LOCUS       NM_001321080            4443 bp    mRNA    linear   PRI 03-SEP-2024
DEFINITION  Homo sapiens HECT domain and ankyrin repeat containing E3 ubiquitin
            protein ligase 1 (HACE1), transcript variant 3, mRNA.
ACCESSION   NM_001321080 XM_006715529
VERSION     NM_001321080.2
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 4443)
  AUTHORS   Usmani,M.A., Ghaffar,A., Shahzad,M., Akram,J., Majeed,A.I.,
            Malik,K., Fatima,K., Khan,A.A., Ahmed,Z.M., Riazuddin,S. and
            Riazuddin,S.
  TITLE     A Missense Variant in HACE1 Is Associated with Intellectual
            Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a
            Pakistani Kindred
  JOURNAL   Genes (Basel) 15 (5), 580 (2024)
   PUBMED   38790209
  REMARK    GeneRIF: A Missense Variant in HACE1 Is Associated with
            Intellectual Disability, Epilepsy, Spasticity, and Psychomotor
            Impairment in a Pakistani Kindred.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4443)
  AUTHORS   Zang,C., Liu,H., Ning,J., Chen,Q., Jiang,Y., Shang,M., Yang,Y.,
            Ma,J., Dong,Y., Wang,J., Li,F., Bao,X. and Zhang,D.
  TITLE     Emerging role and mechanism of HACE1 in the pathogenesis of
            neurodegenerative diseases: A promising target
  JOURNAL   Biomed Pharmacother 172, 116204 (2024)
   PUBMED   38364733
  REMARK    GeneRIF: Emerging role and mechanism of HACE1 in the pathogenesis
            of neurodegenerative diseases: A promising target.
            Review article
REFERENCE   3  (bases 1 to 4443)
  AUTHORS   Yin,P., Wu,Y., Long,X., Zhu,S., Chen,S., Lu,F., Lin,K. and Xu,J.
  TITLE     HACE1 expression in heart failure patients might promote
            mitochondrial oxidative stress and ferroptosis by targeting NRF2
  JOURNAL   Aging (Albany NY) 15 (23), 13888-13900 (2023)
   PUBMED   38070140
  REMARK    GeneRIF: HACE1 expression in heart failure patients might promote
            mitochondrial oxidative stress and ferroptosis by targeting NRF2.
REFERENCE   4  (bases 1 to 4443)
  AUTHORS   Singh,S., Machida,S., Tulsian,N.K., Choong,Y.K., Ng,J., Shankar,S.,
            Liu,Y., Chandiramani,K.V., Shi,J. and Sivaraman,J.
  TITLE     Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type
            E3 Ligase Through N-Terminal Helix Dimerization
  JOURNAL   Adv Sci (Weinh) 10 (27), e2207672 (2023)
   PUBMED   37537642
  REMARK    GeneRIF: Structural Basis for the Enzymatic Activity of the HACE1
            HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.
REFERENCE   5  (bases 1 to 4443)
  AUTHORS   Da,C., Pu,J., Liu,Z., Wei,J., Qu,Y., Wu,Y., Shi,B., Yang,J., He,N.
            and Hou,P.
  TITLE     HACE1-mediated NRF2 activation causes enhanced malignant phenotypes
            and decreased radiosensitivity of glioma cells
  JOURNAL   Signal Transduct Target Ther 6 (1), 399 (2021)
   PUBMED   34815381
  REMARK    GeneRIF: HACE1-mediated NRF2 activation causes enhanced malignant
            phenotypes and decreased radiosensitivity of glioma cells.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4443)
  AUTHORS   Sulem,P., Gudbjartsson,D.F., Rafnar,T., Holm,H., Olafsdottir,E.J.,
            Olafsdottir,G.H., Jonsson,T., Alexandersen,P., Feenstra,B.,
            Boyd,H.A., Aben,K.K., Verbeek,A.L., Roeleveld,N., Jonasdottir,A.,
            Styrkarsdottir,U., Steinthorsdottir,V., Karason,A., Stacey,S.N.,
            Gudmundsson,J., Jakobsdottir,M., Thorleifsson,G., Hardarson,G.,
            Gulcher,J., Kong,A., Kiemeney,L.A., Melbye,M., Christiansen,C.,
            Tryggvadottir,L., Thorsteinsdottir,U. and Stefansson,K.
