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Protein

Endothelin-2

Gene

EDN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Endothelins are endothelium-derived vasoconstrictor peptides.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei69 – 702Cleavage; by KEL

GO - Molecular functioni

  1. hormone activity Source: BHF-UCL

GO - Biological processi

  1. artery smooth muscle contraction Source: BHF-UCL
  2. calcium-mediated signaling Source: BHF-UCL
  3. cell surface receptor signaling pathway Source: BHF-UCL
  4. cytokine-mediated signaling pathway Source: BHF-UCL
  5. energy homeostasis Source: Ensembl
  6. hormonal regulation of the force of heart contraction Source: BHF-UCL
  7. inositol phosphate-mediated signaling Source: BHF-UCL
  8. lung alveolus development Source: Ensembl
  9. macrophage activation Source: BHF-UCL
  10. macrophage chemotaxis Source: BHF-UCL
  11. neutrophil chemotaxis Source: BHF-UCL
  12. positive regulation of cell proliferation Source: BHF-UCL
  13. positive regulation of cytosolic calcium ion concentration Source: BHF-UCL
  14. positive regulation of heart rate Source: BHF-UCL
  15. positive regulation of leukocyte chemotaxis Source: BHF-UCL
  16. positive regulation of prostaglandin-endoperoxide synthase activity Source: BHF-UCL
  17. positive regulation of smooth muscle contraction Source: Ensembl
  18. positive regulation of the force of heart contraction by chemical signal Source: BHF-UCL
  19. prostaglandin biosynthetic process Source: BHF-UCL
  20. regulation of systemic arterial blood pressure by endothelin Source: BHF-UCL
  21. regulation of vasoconstriction Source: InterPro
  22. temperature homeostasis Source: Ensembl
  23. vasoconstriction Source: BHF-UCL
  24. vein smooth muscle contraction Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Vasoactive, Vasoconstrictor

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_18283. G alpha (q) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Endothelin-2
Short name:
ET-2
Alternative name(s):
Preproendothelin-2
Short name:
PPET2
Gene namesi
Name:EDN2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:3177. EDN2.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27615.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Propeptidei25 – 4622PRO_0000008093Add
BLAST
Peptidei49 – 6921Endothelin-2PRO_0000008094Add
BLAST
Propeptidei70 – 178109PRO_0000008095Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi49 ↔ 63By similarity
Disulfide bondi51 ↔ 59By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiP20800.
PRIDEiP20800.

Miscellaneous databases

PMAP-CutDBP20800.

Expressioni

Tissue specificityi

Expressed in lung, but not in placental stem villi vessels or cultured placental villi smooth muscle cells.1 Publication

Gene expression databases

BgeeiP20800.
CleanExiHS_EDN2.
GenevestigatoriP20800.

Organism-specific databases

HPAiHPA028459.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000361668.

Structurei

3D structure databases

ProteinModelPortaliP20800.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni96 – 11116Endothelin-likeAdd
BLAST

Sequence similaritiesi

Belongs to the endothelin/sarafotoxin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG43933.
GeneTreeiENSGT00530000063310.
HOGENOMiHOG000231110.
HOVERGENiHBG051441.
InParanoidiP20800.
KOiK16367.
OMAiPTAWCSV.
OrthoDBiEOG7F7WBX.
PhylomeDBiP20800.
TreeFamiTF333184.

Family and domain databases

InterProiIPR020475. Bibrotoxin/Sarafotoxin-D.
IPR019764. Endothelin_toxin_CS.
IPR001928. Endothln-like_toxin.
IPR015658. ET-2.
[Graphical view]
PANTHERiPTHR13874:SF8. PTHR13874:SF8. 1 hit.
PfamiPF00322. Endothelin. 1 hit.
[Graphical view]
PRINTSiPR00365. ENDOTHELIN.
SMARTiSM00272. END. 2 hits.
[Graphical view]
PROSITEiPS00270. ENDOTHELIN. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P20800-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVSVPTTWCS VALALLVALH EGKGQAAATL EQPASSSHAQ GTHLRLRRCS
60 70 80 90 100
CSSWLDKECV YFCHLDIIWV NTPEQTAPYG LGNPPRRRRR SLPRRCQCSS
110 120 130 140 150
ARDPACATFC LRRPWTEAGA VPSRKSPADV FQTGKTGATT GELLQRLRDI
160 170
STVKSLFAKR QQEAMREPRS THSRWRKR
Length:178
Mass (Da):19,960
Last modified:November 1, 1991 - v2
Checksum:i7711B2B6F075CFB4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1311F → L.
Corresponds to variant rs5798 [ dbSNP | Ensembl ].
VAR_033914
Natural varianti168 – 1681P → L.1 Publication
Corresponds to variant rs11572371 [ dbSNP | Ensembl ].
VAR_018817

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55177 mRNA. Translation: CAA38962.1.
M65199 mRNA. Translation: AAA52404.1.
AY518541 Genomic DNA. Translation: AAR89914.1.
AL445933 Genomic DNA. Translation: CAI14535.1.
CH471059 Genomic DNA. Translation: EAX07175.1.
BC034393 mRNA. Translation: AAH34393.1.
M25550 Genomic DNA. Translation: AAA52340.1.
CCDSiCCDS462.1.
PIRiA39070.
RefSeqiNP_001289198.1. NM_001302269.1.
NP_001947.1. NM_001956.4.
UniGeneiHs.1407.

