LOCUS       NM_000741               3044 bp    mRNA    linear   PRI 07-APR-2024
DEFINITION  Homo sapiens cholinergic receptor muscarinic 4 (CHRM4), transcript
            variant 1, mRNA.
ACCESSION   NM_000741
VERSION     NM_000741.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3044)
  AUTHORS   Reale,M., Carrarini,C., Russo,M., Dono,F., Ferri,L., Di Pietro,M.,
            Costantini,E., Porreca,A., Di Nicola,M., Onofrj,M. and Bonanni,L.
  TITLE     Muscarinic Receptors Expression in the Peripheral Blood Cells
            Differentiate Dementia with Lewy Bodies from Alzheimer's Disease
  JOURNAL   J Alzheimers Dis 85 (1), 323-330 (2022)
   PUBMED   34806612
  REMARK    GeneRIF: Muscarinic Receptors Expression in the Peripheral Blood
            Cells Differentiate Dementia with Lewy Bodies from Alzheimer's
            Disease.
REFERENCE   2  (bases 1 to 3044)
  AUTHORS   Luo,L., Zhang,G., Mao,L., Wang,P., Xi,C., Shi,G. and
            Leavenworth,J.W.
  TITLE     Group II muscarinic acetylcholine receptors attenuate hepatic
            injury via Nrf2/ARE pathway
  JOURNAL   Toxicol Appl Pharmacol 395, 114978 (2020)
   PUBMED   32234387
  REMARK    GeneRIF: Group II muscarinic acetylcholine receptors attenuate
            hepatic injury via Nrf2/ARE pathway.
REFERENCE   3  (bases 1 to 3044)
  AUTHORS   Moehle,M.S. and Conn,P.J.
  TITLE     Roles of the M4 acetylcholine receptor in the basal ganglia and the
            treatment of movement disorders
  JOURNAL   Mov Disord 34 (8), 1089-1099 (2019)
   PUBMED   31211471
  REMARK    GeneRIF: Authors discuss how M4 activity regulates DA release and
            signaling, the potential sources of ACh that can regulate M4
            activity, and the implications of targeting M4 activity for the
            treatment of the motor symptoms in movement disorders. [Review]
            Review article
REFERENCE   4  (bases 1 to 3044)
  AUTHORS   Levran,O., Randesi,M., Peles,E., Correa da Rosa,J., Ott,J.,
            Rotrosen,J., Adelson,M. and Kreek,M.J.
  TITLE     African-specific variability in the acetylcholine muscarinic
            receptor M4: association with cocaine and heroin addiction
  JOURNAL   Pharmacogenomics 17 (9), 995-1003 (2016)
   PUBMED   27269905
  REMARK    GeneRIF: the association of the African-specific CHRM4 SNP with
            cocaine dependence survived correction for multiple testing
REFERENCE   5  (bases 1 to 3044)
  AUTHORS   Thal,D.M., Sun,B., Feng,D., Nawaratne,V., Leach,K., Felder,C.C.,
            Bures,M.G., Evans,D.A., Weis,W.I., Bachhawat,P., Kobilka,T.S.,
            Sexton,P.M., Kobilka,B.K. and Christopoulos,A.
  TITLE     Crystal structures of the M1 and M4 muscarinic acetylcholine
            receptors
  JOURNAL   Nature 531 (7594), 335-340 (2016)
   PUBMED   26958838
  REMARK    GeneRIF: crystal structures of the M1 and M4 muscarinic receptors
            bound to the inverse agonist, tiotropium
REFERENCE   6  (bases 1 to 3044)
  AUTHORS   Grewal,R.P., Martinez,M., Hoehe,M., Bonner,T.I., Gershon,E.S. and
            Detera-Wadleigh,S.
  TITLE     Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4)
  JOURNAL   Genomics 13 (1), 239-240 (1992)
   PUBMED   1577490
REFERENCE   7  (bases 1 to 3044)
  AUTHORS   Goyal,R.K.
  TITLE     Muscarinic receptor subtypes. Physiology and clinical implications
  JOURNAL   N Engl J Med 321 (15), 1022-1029 (1989)
   PUBMED   2674717
  REMARK    Review article
REFERENCE   8  (bases 1 to 3044)
  AUTHORS   Detera-Wadleigh,S.D., Wiesch,D. and Bonner,T.I.
  TITLE     An SstI polymorphism for the human muscarinic acetylcholine
            receptor gene, m4 (CHRM 4)
  JOURNAL   Nucleic Acids Res 17 (15), 6431 (1989)
   PUBMED   2570410
REFERENCE   9  (bases 1 to 3044)
  AUTHORS   Ashkenazi,A., Ramachandran,J. and Capon,D.J.
  TITLE     Acetylcholine analogue stimulates DNA synthesis in brain-derived
            cells via specific muscarinic receptor subtypes
  JOURNAL   Nature 340 (6229), 146-150 (1989)
   PUBMED   2739737
REFERENCE   10 (bases 1 to 3044)
  AUTHORS   Itoh,H., Toyama,R., Kozasa,T., Tsukamoto,T., Matsuoka,M. and
            Kaziro,Y.
