LOCUS       NM_016056               2876 bp    mRNA    linear   PRI 07-APR-2024
DEFINITION  Homo sapiens transmembrane BAX inhibitor motif containing 4
            (TMBIM4), transcript variant 2, mRNA.
ACCESSION   NM_016056
VERSION     NM_016056.4
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 2876)
  AUTHORS   Almeida,N., Carrara,G., Palmeira,C.M., Fernandes,A.S., Parsons,M.,
            Smith,G.L. and Saraiva,N.
  TITLE     Stimulation of cell invasion by the Golgi Ion Channel GAAP/TMBIM4
            via an H2O2-Dependent Mechanism
  JOURNAL   Redox Biol 28, 101361 (2020)
   PUBMED   31693977
  REMARK    GeneRIF: Stimulation of cell invasion by the Golgi Ion Channel
            GAAP/TMBIM4 via an H2O2-Dependent Mechanism.
REFERENCE   2  (bases 1 to 2876)
  AUTHORS   Carrara,G., Parsons,M., Saraiva,N. and Smith,G.L.
  TITLE     Golgi anti-apoptotic protein: a tale of camels, calcium, channels
            and cancer
  JOURNAL   Open Biol 7 (5) (2017)
   PUBMED   28469007
  REMARK    GeneRIF: Residues contributing to the ion-conducting pore have been
            defined and provide the first clues about the mechanistic link
            between these very different functions of golgi anti-apoptotic
            protein (GAAP) [review].
            Review article
REFERENCE   3  (bases 1 to 2876)
  AUTHORS   Lisak,D.A., Schacht,T., Enders,V., Habicht,J., Kiviluoto,S.,
            Schneider,J., Henke,N., Bultynck,G. and Methner,A.
  TITLE     The transmembrane Bax inhibitor motif (TMBIM) containing protein
            family: Tissue expression, intracellular localization and effects
            on the ER CA(2)-filling state
  JOURNAL   Biochim Biophys Acta 1853 (9), 2104-2114 (2015)
   PUBMED   25764978
  REMARK    GeneRIF: These results suggest that the TMBIM family has comparable
            functions in the maintenance of intracellular Ca(2) homeostasis in
            a wide variety of tissues
REFERENCE   4  (bases 1 to 2876)
  AUTHORS   Saraiva,N., Prole,D.L., Carrara,G., Johnson,B.F., Taylor,C.W.,
            Parsons,M. and Smith,G.L.
  TITLE     hGAAP promotes cell adhesion and migration via the stimulation of
            store-operated Ca2+ entry and calpain 2
  JOURNAL   J Cell Biol 202 (4), 699-713 (2013)
   PUBMED   23940116
  REMARK    GeneRIF: The hGAAP is a novel regulator of focal adhesion dynamics,
            cell adhesion, and migration by controlling localized
            Ca(2+)-dependent activation of calpain.
REFERENCE   5  (bases 1 to 2876)
  AUTHORS   Saraiva,N., Prole,D.L., Carrara,G., Maluquer de Motes,C.,
            Johnson,B.F., Byrne,B., Taylor,C.W. and Smith,G.L.
  TITLE     Human and viral Golgi anti-apoptotic proteins (GAAPs) oligomerize
            via different mechanisms and monomeric GAAP inhibits apoptosis and
            modulates calcium
  JOURNAL   J Biol Chem 288 (18), 13057-13067 (2013)
   PUBMED   23508950
  REMARK    GeneRIF: GAAP can oligomerize in a pH-regulated manner, and
            monomeric GAAP is functional.
REFERENCE   6  (bases 1 to 2876)
  AUTHORS   Markkula,E., Hulkkonen,J., Penttila,T. and Puolakkainen,M.
  TITLE     Host cell Golgi anti-apoptotic protein (GAAP) and growth of
            Chlamydia pneumoniae
  JOURNAL   Microb Pathog 54, 46-53 (2013)
   PUBMED   23000903
  REMARK    GeneRIF: Taken together, the proposed interaction between Chlamydia
            pneumoniae protein CPn0809 and GAAP modulates bacterial growth in
            A549 cells.
REFERENCE   7  (bases 1 to 2876)
  AUTHORS   Carrara,G., Saraiva,N., Gubser,C., Johnson,B.F. and Smith,G.L.
  TITLE     Six-transmembrane topology for Golgi anti-apoptotic protein (GAAP)
            and Bax inhibitor 1 (BI-1) provides model for the transmembrane Bax
            inhibitor-containing motif (TMBIM) family
  JOURNAL   J Biol Chem 287 (19), 15896-15905 (2012)
   PUBMED   22418439
  REMARK    GeneRIF: Data indicate that GAAP and BI-1 have a six
            membrane-spanning topology with cytosolic N and C termini and a
            C-terminal reentrant loop.
REFERENCE   8  (bases 1 to 2876)
  AUTHORS   de Mattia,F., Gubser,C., van Dommelen,M.M., Visch,H.J.,
            Distelmaier,F., Postigo,A., Luyten,T., Parys,J.B., de Smedt,H.,
            Smith,G.L., Willems,P.H. and van Kuppeveld,F.J.
