ID   MOTI_HUMAN              Reviewed;         115 AA.
AC   P12872; B7ZLR7; E9PDN2; J3KN51; Q2M1L2; Q5T975; Q6NSY7;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   27-MAR-2024, entry version 193.
DE   RecName: Full=Promotilin;
DE   Contains:
DE     RecName: Full=Motilin;
DE   Contains:
DE     RecName: Full=Motilin-associated peptide;
DE              Short=MAP;
DE   Flags: Precursor;
GN   Name=MLN;
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] (ISOFORM 1).
RX   PubMed=3666144; DOI=10.1016/0014-5793(87)80512-4;
RA   Seino Y., Tanaka K., Takeda J., Takahashi H., Mitani T., Kurono M.,
RA   Kayano T., Koh G., Fukumoto H., Yano H., Fujita J., Inagaki N., Yamada Y.,
RA   Imura H.;
RT   "Sequence of an intestinal cDNA encoding human motilin precursor.";
RL   FEBS Lett. 223:74-76(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2737284; DOI=10.1016/0014-5793(89)80633-7;
RA   Yano H., Seino Y., Fujita J., Yamada Y., Inagaki N., Takeda J., Bell G.I.,
RA   Eddy R.L., Fan Y.-S., Byers M.G., Shows T.B., Imura H.;
RT   "Exon-intron organization, expression, and chromosomal localization of the
RT   human motilin gene.";
RL   FEBS Lett. 249:248-252(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2574660; DOI=10.1089/dna.1989.8.615;
RA   Daikh D.I., Douglass J.O., Adelman J.P.;
RT   "Structure and expression of the human motilin gene.";
RL   DNA 8:615-621(1989).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=2914635; DOI=10.1016/0016-5085(89)90892-5;
RA   Dea D., Boileau G., Poitras P., Lahaie R.G.;
RT   "Molecular heterogeneity of human motilin-like immunoreactivity explained
RT   by the processing of prepromotilin.";
RL   Gastroenterology 96:695-703(1989).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP   ALA-15.
RC   TISSUE=Brain;
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   [8]
RP   PROTEIN SEQUENCE OF 26-40.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [9]
RP   STRUCTURE BY NMR OF 26-47.
RX   PubMed=12495026; DOI=10.1023/a:1020902915969;
RA   Andersson A., Maler L.;
RT   "NMR solution structure and dynamics of motilin in isotropic phospholipid
RT   bicellar solution.";
RL   J. Biomol. NMR 24:103-112(2002).
CC   -!- FUNCTION: Plays an important role in the regulation of interdigestive
CC       gastrointestinal motility and indirectly causes rhythmic contraction of
CC       duodenal and colonic smooth muscle.
CC   -!- INTERACTION:
CC       P12872; Q9Y320: TMX2; NbExp=3; IntAct=EBI-18053274, EBI-6447886;
CC       P12872; Q6DKK2: TTC19; NbExp=3; IntAct=EBI-18053274, EBI-948354;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P12872-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P12872-2; Sequence=VSP_045484;
CC       Name=3;
CC         IsoId=P12872-3; Sequence=VSP_047653;
CC   -!- SIMILARITY: Belongs to the motilin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Motilin entry;
CC       URL="https://en.wikipedia.org/wiki/Motilin";
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DR   EMBL; Y00695; CAA68690.1; -; mRNA.
DR   EMBL; X15393; CAA33448.1; -; Genomic_DNA.
DR   EMBL; X15396; CAA33448.1; JOINED; Genomic_DNA.
DR   EMBL; X15395; CAA33448.1; JOINED; Genomic_DNA.
DR   EMBL; X15394; CAA33448.1; JOINED; Genomic_DNA.
DR   EMBL; M30281; AAA59860.1; -; Genomic_DNA.
DR   EMBL; M30278; AAA59860.1; JOINED; Genomic_DNA.
DR   EMBL; M30279; AAA59860.1; JOINED; Genomic_DNA.
DR   EMBL; M30280; AAA59860.1; JOINED; Genomic_DNA.
DR   EMBL; AL138889; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL158049; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471081; EAX03752.1; -; Genomic_DNA.
DR   EMBL; CH471081; EAX03753.1; -; Genomic_DNA.
DR   EMBL; BC069675; AAH69675.1; -; mRNA.
DR   EMBL; BC112314; AAI12315.1; -; mRNA.
DR   EMBL; BC143981; AAI43982.1; -; mRNA.
DR   CCDS; CCDS47412.1; -. [P12872-3]
DR   CCDS; CCDS4786.1; -. [P12872-1]
DR   CCDS; CCDS54993.1; -. [P12872-2]
DR   PIR; A33323; A33323.
DR   RefSeq; NP_001035198.1; NM_001040109.1. [P12872-3]
DR   RefSeq; NP_001171627.1; NM_001184698.1. [P12872-2]
DR   RefSeq; NP_002409.1; NM_002418.2. [P12872-1]
DR   PDB; 1LBJ; NMR; -; A=26-47.
