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 27-MAR-2024, entry version 201. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-32133; -. DR SMR; P35318; -. DR BioGRID; 106645; 6. DR IntAct; P35318; 1. DR STRING; 9606.ENSP00000436607; -. DR ChEMBL; CHEMBL2062356; -. DR GlyGen; P35318; 12 sites, 2 O-linked glycans (11 sites). DR iPTMnet; P35318; -. DR PhosphoSitePlus; P35318; -. DR BioMuta; ADM; -. DR DMDM; 461474; -. DR MassIVE; P35318; -. DR PaxDb; 9606-ENSP00000436607; -. DR PeptideAtlas; P35318; -. DR ProteomicsDB; 55021; -. DR Antibodypedia; 4233; 686 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 AGR; HGNC:259; -. 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; 4548241at2759; -. 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 SignaLink; P35318; -. DR SIGNOR; P35318; -. DR BioGRID-ORCS; 133; 16 hits in 1152 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 195 other cell types or tissues. DR ExpressionAtlas; P35318; baseline and differential. 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:0008209; P:androgen metabolic process; IEA:Ensembl. DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl. DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; 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: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: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: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: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 PANTHER; PTHR23414; ADRENOMEDULLIN, ADM; 1. DR PANTHER; PTHR23414:SF3; PRO-ADRENOMEDULLIN; 1. DR Pfam; PF00214; Calc_CGRP_IAPP; 1. DR PRINTS; PR00801; ADRENOMEDULN. DR Genevisible; P35318; HS. 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 //