UniProtKB - P35318 (ADML_HUMAN)
Pro-adrenomedullin
ADM
Functioni
AM and PAMP are potent hypotensive and vasodilatator agents. Numerous actions have been reported most related to the physiologic control of fluid and electrolyte homeostasis. In the kidney, am is diuretic and natriuretic, and both am and pamp inhibit aldosterone secretion by direct adrenal actions. In pituitary gland, both peptides at physiologically relevant doses inhibit basal ACTH secretion. Both peptides appear to act in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in blood vessels.
GO - Molecular functioni
- adrenomedullin receptor binding Source: UniProtKB
- hormone activity Source: UniProtKB-KW
- signaling receptor binding Source: ProtInc
GO - Biological processi
- adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: UniProtKB
- adrenomedullin receptor signaling pathway Source: UniProtKB
- aging Source: Ensembl
- amylin receptor signaling pathway Source: ARUK-UCL
- androgen metabolic process Source: Ensembl
- animal organ regeneration Source: Ensembl
- antibacterial humoral response Source: UniProtKB
- antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
- branching involved in labyrinthine layer morphogenesis Source: Ensembl
- cAMP-mediated signaling Source: Ensembl
- defense response to Gram-negative bacterium Source: UniProtKB
- defense response to Gram-positive bacterium Source: UniProtKB
- developmental growth Source: Ensembl
- female pregnancy Source: Ensembl
- G protein-coupled receptor internalization Source: UniProtKB
- heart development Source: Ensembl
- hormone secretion Source: Ensembl
- inflammatory response Source: GO_Central
- negative regulation of cell population proliferation Source: Ensembl
- negative regulation of vascular permeability Source: Ensembl
- negative regulation of vasoconstriction Source: BHF-UCL
- neural tube closure Source: Ensembl
- neuron projection regeneration Source: Ensembl
- odontogenesis of dentin-containing tooth Source: Ensembl
- positive regulation of angiogenesis Source: Ensembl
- positive regulation of apoptotic process Source: Ensembl
- positive regulation of cell population proliferation Source: Ensembl
- positive regulation of cytosolic calcium ion concentration Source: Ensembl
- positive regulation of heart rate Source: UniProtKB
- positive regulation of progesterone biosynthetic process Source: GO_Central
- positive regulation of vasculogenesis Source: Ensembl
- receptor internalization Source: UniProtKB
- regulation of systemic arterial blood pressure Source: UniProtKB
- regulation of the force of heart contraction Source: Ensembl
- regulation of urine volume Source: UniProtKB
- response to cold Source: Ensembl
- response to glucocorticoid Source: Ensembl
- response to hypoxia Source: Ensembl
- response to insulin Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- response to starvation Source: Ensembl
- response to wounding Source: Ensembl
- signal transduction Source: ProtInc
- spongiotrophoblast layer development Source: Ensembl
- vascular associated smooth muscle cell development Source: Ensembl
- vasculogenesis Source: UniProtKB
Keywordsi
Molecular function | Hormone |
Enzyme and pathway databases
PathwayCommonsi | P35318 |
Reactomei | R-HSA-418555, G alpha (s) signalling events R-HSA-419812, Calcitonin-like ligand receptors R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | P35318 |
SIGNORi | P35318 |
Names & Taxonomyi
Protein namesi | Recommended name: Pro-adrenomedullinCleaved into the following 2 chains: Alternative name(s): ProAM N-terminal 20 peptide Short name: PAMP Short name: ProAM-N20 |
Gene namesi | Name:ADM Synonyms:AM |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:259, ADM |
MIMi | 103275, gene |
neXtProti | NX_P35318 |
VEuPathDBi | HostDB:ENSG00000148926 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: BHF-UCL
Other locations
- cytoplasm Source: BHF-UCL
Keywords - Cellular componenti
SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 133 |
OpenTargetsi | ENSG00000148926 |
PharmGKBi | PA24580 |
