LOCUS       NM_003585               6062 bp    mRNA    linear   PRI 01-AUG-2024
DEFINITION  Homo sapiens double C2 domain beta (DOC2B), mRNA.
ACCESSION   NM_003585
VERSION     NM_003585.5
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 6062)
  AUTHORS   Adiga,D., Bhat,S., Shukla,V., Shah,H.V., Kuthethur,R.,
            Chakrabarty,S. and Kabekkodu,S.P.
  TITLE     Double C-2 like domain beta (DOC2B) induces calcium dependent
            oxidative stress to promote lipotoxicity and mitochondrial
            dysfunction for its tumor suppressive function
  JOURNAL   Free Radic Biol Med 201, 1-13 (2023)
   PUBMED   36913987
  REMARK    GeneRIF: Double C-2 like domain beta (DOC2B) induces calcium
            dependent oxidative stress to promote lipotoxicity and
            mitochondrial dysfunction for its tumor suppressive function.
REFERENCE   2  (bases 1 to 6062)
  AUTHORS   Aslamy,A., Oh,E., Ahn,M., Moin,A.S.M., Chang,M., Duncan,M.,
            Hacker-Stratton,J., El-Shahawy,M., Kandeel,F., DiMeglio,L.A. and
            Thurmond,D.C.
  TITLE     Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes
  JOURNAL   J Clin Endocrinol Metab 103 (5), 1966-1976 (2018)
   PUBMED   29506054
  REMARK    GeneRIF: Reduction of DOC2B is an early feature of T1 diabetes
            (T1D), and DOC2B abundance may serve as a valuable in vivo
            indicator of beta-cell mass and an early biomarker of T1D.
REFERENCE   3  (bases 1 to 6062)
  AUTHORS   Zanetti,M.N., Bello,O.D., Wang,J., Coleman,J., Cai,Y.,
            Sindelar,C.V., Rothman,J.E. and Krishnakumar,S.S.
  TITLE     Ring-like oligomers of Synaptotagmins and related C2 domain
            proteins
  JOURNAL   Elife 5, e17262 (2016)
   PUBMED   27434670
  REMARK    GeneRIF: Here the authors report that analogous ring-like oligomers
            assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7,
            Syt9) as well as related C2 domain containing protein, Doc2B and
            extended Synaptotagmins (E-Syts).
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 6062)
  AUTHORS   Kabekkodu,S.P., Bhat,S., Radhakrishnan,R., Aithal,A.,
            Mascarenhas,R., Pandey,D., Rai,L., Kushtagi,P., Mundyat,G.P. and
            Satyamoorthy,K.
  TITLE     DNA promoter methylation-dependent transcription of the double
            C2-like domain beta (DOC2B) gene regulates tumor growth in human
            cervical cancer
  JOURNAL   J Biol Chem 289 (15), 10637-10649 (2014)
   PUBMED   24570007
  REMARK    GeneRIF: promoter hypermethylation and silencing of the DOC2B gene
            is an early and frequent event during cervical carcinogenesis and
            whose reduced expression due to DNA promoter methylation may lead
            to selective cervical tumor growth
REFERENCE   5  (bases 1 to 6062)
  AUTHORS   Yao,J., Gaffaney,J.D., Kwon,S.E. and Chapman,E.R.
  TITLE     Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter
            release
  JOURNAL   Cell 147 (3), 666-677 (2011)
   PUBMED   22036572
  REMARK    GeneRIF: Study analyzed Doc2alpha and Doc2beta and found that Doc2
            responds to changes in [Ca2+], with markedly slower kinetics as
            compared to the cytosolic domain of syt I (syt), and operates on a
            timescale consistent with asynchronous neurotransmitter release.
REFERENCE   6  (bases 1 to 6062)
  AUTHORS   Orita,S., Naito,A., Sakaguchi,G., Maeda,M., Igarashi,H., Sasaki,T.
            and Takai,Y.
  TITLE     Physical and functional interactions of Doc2 and Munc13 in
            Ca2+-dependent exocytotic machinery
  JOURNAL   J Biol Chem 272 (26), 16081-16084 (1997)
   PUBMED   9195900
REFERENCE   7  (bases 1 to 6062)
  AUTHORS   Verhage,M., de Vries,K.J., Roshol,H., Burbach,J.P., Gispen,W.H. and
            Sudhof,T.C.
