P35318 (ADML_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor internalization Inferred from direct assay PubMed 10882736. Source: UniProtKB aging Inferred from electronic annotation. Source: Compara androgen metabolic process Inferred from electronic annotation. Source: Compara blood circulation Traceable author statement Ref.2. Source: ProtInc branching involved in labyrinthine layer morphogenesis Inferred from electronic annotation. Source: Compara cAMP biosynthetic process Inferred from direct assay PubMed 20074556. Source: UniProtKB cAMP-mediated signaling Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement Ref.2. Source: ProtInc developmental growth Inferred from electronic annotation. Source: Compara elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara female pregnancy Traceable author statement PubMed 10822232. Source: ProtInc heart development Inferred from electronic annotation. Source: Compara hormone secretion Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of vascular permeability Inferred from electronic annotation. Source: Compara negative regulation of vasoconstriction Inferred from direct assay PubMed 11410113. Source: BHF-UCL neural tube closure Inferred from electronic annotation. Source: Compara neuron projection regeneration Inferred from electronic annotation. Source: Compara odontogenesis of dentin-containing tooth Inferred from electronic annotation. Source: Compara organ regeneration Inferred from electronic annotation. Source: Compara positive regulation of angiogenesis Inferred from electronic annotation. Source: Compara positive regulation of cAMP biosynthetic process Inferred from direct assay PubMed 10882736. Source: UniProtKB positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of heart rate Inferred from electronic annotation. Source: Compara positive regulation of vasculogenesis Inferred from electronic annotation. Source: Compara positive regulation of vasodilation Inferred from electronic annotation. Source: Compara progesterone biosynthetic process Traceable author statement PubMed 10822232. Source: ProtInc regulation of the force of heart contraction Inferred from electronic annotation. Source: Compara response to cold Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to insulin stimulus Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara 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: Compara vascular smooth muscle cell development Inferred from electronic annotation. Source: Compara vasculogenesis Inferred from direct assay PubMed 16964401. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay PubMed 12379507. Source: BHF-UCL extracellular space Inferred from direct assay PubMed 12379507. Source: BHF-UCL
Molecular_function	receptor binding Traceable author statement Ref.2PubMed 8524787. Source: ProtInc
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 Ref.12

Modified residue

146

1

Tyrosine amide Ref.9

Disulfide bond

110 ↔ 115

Ref.9

Natural variations

Natural variant

50

1

S → R. Ref.6
Corresponds to variant rs5005 [ dbSNP | Ensembl ].

VAR_014861

Natural variant

85

1

P → R.
Corresponds to variant rs2228573 [ dbSNP | Ensembl ].

VAR_048205

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

185

Helix Strand Turn

Details...

Helix

24 – 40

17

Beta strand

102 – 107

6

Beta strand

111 – 116

6

Helix

117 – 124

8

Helix

137 – 140

4

Sequences

	Sequence		Length	Mass (Da)
	P35318 [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] [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. , 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. , 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

NIEHS-SNPs

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.

IPI

IPI00017968.

PIR

JN0684. JC2351.

RefSeq

NP_001115.1. NM_001124.1.

UniGene

Hs.441047.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FLY	NMR	-	A	22-41	[»]
2L7S	NMR	-	A	95-146	[»]

ProteinModelPortal

P35318.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000278175.

PTM databases

PhosphoSite

P35318.

Polymorphism databases

DMDM

461474.

Proteomic databases

PaxDb

P35318.

PeptideAtlas

P35318.

PRIDE

P35318.

Protocols and materials databases

DNASU

133.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000278175; ENSP00000278175; ENSG00000148926.
ENST00000525063; ENSP00000435124; ENSG00000148926.
ENST00000528655; ENSP00000436607; ENSG00000148926.

GeneID

133.

KEGG

hsa:133.

UCSC

uc001mil.1. human.

Organism-specific databases

CTD

133.

GeneCards

GC11P010326.

HGNC

HGNC:259. ADM.

HPA

CAB016075.

MIM

103275. gene.

neXtProt

NX_P35318.

PharmGKB

PA24580.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46109.

HOGENOM

HOG000033821.

HOVERGEN

HBG004181.

InParanoid

P35318.

KO

K12333.

OMA

PQDVKGA.

OrthoDB

EOG4894NP.

PhylomeDB

P35318.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P35318.

Bgee

P35318.

CleanEx

HS_ADM.

Genevestigator

P35318.

GermOnline

ENSG00000148926. Homo sapiens.

Family and domain databases

InterPro

IPR001710. Adrenomedullin.
IPR021116. Procalcitonin/adrenomedullin.
[Graphical view]

Pfam

PF00214. Calc_CGRP_IAPP. 1 hit.
[Graphical view]

PRINTS

PR00801. ADRENOMEDULN.

ProtoNet

Search...

Other

ChiTaRS

ADM. human.

EvolutionaryTrace

P35318.

GenomeRNAi

133.

NextBio

533.

PMAP-CutDB

P35318.

SOURCE

Search...

Entry information

Entry name

ADML_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.