Miscellaneous databases
Pharosi | P35318, Tbio |
Chemistry databases
ChEMBLi | CHEMBL2062356 |
Genetic variation databases
BioMutai | ADM |
DMDMi | 461474 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | By similarityAdd BLAST | 21 | |
PeptideiPRO_0000000961 | 22 – 41 | Proadrenomedullin N-20 terminal peptideBy similarityAdd BLAST | 20 | |
PropeptideiPRO_0000000962 | 45 – 92 | By similarityAdd BLAST | 48 | |
PeptideiPRO_0000000963 | 95 – 146 | Adrenomedullin1 PublicationAdd BLAST | 52 | |
PropeptideiPRO_0000000964 | 148 – 185 | PreproAM C-terminal fragmentAdd BLAST | 38 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 41 | Arginine amide1 Publication | 1 | |
Disulfide bondi | 110 ↔ 115 | 1 Publication | ||
Modified residuei | 146 | Tyrosine amide1 Publication | 1 |
Keywords - PTMi
Amidation, Cleavage on pair of basic residues, Disulfide bondProteomic databases
MassIVEi | P35318 |
PaxDbi | P35318 |
PeptideAtlasi | P35318 |
PRIDEi | P35318 |
ProteomicsDBi | 55021 |
PTM databases
GlyGeni | P35318, 1 site |
iPTMneti | P35318 |
PhosphoSitePlusi | P35318 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000148926, Expressed in chorionic villus and 239 other tissues |
ExpressionAtlasi | P35318, baseline and differential |
Genevisiblei | P35318, HS |
Organism-specific databases
HPAi | ENSG00000148926, Tissue enhanced (adipose) |
Interactioni
GO - Molecular functioni
- adrenomedullin receptor binding Source: UniProtKB
- hormone activity Source: UniProtKB-KW
- signaling receptor binding Source: ProtInc
Protein-protein interaction databases
BioGRIDi | 106645, 5 interactors |
IntActi | P35318, 1 interactor |
STRINGi | 9606.ENSP00000436607 |
Miscellaneous databases
RNActi | P35318, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P35318 |
SMRi | P35318 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P35318 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 60 – 87 | DisorderedSequence analysisAdd BLAST | 28 | |
Regioni | 133 – 185 | DisorderedSequence analysisAdd BLAST | 53 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502S4SF, Eukaryota |
GeneTreei | ENSGT00940000154380 |
HOGENOMi | CLU_099291_1_0_1 |
InParanoidi | P35318 |
OMAi | QSFLYCC |
OrthoDBi | 1555764at2759 |
PhylomeDBi | P35318 |
TreeFami | TF333447 |
Family and domain databases
InterProi | View protein in InterPro IPR021116, Calcitonin/adrenomedullin IPR001710, Pro-ADM |
Pfami | View protein in Pfam PF00214, Calc_CGRP_IAPP, 1 hit |
PRINTSi | PR00801, ADRENOMEDULN |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MKLVSVALMY LGSLAFLGAD TARLDVASEF RKKWNKWALS RGKRELRMSS
60 70 80 90 100
SYPTGLADVK AGPAQTLIRP QDMKGASRSP EDSSPDAARI RVKRYRQSMN
110 120 130 140 150
NFQGLRSFGC RFGTCTVQKL AHQIYQFTDK DKDNVAPRSK ISPQGYGRRR
160 170 180
RRSLPEAGPG RTLVSSKPQA HGAPAPPSGS APHFL
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PL83 | E9PL83_HUMAN | Pro-adrenomedullin | ADM | 138 | Annotation score: | ||
E9PQE6 | E9PQE6_HUMAN | Pro-adrenomedullin | ADM | 117 | Annotation score: | ||
E9PQT2 | E9PQT2_HUMAN | Pro-adrenomedullin | ADM | 139 | Annotation score: | ||
E9PML4 | E9PML4_HUMAN | Pro-adrenomedullin | ADM | 83 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014861 | 50 | S → R1 PublicationCorresponds to variant dbSNP:rs5005EnsemblClinVar. | 1 | |
Natural variantiVAR_048205 | 85 | P → R. Corresponds to variant dbSNP:rs2228573EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D14874 mRNA Translation: BAA03589.1 S73906 Genomic DNA Translation: AAC60642.1 D43639 Genomic DNA Translation: BAA07756.1 Sequence problems. CR541995 mRNA Translation: CAG46792.1 BT006902 mRNA Translation: AAP35548.1 AK312893 mRNA Translation: BAG35740.1 DQ143945 Genomic DNA Translation: AAZ38717.1 CH471064 Genomic DNA Translation: EAW68571.1 CH471064 Genomic DNA Translation: EAW68572.1 BC015961 mRNA Translation: AAH15961.1 |
CCDSi | CCDS7801.1 |
PIRi | JC2351, JN0684 |
RefSeqi | NP_001115.1, NM_001124.2 |
Genome annotation databases
Ensembli | ENST00000278175.10; ENSP00000278175.5; ENSG00000148926.10 ENST00000525063.2; ENSP00000435124.1; ENSG00000148926.10 ENST00000528655.5; ENSP00000436607.1; ENSG00000148926.10 |
