LOCUS       NM_001005498            3511 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens rhomboid 5 homolog 2 (RHBDF2), transcript variant 2,
            mRNA.
ACCESSION   NM_001005498 XM_005257670
VERSION     NM_001005498.4
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 3511)
  AUTHORS   Lu,F., Zhao,H., Dai,Y., Wang,Y., Lee,C.H. and Freeman,M.
  TITLE     Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to
            control the release of growth factor and inflammatory signals
  JOURNAL   Mol Cell 84 (11), 2152-2165 (2024)
   PUBMED   38781971
  REMARK    GeneRIF: Cryo-EM reveals that iRhom2 restrains ADAM17 protease
            activity to control the release of growth factor and inflammatory
            signals.
REFERENCE   2  (bases 1 to 3511)
  AUTHORS   Calligaris,M., Spano,D.P., Bonelli,S., Muller,S.A., Carcione,C.,
            D'apolito,D., Amico,G., Miele,M., Di Bella,M., Zito,G., Nuti,E.,
            Rossello,A., Blobel,C.P., Lichtenthaler,S.F. and Scilabra,S.D.
  TITLE     iRhom2 regulates ectodomain shedding and surface expression of the
            major histocompatibility complex (MHC) class I
  JOURNAL   Cell Mol Life Sci 81 (1), 163 (2024)
   PUBMED   38570362
  REMARK    GeneRIF: iRhom2 regulates ectodomain shedding and surface
            expression of the major histocompatibility complex (MHC) class I.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3511)
  AUTHORS   Dulloo,I., Tellier,M., Levet,C., Chikh,A., Zhang,B., Blaydon,D.C.,
            Webb,C.M., Kelsell,D.P. and Freeman,M.
  TITLE     Cleavage of the pseudoprotease iRhom2 by the signal peptidase
            complex reveals an ER-to-nucleus signaling pathway
  JOURNAL   Mol Cell 84 (2), 277-292 (2024)
   PUBMED   38183983
  REMARK    GeneRIF: Cleavage of the pseudoprotease iRhom2 by the signal
            peptidase complex reveals an ER-to-nucleus signaling pathway.
REFERENCE   4  (bases 1 to 3511)
  AUTHORS   Xu,M., Tan,J., Zhu,L., Ge,C., Zhang,Y., Gao,F., Dai,X., Kuang,Q.,
            Chai,J., Zou,B. and Wang,B.
  TITLE     Palmitoyltransferase ZDHHC3 Aggravates Nonalcoholic Steatohepatitis
            by Targeting S-Palmitoylated IRHOM2
  JOURNAL   Adv Sci (Weinh) 10 (28), e2302130 (2023)
   PUBMED   37544908
  REMARK    GeneRIF: Palmitoyltransferase ZDHHC3 Aggravates Nonalcoholic
            Steatohepatitis by Targeting S-Palmitoylated IRHOM2.
            Erratum:[Adv Sci (Weinh). 2023 Dec;10(36):e2308024. doi:
            10.1002/advs.202308024.. PMID: 38153358]
REFERENCE   5  (bases 1 to 3511)
  AUTHORS   Schumacher,N., Thomsen,I., Brundert,F., Hejret,V., Dusterhoft,S.,
            Tichy,B., Schmidt-Arras,D., Voss,M. and Rose-John,S.
  TITLE     EGFR stimulation enables IL-6 trans-signalling via iRhom2-dependent
            ADAM17 activation in mammary epithelial cells
  JOURNAL   Biochim Biophys Acta Mol Cell Res 1870 (7), 119489 (2023)
   PUBMED   37271223
  REMARK    GeneRIF: EGFR stimulation enables IL-6 trans-signalling via
            iRhom2-dependent ADAM17 activation in mammary epithelial cells.
REFERENCE   6  (bases 1 to 3511)
  AUTHORS   Bailey,S.D., Xie,C., Do,R., Montpetit,A., Diaz,R., Mohan,V.,
            Keavney,B., Yusuf,S., Gerstein,H.C., Engert,J.C. and Anand,S.
  CONSRTM   DREAM investigators
  TITLE     Variation at the NFATC2 locus increases the risk of
            thiazolidinedione-induced edema in the Diabetes REduction
            Assessment with ramipril and rosiglitazone Medication (DREAM) study
  JOURNAL   Diabetes Care 33 (10), 2250-2253 (2010)
   PUBMED   20628086
  REMARK    GeneRIF: Observational study of gene-disease association,
            gene-environment interaction, and pharmacogenomic / toxicogenomic.
