 · 89 citations - Autoantibodies specific for alpha-enolase in systemic autoimmune disorders.
2000 · J Rheumatol · RCR 3.1 · 118 citations - Presence of autoantibodies to the glycolytic enzyme alpha-enolase in sera from patients with early rheumatoid arthritis.
2002 · Arthritis Rheum · RCR 3.1 · 125 citations
Show 20 more of 92 total
- Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized αenolase (methionine sulfoxide 93).
2019 · Sci Rep · RCR 3.1 · 65 citations - Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto's encephalopathy.
2002 · FEBS Lett · RCR 3 · 105 citations - Anti-enolase-alpha autoantibodies in cancer-associated retinopathy: epitope mapping and cytotoxicity on retinal cells.
1998 · J Autoimmun · RCR 3 · 99 citations - Proteomics-based identification of alpha-enolase as a tumor antigen in non-small lung cancer.
2007 · Cancer Sci · RCR 2.4 · 96 citations - The role of anti-alpha-enolase autoantibodies in pathogenicity of autoimmune-mediated retinopathy.
2007 · J Clin Immunol · RCR 2.2 · 78 citations - An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated antigen.
2009 · Int J Cancer · RCR 2.2 · 100 citations - Prevalence and clinico-serological correlations of anti-alpha-enolase, anti-C1q, and anti-dsDNA antibodies in patients with systemic lupus erythematosus.
2006 · J Rheumatol · RCR 1.9 · 67 citations - Identification and characterization of autoantibodies against catalase and alpha-enolase in patients with primary sclerosing cholangitis.
1998 · Clin Exp Immunol · RCR 1.8 · 68 citations - Association between anti-Porphyromonas gingivalis or anti-α-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA.
2015 · BMC Musculoskelet Disord · RCR 1.7 · 41 citations - Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy.
2020 · Clin J Am Soc Nephrol · RCR 1.6 · 28 citations - Cellular targets of anti-alpha-enolase autoantibodies of patients with autoimmune retinopathy.
2004 · J Autoimmun · RCR 1.6 · 57 citations - Hashimoto's encephalopathy as a treatable adult-onset cerebellar ataxia mimicking spinocerebellar degeneration.
2013 · Eur Neurol · RCR 1.5 · 34 citations - Circulating antibodies against alpha-enolase in patients with primary membranous nephropathy (MN).
1999 · Clin Exp Immunol · RCR 1.4 · 54 citations - Anti-alpha-enolase antibodies in patients with inflammatory Bowel disease.
2008 · Clin Chem · RCR 1.3 · 42 citations - Surface expression of a glycolytic enzyme, alpha-enolase, recognized by autoantibodies in connective tissue disorders.
2000 · Eur J Immunol · RCR 1.3 · 56 citations - Antifibroblast antibodies from systemic sclerosis patients bind to {alpha}-enolase and are associated with interstitial lung disease.
2010 · Ann Rheum Dis · RCR 1.3 · 46 citations - Circulating antibodies to α-enolase and phospholipase A2 receptor and composition of glomerular deposits in Japanese patients with primary or secondary membranous nephropathy.
2017 · Clin Exp Nephrol · RCR 1.2 · 27 citations - Anti-alpha-enolase antibodies in pituitary disease.
2003 · Endocr J · RCR 1.2 · 44 citations - Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies: A clinical subtype of Hashimoto encephalopathy.
2017 · Medicine (Baltimore) · RCR 1.2 · 22 citations - Anti-alpha-enolase antibodies in cancer-associated retinopathy with small cell carcinoma of the lung.
2005 · Am J Ophthalmol · RCR 1.2 · 41 citations
Reference: B cellIEDB
36 publications
- Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase.
2008 · Arthritis Rheum · RCR 7.6 · 304 citations - Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis.
2011 · Arthritis Rheum · RCR 5 · 181 citations - Environmental and genetic factors in the development of anticitrullinated protein antibodies (ACPAs) and ACPA-positive rheumatoid arthritis: an epidemiological investigation in twins.
2015 · Ann Rheum Dis · RCR 4.7 · 133 citations - Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile.
2013 · Ann Rheum Dis · RCR 4.3 · 130 citations - Antibodies to a Citrullinated Porphyromonas gingivalis Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells: Implications for a Bacterial Origin in RA Etiology.
2022 · Front Immunol · RCR 3.6 · 37 citations
Show 20 more of 36 total
- Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized αenolase (methionine sulfoxide 93).
2019 · Sci Rep · RCR 3.1 · 65 citations - High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.
2016 · Mol Cell Proteomics · RCR 2.5 · 66 citations - Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis.
2018 · Arthritis Rheumatol · RCR 2.5 · 66 citations - Validation of a multiplex chip-based assay for the detection of autoantibodies against citrullinated peptides.
2012 · Arthritis Res Ther · RCR 2.4 · 83 citations - Identification of an immunodominant peptide from citrullinated tenascin-C as a major target for autoantibodies in rheumatoid arthritis.
