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P35318 (ADML_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ADM

Cleaved into the following 2 chains:

  1. Adrenomedullin
    Short name=AM
  2. Proadrenomedullin N-20 terminal peptide
    Alternative name(s):
    ProAM N-terminal 20 peptide
    Short name=PAMP
    Short name=ProAM-N20
Gene names
Name:ADM
Synonyms:AM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length185 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Secreted.

Tissue specificity

Highest levels found in pheochromocytoma and adrenal medulla. Also found in lung, ventricle and kidney tissues.

Sequence similarities

Belongs to the adrenomedullin family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHormone
   PTMAmidation
Cleavage on pair of basic residues
Disulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor internalization

Inferred from direct assay PubMed 10882736. Source: UniProtKB

aging

Inferred from electronic annotation. Source: Ensembl

androgen metabolic process

Inferred from electronic annotation. Source: Ensembl

blood circulation

Traceable author statement Ref.2. Source: ProtInc

branching involved in labyrinthine layer morphogenesis

Inferred from electronic annotation. Source: Ensembl

cAMP biosynthetic process

Inferred from direct assay PubMed 20074556. Source: UniProtKB

cAMP-mediated signaling

Inferred from electronic annotation. Source: Ensembl

cell-cell signaling

Traceable author statement Ref.2. Source: ProtInc

developmental growth

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Traceable author statement PubMed 10822232. Source: ProtInc

heart development

Inferred from electronic annotation. Source: Ensembl

hormone secretion

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of vascular permeability

Inferred from electronic annotation. Source: Ensembl

negative regulation of vasoconstriction

Inferred from direct assay PubMed 11410113. Source: BHF-UCL

neural tube closure

Inferred from electronic annotation. Source: Ensembl

neuron projection regeneration

Inferred from electronic annotation. Source: Ensembl

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 10882736. Source: UniProtKB

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of heart rate

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasculogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasodilation

Inferred from electronic annotation. Source: Ensembl

progesterone biosynthetic process

Traceable author statement PubMed 10822232. Source: ProtInc

receptor internalization

Inferred from direct assay PubMed 10882736PubMed 15613468PubMed 20074556. Source: UniProtKB

regulation of the force of heart contraction

Inferred from electronic annotation. Source: Ensembl

response to cold

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to starvation

Inferred from electronic annotation. Source: Ensembl

response to wounding

Traceable author statement PubMed 8524787. Source: ProtInc

signal transduction

Traceable author statement PubMed 10822232. Source: ProtInc

spongiotrophoblast layer development

Inferred from electronic annotation. Source: Ensembl

vascular smooth muscle cell development

Inferred from electronic annotation. Source: Ensembl

vasculogenesis

Inferred from direct assay PubMed 16964401. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 12379507. Source: BHF-UCL

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 12379507. Source: BHF-UCL

   Molecular_functionreceptor binding

Traceable author statement Ref.2PubMed 8524787. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Peptide22 – 4120Proadrenomedullin N-20 terminal peptide
PRO_0000000961
Propeptide45 – 9248
PRO_0000000962
Peptide95 – 14652Adrenomedullin Ref.9
PRO_0000000963
Propeptide148 – 18538PreproAM C-terminal fragment
PRO_0000000964

Amino acid modifications

Modified residue411Arginine amide Ref.12
Modified residue1461Tyrosine amide Ref.9
Disulfide bond110 ↔ 115 Ref.9

Natural variations

Natural variant501S → R. Ref.6
Corresponds to variant rs5005 [ dbSNP | Ensembl ].
VAR_014861
Natural variant851P → R.
Corresponds to variant rs2228573 [ dbSNP | Ensembl ].
VAR_048205

Secondary structure

.......... 185
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P35318 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 64C7D2A0B4654DFE

FASTA18520,420
        10         20         30         40         50         60 
MKLVSVALMY LGSLAFLGAD TARLDVASEF RKKWNKWALS RGKRELRMSS SYPTGLADVK 

