LOCUS       NM_021804               3596 bp    mRNA    linear   PRI 17-NOV-2024
DEFINITION  Homo sapiens angiotensin converting enzyme 2 (ACE2), transcript
            variant 2, mRNA.
ACCESSION   NM_021804 XM_005274571
VERSION     NM_021804.3
KEYWORDS    RefSeq.
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 3596)
  AUTHORS   Do,T.L., Tachibana,K., Yamamoto,N., Ando,K., Isoda,T. and Kihara,T.
  TITLE     Interaction of SARS-CoV-2 Spike protein with ACE2 induces cortical
            actin modulation, including dephosphorylation of ERM proteins and
            reduction of cortical stiffness
  JOURNAL   Hum Cell 38 (1), 3 (2024)
   PUBMED   39436480
  REMARK    GeneRIF: Interaction of SARS-CoV-2 Spike protein with ACE2 induces
            cortical actin modulation, including dephosphorylation of ERM
            proteins and reduction of cortical stiffness.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3596)
  AUTHORS   Thiede,J.M., Dick,J.K., Jarjour,N.N., Krishna,V.D., Qian,L.,
            Sangala,J., Benzow,K., Karanjeet,K., Chin,S., Rainwater,O.,
            Cheeran,M.C., Hogquist,K.A., Jameson,S.C., Hart,G.T., Bold,T.D. and
            Koob,M.D.
  TITLE     Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral
            Replication and Nonlethal Disease Progression
  JOURNAL   Immunohorizons 8 (9), 712-720 (2024)
   PUBMED   39287601
  REMARK    GeneRIF: Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral
            Replication and Nonlethal Disease Progression.
REFERENCE   3  (bases 1 to 3596)
  AUTHORS   Wang,R., Wang,R., Zhou,S., Liu,T., Dang,J., Chen,Q., Chen,J. and
            Wang,Z.
  TITLE     Ubiquitination of angiotensin-converting enzyme 2 contributes to
            the development of pulmonary arterial hypertension mediated by
            neural precursor cell-expressed developmentally down-regulated gene
            4-Like
  JOURNAL   Respir Res 25 (1), 326 (2024)
   PUBMED   39210401
  REMARK    GeneRIF: Ubiquitination of angiotensin-converting enzyme 2
            contributes to the development of pulmonary arterial hypertension
            mediated by neural precursor cell-expressed developmentally
            down-regulated gene 4-Like.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3596)
  AUTHORS   Yunita,R., Wahyuni,A.S., Sinaga,B.Y., Yamamoto,Z., Soebandrio,A.,
            Kusumawati,R.L., Sembiring,R.J. and Pandia,P.
  TITLE     Role of ACE2 and TMPRSS2 polymorphisms on COVID-19 outcome and
            disease severity in adult patients: A prospective cohort study in a
            tertiary hospital, Indonesia
  JOURNAL   Narra J 4 (2), e919 (2024)
   PUBMED   39280326
  REMARK    GeneRIF: Role of ACE2 and TMPRSS2 polymorphisms on COVID-19 outcome
            and disease severity in adult patients: A prospective cohort study
            in a tertiary hospital, Indonesia.
REFERENCE   5  (bases 1 to 3596)
  AUTHORS   Onabajo,O.O., Banday,A.R., Stanifer,M.L., Yan,W., Obajemu,A.,
            Santer,D.M., Florez-Vargas,O., Piontkivska,H., Vargas,J.M.,
            Ring,T.J., Kee,C., Doldan,P., Tyrrell,D.L., Mendoza,J.L.,
            Boulant,S. and Prokunina-Olsson,L.
  TITLE     Interferons and viruses induce a novel truncated ACE2 isoform and
            not the full-length SARS-CoV-2 receptor
  JOURNAL   Nat Genet 52 (12), 1283-1293 (2020)
   PUBMED   33077916
  REMARK    GeneRIF: Interferons and viruses induce a novel truncated ACE2
            isoform and not the full-length SARS-CoV-2 receptor.
REFERENCE   6  (bases 1 to 3596)
  AUTHORS   Ng,K.W., Attig,J., Bolland,W., Young,G.R., Major,J., Wrobel,A.G.,
            Gamblin,S., Wack,A. and Kassiotis,G.