  TITLE     Genome-wide association study identifies sequence variants on 6q21
            associated with age at menarche
  JOURNAL   Nat Genet 41 (6), 734-738 (2009)
   PUBMED   19448622
REFERENCE   7  (bases 1 to 4443)
  AUTHORS   Hibi,K., Sakata,M., Sakuraba,K., Shirahata,A., Goto,T.,
            Mizukami,H., Saito,M., Ishibashi,K., Kigawa,G., Nemoto,H. and
            Sanada,Y.
  TITLE     Aberrant methylation of the HACE1 gene is frequently detected in
            advanced colorectal cancer
  JOURNAL   Anticancer Res 28 (3A), 1581-1584 (2008)
   PUBMED   18630515
  REMARK    GeneRIF: Aberrant methylation of the HACE1 gene was detected in 9
            out of the 32 (28%) primary colon carcinomas.
REFERENCE   8  (bases 1 to 4443)
  AUTHORS   Hwang,S.J., Yang,Q., Meigs,J.B., Pearce,E.N. and Fox,C.S.
  TITLE     A genome-wide association for kidney function and endocrine-related
            traits in the NHLBI's Framingham Heart Study
  JOURNAL   BMC Med Genet 8 Suppl 1 (Suppl 1), S10 (2007)
   PUBMED   17903292
  REMARK    Publication Status: Online-Only
REFERENCE   9  (bases 1 to 4443)
  AUTHORS   Zhang,L., Anglesio,M.S., O'Sullivan,M., Zhang,F., Yang,G.,
            Sarao,R., Mai,P.N., Cronin,S., Hara,H., Melnyk,N., Li,L., Wada,T.,
            Liu,P.P., Farrar,J., Arceci,R.J., Sorensen,P.H. and Penninger,J.M.
  TITLE     The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor
            involved in multiple cancers
  JOURNAL   Nat Med 13 (9), 1060-1069 (2007)
   PUBMED   17694067
  REMARK    GeneRIF: HACE1 is a candidate chromosome 6q21 tumor-suppressor gene
            involved in multiple cancers.
REFERENCE   10 (bases 1 to 4443)
  AUTHORS   Anglesio,M.S., Evdokimova,V., Melnyk,N., Zhang,L., Fernandez,C.V.,
            Grundy,P.E., Leach,S., Marra,M.A., Brooks-Wilson,A.R., Penninger,J.
            and Sorensen,P.H.
  TITLE     Differential expression of a novel ankyrin containing E3
            ubiquitin-protein ligase, Hace1, in sporadic Wilms' tumor versus
            normal kidney
  JOURNAL   Hum Mol Genet 13 (18), 2061-2074 (2004)
   PUBMED   15254018
  REMARK    GeneRIF: Hace1 as a novel ubiquitin-protein ligase with very low
            expression Wilms' tumors; hypermethylation of two upstream CpG
            islands correlates with low HACE1 expression in tumor samples.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK131207.1, BC034982.2,
            AL513472.9 and AL590402.10.
            
            On Jun 1, 2019 this sequence version replaced NM_001321080.1.
            
            Summary: This gene encodes a HECT domain and ankyrin
            repeat-containing ubiquitin ligase. The encoded protein is involved
            in specific tagging of target proteins, leading to their
            subcellular localization or proteasomal degradation. The protein is
            a potential tumor suppressor and is involved in the pathophysiology
            of several tumors, including Wilm's tumor. [provided by RefSeq, Mar
            2016].