  TITLE     Presence of three distinct molecular species of Gi protein alpha
            subunit. Structure of rat cDNAs and human genomic DNAs
  JOURNAL   J Biol Chem 263 (14), 6656-6664 (1988)
   PUBMED   2834384
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC116021.5.
            
            On Aug 27, 2019 this sequence version replaced NM_000741.4.
            
            Summary: The muscarinic cholinergic receptors belong to a larger
            family of G protein-coupled receptors. The functional diversity of
            these receptors is defined by the binding of acetylcholine and
            includes cellular responses such as adenylate cyclase inhibition,
            phosphoinositide degeneration, and potassium channel mediation.
            Muscarinic receptors influence many effects of acetylcholine in the
            central and peripheral nervous system. The clinical implications of
            this receptor are unknown; however, mouse studies link its function
            to adenylyl cyclase inhibition. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            RNAseq introns :: single sample supports all introns SAMEA2151119,
                              SAMEA2155751 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000682254.1/ ENSP00000507561.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-246               AC116021.5         158042-158287       c
            247-3044            AC116021.5         150300-153097       c
FEATURES             Location/Qualifiers
     source          1..3044
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11p11.2"
     gene            1..3044
                     /gene="CHRM4"
                     /gene_synonym="HM4; M4R"
                     /note="cholinergic receptor muscarinic 4"
                     /db_xref="GeneID:1132"
                     /db_xref="HGNC:HGNC:1953"
                     /db_xref="MIM:118495"
     exon            1..246
                     /gene="CHRM4"
                     /gene_synonym="HM4; M4R"
                     /inference="alignment:Splign:2.1.0"
     exon            247..3044
                     /gene="CHRM4"
                     /gene_synonym="HM4; M4R"
                     /inference="alignment:Splign:2.1.0"
     CDS             276..1715
                     /gene="CHRM4"
                     /gene_synonym="HM4; M4R"
                     /note="acetylcholine receptor, muscarinic 4"
                     /codon_start=1
                     /product="muscarinic acetylcholine receptor M4"
                     /protein_id="NP_000732.2"
                     /db_xref="CCDS:CCDS44581.1"
                     /db_xref="GeneID:1132"
                     /db_xref="HGNC:HGNC:1953"
                     /db_xref="MIM:118495"
                     /translation="MANFTPVNGSSGNQSVRLVTSSSHNRYETVEMVFIATVTGSLSL
                     VTVVGNILVMLSIKVNRQLQTVNNYFLFSLACADLIIGAFSMNLYTVYIIKGYWPLGA
                     VVCDLWLALDYVVSNASVMNLLIISFDRYFCVTKPLTYPARRTTKMAGLMIAAAWVLS
                     FVLWAPAILFWQFVVGKRTVPDNQCFIQFLSNPAVTFGTAIAAFYLPVVIMTVLYIHI
                     SLASRSRVHKHRPEGPKEKKAKTLAFLKSPLMKQSVKKPPPGEAAREELRNGKLEEAP
                     PPALPPPPRPVADKDTSNESSSGSATQNTKERPATELSTTEATTPAMPAPPLQPRALN
                     PASRWSKIQIVTKQTGNECVTAIEIVPATPAGMRPAANVARKFASIARNQVRKKRQMA
                     ARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCQSCIPDTVWSIGYWLCYVNSTINP
                     ACYALCNATFKKTFRHLLLCQYRNIGTAR"
     regulatory      3011..3016
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHRM4"
                     /gene_synonym="HM4; M4R"
                     /note="hexamer: ATTAAA"
     polyA_site      3044
                     /gene="CHRM4"
                     /gene_synonym="HM4; M4R"
                     /note="major polyA site"
ORIGIN      