  TITLE     Tissue-specific and interferon-inducible expression of
            nonfunctional ACE2 through endogenous retroelement co-option
  JOURNAL   Nat Genet 52 (12), 1294-1302 (2020)
   PUBMED   33077915
  REMARK    GeneRIF: Tissue-specific and interferon-inducible expression of
            nonfunctional ACE2 through endogenous retroelement co-option.
REFERENCE   7  (bases 1 to 3596)
  AUTHORS   Vickers,C., Hales,P., Kaushik,V., Dick,L., Gavin,J., Tang,J.,
            Godbout,K., Parsons,T., Baronas,E., Hsieh,F., Acton,S., Patane,M.,
            Nichols,A. and Tummino,P.
  TITLE     Hydrolysis of biological peptides by human angiotensin-converting
            enzyme-related carboxypeptidase
  JOURNAL   J Biol Chem 277 (17), 14838-14843 (2002)
   PUBMED   11815627
  REMARK    GeneRIF: role in hydrolyzing biological peptides
REFERENCE   8  (bases 1 to 3596)
  AUTHORS   Turner,A.J., Tipnis,S.R., Guy,J.L., Rice,G. and Hooper,N.M.
  TITLE     ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a
            homologue of angiotensin-converting enzyme insensitive to ACE
            inhibitors
  JOURNAL   Can J Physiol Pharmacol 80 (4), 346-353 (2002)
   PUBMED   12025971
  REMARK    Review article
REFERENCE   9  (bases 1 to 3596)
  AUTHORS   Tipnis,S.R., Hooper,N.M., Hyde,R., Karran,E., Christie,G. and
            Turner,A.J.
  TITLE     A human homolog of angiotensin-converting enzyme. Cloning and
            functional expression as a captopril-insensitive carboxypeptidase
  JOURNAL   J Biol Chem 275 (43), 33238-33243 (2000)
   PUBMED   10924499
REFERENCE   10 (bases 1 to 3596)
  AUTHORS   Donoghue,M., Hsieh,F., Baronas,E., Godbout,K., Gosselin,M.,
            Stagliano,N., Donovan,M., Woolf,B., Robison,K., Jeyaseelan,R.,
            Breitbart,R.E. and Acton,S.
  TITLE     A novel angiotensin-converting enzyme-related carboxypeptidase
            (ACE2) converts angiotensin I to angiotensin 1-9
  JOURNAL   Circ Res 87 (5), E1-E9 (2000)
   PUBMED   10969042
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC097625.11 and AB193259.1.
            
            On Jul 11, 2019 this sequence version replaced NM_021804.2.
            
            Summary: The protein encoded by this gene belongs to the
            angiotensin-converting enzyme family of dipeptidyl
            carboxydipeptidases and has considerable homology to human
            angiotensin 1 converting enzyme. This secreted protein catalyzes
            the cleavage of angiotensin I into angiotensin 1-9, and angiotensin
            II into the vasodilator angiotensin 1-7. ACE2 is known to be
            expressed in various human organs, and its organ- and cell-specific
            expression suggests that it may play a role in the regulation of
            cardiovascular and renal function, as well as fertility. In
            addition, the encoded protein is a functional receptor for the
            spike glycoprotein of the human coronavirus HCoV-NL63 and the human
            severe acute respiratory syndrome coronaviruses, SARS-CoV and
            SARS-CoV-2, the latter is the causative agent of coronavirus
            disease-2019 (COVID-19). Multiple splice variants have been found
            for this gene and the dACE2 (or MIRb-ACE2) splice variant has been
            found to be interferon inducible. [provided by RefSeq, Nov 2020].
            
            Transcript Variant: This variant (2) represents the longest
            transcript, with a longer 5' UTR compared to variant 2. Variants 1
            and 2 encode the same isoform (1).