Genome annotation databases

EnsembliENST00000372587; ENSP00000361668; ENSG00000127129.
GeneIDi1907.
KEGGihsa:1907.
UCSCiuc001cgx.3. human.

Polymorphism databases

DMDMi119615.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55177 mRNA. Translation: CAA38962.1.
M65199 mRNA. Translation: AAA52404.1.
AY518541 Genomic DNA. Translation: AAR89914.1.
AL445933 Genomic DNA. Translation: CAI14535.1.
CH471059 Genomic DNA. Translation: EAX07175.1.
BC034393 mRNA. Translation: AAH34393.1.
M25550 Genomic DNA. Translation: AAA52340.1.
CCDSiCCDS462.1.
PIRiA39070.
RefSeqiNP_001289198.1. NM_001302269.1.
NP_001947.1. NM_001956.4.
UniGeneiHs.1407.

3D structure databases

ProteinModelPortaliP20800.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000361668.

Polymorphism databases

DMDMi119615.

Proteomic databases

PaxDbiP20800.
PRIDEiP20800.

Protocols and materials databases

DNASUi1907.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372587; ENSP00000361668; ENSG00000127129.
GeneIDi1907.
KEGGihsa:1907.
UCSCiuc001cgx.3. human.

Organism-specific databases

CTDi1907.
GeneCardsiGC01M041944.
HGNCiHGNC:3177. EDN2.
HPAiHPA028459.
MIMi131241. gene.
neXtProtiNX_P20800.
PharmGKBiPA27615.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG43933.
GeneTreeiENSGT00530000063310.
HOGENOMiHOG000231110.
HOVERGENiHBG051441.
InParanoidiP20800.
KOiK16367.
OMAiPTAWCSV.
OrthoDBiEOG7F7WBX.
PhylomeDBiP20800.
TreeFamiTF333184.

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_18283. G alpha (q) signalling events.

Miscellaneous databases

GeneWikiiEndothelin_2.
GenomeRNAii1907.
NextBioi7761.
PMAP-CutDBP20800.
PROiP20800.
SOURCEiSearch...

Gene expression databases

BgeeiP20800.
CleanExiHS_EDN2.
GenevestigatoriP20800.

Family and domain databases

InterProiIPR020475. Bibrotoxin/Sarafotoxin-D.
IPR019764. Endothelin_toxin_CS.
IPR001928. Endothln-like_toxin.
IPR015658. ET-2.
[Graphical view]
PANTHERiPTHR13874:SF8. PTHR13874:SF8. 1 hit.
PfamiPF00322. Endothelin. 1 hit.
[Graphical view]
PRINTSiPR00365. ENDOTHELIN.
SMARTiSM00272. END. 2 hits.
[Graphical view]
PROSITEiPS00270. ENDOTHELIN. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Specific expression of human endothelin-2 (ET-2) gene in a renal adenocarcinoma cell line. Molecular cloning of cDNA encoding the precursor of ET-2 and its characterization."
    Ohkubo S., Ogi K., Hosoya M., Matsumoto H., Suzuki N., Kimura C., Onda H., Fujino M.
    FEBS Lett. 274:136-140(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "cDNA cloning and chromosomal assignment of the endothelin 2 gene: vasoactive intestinal contractor peptide is rat endothelin 2."
    Bloch K.D., Hong C.C., Eddy R.L. Jr., Shows T.B., Quertermous T.
    Genomics 10:236-242(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Expression of endothelin-2 (ET-2) gene in a human renal adenocarcinoma cell line: purification and cDNA cloning of ET-2."
    Onda H., Ohkubo S., Kosaka T., Yasuhara T., Ogi K., Hosoya M., Matsumoto H., Suzuki N., Kitada C., Ishibashi Y., Kimura C., Kubo K., Fujino M.
    J. Cardiovasc. Pharmacol. 17:S39-S43(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. NIEHS SNPs program
    Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-168.
  5. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Colon, Kidney and Stomach.
  8. "The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes."
    Inoue A., Yanagisawa M., Kimura S., Kasuya Y., Miyauchi T., Goto K., Masaki T.
    Proc. Natl. Acad. Sci. U.S.A. 86:2863-2867(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-73.
  9. "Proteolytic processing of big endothelin-3 by the kell blood group protein."
    Lee S., Lin M., Mele A., Cao Y., Farmar J., Russo D., Redman C.
    Blood 94:1440-1450(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE, CLEAVAGE BY KELL, IDENTIFICATION BY MASS SPECTROMETRY.
  10. "Endothelin-1 and ETA receptor expression in vascular smooth muscle cells from human placenta: a new ETA receptor messenger ribonucleic acid is generated by alternative splicing of exon 3."
    Bourgeois C., Robert B., Rebourcet R., Mondon F., Mignot T.-M., Duc-Goiran P., Ferre F.
    J. Clin. Endocrinol. Metab. 82:3116-3123(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiEDN2_HUMAN
AccessioniPrimary (citable) accession number: P20800
Secondary accession number(s): Q5T1R3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: November 1, 1991
Last modified: January 7, 2015
This is version 142 of the entry and version 2 of the sequence. [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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.