  TITLE     DOC2 proteins in rat brain: complementary distribution and proposed
            function as vesicular adapter proteins in early stages of secretion
  JOURNAL   Neuron 18 (3), 453-461 (1997)
   PUBMED   9115738
REFERENCE   8  (bases 1 to 6062)
  AUTHORS   Kojima,T., Fukuda,M., Aruga,J. and Mikoshiba,K.
  TITLE     Calcium-dependent phospholipid binding to the C2A domain of a
            ubiquitous form of double C2 protein (Doc2 beta)
  JOURNAL   J Biochem 120 (3), 671-676 (1996)
   PUBMED   8902635
REFERENCE   9  (bases 1 to 6062)
  AUTHORS   Sakaguchi,G., Orita,S., Maeda,M., Igarashi,H. and Takai,Y.
  TITLE     Molecular cloning of an isoform of Doc2 having two C2-like domains
  JOURNAL   Biochem Biophys Res Commun 217 (3), 1053-1061 (1995)
   PUBMED   8554557
REFERENCE   10 (bases 1 to 6062)
  AUTHORS   Orita,S., Sasaki,T., Naito,A., Komuro,R., Ohtsuka,T., Maeda,M.,
            Suzuki,H., Igarashi,H. and Takai,Y.
  TITLE     Doc2: a novel brain protein having two repeated C2-like domains
  JOURNAL   Biochem Biophys Res Commun 206 (2), 439-448 (1995)
   PUBMED   7826360
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC108004.3, D70830.1,
            AI478508.1 and AC240565.4.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_003585.4.
            
            Summary: There are at least two protein isoforms of the Double C2
            protein,  namely alpha (DOC2A) and beta (DOC2B), which contain two
            C2-like domains.  DOC2A and DOC2B are encoded by different genes;
            these genes are at times confused with the unrelated DAB2 gene
            which was initially named DOC-2. DOC2B is expressed ubiquitously
            and is suggested to be involved in Ca(2+)-dependent intracellular
            vesicle trafficking in various types of cells. [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##
            Transcript exon combination :: D70830.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000613549.3/ ENSP00000482950.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-20                AC108004.3         31422-31441         c
            21-910              D70830.1           10-899
            911-916             AI478508.1         409-414
            917-1722            D70830.1           906-1711
            1723-2043           D70830.1           1713-2033
            2044-2046           D70830.1           2037-2039
            2047-6062           AC240565.4         82789-86804         c
FEATURES             Location/Qualifiers
     source          1..6062
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17p13.3"
     gene            1..6062
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /note="double C2 domain beta"
                     /db_xref="GeneID:8447"
                     /db_xref="HGNC:HGNC:2986"
                     /db_xref="MIM:604568"
     exon            1..544
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     CDS             172..1410
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /note="doc2-beta; double C2-like domains, beta"
                     /codon_start=1
                     /product="double C2-like domain-containing protein beta"