            (HuGE Navigator)
REFERENCE   7  (bases 1 to 3511)
  AUTHORS   Talmud,P.J., Drenos,F., Shah,S., Shah,T., Palmen,J., Verzilli,C.,
            Gaunt,T.R., Pallas,J., Lovering,R., Li,K., Casas,J.P., Sofat,R.,
            Kumari,M., Rodriguez,S., Johnson,T., Newhouse,S.J., Dominiczak,A.,
            Samani,N.J., Caulfield,M., Sever,P., Stanton,A., Shields,D.C.,
            Padmanabhan,S., Melander,O., Hastie,C., Delles,C., Ebrahim,S.,
            Marmot,M.G., Smith,G.D., Lawlor,D.A., Munroe,P.B., Day,I.N.,
            Kivimaki,M., Whittaker,J., Humphries,S.E. and Hingorani,A.D.
  CONSRTM   ASCOT investigators; NORDIL investigators; BRIGHT Consortium
  TITLE     Gene-centric association signals for lipids and apolipoproteins
            identified via the HumanCVD BeadChip
  JOURNAL   Am J Hum Genet 85 (5), 628-642 (2009)
   PUBMED   19913121
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   8  (bases 1 to 3511)
  AUTHORS   Puente,X.S., Sanchez,L.M., Overall,C.M. and Lopez-Otin,C.
  TITLE     Human and mouse proteases: a comparative genomic approach
  JOURNAL   Nat Rev Genet 4 (7), 544-558 (2003)
   PUBMED   12838346
  REMARK    Review article
REFERENCE   9  (bases 1 to 3511)
  AUTHORS   Risk,J.M., Field,E.A., Field,J.K., Whittaker,J., Fryer,A.,
            Ellis,A., Shaw,J.M., Friedmann,P.S., Bishop,D.T., Bodmer,J. et al.
  TITLE     Tylosis oesophageal cancer mapped
  JOURNAL   Nat Genet 8 (4), 319-321 (1994)
   PUBMED   7534553
REFERENCE   10 (bases 1 to 3511)
  AUTHORS   Sato,K., Mano,H., Ariyama,T., Inazawa,J., Yazaki,Y. and Hirai,H.
  TITLE     Molecular cloning and analysis of the human Tec protein-tyrosine
            kinase
  JOURNAL   Leukemia 8 (10), 1663-1672 (1994)
   PUBMED   7934162
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC015802.21.
            
            On or before Nov 12, 2019 this sequence version replaced
            XM_005257670.1, NM_001005498.3.
            
            Transcript Variant: This variant (2) differs in the 5' UTR and uses
            an alternate, in frame splice site in the 5' coding region compared
            to isoform 1. This results in a shorter protein (isoform 2),
            compared to isoform 1.
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on alignments.
            
            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 :: SRR11853567.13917.1,
                                           SRR11853566.12449.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000675367.1/ ENSP00000501790.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-71                AC015802.21        117977-118047
            72-269              AC015802.21        131491-131688
            270-440             AC015802.21        137855-138025
            441-562             AC015802.21        139546-139667
            563-758             AC015802.21        140123-140318
            759-962             AC015802.21        140391-140594
            963-1091            AC015802.21        141615-141743
            1092-1210           AC015802.21        142102-142220
            1211-1405           AC015802.21        142376-142570
            1406-1517           AC015802.21        144259-144370
            1518-1592           AC015802.21        144596-144670
            1593-1754           AC015802.21        144866-145027
            1755-1864           AC015802.21        145258-145367
            1865-1928           AC015802.21        145498-145561
            1929-2023           AC015802.21        145658-145752
            2024-2099           AC015802.21        146073-146148
            2100-2200           AC015802.21        146295-146395
            2201-2354           AC015802.21        146561-146714
            2355-3511           AC015802.21        147348-148504
FEATURES             Location/Qualifiers
     source          1..3511
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q25.1"
     gene            1..3511
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /note="rhomboid 5 homolog 2"