  TITLE     Human Golgi antiapoptotic protein modulates intracellular calcium
            fluxes
  JOURNAL   Mol Biol Cell 20 (16), 3638-3645 (2009)
   PUBMED   19553469
  REMARK    GeneRIF: Data demonstrate that h-GAAP modulates intracellular
            Ca(2+) fluxes induced by both physiological and apoptotic stimuli.
REFERENCE   9  (bases 1 to 2876)
  AUTHORS   Zhou,J., Zhu,T., Hu,C., Li,H., Chen,G., Xu,G., Wang,S., Zhou,J. and
            Ma,D.
  TITLE     Comparative genomics and function analysis on BI1 family
  JOURNAL   Comput Biol Chem 32 (3), 159-162 (2008)
   PUBMED   18440869
  REMARK    GeneRIF: The tmbim4 may participate in cell death regulation by
            interacting with proteins of Bcl-2 family, promoting tumor
            metastasis, which is deduced from the evolutionary conservation of
            the membrane protein family containing multiple membrane spanning
            segments
REFERENCE   10 (bases 1 to 2876)
  AUTHORS   Gubser,C., Bergamaschi,D., Hollinshead,M., Lu,X., van
            Kuppeveld,F.J. and Smith,G.L.
  TITLE     A new inhibitor of apoptosis from vaccinia virus and eukaryotes
  JOURNAL   PLoS Pathog 3 (2), e17 (2007)
   PUBMED   17319741
  REMARK    GeneRIF: Stable expression of both viral GAAP (v-GAAP) and human
            GAAP (h-GAAP), which is expressed in all human tissues tested,
            inhibited apoptosis induced by intrinsic and extrinsic apoptotic
            stimuli
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC078927.20.
            
            On Feb 27, 2020 this sequence version replaced NM_016056.3.
            
            Transcript Variant: This variant (2) lacks an alternate in-frame
            exon in the 5' coding region, compared to vairant 1, resulting in
            an isoform (b) that is shorter than isoform a.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK225158.1, SRR14038197.1255119.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000358230.8/ ENSP00000350965.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-142               AC078927.20        38804-38945
            143-251             AC078927.20        55352-55460
            252-357             AC078927.20        56424-56529
            358-391             AC078927.20        60859-60892
            392-509             AC078927.20        62842-62959
            510-555             AC078927.20        70031-70076
            556-2876            AC078927.20        70634-72954
FEATURES             Location/Qualifiers
     source          1..2876
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q14.3"
     gene            1..2876
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /note="transmembrane BAX inhibitor motif containing 4"
                     /db_xref="GeneID:51643"
                     /db_xref="HGNC:HGNC:24257"
                     /db_xref="MIM:616874"
     exon            1..142
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /inference="alignment:Splign:2.1.0"
     CDS             46..762
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /note="isoform b is encoded by transcript variant 2;
                     transmembrane BAX inhibitor motif-containing protein 4;
                     Z-protein; Golgi anti-apoptotic protein; protein lifeguard
                     4"
                     /codon_start=1
                     /product="protein lifeguard 4 isoform b"
                     /protein_id="NP_057140.2"
                     /db_xref="CCDS:CCDS41805.1"
                     /db_xref="GeneID:51643"
                     /db_xref="HGNC:HGNC:24257"
                     /db_xref="MIM:616874"
                     /translation="MADPDPRYPRSSIEDDFNYGSSVASATVHIRMAFLRKVYSILSL
                     QVLLTTVTSTVFLYFESVRTFVHESPALILLFALGSLGLIFALILNRHKYPLNLYLLF
                     GFTLLEALTVAVVVTFYDVYIILQAFILTTTVFFGLTVYTLQSKKDFSKFGAGLFALL
                     WILCLSGFLKFFFYSEIMELVLAAAGALLFCGFIIYDTHSLMHKLSPEEYVLAAISLY
                     LDIINLFLHLLRFLEAVNKK"
     exon            143..251
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /inference="alignment:Splign:2.1.0"
     exon            252..357
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /inference="alignment:Splign:2.1.0"
     exon            358..391
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /inference="alignment:Splign:2.1.0"
     exon            392..509
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /inference="alignment:Splign:2.1.0"
     exon            510..555
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /inference="alignment:Splign:2.1.0"
     exon            556..2876