                     /protein_id="NP_003576.2"
                     /db_xref="CCDS:CCDS73934.1"
                     /db_xref="GeneID:8447"
                     /db_xref="HGNC:HGNC:2986"
                     /db_xref="MIM:604568"
                     /translation="MTLRRRGEKATISIQEHMAIDVCPGPIRPIKQISDYFPRFPRGL
                     PPDAGPRAAAPPDAPARPAVAGAGRRSPSDGAREDDEDVDQLFGAYGSSPGPSPGPSP
                     ARPPAKPPEDEPDADGYESDDCTALGTLDFSLLYDQENNALHCTITKAKGLKPMDHNG
                     LADPYVKLHLLPGASKANKLRTKTLRNTLNPTWNETLTYYGITDEDMIRKTLRISVCD
                     EDKFRHNEFIGETRVPLKKLKPNHTKTFSICLEKQLPVDKTEDKSLEERGRILISLKY
                     SSQKQGLLVGIVRCAHLAAMDANGYSDPYVKTYLRPDVDKKSKHKTAVKKKTLNPEFN
                     EEFCYEIKHGDLAKKSLEVTVWDYDIGKSNDFIGGVVLGIHAKGERLKHWFDCLKNKD
                     KRIERWHTLTSELPGAVLSD"
     exon            545..624
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     exon            625..699
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     exon            700..809
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     exon            810..936
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     exon            937..1094
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     exon            1095..1176
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     exon            1177..1273
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     exon            1274..6062
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5134..5139
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /note="hexamer: AGTAAA"
     polyA_site      5158
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /note="major polyA site"
     regulatory      6035..6040
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
                     /note="hexamer: GATAAA"
     polyA_site      6062
                     /gene="DOC2B"
                     /gene_synonym="DOC2BL"
ORIGIN      
        1 actcgctcgc gccgtccgca gcggagcggg cagcggccaa gtcagggccg tccgggggcg
       61 cggccggcga tgcccgcagc ccccgccgcg ccccgccggg cctgctgagc cgcccccggg
      121 ccggggtcgc gccgggccgg gccgcgcccg gggcggggcg gcgctgcctg catgaccctc
      181 cggcggcgcg gggagaaggc gaccatcagc atccaggagc atatggccat cgacgtgtgc
      241 cccggcccca tccgtcccat caagcagatc tccgactact tcccccgctt cccgcggggc
      301 ctgcccccgg acgccgggcc ccgagccgct gcacccccgg acgcccccgc gcgcccggct
      361 gtggccggtg ccggccgccg cagcccctcc gacggcgccc gcgaggacga cgaggatgtg
      421 gaccagctct tcggagccta cggctccagc ccgggcccca gcccgggtcc cagccccgcg
      481 cggccgccag ccaagccgcc ggaggacgag ccggacgccg acggctacga gtcggacgac
      541 tgcactgccc tgggcacgct ggacttcagc ctgctgtatg accaggagaa caacgccctc
      601 cactgcacca tcaccaaggc caagggcctg aagccaatgg accacaatgg gctggcagac
      661 ccctacgtca agctgcacct gctgccagga gccagtaagg caaataagct cagaacaaaa
      721 actctccgta acactctgaa ccccacatgg aacgagaccc tcacttacta cgggatcaca
      781 gatgaagaca tgatccgcaa gaccctgcgg atctctgtgt gtgacgagga caaattccgg
      841 cacaatgagt tcatcgggga gacacgtgtg cccctgaaga agctgaaacc caaccacacc
      901 aagaccttca gcatctgcct ggagaagcag ctgccggtgg acaagactga agacaagtcc
      961 ctggaggagc ggggccgcat cctcatctcc ctcaagtaca gctcacagaa gcaaggcctg