                     /db_xref="GeneID:79651"
                     /db_xref="HGNC:HGNC:20788"
                     /db_xref="MIM:614404"
     exon            1..71
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            72..269
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            270..440
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     CDS             291..2774
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /note="isoform 2 is encoded by transcript variant 2;
                     rhomboid family member 2; inactive rhomboid protein 2;
                     rhomboid veinlet-like protein 5; rhomboid veinlet-like
                     protein 6"
                     /codon_start=1
                     /product="inactive rhomboid protein 2 isoform 2"
                     /protein_id="NP_001005498.2"
                     /db_xref="CCDS:CCDS32744.1"
                     /db_xref="GeneID:79651"
                     /db_xref="HGNC:HGNC:20788"
                     /db_xref="MIM:614404"
                     /translation="MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQ
                     DSMLPERKNPAYLKSVSLQEPRSRWQESSEKRPGFRRQASLSQSIRKGAAQWFGVSGD
                     WEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKPCKMPKIVDP
                     LARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQA
                     AAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDD
                     VFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFD
                     RKKRHYGLGVVGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVIC
                     TYGIAPVGFAQHVTTQLVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRK
                     DGQIEQLVLRERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVKWQDDTGPPMDKS
                     DLGQKRTSGAVCHQDPRTCEEPASSGAHIWPDDITKWPICTEQARSNHTGFLHMDCEI
                     KGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQ
                     FYRLWLSLFLHAGVVHCLVSVVFQMTILRDLEKLAGWHRIAIIFILSGITGNLASAIF
                     LPYRAEVGPAGSQFGLLACLFVELFQSWPLLERPWKAFLNLSAIVLFLFICGLLPWID
                     NIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYP
                     INWPWIEHLTCFPFTSRFCEKYELDQVLH"
     exon            441..562
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            563..758
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            759..962
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            963..1091
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1092..1210
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1211..1405
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1406..1517
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1518..1592
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1593..1754
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1755..1864
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1865..1928
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            1929..2023
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            2024..2099
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            2100..2200
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            2201..2354
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     exon            2355..3511
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3489..3494
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /note="hexamer: ATTAAA"
     polyA_site      3511
                     /gene="RHBDF2"
                     /gene_synonym="iRhom2; RHBDL5; RHBDL6; TOC; TOCG"
                     /note="major polyA site"
ORIGIN      
        1 gaggagccac cgcccagccg ctcgcaggcg ccgcacggag ttgcgtcccg gggacttggg
       61 gccgcaggga gctgtgagta cccaggaagc tgcaccgtgt ggcctggagc tgtctatctg
      121 tccttccagc cacctgtctg tccagccacc cttccacaga ctgaggcttg acaccggagc
      181 atctgtacag agcaaggaga agacaagaac atgctctaaa gcccttcaca gcaagaccca
      241 ggaagccgcg ggcaaactca gactcgaagc cctcccgcct cctgcccaca atggcctctg