            
            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##
            Transcript exon combination :: AB193259.1, AK315144.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN03267769 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            coronavirus related :: involved in SARS-CoV-2 infection
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-3                 AC097625.11        181542-181544       c
            4-3596              AB193259.1         1-3593
FEATURES             Location/Qualifiers
     source          1..3596
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp22.2"
     gene            1..3596
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /note="angiotensin converting enzyme 2"
                     /db_xref="GeneID:59272"
                     /db_xref="HGNC:HGNC:13557"
                     /db_xref="MIM:300335"
     exon            1..203
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            204..492
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     CDS             307..2724
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /EC_number="3.4.17.23"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 2; ACE-related carboxypeptidase; metalloprotease
                     MPROT15; angiotensin-converting enzyme homolog;
                     angiotensin I converting enzyme (peptidyl-dipeptidase A)
                     2; angiotensin-converting enzyme-related carboxypeptidase;
                     angiotensin I converting enzyme 2"
                     /codon_start=1
                     /product="angiotensin-converting enzyme 2 isoform 1
                     precursor"
                     /protein_id="NP_068576.1"
                     /db_xref="CCDS:CCDS14169.1"
                     /db_xref="GeneID:59272"
                     /db_xref="HGNC:HGNC:13557"
                     /db_xref="MIM:300335"
                     /translation="MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSS
                     LASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQ
                     NGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNE
                     RLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYS
                     RGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWT
                     NLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLT
                     DPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLL
                     RNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTL
                     PFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSN
                     DYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPW
                     TLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSIKVRISL
                     KSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFN
                     FFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS
                     IWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENPYASIDISKGENNPGFQNT
                     DDVQTSF"
     exon            493..651
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            652..745
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            746..889
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            890..1002
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1003..1108
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1109..1206
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1207..1376
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1377..1603
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1604..1748
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1749..1847
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1848..1970
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            1971..2143
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            2144..2202
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            2203..2303
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            2304..2420
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            2421..2615
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     exon            2616..3596
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3573..3578
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /note="hexamer: AATAAA"
     polyA_site      3596
                     /gene="ACE2"
                     /gene_synonym="ACEH"
                     /note="major polyA site"
ORIGIN      