     1021 ctggtaggca tcgtgcggtg cgcccacctg gccgccatgg acgccaacgg ctactcggac
     1081 ccctacgtga aaacatacct gaggccagat gtggacaaga aatccaaaca taagacagcg
     1141 gtgaagaaaa aaaccctgaa cccggagttt aatgaggagt tctgttacga gatcaagcat
     1201 ggggacctgg ccaagaagtc cctggaggtc accgtttggg attacgacat tggaaaatcc
     1261 aacgatttca ttggtggtgt ggttctgggc atccacgcca agggggagcg cctgaagcac
     1321 tggtttgact gcctgaagaa caaggacaag cgcatcgagc gctggcacac gctcaccagc
     1381 gagctcccag gggctgtgct cagcgactga cgcccacccg ccactgctac ccctgccgcc
     1441 acctgcgccc agcacggccg gccccgggct tccccagcag ccaccaaggc ctgtggcccc
     1501 cacactgggg gagatccaga acccctgctt ggacacagag ccactgcagt ccccgctcgg
     1561 aggatgtgga gggctcagcc actctgggac ggggagggca aggagctggg gtggggggct
     1621 ctcagctctc tggggcccaa gaggccggtg gtggaaagag acctcagcac ctgcccaggg
     1681 gaaggggaca cgcccatctg ggagcaaaga cccttctaga ggccagcccc ggctgagagg
     1741 acaggagtgt gggggcgcct tggcggacag tgggaacaga ggagggaggt ggtgagcaga
     1801 cagacaggtg gaggatggga ccttgaagac tggctgctcc agcccaagaa agcctaactg
     1861 catccctcat ctccttcgct gctggacaga tggaagaagc gggcctgccg gccgaaagtc
     1921 tgccagagtt cccggaggct cctgatgatg ggtaaattgg cacatgcttc actcaatgat
     1981 tccacaagcc ctgggggtga atgagacaca gggcctgccc tcagggagtt cccatctagt
     2041 caggaagctg ggaacaaacc attccaactg gggtgagaaa taccaagacc agcttggcca
     2101 gtctgcaagt accgtgggct ctgctgactc tgccgggagg tcagggacgg cttcctggag
     2161 gaggcggtgc ttccgtaagg ccttggaggg tgagtgaggg cttctaaaag cagtccaggc
     2221 agtgggagtg gtctaaaacg cctggagaga gaaagccaat ggggccgggg tgctgtggac
     2281 ccagggtctc ctctccaggg gagggtttgt taggaaggtg tgaggctcga ggcaggaggt
     2341 gggggacgtg atggaaacac catggagaaa ctggtgtagg ctcaagttca gacctcagac
     2401 ccaagtctcc cactctgatc tctttctact cctgagggac ctcaaggacg gagcccgccc
     2461 ctcctccttc ctggcataag catcaggtca gctgcagtgg agaaaagggt cccttgtgct
     2521 tgggaaaaaa agcaagcatt cctacacgtc ctgactctgc cctttcccct cccctccact
     2581 ccatggctca cactgggggc ctccgggtgc ttgctcgtgg catcttggtc ccactaccgc
     2641 cacagatgtc ccttttggga gtaatcagtg gccgtccagg gccttgtctc tggggaggcc
     2701 tgtggggcca gctccaccct ccaggagctg agcaagaatc accctggctg gtgggcctgt
     2761 ctgctcccct gagtgagact ccccaggagg cttgagagta tctgaatctt ggggcccatg
     2821 cctgaagccc acaaactttc tctgcctacc aagggcccct caggaacgct gggtgaacaa
     2881 atgcagagcc aaggagttgc acagccagag tcccagtgtg ctcagcccat cagtgtgtga
     2941 tggaaacagg cccagagagg tcaggtgacc tgcccagggc cttccaggcc ccacacagct
     3001 ggaaccagga tccacagccc ccagcccaga gtgctggaca ccacgcttca ggggaattgg
     3061 cgtgctgagc tcacaccaga gaggtcctgc tagctgccag cctggggctc ccccgcctgc
     3121 tgcccacccc ttcaacaccg atagagggac tcacaggcac gacggtggga ccttccactg
     3181 cagacacaaa gcacaccacc acctgaggtc cagggttatg atttgaatcc taccaagtgc
     3241 ccatcaggcc tttcccaggt tgcggggaaa acaggacccc agcccccaca cagtccctgg
     3301 ccacctgctg ctcctggaga cttgtctccc tgcctttagg aagggttttt gtgtgaaggt
     3361 ttttgcatgc actggtctga acgcatgttc acagccctgc aaggtgggtt tgattctcat
     3421 ccccatcttg caggtgaaac aggttcccag agtctgagta gtttgccaag gccacacagc
     3481 caggaagggg tgaaccagga ctcaaaccca ggtcctctga ctgccgcttt ctctctctgg