GeneIDi | 133 |
KEGGi | hsa:133 |
MANE-Selecti | ENST00000278175.10; ENSP00000278175.5; NM_001124.3; NP_001115.1 |
UCSCi | uc001mil.2, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D14874 mRNA Translation: BAA03589.1 S73906 Genomic DNA Translation: AAC60642.1 D43639 Genomic DNA Translation: BAA07756.1 Sequence problems. CR541995 mRNA Translation: CAG46792.1 BT006902 mRNA Translation: AAP35548.1 AK312893 mRNA Translation: BAG35740.1 DQ143945 Genomic DNA Translation: AAZ38717.1 CH471064 Genomic DNA Translation: EAW68571.1 CH471064 Genomic DNA Translation: EAW68572.1 BC015961 mRNA Translation: AAH15961.1 |
CCDSi | CCDS7801.1 |
PIRi | JC2351, JN0684 |
RefSeqi | NP_001115.1, NM_001124.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2FLY | NMR | - | A | 22-41 | [»] | |
2L7S | NMR | - | A | 95-146 | [»] | |
4RWF | X-ray | 1.76 | B | 119-146 | [»] | |
5V6Y | X-ray | 2.80 | E/F/G/H | 131-146 | [»] | |
6UUN | electron microscopy | 3.00 | P | 95-146 | [»] | |
6UUS | electron microscopy | 2.40 | P | 95-146 | [»] | |
6V2E | X-ray | 1.83 | B | 131-146 | [»] | |
7VV0 | electron microscopy | 3.50 | L | 30-41 | [»] | |
AlphaFoldDBi | P35318 | |||||
SMRi | P35318 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106645, 5 interactors |
IntActi | P35318, 1 interactor |
STRINGi | 9606.ENSP00000436607 |
Chemistry databases
ChEMBLi | CHEMBL2062356 |
PTM databases
GlyGeni | P35318, 1 site |
iPTMneti | P35318 |
PhosphoSitePlusi | P35318 |
Genetic variation databases
BioMutai | ADM |
DMDMi | 461474 |
Proteomic databases
MassIVEi | P35318 |
PaxDbi | P35318 |
PeptideAtlasi | P35318 |
PRIDEi | P35318 |
ProteomicsDBi | 55021 |
Protocols and materials databases
Antibodypediai | 4233, 629 antibodies from 34 providers |
DNASUi | 133 |
Genome annotation databases
Ensembli | ENST00000278175.10; ENSP00000278175.5; ENSG00000148926.10 ENST00000525063.2; ENSP00000435124.1; ENSG00000148926.10 ENST00000528655.5; ENSP00000436607.1; ENSG00000148926.10 |
GeneIDi | 133 |
KEGGi | hsa:133 |
MANE-Selecti | ENST00000278175.10; ENSP00000278175.5; NM_001124.3; NP_001115.1 |
UCSCi | uc001mil.2, human |
Organism-specific databases
CTDi | 133 |
DisGeNETi | 133 |
GeneCardsi | ADM |
HGNCi | HGNC:259, ADM |
HPAi | ENSG00000148926, Tissue enhanced (adipose) |
MIMi | 103275, gene |
neXtProti | NX_P35318 |
OpenTargetsi | ENSG00000148926 |
PharmGKBi | PA24580 |
VEuPathDBi | HostDB:ENSG00000148926 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S4SF, Eukaryota |
GeneTreei | ENSGT00940000154380 |
HOGENOMi | CLU_099291_1_0_1 |
InParanoidi | P35318 |
OMAi | QSFLYCC |
OrthoDBi | 1555764at2759 |
PhylomeDBi | P35318 |
TreeFami | TF333447 |
Enzyme and pathway databases
PathwayCommonsi | P35318 |
Reactomei | R-HSA-418555, G alpha (s) signalling events R-HSA-419812, Calcitonin-like ligand receptors R-HSA-9660821, ADORA2B mediated anti-inflammatory cytokines production |
SignaLinki | P35318 |
SIGNORi | P35318 |
Miscellaneous databases
BioGRID-ORCSi | 133, 16 hits in 1076 CRISPR screens |
ChiTaRSi | ADM, human |
EvolutionaryTracei | P35318 |
GeneWikii | Adrenomedullin |
GenomeRNAii | 133 |
Pharosi | P35318, Tbio |
PROi | PR:P35318 |
RNActi | P35318, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000148926, Expressed in chorionic villus and 239 other tissues |
ExpressionAtlasi | P35318, baseline and differential |
Genevisiblei | P35318, HS |
Family and domain databases
InterProi | View protein in InterPro IPR021116, Calcitonin/adrenomedullin IPR001710, Pro-ADM |
Pfami | View protein in Pfam PF00214, Calc_CGRP_IAPP, 1 hit |
PRINTSi | PR00801, ADRENOMEDULN |
MobiDBi | Search... |
Entry informationi
Entry namei | ADML_HUMAN | |
Accessioni | P35318Primary (citable) accession number: P35318 Secondary accession number(s): B2R793, D3DQV3, Q6FGW2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1994 |
Last sequence update: | February 1, 1994 | |
Last modified: | May 25, 2022 | |
This is version 191 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families