      301 ctgacaagaa tggcgggagc gtgtcctctg tgtccagcag ccgcctgcag agccggaagc
      361 cacccaacct ctccatcacc atcccgccac ccgagaaaga gacccaggcc cctggcgagc
      421 aggacagcat gctgcctgag aggaagaacc cagcctactt gaagagcgtc agcctccagg
      481 agccacgcag ccgatggcag gagagttcag agaagcgccc tggcttccgc cgccaggcct
      541 cactgtccca gagcatccgc aagggcgcag cccagtggtt tggagtcagc ggcgactggg
      601 aggggcagcg gcagcagtgg cagcgccgca gcctgcacca ctgcagcatg cgctacggcc
      661 gcctgaaggc ctcgtgccag cgtgacctgg agctccccag ccaggaggca ccgtccttcc
      721 agggcactga gtccccaaag ccctgcaaga tgcccaagat tgtggatccg ctggcccggg
      781 gccgggcctt ccgccacccg gaggagatgg acaggcccca cgccccgcac ccaccgctga
      841 cccccggagt cctgtccctc acctccttca ccagtgtccg ttctggctac tcccacctgc
      901 cacgccgcaa gagaatgtct gtggcccaca tgagcttgca agctgccgct gccctcctca
      961 aggggcgctc ggtgctggat gccaccggac agcggtgccg ggtggtcaag cgcagctttg
     1021 ccttcccgag cttcctggag gaggatgtgg tcgatggggc agacacgttt gactcctcct
     1081 tttttagtaa ggaagaaatg agctccatgc ctgatgatgt ctttgagtcc cccccactct
     1141 ctgccagcta cttccgaggg atcccacact cagcctcccc tgtctccccc gatggggtgc
     1201 aaatccctct gaaggagtat ggccgagccc cagtccccgg gccccggcgc ggcaagcgca
     1261 tcgcctccaa ggtgaagcac tttgcctttg atcggaagaa gcggcactac ggcctcggcg
     1321 tggtgggcaa ctggctgaac cgcagctacc gccgcagcat cagcagcact gtgcagcggc
     1381 agctggagag cttcgacagc caccggccct acttcaccta ctggctgacc ttcgtccatg
     1441 tcatcatcac gctgctggtg atttgcacgt atggcatcgc acccgtgggc tttgcccagc
     1501 acgtcaccac ccagctggtg ctgcggaaca aaggtgtgta cgagagcgtg aagtacatcc
     1561 agcaggagaa cttctgggtt ggccccagct cgattgacct gatccacctg ggggccaagt
     1621 tctcaccctg catccggaag gacgggcaga tcgagcagct ggtgctgcgc gagcgagacc
     1681 tggagcggga ctcaggctgc tgtgtccaga atgaccactc cggatgcatc cagacccagc
     1741 ggaaggactg ctcggagact ttggccactt ttgtcaagtg gcaggatgac actgggcccc
     1801 ccatggacaa gtctgatctg ggccagaagc ggacttcggg ggctgtctgc caccaggacc
     1861 ccaggacctg cgaggagcca gcctccagcg gtgcccacat ctggcccgat gacatcacta
     1921 agtggccgat ctgcacagag caggccagga gcaaccacac aggcttcctg cacatggact
     1981 gcgagatcaa gggccgcccc tgctgcatcg gcaccaaggg cagctgtgag atcaccaccc
     2041 gggaatactg tgagttcatg cacggctatt tccatgagga agcaacactc tgctcccagg
     2101 tgcactgctt ggacaaggtg tgtgggctgc tgcccttcct caaccctgag gtcccagatc
     2161 agttctacag gctctggctg tctctcttcc tacatgctgg cgtggtgcac tgcctcgtgt
     2221 ctgtggtctt tcaaatgacc atcctgaggg acctggagaa gctggccggc tggcaccgta
     2281 tcgccatcat cttcatcctc agtggcatca caggcaacct cgccagtgcc atctttctcc
     2341 cataccgggc agaggtgggc ccggccggct cacagttcgg cctcctcgcc tgcctcttcg
     2401 tggagctctt ccagagctgg ccgctgctgg agaggccctg gaaggccttc ctcaacctct
     2461 cggccatcgt gctcttcctg ttcatctgtg gcctcctgcc ctggatcgac aacatcgccc
     2521 acatcttcgg cttcctcagt ggcctgctgc tggccttcgc cttcctgccc tacatcacct
     2581 tcggcaccag cgacaagtac cgcaagcggg cactcatcct ggtgtcactg ctggcctttg
     2641 ccggcctctt cgccgccctc gtgctgtggc tgtacatcta ccccattaac tggccctgga
     2701 tcgagcacct cacctgcttc cccttcacca gccgcttctg cgagaagtat gagctggacc
     2761 aggtgctgca ctgaccgctg ggccacacgg ctgcccctca gccctgctgg aacagggtct
     2821 gcctgcgagg gctgccctct gcagagcgct ctctgtgtgc cagagagcca gagacccaag
     2881 acagggcccg ggctctggac ctgggtgccc ccctgccagg cgaggctgac tccgcgtgag
     2941 atggttggtt aaggcggggt ttttctgggg cgtgaggcct gtgagatcct gacccaagct
     3001 caggcacacc caaggcacct gcctctctga gtcttgggtc tcagttccta atatcccgct
     3061 ccttgctgag accatctcct ggggcagggt ccttttcttc ccaggtcctc agcgctgcct
     3121 ctgctggtgc cttctccccc actactactg gagcgtgccc ttgctgggga cgtggctgtg
     3181 ccctcagttg cccccagggc tgggtgccca ccatgcccct tcctctttct cctcctacct
     3241 ctgccctgtg agcccatcca taaggctctc agatgggaca ttgtgggaaa ggctttggcc
     3301 atggtctggg ggcagagaac aaggggggag acacaagtag acctcaggta gaacgacact
     3361 gggcggagcc accccagggc ctgctcccag ggagtgctcg aggcgcatca ggcccgtttt
     3421 ttaccagttt atatcacggt cttcattttt aaaagtaacg ctaactttgt acggacgatg
     3481 tctcatggat taaataatat tctttatggc a
//