2016 · Ann Rheum Dis · RCR 2.4 · 62 citations - Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy.
2017 · J Proteome Res · RCR 2.2 · 57 citations - Antibodies to carbamylated α-enolase epitopes in rheumatoid arthritis also bind citrullinated epitopes and are largely indistinct from anti-citrullinated protein antibodies.
2016 · Arthritis Res Ther · RCR 2.2 · 57 citations - Association of Distinct Fine Specificities of Anti-Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis.
2017 · Arthritis Rheumatol · RCR 2.1 · 47 citations - Autoantibodies From Single Circulating Plasmablasts React With Citrullinated Antigens and Porphyromonas gingivalis in Rheumatoid Arthritis.
2016 · Arthritis Rheumatol · RCR 2 · 50 citations - Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis.
2016 · Front Immunol · RCR 2 · 58 citations - Anticitrullinated protein/peptide antibody multiplexing defines an extended group of ACPA-positive rheumatoid arthritis patients with distinct genetic and environmental determinants.
2018 · Ann Rheum Dis · RCR 1.9 · 46 citations - Identification of new citrulline-specific autoantibodies, which bind to human arthritic cartilage, by mass spectrometric analysis of citrullinated type II collagen.
2014 · Arthritis Rheumatol · RCR 1.8 · 59 citations - Antibodies directed against endogenous and exogenous citrullinated antigens pre-date the onset of rheumatoid arthritis.
2016 · Arthritis Res Ther · RCR 1.8 · 46 citations - Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.
2020 · Arthritis Rheumatol · RCR 1.7 · 30 citations - Associations of antibodies against citrullinated peptides with human leukocyte antigen-shared epitope and smoking prior to the development of rheumatoid arthritis.
2015 · Arthritis Res Ther · RCR 1.6 · 45 citations - Peptides of neuron specific enolase as potential ASD biomarkers: From discovery to epitope mapping.
2020 · Brain Behav Immun · RCR 1.4 · 25 citations - Affinity purified anti-citrullinated protein/peptide antibodies target antigens expressed in the rheumatoid joint.
2014 · Arthritis Res Ther · RCR 1.4 · 41 citations - Monoclonal anti-citrullinated protein antibodies selected on citrullinated fibrinogen have distinct targets with different cross-reactivity patterns.
2013 · Rheumatology (Oxford) · RCR 1.3 · 44 citations - The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis.
2023 · Rheumatology (Oxford) · RCR 1 · 6 citations - Particular association of clinical and genetic features with autoimmunity to citrullinated α-enolase in rheumatoid arthritis.
2011 · Arthritis Rheum · RCR 0.9 · 33 citations
Reference: T cellIEDB
10 publications
- Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their frequency is influenced by disease duration and therapy.
2014 · Arthritis Rheumatol · RCR 5 · 179 citations - The molecular basis underlying T cell specificity towards citrullinated epitopes presented by HLA-DR4.
2024 · Nat Commun · RCR 3.1 · 22 citations - Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis.
2021 · JCI Insight · RCR 2.8 · 43 citations - Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses.
2020 · J Immunother Cancer · RCR 2 · 46 citations - Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals.
2013 · Proc Natl Acad Sci U S A · RCR 1.8 · 59 citations
Show 5 more
- Memory T cells specific to citrullinated α-enolase are enriched in the rheumatic joint.
2018 · J Autoimmun · RCR 1.8 · 48 citations - Allergen and Epitope Targets of Mouse-Specific T Cell Responses in Allergy and Asthma.
2018 · Front Immunol · RCR 1.1 · 25 citations - Immune responses to citrullinated and homocitrullinated peptides in healthy donors are not restricted to the HLA SE shared allele and can be selected into the memory pool.
2023 · Immunology · RCR 0.8 · 6 citations - T cell repertoire to citrullinated self-peptides in healthy humans is not confined to the HLA-DR SE alleles; Targeting of citrullinated self-peptides presented by HLA-DP4 for tumour therapy.
2019 · Oncoimmunology · RCR 0.7 · 19 citations - Antigen-specific T-cell frequency and phenotype mirrors disease activity in DRB1*04:04+ rheumatoid arthritis patients.
2025 · Clin Exp Immunol · 3 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.86
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.84
- DepMap mean gene effect
- -0.38
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- canonical glycolysis
- gluconeogenesis
- glycolytic process
- negative regulation of cell growth
- negative regulation of DNA-templated transcription
- negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway
- negative regulation of transcription by RNA polymerase II
- positive regulation of ATP biosynthetic process
- positive regulation of muscle contraction
- positive regulation of plasminogen activation
- response to virus
Molecular functions
- cadherin binding
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- GTPase binding
- magnesium ion binding
- phosphopyruvate hydratase activity
- protein homodimerization activity
- RNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- transcription corepressor activity
- transcription corepressor binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of ENO1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ENO1 as an antibody target. Whether an autoantibody or antibody against ENO1 could matter depends on whether native ENO1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ENO1 is annotated at the cell surface, where native ENO1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Source-annotated serology context
The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.
- Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy.
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