ADML_HUMAN
ID ADML_HUMAN Reviewed; 185 AA.
AC P35318; B2R793; D3DQV3; Q6FGW2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Pro-adrenomedullin;
DE Contains:
DE RecName: Full=Adrenomedullin;
DE Short=AM;
DE Contains:
DE RecName: Full=Proadrenomedullin N-20 terminal peptide;
DE AltName: Full=ProAM N-terminal 20 peptide;
DE Short=PAMP;
DE Short=ProAM-N20;
DE Flags: Precursor;
GN Name=ADM; Synonyms=AM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pheochromocytoma;
RX PubMed=7688224; DOI=10.1006/bbrc.1993.1881;
RA Kitamura K., Sakata J., Kangawa K., Kojima M., Matsuo H., Eto T.;
RT "Cloning and characterization of cDNA encoding a precursor for human
RT adrenomedullin.";
RL Biochem. Biophys. Res. Commun. 194:720-725(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8074714; DOI=10.1006/bbrc.1994.2229;
RA Ishimitsu T., Kojima M., Kangawa K., Hino J., Matsuoka H., Kitamura K.,
RA Eto T., Matsuo H.;
RT "Genomic structure of human adrenomedullin gene.";
RL Biochem. Biophys. Res. Commun. 203:631-639(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-50.
RG NIEHS SNPs program;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 95-146, AMIDATION AT TYR-146, AND DISULFIDE BOND.
RC TISSUE=Pheochromocytoma;
RX PubMed=8387282; DOI=10.1006/bbrc.1993.1451;
RA Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Nakamura S., Matsuo H.,
RA Eto T.;
RT "Adrenomedullin: a novel hypotensive peptide isolated from human
RT pheochromocytoma.";
RL Biochem. Biophys. Res. Commun. 192:553-560(1993).
RN [10]
RP REVIEW.
RX PubMed=9578982; DOI=10.1006/frne.1998.0164;
RA Samson W.K.;
RT "Proadrenomedullin-derived peptides.";
RL Front. Neuroendocrinol. 19:100-127(1998).
RN [11]
RP REVIEW.
RX PubMed=10588445; DOI=10.1016/s0167-0115(99)00025-7;
RA Champion H.C., Nussdorfer G.G., Kadowitz P.J.;
RT "Structure-activity relationships of adrenomedullin in the circulation and
RT adrenal gland.";
RL Regul. Pept. 85:1-8(1999).
RN [12]
RP STRUCTURE BY NMR OF 22-41, AND AMIDATION AT ARG-41.
RX PubMed=16315141; DOI=10.1002/bip.20418;
RA Lucyk S., Taha H., Yamamoto H., Miskolzie M., Kotovych G.;
RT "NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a
RT proangiogenic factor involved in tumor growth.";
RL Biopolymers 81:295-308(2006).
CC -!- FUNCTION: AM and PAMP are potent hypotensive and vasodilatator agents.
CC Numerous actions have been reported most related to the physiologic
CC control of fluid and electrolyte homeostasis. In the kidney, am is
CC diuretic and natriuretic, and both am and pamp inhibit aldosterone
CC secretion by direct adrenal actions. In pituitary gland, both peptides
CC at physiologically relevant doses inhibit basal ACTH secretion. Both
CC peptides appear to act in brain and pituitary gland to facilitate the
CC loss of plasma volume, actions which complement their hypotensive
CC effects in blood vessels.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highest levels found in pheochromocytoma and
CC adrenal medulla. Also found in lung, ventricle and kidney tissues.
CC -!- SIMILARITY: Belongs to the adrenomedullin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/adm/";
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DR EMBL; D14874; BAA03589.1; -; mRNA.
DR EMBL; S73906; AAC60642.1; -; Genomic_DNA.
DR EMBL; D43639; BAA07756.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CR541995; CAG46792.1; -; mRNA.
DR EMBL; BT006902; AAP35548.1; -; mRNA.
DR EMBL; AK312893; BAG35740.1; -; mRNA.
DR EMBL; DQ143945; AAZ38717.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68571.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68572.1; -; Genomic_DNA.
DR EMBL; BC015961; AAH15961.1; -; mRNA.
DR CCDS; CCDS7801.1; -.
DR PIR; JC2351; JN0684.
DR RefSeq; NP_001115.1; NM_001124.2.
DR PDB; 2FLY; NMR; -; A=22-41.
DR PDB; 2L7S; NMR; -; A=95-146.
DR PDB; 4RWF; X-ray; 1.76 A; B=119-146.
DR PDB; 5V6Y; X-ray; 2.80 A; E/F/G/H=131-146.
DR PDB; 6UUN; EM; 3.00 A; P=95-146.
DR PDB; 6UUS; EM; 2.40 A; P=95-146.
DR PDB; 6V2E; X-ray; 1.83 A; B=131-146.
DR PDB; 7VV0; EM; 3.50 A; L=30-41.
DR PDBsum; 2FLY; -.
DR PDBsum; 2L7S; -.
DR PDBsum; 4RWF; -.
DR PDBsum; 5V6Y; -.
DR PDBsum; 6UUN; -.
DR PDBsum; 6UUS; -.
DR PDBsum; 6V2E; -.
DR PDBsum; 7VV0; -.
DR AlphaFoldDB; P35318; -.
DR SMR; P35318; -.
DR BioGRID; 106645; 5.
DR IntAct; P35318; 1.
DR STRING; 9606.ENSP00000436607; -.
DR ChEMBL; CHEMBL2062356; -.
DR GlyGen; P35318; 1 site.
DR iPTMnet; P35318; -.
DR PhosphoSitePlus; P35318; -.
DR BioMuta; ADM; -.
DR DMDM; 461474; -.
DR MassIVE; P35318; -.