            
            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 :: SRR11853558.20895.1,
                                           SRR14372079.3805.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-327               AK131207.1         1-327
            328-679             BC034982.2         292-643
            680-1265            BC034982.2         776-1361
            1266-1266           AL513472.9         37059-37059         c
            1267-3208           BC034982.2         1363-3304
            3209-3209           AL590402.10        24240-24240         c
            3210-4443           BC034982.2         3306-4539
FEATURES             Location/Qualifiers
     source          1..4443
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q16.3"
     gene            1..4443
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /note="HECT domain and ankyrin repeat containing E3
                     ubiquitin protein ligase 1"
                     /db_xref="GeneID:57531"
                     /db_xref="HGNC:HGNC:21033"
                     /db_xref="MIM:610876"
     exon            1..353
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     CDS             278..2875
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /EC_number="2.3.2.26"
                     /note="isoform b is encoded by transcript variant 3;
                     HECT-type E3 ubiquitin transferase HACE1"
                     /codon_start=1
                     /product="E3 ubiquitin-protein ligase HACE1 isoform b"
                     /protein_id="NP_001308009.1"
                     /db_xref="GeneID:57531"
                     /db_xref="HGNC:HGNC:21033"
                     /db_xref="MIM:610876"
                     /translation="MERAMEQLNRLTRSLRRARTVELPEDNETAVYTLMPMVMADQHR
                     SVSELLSNSKFDVNYAFGRVKRSLLHIAANCGSVECLVLLLKKGANPNYQDISGCTPL
                     HLAARNGQKKCMSKLLEYSADVNICNNEGLTATVQCLLDSGADINRPNVSGATPLYFA
                     CSHGQRDTAQILLLRGAKYLPDKNGVTPLDLCVQGGYGETCEVLIQYHPRLFQTIIQM
                     TQNEDLRENMLRQVLEHLSQQSESQYLKILTSLAEVATTNGHKLLSLSSNYDAQMKSL
                     LRIVRMFCHVFRIGPSSPSNGIDMGYNGNKTPRSQVFKPLELLWHSLDEWLVLIATEL
                     MKNKRDSTEITSILLKQKGQDQDAASIPPFEPPGPGSYENLSTGTRESKPDALAGRQE
                     ASADCQDVISMTANRLSAVIQAFYMCCSCQMPPGMTSPRFIEFVCKHDEVLKCFVNRN
                     PKIIFDHFHFLLECPELMSRFMHIIKAQPFKDRCEWFYEHLHSGQPDSDMVHRPVNEN
                     DILLVHRDSIFRSSCEVVSKANCAKLKQGIAVRFHGEEGMGQGVVREWFDILSNEIVN
                     PDYALFTQSADGTTFQPNSNSYVNPDHLNYFRFAGQILGLALNHRQLVNIYFTRSFYK
                     HILGIPVNYQDVASIDPEYAKNLQWILDNDISDLGLELTFSVETDVFGAMEEVPLKPG
                     GGSILVTQNNKAEYVQLVTELRMTRAIQPQINAFLQGFHMFIPPSLIQLFDEYELELL
                     LSGMPEIDVSDWIKNTEYTSGYEREDPVIQWFWEVVEDITQEERVLLLQFVTGSSRVP
                     HGGFANIMGGSGLQNFTIAAVPYTPNLLPTSSTCINMLKLPEYPSKEILKDRLLVALH
                     CGSYGYTMA"
     exon            354..408
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            409..498
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            499..603
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            604..679
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            680..762
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            763..859
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            860..961