DR   PDB; 8IBV; EM; 3.19 A; C=26-47.
DR   PDBsum; 1LBJ; -.
DR   PDBsum; 8IBV; -.
DR   AlphaFoldDB; P12872; -.
DR   BMRB; P12872; -.
DR   SMR; P12872; -.
DR   BioGRID; 110441; 2.
DR   IntAct; P12872; 2.
DR   STRING; 9606.ENSP00000388825; -.
DR   BindingDB; P12872; -.
DR   ChEMBL; CHEMBL5214853; -.
DR   iPTMnet; P12872; -.
DR   PhosphoSitePlus; P12872; -.
DR   BioMuta; MLN; -.
DR   DMDM; 127253; -.
DR   MassIVE; P12872; -.
DR   PaxDb; 9606-ENSP00000388825; -.
DR   PeptideAtlas; P12872; -.
DR   ProteomicsDB; 19710; -.
DR   ProteomicsDB; 52881; -. [P12872-1]
DR   Antibodypedia; 45691; 235 antibodies from 25 providers.
DR   DNASU; 4295; -.
DR   Ensembl; ENST00000266003.9; ENSP00000266003.5; ENSG00000096395.11. [P12872-3]
DR   Ensembl; ENST00000430124.7; ENSP00000388825.2; ENSG00000096395.11. [P12872-1]
DR   Ensembl; ENST00000507738.1; ENSP00000425467.1; ENSG00000096395.11. [P12872-2]
DR   GeneID; 4295; -.
DR   KEGG; hsa:4295; -.
DR   MANE-Select; ENST00000430124.7; ENSP00000388825.2; NM_002418.3; NP_002409.1.
DR   UCSC; uc003off.2; human. [P12872-1]
DR   AGR; HGNC:7141; -.
DR   CTD; 4295; -.
DR   DisGeNET; 4295; -.
DR   GeneCards; MLN; -.
DR   HGNC; HGNC:7141; MLN.
DR   HPA; ENSG00000096395; Tissue enriched (intestine).
DR   MIM; 158270; gene.
DR   neXtProt; NX_P12872; -.
DR   OpenTargets; ENSG00000096395; -.
DR   PharmGKB; PA30856; -.
DR   VEuPathDB; HostDB:ENSG00000096395; -.
DR   eggNOG; ENOG502SS7F; Eukaryota.
DR   GeneTree; ENSGT00390000000489; -.
DR   HOGENOM; CLU_154278_0_0_1; -.
DR   InParanoid; P12872; -.
DR   OMA; VPIFTHS; -.
DR   OrthoDB; 5348470at2759; -.
DR   PhylomeDB; P12872; -.
DR   TreeFam; TF336217; -.
DR   PathwayCommons; P12872; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-416476; G alpha (q) signalling events.
DR   SignaLink; P12872; -.
DR   SIGNOR; P12872; -.
DR   BioGRID-ORCS; 4295; 11 hits in 1142 CRISPR screens.
DR   ChiTaRS; MLN; human.
DR   EvolutionaryTrace; P12872; -.
DR   GenomeRNAi; 4295; -.
DR   Pharos; P12872; Tbio.
DR   PRO; PR:P12872; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; P12872; Protein.
DR   Bgee; ENSG00000096395; Expressed in duodenum and 102 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0031788; F:motilin receptor binding; IPI:GO_Central.
DR   InterPro; IPR006737; Motilin_assoc.
DR   InterPro; IPR006738; Motilin_ghrelin.
DR   InterPro; IPR015662; Promotilin.
DR   PANTHER; PTHR14156; MOTILIN; 1.
DR   PANTHER; PTHR14156:SF0; PROMOTILIN; 1.
DR   Pfam; PF04643; Motilin_assoc; 1.
DR   Pfam; PF04644; Motilin_ghrelin; 1.
DR   Genevisible; P12872; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Hormone; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   CHAIN           26..115
FT                   /note="Promotilin"
FT                   /id="PRO_0000342171"
FT   PEPTIDE         26..47
FT                   /note="Motilin"
FT                   /id="PRO_0000019184"
FT   PEPTIDE         50..115
FT                   /note="Motilin-associated peptide"
FT                   /id="PRO_0000019185"
FT   REGION          39..72
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         106..113
FT                   /note="SEMLPQHA -> T (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_045484"
FT   VAR_SEQ         114..115
FT                   /note="AK -> K (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_047653"
FT   VARIANT         15
FT                   /note="V -> A (in dbSNP:rs2281820)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_020372"
FT   HELIX           32..42
FT                   /evidence="ECO:0007829|PDB:8IBV"
SQ   SEQUENCE   115 AA;  12920 MW;  30D4BB59B2F42783 CRC64;
     MVSRKAVAAL LVVHVAAMLA SQTEAFVPIF TYGELQRMQE KERNKGQKKS LSVWQRSGEE
     GPVDPAEPIR EEENEMIKLT APLEIGMRMN SRQLEKYPAT LEGLLSEMLP QHAAK
//