        1 gccacagcgc cgggagctgc gggcggagca ggggccgccc ctcgacaccc cgtccccgcc
       61 cccggccctc ggcccggccg cccgccccgc cggcccgcgg ggccgcgcgt ccgtcccgcc
      121 gtctgtctgg cgcgagggga gctgggcaga ggcggcgggt aagtggctcc gcggcggcgc
      181 gggggcgggg ggctcgccgg gaagagcagg aagcaggtcc ccgggacgct ctgaggctcc
      241 ccagagacac ggcctaccca cccctggcaa ccaacatggc caacttcaca cctgtcaatg
      301 gcagctcggg caatcagtcc gtgcgcctgg tcacgtcatc atcccacaat cgctatgaga
      361 cggtggaaat ggtcttcatt gccacagtga caggctccct gagcctggtg actgtcgtgg
      421 gcaacatcct ggtgatgctg tccatcaagg tcaacaggca gctgcagaca gtcaacaact
      481 acttcctctt cagcctggcg tgtgctgatc tcatcatagg cgccttctcc atgaacctct
      541 acaccgtgta catcatcaag ggctactggc ccctgggcgc cgtggtctgc gacctgtggc
      601 tggccctgga ctacgtggtg agcaacgcct ccgtcatgaa ccttctcatc atcagctttg
      661 accgctactt ctgcgtcacc aagcctctca cctaccctgc ccggcgcacc accaagatgg
      721 caggcctcat gattgctgct gcctgggtac tgtccttcgt gctctgggcg cctgccatct
      781 tgttctggca gtttgtggtg ggtaagcgga cggtgcccga caaccagtgc ttcatccagt
      841 tcctgtccaa cccagcagtg acctttggca cagccattgc tgccttctac ctgcctgtgg
      901 tcatcatgac ggtgctgtac atccacatct ccctggccag tcgcagccga gtccacaagc
      961 accggcccga gggcccgaag gagaagaaag ccaagacgct ggccttcctc aagagcccac
     1021 taatgaagca gagcgtcaag aagcccccgc ccggggaggc cgcccgggag gagctgcgca
     1081 atggcaagct ggaggaggcc cccccgccag cgctgccacc gccaccgcgc cccgtggctg
     1141 ataaggacac ttccaatgag tccagctcag gcagtgccac ccagaacacc aaggaacgcc
     1201 cagccacaga gctgtccacc acagaggcca ccacgcccgc catgcccgcc cctcccctgc
     1261 agccgcgggc cctcaaccca gcctccagat ggtccaagat ccagattgtg acgaagcaga
     1321 caggcaatga gtgtgtgaca gccattgaga ttgtgcctgc cacgccggct ggcatgcgcc
     1381 ctgcggccaa cgtggcccgc aagttcgcca gcatcgctcg caaccaggtg cgcaagaagc
     1441 ggcagatggc ggcccgggag cgcaaagtga cacgaacgat ctttgccatt ctgctagcct
     1501 tcatcctcac ctggacgccc tacaacgtca tggtcctggt gaacaccttc tgccagagct
     1561 gcatccctga cacggtgtgg tccattggct actggctctg ctacgtcaac agcaccatca
     1621 accctgcctg ctatgctctg tgcaacgcca cctttaaaaa gaccttccgg cacctgctgc
     1681 tgtgccagta tcggaacatc ggcactgcca ggtaggcagg caggagtgcc ctaggaggtg
     1741 ctggtgttgc gtgcgtgtgc tggggggacc acacggctca cttgctgtgg ggaagagttg
     1801 caggcaccat tctgcgttca cgtttgctga ggaggaagtt cagaagaggc tctgtggctg
     1861 cattcagaga ccagatctct gctcaggctg aggaggctca ccccagggag tgtctgaact
     1921 ggggctgcct ggcccacctc tgtggccctg cttcagcgag ctgcggggca ctggcctggg
     1981 tgggcacctg ccccactgtg accaaccatc agcagtgctg gaagaatgga catctggatg
     2041 ggggccgaag cccagggccc cctcaggaag aacaaagggg ccagtgcttg gaaaaggagg
     2101 cttgggaagg gagtagaagg gtggggtccc ccattctgct gtaatcggtg ctttctgccc
     2161 ccttgcaccc cgcatgtagg ctcagccccc tctccccaaa tcccactcca ggggcagaaa
     2221 tctcctctgg ctgcagctac ttagccaggt tctgggtggg tatgatggag gccaggtccc
     2281 ccccgcccca gcagcactgc ccttgtcaca ttaagatggg gcagctggga ggtcagaggt
     2341 tctgtctcag gaactgaggt ctggccttct gcgatcccag gctgagccgt gagtggtcca
     2401 cgtattcaga agacagcccc ctgcagcccc ggccttagaa ggctgtccca ggtcacacat
     2461 cgagtcaggg tgaggctgtg gtggatggca ttcccatctg ccctcttcaa acctctcacc
     2521 ccctggcttc tgcagggtgg aggcctgggt cacacaggca agaggaaagg ggtcaacctg
     2581 gtggctcact cgggtttcca tgacagtggg aaggggggag gtgggcagtg aggtaggcac
     2641 gcagccctcg catctgctct cccccatggg tagaaccttc ctgattggct gtgggttgta
     2701 tcaaaagacc tttgactggg tgaggctgag atgggtgtgg tggttccagt gagtcagcca
     2761 ggttcccttc cccagccctg gtccctgagg gagatgagga ccgaaaggct taggtgactt
     2821 gatggggagc accctttcag gggccctgga agaaatgttt gtaattgttc tgctttttcc
     2881 atgagctctg gagagcaccc accaccaagc cccctgaaac ccaccagtcc ctacagcctg
     2941 gtctttctcc ccaccttccc actcccaaac acatttccac agcaaactcc ttgggaaggg
     3001 gcttttatat attaaaaaag aagagctttt attgggggga aaaa
//