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            962..1068
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1069..1219
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1220..1554
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1555..1623
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1624..1711
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1712..1823
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1824..1921
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1922..2009
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2010..2159
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2160..2356
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2357..2488
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2489..2587
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2588..2658
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2659..2772
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2773..4443
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4423..4428
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /note="hexamer: AATAAA"
     polyA_site      4443
                     /gene="HACE1"
                     /gene_synonym="SPPRS"
                     /note="major polyA site"
ORIGIN      
        1 agaaggccac gcgagcccgg gagggacgcg gcggcggggg ctgcaggaaa ggcgcgagca
       61 gaggcggcgg cgggtgtact gtaggtggtc ggtccggcag cagcccggcc cccggacgca
      121 ggacgtggcc ccaggcagcc ctcgcagctc agtgctctag ccggggcaag cccgcgtctc
      181 cgcctgctgg acgggcccag gcgagatgta gggctctggg cgcggaggcc gccggtgggg
      241 cggctgatcg cggaggatcg cggagggcgc gccgaggatg gagagagcga tggagcaact
      301 caaccgcctg acgcgctcgc tgcgccgcgc gcgcaccgtg gagttgcccg aggataatga
      361 aactgctgtt tatacattaa tgccaatggt tatggctgat caacacaggt ctgtttctga
      421 actactatca aattcaaaat ttgatgtcaa ttatgcattc ggacgtgtga aaagaagctt
      481 gcttcacatt gcagcaaatt gtggatcggt ggaatgcttg gttttgctgt taaagaaagg
      541 agcaaatcct aactatcaag atatttcagg ctgtacaccc cttcatttgg cagcaagaaa
      601 tgggcagaag aaatgtatga gtaaattatt agaatatagc gctgatgtca acatttgtaa
      661 taatgaaggc cttacagcaa cagtgcagtg cttgctagac agtggtgctg atattaacag
      721 gccaaatgta tcaggagcaa ctccattgta ctttgcttgc agtcatggtc agagagatac
      781 agcacagatc ctactattac gaggagccaa atatctgcca gataaaaatg gagtaactcc
      841 tctggattta tgtgtacagg gtggatatgg agagacttgt gaagtattaa ttcaatatca
      901 cccgaggctt tttcagacta ttattcaaat gacacagaat gaagacctcc gagaaaacat
      961 gttacggcaa gttctggagc atttgtctca gcaaagtgaa agccagtacc taaagattct
     1021 aacaagcctt gctgaagttg ctacaacaaa tggtcataaa ctgcttagcc tctctagcaa
     1081 ttatgatgct caaatgaaga gccttttaag gattgtgaga atgttttgtc acgtctttcg
     1141 aattggtcca tcctccccca gtaatggaat tgatatgggc tacaatggga ataaaactcc
     1201 aagaagccag gtgttcaagc ctctggaatt gctttggcac tcgttagatg aatggctagt
     1261 tttaatagcc acagaattga tgaaaaacaa aagagactca acagagatca cttctatttt
     1321 actgaaacaa aaaggccaag atcaagatgc tgcttccatt cctccatttg aacctccagg
     1381 acctgggagc tatgaaaatc tgtccactgg cacaagggaa tctaaaccag atgctcttgc
     1441 agggagacag gaagccagtg cagattgtca ggatgttatt tctatgacag ctaaccggct
     1501 aagtgctgtc attcaagctt tttacatgtg ctgttcttgt cagatgcctc cgggaatgac
     1561 ttcacctcgt ttcattgaat ttgtctgcaa acatgatgaa gttttaaaat gctttgttaa
     1621 tagaaatccc aaaattatat ttgaccactt tcactttctc cttgaatgtc ctgagttgat
     1681 gtcaagattc atgcatatca taaaagcaca gccttttaaa gatcgctgtg aatggttcta
