Reviewed, UniProtKB/Swiss-Prot P35318 (ADML_HUMAN)

Names and origin

Protein names

Recommended name:
    ADM
Cleaved into the following 2 chains:
    1- Recommended name:
            Adrenomedullin
                Short name=AM
    2- Recommended name:
            Proadrenomedullin N-20 terminal peptide
        Alternative name(s):
            ProAM N-terminal 20 peptide
              Short name=ProAM-N20
              Short name=PAMP

Gene names

Name:	ADM
Synonyms:	AM

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	185 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Amidation Cleavage on pair of basic residues Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from Experiment. Source: Reactome blood circulation Ref.2 Traceable author statement. Source: ProtInc cAMP biosynthetic process Ref.2 Traceable author statement. Source: ProtInc cell-cell signaling Ref.2 Traceable author statement. Source: ProtInc female pregnancy Traceable author statement. Source: ProtInc negative regulation of vasoconstriction Inferred from direct assay. Source: UniProtKB progesterone biosynthetic process Traceable author statement. Source: ProtInc response to wounding Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB extracellular space Inferred from direct assay. Source: UniProtKB soluble fraction Traceable author statement. Source: ProtInc
Molecular function	hormone activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Peptide

22 – 41

20

Proadrenomedullin N-20 terminal peptide

PRO_0000000961

Propeptide

45 – 92

48

PRO_0000000962

Peptide

95 – 146

52

Adrenomedullin Ref.9

PRO_0000000963

Propeptide

148 – 185

38

PreproAM C-terminal fragment

PRO_0000000964

Amino acid modifications

Modified residue

41

1

Arginine amide

Modified residue

146

1

Tyrosine amide

Disulfide bond

110 ↔ 115

Natural variations

Natural variant

50

1

S → R: dbSNP rs5005. Ref.6

VAR_014861

Natural variant

85

1

P → R: dbSNP rs2228573.

VAR_048205

Secondary structure

1

.

.

.

185

Helix Strand Turn

Details...

Helix

24 – 40

17

Sequences

	Sequence		Length	Mass (Da)
	P35318-1 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 64C7D2A0B4654DFE	FASTA	185	20,420
	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

References

	« Hide 'large scale' referencesShow '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: 7688224] [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: 8074714] [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. , 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: 14702039] [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. , 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: 15489334] [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: 8387282] [Abstract] Cited for: PROTEIN SEQUENCE OF 95-146. Tissue: Pheochromocytoma.
[10]	"Proadrenomedullin-derived peptides." Samson W.K. Front. Neuroendocrinol. 19:100-127(1998) [PubMed: 9578982] [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: 10588445] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
BC015961 mRNA. Translation: AAH15961.1.

IPI

IPI00017968.

PIR

JN0684. JC2351.

RefSeq

NP_001115.1.

UniGene

Hs.441047

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FLY	NMR	-	A	22-41	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P35318.

PTM databases

PhosphoSite

P35318.

Proteomic databases

PeptideAtlas

P35318.

PRIDE

P35318.

Genome annotation databases

Ensembl

ENST00000278175; ENSP00000278175; ENSG00000148926; Homo sapiens. [Genome view]

GeneID

133.

KEGG

hsa:133.

UCSC

uc001mik.1. human.

Organism-specific databases

CTD

133.

GeneCards

GC11P010283.

H-InvDB

HIX0009441.

HGNC

HGNC:259. ADM.

HPA

CAB016075.

MIM

103275. gene.

PharmGKB

PA24425.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P35318.

HOVERGEN

P35318.

OMA

KDGVAPR

OrthoDB

EOG9Z3914

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpress

P35318.

Bgee

P35318.

CleanEx

HS_ADM.

Genevestigator

P35318.

GermOnline

ENSG00000148926. Homo sapiens.

Family and domain databases

InterPro

IPR001710. Adrenomedullin.
IPR018014. Adrenomedullin/Adrenomedullin2.
[Graphical view]

Pfam

PF02039. Adrenomedullin. 1 hit.
[Graphical view]

PRINTS

PR00801. ADRENOMEDULN.

ProtoNet

Search...

Other Resources

NextBio

533.

PMAP-CutDB

P35318.

SOURCE

Search...

Entry information

Entry name

ADML_HUMAN

Accession

Primary (citable) accession number: P35318
Secondary accession number(s): B2R793, Q6FGW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	November 24, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.