        1 ggcactcata catacactct ggcaatgagg acactgagct cgcttctgaa atttgacaag
       61 ataaccacta aaatctcttt gaattctatg ttgttgtgat cccatggcta cagaggatca
      121 ggagttgaca tagatactct ttggatttca taccatgtgg aggctttctt acttccacgt
      181 gaccttgact gagttttgaa tagcgcccaa cccaagttca aaggctgata agagagaaaa
      241 tctcatgagg aggttttagt ctagggaaag tcattcagtg gatgtgatct tggctcacag
      301 gggacgatgt caagctcttc ctggctcctt ctcagccttg ttgctgtaac tgctgctcag
      361 tccaccattg aggaacaggc caagacattt ttggacaagt ttaaccacga agccgaagac
      421 ctgttctatc aaagttcact tgcttcttgg aattataaca ccaatattac tgaagagaat
      481 gtccaaaaca tgaataatgc tggggacaaa tggtctgcct ttttaaagga acagtccaca
      541 cttgcccaaa tgtatccact acaagaaatt cagaatctca cagtcaagct tcagctgcag
      601 gctcttcagc aaaatgggtc ttcagtgctc tcagaagaca agagcaaacg gttgaacaca
      661 attctaaata caatgagcac catctacagt actggaaaag tttgtaaccc agataatcca
      721 caagaatgct tattacttga accaggtttg aatgaaataa tggcaaacag tttagactac
      781 aatgagaggc tctgggcttg ggaaagctgg agatctgagg tcggcaagca gctgaggcca
      841 ttatatgaag agtatgtggt cttgaaaaat gagatggcaa gagcaaatca ttatgaggac
      901 tatggggatt attggagagg agactatgaa gtaaatgggg tagatggcta tgactacagc
      961 cgcggccagt tgattgaaga tgtggaacat acctttgaag agattaaacc attatatgaa
     1021 catcttcatg cctatgtgag ggcaaagttg atgaatgcct atccttccta tatcagtcca
     1081 attggatgcc tccctgctca tttgcttggt gatatgtggg gtagattttg gacaaatctg
     1141 tactctttga cagttccctt tggacagaaa ccaaacatag atgttactga tgcaatggtg
     1201 gaccaggcct gggatgcaca gagaatattc aaggaggccg agaagttctt tgtatctgtt
     1261 ggtcttccta atatgactca aggattctgg gaaaattcca tgctaacgga cccaggaaat
     1321 gttcagaaag cagtctgcca tcccacagct tgggacctgg ggaagggcga cttcaggatc
     1381 cttatgtgca caaaggtgac aatggacgac ttcctgacag ctcatcatga gatggggcat
     1441 atccagtatg atatggcata tgctgcacaa ccttttctgc taagaaatgg agctaatgaa
     1501 ggattccatg aagctgttgg ggaaatcatg tcactttctg cagccacacc taagcattta
     1561 aaatccattg gtcttctgtc acccgatttt caagaagaca atgaaacaga aataaacttc
     1621 ctgctcaaac aagcactcac gattgttggg actctgccat ttacttacat gttagagaag
     1681 tggaggtgga tggtctttaa aggggaaatt cccaaagacc agtggatgaa aaagtggtgg
     1741 gagatgaagc gagagatagt tggggtggtg gaacctgtgc cccatgatga aacatactgt
     1801 gaccccgcat ctctgttcca tgtttctaat gattactcat tcattcgata ttacacaagg
     1861 accctttacc aattccagtt tcaagaagca ctttgtcaag cagctaaaca tgaaggccct
     1921 ctgcacaaat gtgacatctc aaactctaca gaagctggac agaaactgtt caatatgctg
     1981 aggcttggaa aatcagaacc ctggacccta gcattggaaa atgttgtagg agcaaagaac
     2041 atgaatgtaa ggccactgct caactacttt gagcccttat ttacctggct gaaagaccag
     2101 aacaagaatt cttttgtggg atggagtacc gactggagtc catatgcaga ccaaagcatc
     2161 aaagtgagga taagcctaaa atcagctctt ggagataaag catatgaatg gaacgacaat
     2221 gaaatgtacc tgttccgatc atctgttgca tatgctatga ggcagtactt tttaaaagta
     2281 aaaaatcaga tgattctttt tggggaggag gatgtgcgag tggctaattt gaaaccaaga
     2341 atctccttta atttctttgt cactgcacct aaaaatgtgt ctgatatcat tcctagaact
     2401 gaagttgaaa aggccatcag gatgtcccgg agccgtatca atgatgcttt ccgtctgaat
     2461 gacaacagcc tagagtttct ggggatacag ccaacacttg gacctcctaa ccagccccct
     2521 gtttccatat ggctgattgt ttttggagtt gtgatgggag tgatagtggt tggcattgtc
     2581 atcctgatct tcactgggat cagagatcgg aagaagaaaa ataaagcaag aagtggagaa
     2641 aatccttatg cctccatcga tattagcaaa ggagaaaata atccaggatt ccaaaacact
     2701 gatgatgttc agacctcctt ttagaaaaat ctatgttttt cctcttgagg tgattttgtt
     2761 gtatgtaaat gttaatttca tggtatagaa aatataagat gataaagata tcattaaatg
     2821 tcaaaactat gactctgttc agaaaaaaaa ttgtccaaag acaacatggc caaggagaga
     2881 gcatcttcat tgacattgct ttcagtattt atttctgtct ctggatttga cttctgttct
     2941 gtttcttaat aaggattttg tattagagta tattagggaa agtgtgtatt tggtctcaca
     3001 ggctgttcag ggataatcta aatgtaaatg tctgttgaat ttctgaagtt gaaaacaagg
     3061 atatatcatt ggagcaagtg ttggatcttg tatggaatat ggatggatca cttgtaagga
     3121 cagtgcctgg gaactggtgt agctgcaagg attgagaatg gcatgcatta gctcactttc
     3181 atttaatcca ttgtcaagga tgacatgctt tcttcacagt aactcagttc aagtactatg
     3241 gtgatttgcc tacagtgatg tttggaatcg atcatgcttt cttcaaggtg acaggtctaa
     3301 agagagaaga atccagggaa caggtagagg acattgcttt ttcacttcca aggtgcttga
     3361 tcaacatctc cctgacaaca caaaactaga gccaggggcc tccgtgaact cccagagcat
     3421 gcctgataga aactcatttc tactgttctc taactgtgga gtgaatggaa attccaactg
     3481 tatgttcacc ctctgaagtg ggtacccagt ctcttaaatc ttttgtattt gctcacagtg
     3541 tttgagcagt gctgagcaca aagcagacac tcaataaatg ctagatttac acactc
//