     1741 tgaacatttg cattcaggac agccagattc agatatggtg cacaggccag tgaatgaaaa
     1801 tgatatcctg ctggttcaca gagattctat ttttaggagt agctgtgaag ttgtgtcaaa
     1861 agcaaattgt gcaaagctaa agcaagggat tgctgtacgg ttccatggag aagaaggcat
     1921 gggtcaaggt gttgtgcgtg agtggtttga tattctgtcc aatgagatag tcaatcctga
     1981 ttatgcattg tttacccagt cagctgatgg aacaactttt cagcctaata gcaactctta
     2041 tgtaaatcct gatcacttga actattttcg gtttgctggg cagatcttgg gattagcgtt
     2101 gaaccacagg cagctggtca atatttactt cacacgatcc ttctacaagc acattcttgg
     2161 tattcctgta aattaccaag atgtggcatc cattgatcca gaatatgcga aaaatttgca
     2221 atggatttta gataatgata taagtgatct gggtctagaa ctaacttttt ctgttgagac
     2281 tgatgtgttt ggagcaatgg aagaggtgcc tttgaaacct gggggtggga gtattcttgt
     2341 gacacaaaat aataaagcgg agtacgtcca gcttgttact gaacttcgaa tgacaagagc
     2401 cattcagcct cagatcaatg cttttttaca gggctttcat atgttcattc caccctccct
     2461 catacagctt tttgatgaat atgaattgga gctactgctt tctggcatgc cagaaattga
     2521 tgtgagtgat tggataaaaa atacagaata cacaagtggc tatgaaagag aagatccagt
     2581 tattcagtgg ttctgggaag ttgtagaaga cattactcaa gaggagagag ttcttctctt
     2641 acagtttgtt acgggcagtt ccagggtccc acatggtggg tttgctaata tcatgggtgg
     2701 aagtggattg caaaacttta caatcgctgc tgtgccatat actccaaatc ttttaccaac
     2761 ttcaagcaca tgcatcaaca tgctcaagtt acctgaatac ccaagtaaag aaatactcaa
     2821 ggacagactt cttgtggcac tacattgtgg cagctatggt tacacaatgg cataatgaag
     2881 tctggaaaac tcctctgact actgatgcac aattcagaat ggcagaagta atttgggaaa
     2941 atgtcaacaa aaaagcagcc taaatgcaac ccataggcag ggctgatgct tccaatttat
     3001 aaaggatcat caggttttct gtttctctct tttccctttt atgttttctc tgtttgtgat
     3061 acaattagaa aatataaaat cacagtagat tttatttttt aaaatgctaa ctgaaagtaa
     3121 tagagactgt cctttttcat aattaatttt atccaagatt gtattaaggc aaaatctgat
     3181 tctacattcc acctctgcta tgtaactgtc ttgttaaaag ggtgttttct cctaatttct
     3241 gatatattat atgaggtcat ccagctggtg tgttcttttg catgtaaact gccatttata
     3301 ttttagaaaa ctattgtata gaatggattt agattgtcta taaagccaca aatacgtatt
     3361 ttgccacagt gtattctata ttgcaatgat ttttttagca ttttaatatt ttaatatata
     3421 ttgtaaaatt tagactgatg atactaacag ttgatgaaat gacatataat ttatatatga
     3481 aagcttacgc tatattgtat gaattatttg catctttcag tggccagttt tccatatgta
     3541 tatattatgg tctcaatgtt tttcttacgc ctcattttaa tttataatga aggtaaaatt
     3601 aaaatgtatt ttaccacgtt tcttttcatt acttttatct gtgagctctg acacatctga
     3661 aaaagtaatc tgatgtgcaa attataattt aaatatgtta atttttttgc ttcttaaatt
     3721 tgcttttcat cattaaaatg tcaagttcaa gtgatatgtg cctaatatca cttggatgtt
     3781 ggtgggtttt tgaatttttg ggtggttaat cagttttatt ttgaaaagac gtacttgaat
     3841 agttacagca tatgtttgaa caggaagtag gaacatgcat acacgaagaa atgctaacgg
     3901 aaggatttgt tatgtttagg atcttccctt ggaaactaaa aatagaatat taatgacatt
     3961 actgtttgta gaatgacata tgcagatttt ctcataagca gtcattgtgt ttgccagtaa
     4021 tgtttgagag acatgtaagt tgaaagtttt gctaaattat aaagctcctt taattcgttg
     4081 gttttgattc tcttattctc ttgtcttttc taaatgttaa caaaatatat cttaacagat
     4141 tacatgaaat ttaggaatta tttaaaagtt accattagct ctaaaattaa gattcggatg
     4201 ctttatttat agtaactgaa gctaataatg ttttatgttt tgattttttg aaatttaatt
     4261 gtagaagtca ctgccttctg agttttcaaa tagataacca cctttaatat tacactgctt
     4321 ataatactaa tgtttacaga tatgtttctg tttataacca tataatacat tggctttgtc
     4381 atattagttt tttttgcaag tagttatgta aaagagatag ataataaaat attaaataac
     4441 tga
//