DR PaxDb; P35318; -.
DR PeptideAtlas; P35318; -.
DR PRIDE; P35318; -.
DR ProteomicsDB; 55021; -.
DR Antibodypedia; 4233; 630 antibodies from 34 providers.
DR DNASU; 133; -.
DR Ensembl; ENST00000278175.10; ENSP00000278175.5; ENSG00000148926.10.
DR Ensembl; ENST00000525063.2; ENSP00000435124.1; ENSG00000148926.10.
DR Ensembl; ENST00000528655.5; ENSP00000436607.1; ENSG00000148926.10.
DR GeneID; 133; -.
DR KEGG; hsa:133; -.
DR MANE-Select; ENST00000278175.10; ENSP00000278175.5; NM_001124.3; NP_001115.1.
DR UCSC; uc001mil.2; human.
DR CTD; 133; -.
DR DisGeNET; 133; -.
DR GeneCards; ADM; -.
DR HGNC; HGNC:259; ADM.
DR HPA; ENSG00000148926; Tissue enhanced (adipose).
DR MIM; 103275; gene.
DR neXtProt; NX_P35318; -.
DR OpenTargets; ENSG00000148926; -.
DR PharmGKB; PA24580; -.
DR VEuPathDB; HostDB:ENSG00000148926; -.
DR eggNOG; ENOG502S4SF; Eukaryota.
DR GeneTree; ENSGT00940000154380; -.
DR HOGENOM; CLU_099291_1_0_1; -.
DR InParanoid; P35318; -.
DR OMA; QSFLYCC; -.
DR OrthoDB; 1555764at2759; -.
DR PhylomeDB; P35318; -.
DR TreeFam; TF333447; -.
DR PathwayCommons; P35318; -.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-419812; Calcitonin-like ligand receptors.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P35318; -.
DR SIGNOR; P35318; -.
DR BioGRID-ORCS; 133; 16 hits in 1076 CRISPR screens.
DR ChiTaRS; ADM; human.
DR EvolutionaryTrace; P35318; -.
DR GeneWiki; Adrenomedullin; -.
DR GenomeRNAi; 133; -.
DR Pharos; P35318; Tbio.
DR PRO; PR:P35318; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P35318; protein.
DR Bgee; ENSG00000148926; Expressed in vena cava and 194 other tissues.
DR ExpressionAtlas; P35318; baseline and differential.
DR Genevisible; P35318; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0031700; F:adrenomedullin receptor binding; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1990410; P:adrenomedullin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0097647; P:amylin receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0008209; P:androgen metabolic process; IEA:Ensembl.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl.
DR GO; GO:0055074; P:calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0019933; P:cAMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0046879; P:hormone secretion; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; TAS:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IEA:Ensembl.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; IDA:BHF-UCL.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0031102; P:neuron projection regeneration; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0010460; P:positive regulation of heart rate; IDA:UniProtKB.
DR GO; GO:2000184; P:positive regulation of progesterone biosynthetic process; TAS:GO_Central.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; IEA:Ensembl.
DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IDA:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IEA:Ensembl.
DR GO; GO:0035809; P:regulation of urine volume; IDA:UniProtKB.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0060712; P:spongiotrophoblast layer development; IEA:Ensembl.
DR GO; GO:0097084; P:vascular associated smooth muscle cell development; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IDA:UniProtKB.
DR InterPro; IPR021116; Calcitonin/adrenomedullin.
DR InterPro; IPR001710; Pro-ADM.
DR Pfam; PF00214; Calc_CGRP_IAPP; 1.
DR PRINTS; PR00801; ADRENOMEDULN.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hormone; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000250|UniProtKB:P53366"
FT PEPTIDE 22..41
FT /note="Proadrenomedullin N-20 terminal peptide"
FT /evidence="ECO:0000250|UniProtKB:P43145"
FT /id="PRO_0000000961"
FT PROPEP 45..92
FT /evidence="ECO:0000250|UniProtKB:P43145"
FT /id="PRO_0000000962"
FT PEPTIDE 95..146
FT /note="Adrenomedullin"
FT /evidence="ECO:0000269|PubMed:8387282"
FT /id="PRO_0000000963"
FT PROPEP 148..185
FT /note="PreproAM C-terminal fragment"
FT /id="PRO_0000000964"
FT REGION 60..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 133..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 41
FT /note="Arginine amide"
FT /evidence="ECO:0000269|PubMed:16315141"
FT MOD_RES 146
FT /note="Tyrosine amide"
FT /evidence="ECO:0000269|PubMed:8387282"
FT DISULFID 110..115
FT /evidence="ECO:0000269|PubMed:8387282"
FT VARIANT 50
FT /note="S -> R (in dbSNP:rs5005)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_014861"
FT VARIANT 85
FT /note="P -> R (in dbSNP:rs2228573)"
FT /id="VAR_048205"
FT HELIX 24..40
FT /evidence="ECO:0007829|PDB:2FLY"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:2L7S"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:6UUN"
FT HELIX 116..126
FT /evidence="ECO:0007829|PDB:6UUS"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:4RWF"
FT HELIX 138..141
FT /evidence="ECO:0007829|PDB:4RWF"
SQ SEQUENCE 185 AA; 20420 MW; 64C7D2A0B4654DFE CRC64;
MKLVSVALMY LGSLAFLGAD TARLDVASEF RKKWNKWALS RGKRELRMSS SYPTGLADVK
AGPAQTLIRP QDMKGASRSP EDSSPDAARI RVKRYRQSMN NFQGLRSFGC RFGTCTVQKL
AHQIYQFTDK DKDNVAPRSK ISPQGYGRRR RRSLPEAGPG RTLVSSKPQA HGAPAPPSGS
APHFL