        70         80         90        100        110        120 
AGPAQTLIRP QDMKGASRSP EDSSPDAARI RVKRYRQSMN NFQGLRSFGC RFGTCTVQKL 

       130        140        150        160        170        180 
AHQIYQFTDK DKDNVAPRSK ISPQGYGRRR RRSLPEAGPG RTLVSSKPQA HGAPAPPSGS 


APHFL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of cDNA encoding a precursor for human adrenomedullin."
Kitamura K., Sakata J., Kangawa K., Kojima M., Matsuo H., Eto T.
Biochem. Biophys. Res. Commun. 194:720-725(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pheochromocytoma.
[2]"Genomic structure of human adrenomedullin gene."
Ishimitsu T., Kojima M., Kangawa K., Hino J., Matsuoka H., Kitamura K., Eto T., Matsuo H.
Biochem. Biophys. Res. Commun. 203:631-639(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Liver.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain cortex.
[6]NIEHS SNPs program
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-50.
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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: Kidney.
[9]"Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma."
Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Nakamura S., Matsuo H., Eto T.
Biochem. Biophys. Res. Commun. 192:553-560(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 95-146, AMIDATION AT TYR-146, DISULFIDE BOND.
Tissue: Pheochromocytoma.
[10]"Proadrenomedullin-derived peptides."
Samson W.K.
Front. Neuroendocrinol. 19:100-127(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Structure-activity relationships of adrenomedullin in the circulation and adrenal gland."
Champion H.C., Nussdorfer G.G., Kadowitz P.J.
Regul. Pept. 85:1-8(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[12]"NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a proangiogenic factor involved in tumor growth."
Lucyk S., Taha H., Yamamoto H., Miskolzie M., Kotovych G.
Biopolymers 81:295-308(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 22-41, AMIDATION AT ARG-41.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJN0684. JC2351.
RefSeqNP_001115.1. NM_001124.1.
UniGeneHs.441047.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2FLYNMR-A22-41[»]
2L7SNMR-A95-146[»]
ProteinModelPortalP35318.
SMRP35318. Positions 95-146.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000278175.

Chemistry

ChEMBLCHEMBL2062356.

PTM databases

PhosphoSiteP35318.

Polymorphism databases

DMDM461474.

Proteomic databases

PaxDbP35318.
PeptideAtlasP35318.
PRIDEP35318.

Protocols and materials databases

DNASU133.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278175; ENSP00000278175; ENSG00000148926.
ENST00000525063; ENSP00000435124; ENSG00000148926.
ENST00000528655; ENSP00000436607; ENSG00000148926.
GeneID133.
KEGGhsa:133.
UCSCuc001mil.1. human.

Organism-specific databases

CTD133.
GeneCardsGC11P010326.
HGNCHGNC:259. ADM.
HPACAB016075.
HPA031806.
MIM103275. gene.
neXtProtNX_P35318.
PharmGKBPA24580.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46109.
HOGENOMHOG000033821.
HOVERGENHBG004181.
InParanoidP35318.
KOK12333.
OMAVAPRNKI.
OrthoDBEOG7DC266.
PhylomeDBP35318.
TreeFamTF333447.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP35318.
BgeeP35318.
CleanExHS_ADM.
GenevestigatorP35318.

Family and domain databases

InterProIPR001710. Adrenomedullin.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view]
PfamPF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]
PRINTSPR00801. ADRENOMEDULN.
ProtoNetSearch...

Other

ChiTaRSADM. human.
EvolutionaryTraceP35318.
GeneWikiAdrenomedullin.
GenomeRNAi133.
NextBio533.
PMAP-CutDBP35318.
PROP35318.
SOURCESearch...

Entry information

Entry nameADML_HUMAN
AccessionPrimary (citable) accession number: P35318
Secondary accession number(s): B2R793, D3DQV3, Q6FGW2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM