ADM2_HUMAN
ID ADM2_HUMAN Reviewed; 148 AA.
AC Q7Z4H4; Q3LFQ0;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Protein ADM2;
DE AltName: Full=Intermedin;
DE Contains:
DE RecName: Full=Adrenomedullin-2;
DE Short=AM2;
DE AltName: Full=Intermedin-long;
DE Short=IMDL;
DE Contains:
DE RecName: Full=Intermedin-short;
DE Short=IMDS;
DE Flags: Precursor;
GN Name=ADM2; Synonyms=AM2;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14615490; DOI=10.1074/jbc.m305332200;
RA Roh J., Chang C.L., Bhalla A., Klein C., Hsu S.Y.T.;
RT "Intermedin is a calcitonin/calcitonin gene-related peptide family peptide
RT acting through the calcitonin receptor-like receptor/receptor activity-
RT modifying protein receptor complexes.";
RL J. Biol. Chem. 279:7264-7274(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=14706825; DOI=10.1016/s0014-5793(03)01368-1;
RA Takei Y., Inoue K., Ogoshi M., Kawahara T., Bannai H., Miyano S.;
RT "Identification of novel adrenomedullin in mammals: a potent cardiovascular
RT and renal regulator.";
RL FEBS Lett. 556:53-58(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=16359754; DOI=10.1016/j.peptides.2005.11.004;
RA Takahashi K., Kikuchi K., Maruyama Y., Urabe T., Nakajima K., Sasano H.,
RA Imai Y., Murakami O., Totsune K.;
RT "Immunocytochemical localization of adrenomedullin 2/intermedin-like
RT immunoreactivity in human hypothalamus, heart and kidney.";
RL Peptides 27:1383-1389(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
CC -!- FUNCTION: [Adrenomedullin-2]: May play a role as physiological
CC regulators of gastrointestinal, cardiovascular bioactivities mediated
CC by the CALCRL/RAMPs receptor complexes. Activates the cAMP-dependent
CC pathway. {ECO:0000269|PubMed:14615490}.
CC -!- FUNCTION: [Intermedin-short]: May play a role as physiological
CC regulators of gastrointestinal, cardiovascular bioactivities mediated
CC by the CALCRL/RAMPs receptor complexes. Activates the cAMP-dependent
CC pathway. {ECO:0000269|PubMed:14615490}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in the esophagus, stomach, jejunum,
CC ileum, ileocecum, ascending colon, transverse colon, descending colon
CC and rectum. Expressed in myocardial cells of the heart, renal tubular
CC cells, hypothalamus, and pituitary. {ECO:0000269|PubMed:14615490,
CC ECO:0000269|PubMed:16359754}.
CC -!- SIMILARITY: Belongs to the adrenomedullin family. {ECO:0000305}.
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DR EMBL; AF529213; AAQ09100.1; -; mRNA.
DR EMBL; AB121034; BAD07411.1; -; mRNA.
DR EMBL; AB236970; BAE46395.1; -; mRNA.
DR EMBL; AL096767; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS33682.1; -.
DR RefSeq; NP_001240774.1; NM_001253845.1.
DR RefSeq; XP_016884429.1; XM_017028940.1.
DR PDB; 6D1U; X-ray; 2.05 A; D/E/F=129-147.
DR PDB; 6UVA; EM; 2.30 A; P=101-147.
DR PDBsum; 6D1U; -.
DR PDBsum; 6UVA; -.
DR AlphaFoldDB; Q7Z4H4; -.
DR SMR; Q7Z4H4; -.
DR BioGRID; 123001; 1.
DR STRING; 9606.ENSP00000379087; -.
DR BindingDB; Q7Z4H4; -.
DR PhosphoSitePlus; Q7Z4H4; -.
DR BioMuta; ADM2; -.
DR DMDM; 47115749; -.
DR jPOST; Q7Z4H4; -.
DR PaxDb; Q7Z4H4; -.
DR PeptideAtlas; Q7Z4H4; -.
DR PRIDE; Q7Z4H4; -.
DR ProteomicsDB; 69182; -.
DR Antibodypedia; 52597; 171 antibodies from 19 providers.
DR DNASU; 79924; -.
DR Ensembl; ENST00000395737.2; ENSP00000379086.1; ENSG00000128165.9.
DR Ensembl; ENST00000395738.2; ENSP00000379087.2; ENSG00000128165.9.
DR GeneID; 79924; -.
DR KEGG; hsa:79924; -.
DR MANE-Select; ENST00000395737.2; ENSP00000379086.1; NM_001253845.2; NP_001240774.1.
DR UCSC; uc003blj.4; human.
DR CTD; 79924; -.
DR DisGeNET; 79924; -.
DR GeneCards; ADM2; -.
DR HGNC; HGNC:28898; ADM2.
DR HPA; ENSG00000128165; Tissue enhanced (kidney, pancreas, thyroid gland).
DR MIM; 608682; gene.
DR neXtProt; NX_Q7Z4H4; -.
DR OpenTargets; ENSG00000128165; -.
DR PharmGKB; PA134898869; -.
DR VEuPathDB; HostDB:ENSG00000128165; -.
DR eggNOG; ENOG502S7F2; Eukaryota.
DR GeneTree; ENSGT00940000154380; -.
DR HOGENOM; CLU_134508_0_0_1; -.
DR InParanoid; Q7Z4H4; -.
DR OMA; RLWQLVR; -.
DR OrthoDB; 1381783at2759; -.
DR PhylomeDB; Q7Z4H4; -.
DR TreeFam; TF338591; -.
DR PathwayCommons; Q7Z4H4; -.
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 BioGRID-ORCS; 79924; 15 hits in 1073 CRISPR screens.
DR ChiTaRS; ADM2; human.
DR GeneWiki; ADM2; -.
DR GenomeRNAi; 79924; -.
DR Pharos; Q7Z4H4; Tbio.
DR PRO; PR:Q7Z4H4; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q7Z4H4; protein.
DR Bgee; ENSG00000128165; Expressed in body of pancreas and 101 other tissues.
DR Genevisible; Q7Z4H4; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
DR GO; GO:0007586; P:digestion; IEA:Ensembl.
DR GO; GO:0007631; P:feeding behavior; IEA:Ensembl.
DR GO; GO:0045776; P:negative regulation of blood pressure; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0010460; P:positive regulation of heart rate; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IBA:GO_Central.
DR InterPro; IPR021116; Calcitonin/adrenomedullin.
DR Pfam; PF00214; Calc_CGRP_IAPP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Cleavage on pair of basic residues;
KW Disulfide bond; Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000250|UniProtKB:P61312"
FT PROPEP 25..98
FT /evidence="ECO:0000250"
FT /id="PRO_0000000977"
FT PEPTIDE 101..147
FT /note="Adrenomedullin-2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000000978"
FT PEPTIDE 108..147
FT /note="Intermedin-short"
FT /evidence="ECO:0000255"
FT /id="PRO_0000000979"
FT REGION 26..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 70..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 147
FT /note="Tyrosine amide"
FT /evidence="ECO:0000250|UniProtKB:P35318"
FT DISULFID 110..115
FT /evidence="ECO:0000250"
FT HELIX 116..127
FT /evidence="ECO:0007829|PDB:6UVA"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:6UVA"
SQ SEQUENCE 148 AA; 15865 MW; 6E0E3098CFCE5BF2 CRC64;
MARIPTAALG CISLLCLQLP GSLSRSLGGD PRPVKPREPP ARSPSSSLQP RHPAPRPVVW
KLHRALQAQR GAGLAPVMGQ PLRDGGRQHS GPRRHSGPRR TQAQLLRVGC VLGTCQVQNL
SHRLWQLMGP AGRQDSAPVD PSSPHSYG