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /inference="alignment:Splign:2.1.0"
     regulatory      864..869
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /note="hexamer: AATAAA"
     polyA_site      888
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /note="major polyA site"
     regulatory      1614..1619
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /note="hexamer: ATTAAA"
     polyA_site      1636
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
     regulatory      1766..1771
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /note="hexamer: ATTAAA"
     polyA_site      1785
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
     regulatory      2575..2580
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
                     /note="hexamer: ACTAAA"
     polyA_site      2592
                     /gene="TMBIM4"
                     /gene_synonym="CGI-119; GAAP; LFG4; S1R; ZPRO"
ORIGIN      
        1 ggttgcggtt agtggaccgg gaccggtagg ggtgctgttg ccatcatggc tgaccccgac
       61 ccccggtacc ctcgctcctc gatcgaggac gacttcaact atggcagcag cgtggcctcc
      121 gccaccgtgc acatccgaat ggcctttctg agaaaagtct acagcattct ttctctgcag
      181 gttctcttaa ctacagtgac ttcaacagtt tttttatact ttgagtctgt acggacattt
      241 gtacatgaga gtcctgcctt aattttgctg tttgccctcg gatctctggg tttgattttt
      301 gcgttgattt taaacagaca taagtatccc cttaacctgt acctactttt tggatttacg
      361 ctgttggaag ctctgactgt ggcagttgtt gttactttct atgatgtata tattattctg
      421 caagctttca tactgactac tacagtattt tttggtttga ctgtgtatac tctacaatct
      481 aagaaggatt tcagcaaatt tggagcaggg ctgtttgctc ttttgtggat attgtgcctg
      541 tcaggattct tgaagttttt tttttatagt gagataatgg agttggtctt agccgctgca
      601 ggagcccttc ttttctgtgg attcatcatc tatgacacac actcactgat gcataaactg
      661 tcacctgaag agtacgtatt agctgccatc agcctctact tggatatcat caatctattc
      721 ctgcacctgt tacggtttct ggaagcagtt aataaaaagt aattaaaagt atctcagctc
      781 aactgaagaa caacaaaaaa aatttaatga gaaaaaagga ttaaagtaat tggaagcagt
      841 atatagaaac tgtttcatta agtaataaag tttgaaacaa tgattaaata ctgttacaat
      901 ctttatttgt atcatatgta attttgagag ctttaaaatc ttactattct ttatgatacc
      961 tcatttctaa atccttgatt taggatctca gttaagagct atcaaaattc tattaaaaat
     1021 gcttttctgg ctgggcacag tggctcacgc ctgtaatccc accactttgg gagaccgagg
     1081 caggtggatc acgaggtcaa gaggttgaga ccatcctggc caacatggtg aaaccccgtc
     1141 tctactaaaa atacaaaaat tagctggatg tggtggcaca cacctgtagt cccagctagt
     1201 caagaggctg aggccagaga atcgcttgaa cctgggaggt ggaggttgca ttgagccaag
     1261 atcacgccac tgcattccag cctggtgaca gagcgagact cagtctcaaa aaaaaaaaaa
     1321 aaatttttct tcctaaatta gccacgcata gcagttcgtt tgcaattcaa aaataatttt
     1381 atgagtagat aagaatatca gtttaccgtt gtctagtgat tttatctaaa ttttccctga
     1441 attattaagt aatattgatt tggctttgat tctgaagtag tagagtcttt accattataa
     1501 actgtaaatc tctttttgct taaaaggaaa aaaatgtaaa agataaattc cacagagaat
     1561 tattcagtat tacattaaaa tgttaatgac tttttatttt aaattgtact aacattaaaa
     1621 gttggcctga aagtcagata ttatgacaaa atttgacatt aattgttttt aaagtataga
     1681 tttcatttga aattatagaa tggtaatgtg gttagaggac accaaagata ctgggtcatc
     1741 agccattaag tatatctatt tcaaaattaa aatatttggg aagtattgtc ttatggtttc
     1801 atttgtgttg gtccacacag catgttaggt cagtgtacca gtaaccaatg aaattttgtc
     1861 aaattccctc actgtactag tttgttaggc tgccataaca aagttctaca gcttgggtgg
     1921 cttcaacaag aaatttgttt tcccacagtt ctggaggcta aaagtccaag atcaaggtgt
     1981 tagcagggtt ggtttccttt gaggcctttc tctttgattt gtagatggcc atcttctccc
     2041 tgtgtcttta aatggccttc cctctgtact tgtctgtgcc caaatttctt cttcttatga
     2101 ggacaccagt catactggat tagggcccac actgaggacc tcatttttcc ttaattatct
     2161 ctttcaaaac ctatctccaa atacagtcac attctgaagt gctgggatta ggatttcttc
     2221 atgtgaattt tggggggact acaactcagc ccataacacc ccctaagtat ttcccagcta
     2281 ttaagttgaa ataaacttgt agtatcaatt taagcttgca tgatttgtag atgtaaattt
     2341 gactttatta tcattaactg ttgaattatc aagtgtatga tgcagtgcaa tcaagtttaa
     2401 cagcatggtg ggtaagagca tctagattag aatcattgca gtccaaccag gtgcttaagt
     2461 gacatttggc gaattattta tccttcctta ggtcttctgc ctcatcttca taatgggaat
     2521 aatgatgtct agcttattgg gctgttataa ggattaaatg agatagataa ataaactaaa
     2581 ctaagtgctt aattaatgtc agctgatggt attaatacca ttttcttttt tttttttttt
     2641 tttttttttt aatttatttt tttattgata attcttggtt gtttctcaca gagggggatt
     2701 tggcagggtc atgggacaat agtggaggga aggtcagcag ataaacaagt gaacaaaggt
     2761 ctctggtttt cctaggcaga ggaccctgca gccttccgca gtgtttgtgt ccctgattac
     2821 ttgagattag ggattggtga tgactcttaa cgagcatgct gccttcaagc atctgt
//
