ENG

Protein identityUniProt · HPA

UniProt accession

P17813

Gene

ENG

Ensembl

ENSG00000106991

Chromosome

9

Canonical length

658 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, Human disease related genes, Plasma proteins, Predicted membrane proteins

Subcellular location

Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

Canonical amino-acid sequenceUniProt

658 residues, UniProt reviewed canonical sequence.

>P17813|ENG
     1  MDRGTLPLAV ALLLASCSLS PTSLAETVHC DLQPVGPERG EVTYTTSQVS KGCVAQAPNA
    61  ILEVHVLFLE FPTGPSQLEL TLQASKQNGT WPREVLLVLS VNSSVFLHLQ ALGIPLHLAY
   121  NSSLVTFQEP PGVNTTELPS FPKTQILEWA AERGPITSAA ELNDPQSILL RLGQAQGSLS
   181  FCMLEASQDM GRTLEWRPRT PALVRGCHLE GVAGHKEAHI LRVLPGHSAG PRTVTVKVEL
   241  SCAPGDLDAV LILQGPPYVS WLIDANHNMQ IWTTGEYSFK IFPEKNIRGF KLPDTPQGLL
   301  GEARMLNASI VASFVELPLA SIVSLHASSC GGRLQTSPAP IQTTPPKDTC SPELLMSLIQ
   361  TKCADDAMTL VLKKELVAHL KCTITGLTFW DPSCEAEDRG DKFVLRSAYS SCGMQVSASM
   421  ISNEAVVNIL SSSSPQRKKV HCLNMDSLSF QLGLYLSPHF LQASNTIEPG QQSFVQVRVS
   481  PSVSEFLLQL DSCHLDLGPE GGTVELIQGR AAKGNCVSLL SPSPEGDPRF SFLLHFYTVP
   541  IPKTGTLSCT VALRPKTGSQ DQEVHRTVFM RLNIISPDLS GCTSKGLVLP AVLGITFGAF
   601  LIGALLTAAL WYIYSHTRSP SKREPVVAVA APASSESSST NHSIGSTQST PCSTSSMA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ENG 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

1

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

519 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ENG.

Disease | AllUniProt

Conditions ENG is implicated in, by any mechanism.

• Telangiectasia, hereditary hemorrhagic, 1 (HHT1) MIM:187300

Disease | GeneticClinVar

629 pathogenic / likely-pathogenic of 1,989 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary hemorrhagic telangiectasia
• Cardiovascular phenotype
• Telangiectasia, hereditary hemorrhagic, type 1
• ENG-related disorder
• See cases

ReferencesPubMed · IEDB

Publications for ENG 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.

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)

0.24

gnomAD pLI

1

gnomAD missense Z

0.93

DepMap mean gene effect

0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• artery morphogenesis
• atrial cardiac muscle tissue morphogenesis
• atrioventricular canal morphogenesis
• BMP signaling pathway
• branching involved in blood vessel morphogenesis
• cardiac atrium morphogenesis
• cardiac ventricle morphogenesis
• cell adhesion
• cell chemotaxis
• cell migration
• cell migration involved in endocardial cushion formation
• cell motility
• central nervous system vasculogenesis
• detection of hypoxia
• dorsal aorta morphogenesis
• endocardial cushion morphogenesis
• epithelial to mesenchymal transition involved in endocardial cushion formation
• extracellular matrix disassembly
• heart looping
• negative regulation of cell migration
• negative regulation of endothelial cell proliferation
• negative regulation of gene expression
• negative regulation of SMAD protein signal transduction
• negative regulation of transcription by RNA polymerase II
• negative regulation of transforming growth factor beta receptor signaling pathway
• outflow tract septum morphogenesis
• positive regulation of angiogenesis
• positive regulation of BMP signaling pathway
• positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of SMAD protein signal transduction
• positive regulation of systemic arterial blood pressure
• positive regulation of transcription by RNA polymerase II
• positive regulation of vascular associated smooth muscle cell differentiation
• regulation of cell adhesion
• regulation of cell population proliferation
• regulation of DNA-templated transcription
• regulation of transforming growth factor beta receptor signaling pathway
• response to hypoxia
• smooth muscle tissue development
• transforming growth factor beta receptor signaling pathway
• vascular associated smooth muscle cell development
• vasculogenesis
• venous blood vessel morphogenesis
• ventricular trabecula myocardium morphogenesis
• wound healing

Molecular functions

• activin binding
• coreceptor activity
• galactose binding
• glycosaminoglycan binding
• identical protein binding
• protein homodimerization activity
• signaling receptor activator activity
• transforming growth factor beta binding
• transmembrane signaling receptor activity
• type I transforming growth factor beta receptor binding
• type II transforming growth factor beta receptor binding

Cellular components

• cell surface
• endothelial microparticle
• external side of plasma membrane
• extracellular space
• focal adhesion
• nuclear body
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• TGFBR3/Endoglin-like, N-terminal domain
• TGFBR3-like, N-terminal domain

KeywordsUniProt

• Angiogenesis
• Cell adhesion
• Cell membrane
• Disulfide bond
• Glycoprotein
• Membrane
• Phosphoprotein
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of ENG in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ACVRL1
• ARRB2
• BMP10
• DYNLT4
• GDF2
• LGALS3
• TRIM21