     3541 gggtcggtac ccccagtccc ttccctcttg gtctgtcgga gactcagcag agacaccagg
     3601 tgaaggctca gtaagctcag gtgcatgatg gagacctggg gtcttgtcac tgtcctgcca
     3661 cctcatccgc tggctttgaa accatccgtg ctacttcagg cttccccaga ggtgtctaac
     3721 ctggccccaa aactcagcca ccccacccta gcctctgggg gctgaggcaa gggctcctct
     3781 tttctccaca cagaatgggc accctctggg ggcctaaggt aagaggtggt ctatttctaa
     3841 aaggcctggt gtctagttaa gctctgggta tcttcttagc tttgcttttt tgggggtctc
     3901 attcagagag gagatttgac agcctctctg aagacacaga agtgaatggc aaagcgagaa
     3961 gaggctgtac cccccaccta ccatgacttc cttattaggc acatggggaa tgtgaggccc
     4021 agtgggtgaa aggggcctga aggggcacag ctgggacaag aacccagaac tccagccccc
     4081 cagtccaggg ccctctactg cccaggctgt gcaaatgggg ctgggaccga aagatgggga
     4141 cagtcaggct gggaggcggg cttactggcc agccagccca ggggcagcac aggcactcgg
     4201 gcaggaactc cccaggaagt ttggatcctt ccttccctag gatctcagca cccttttaga
     4261 tcccgtgcag attgtctttc tgttaaagcg ttttgaggca cgatggctca cgcctgtaat
     4321 tgcagcactt tgggaggccg aggctggcgg atcacctgag gtcaggagtt cgaaacccgc
     4381 ctggccaaca gggcgaaacc ccatctctac taaaaataca aaaattagcc gggtgtggtg
     4441 gcgcacgcct gtagtcccag ctactcaggg aggctgaggc acgagaatcg cttgaacccg
     4501 ggaggtgaag gctgcagtga gccaagatcg cggcactgca ctccagcctg ggcgacagag
     4561 caagactccg tctcagaaaa aaaacaaaca aacaacgctt tgagaagctg cagaagcggc
     4621 tctgcctttg accccgaatg ggcatcttta ctcgggtcca tcatccccac aaagacagga
     4681 aatctgatgc caaaaaaaaa aagtcattcc aggtgtcagt aaccaggcgc tgcctccagc
     4741 gccgccccgc ccgccgcccc gcccgccgcc ccgcccgccg cctgcgccaa tccccgacgg
     4801 gcccgtcttc cagccccgaa gcggtcacct cctgacctct agtggcgagc gcggggaact
     4861 gcgccccggc ccgtccgccc gccgagcccg ggccgtgcat gccgagcccg ttgttccttc
     4921 gcaaaccgag tgaacctccc gatgcatgga ctctggctgt cgtcgacgca gactctcgtg
     4981 cactgcttaa ccccgttttg ctgccatgtg acggctgcag acactgtcct caaactgcag
     5041 tcccacagac aagttttgta ttttggtctg acctacccga aggtgtcctt tttaagtctt
     5101 atttgttaat atttataatg acatataatc caaagtaaat ggaaacgtca tattgcgatc
     5161 tcattgcctt ggcgagactc tcacctttta atagatttga aggggtgggg gcggtggctc
     5221 acgcctgtaa gtcctagcac ttttggaggt cgaggtggga gaattgcttg aggcctggag
     5281 ttcgagacca gcctggtcaa catggagaaa ccacgcctct acacacacag agacacacac
     5341 aatgacaatt agcctagcgt ggtggcacac acctgtagcc ccagcttttc aggaggctga
     5401 ggtaggagga ggaggatcgc ttgagcctgg aaagtgggga ttgcagtgag ccgagatcac
     5461 gccaccgcac tccagcctgg gcaacagagg gagaccttgt caaaaaaaaa aaaaaaagat
     5521 ttggaagggt aggaggggag ggtggaaaga cggaggaaaa ggcaactgaa acctactccg
     5581 gatatagtct tgttactctt caccagggac ccatttgagg taggccctca agttacagat
     5641 ggggaaacta aggcccagag aggttaaaat acttttacag aatcacacgg ctggtcgatg
     5701 gcagaagcag gattcaaact gaggcagccc aagacatttt gcaccaggac ctgtcgacca
     5761 tgctgttgtc cactcatcca acaaacagcc gtggagtatt gactaacgcc agcccgtctg
     5821 aggctccaag agtcttacgt tttggaaggt aatttaagac atgtactgct taggtttgga
     5881 gggaaaaaaa taaaccttcc taaccacaga ttagtgtatt aggactagta gcaatcccca
     5941 cactttatat tttcattcca ccttgttaga aaatgttgat caattgttga atacagttta
     6001 ttgtacatca ttctttaggt cagaaatttc tcgagataaa agcctttgct ttctaacatc
     6061 ga
//
