LOCUS       NM_013314               4344 bp    mRNA    linear   PRI 07-APR-2024
DEFINITION  Homo sapiens B cell linker (BLNK), transcript variant 1, mRNA.
ACCESSION   NM_013314
VERSION     NM_013314.4
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 4344)
  AUTHORS   Liu,X., Chipurupalli,S., Jiang,P., Tavasoli,M., Yoo,B.H.,
            McPhee,M., Mazinani,S., Francia,G., Kerbel,R.S. and Rosen,K.V.
  TITLE     ErbB2/Her2-dependent downregulation of a cell death-promoting
            protein BLNK in breast cancer cells is required for 3D breast tumor
            growth
  JOURNAL   Cell Death Dis 13 (8), 687 (2022)
   PUBMED   35933456
  REMARK    GeneRIF: ErbB2/Her2-dependent downregulation of a cell
            death-promoting protein BLNK in breast cancer cells is required for
            3D breast tumor growth.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4344)
  AUTHORS   Kurata,M., Onishi,I., Takahara,T., Yamazaki,Y., Ishibashi,S.,
            Goitsuka,R., Kitamura,D., Takita,J., Hayashi,Y., Largaesapda,D.A.,
            Kitagawa,M. and Nakamura,T.
  TITLE     C/EBPbeta induces B-cell acute lymphoblastic leukemia and
            cooperates with BLNK mutations
  JOURNAL   Cancer Sci 112 (12), 4920-4930 (2021)
   PUBMED   34653294
  REMARK    GeneRIF: C/EBPbeta induces B-cell acute lymphoblastic leukemia and
            cooperates with BLNK mutations.
REFERENCE   3  (bases 1 to 4344)
  AUTHORS   Cheng,Y., Li,F., Zhang,W.S., Zou,G.Y. and Shen,Y.X.
  TITLE     Silencing BLNK protects against interleukin-1beta-induced
            chondrocyte injury through the NF-kappaB signaling pathway
  JOURNAL   Cytokine 148, 155686 (2021)
   PUBMED   34521030
  REMARK    GeneRIF: Silencing BLNK protects against interleukin-1beta-induced
            chondrocyte injury through the NF-kappaB signaling pathway.
REFERENCE   4  (bases 1 to 4344)
  AUTHORS   Zhang,P., Wang,Y., Qin,M., Li,D., Odhiambo,W.O., Yuan,M., Lv,Z.,
            Liu,C., Ma,Y., Dong,Y. and Ji,Y.
  TITLE     Involvement of Blnk and Foxo1 in tumor suppression in
            BCR-ABL1-transformed pro-B cells
  JOURNAL   Oncol Rep 45 (2), 693-705 (2021)
   PUBMED   33416167
  REMARK    GeneRIF: Involvement of Blnk and Foxo1 in tumor suppression in
            BCRABL1transformed proB cells.
REFERENCE   5  (bases 1 to 4344)
  AUTHORS   Li,N., Wu,J., Wu,Y., Xu,Y., Yao,R., Li,G., Zhang,J., Zhou,Y.,
            Yin,L., Yin,Y., Yu,T. and Wang,J.
  TITLE     Further delineation of primary B cell immunodeficiency caused by
            novel variants of the BLNK gene in two Chinese patients
  JOURNAL   Clin Immunol 214, 108387 (2020)
   PUBMED   32194234
  REMARK    GeneRIF: Further delineation of primary B cell immunodeficiency
            caused by novel variants of the BLNK gene in two Chinese patients.
REFERENCE   6  (bases 1 to 4344)
  AUTHORS   Su,Y.W., Zhang,Y., Schweikert,J., Koretzky,G.A., Reth,M. and
            Wienands,J.
  TITLE     Interaction of SLP adaptors with the SH2 domain of Tec family
            kinases
  JOURNAL   Eur J Immunol 29 (11), 3702-3711 (1999)
   PUBMED   10556826
REFERENCE   7  (bases 1 to 4344)
  AUTHORS   Hashimoto,S., Iwamatsu,A., Ishiai,M., Okawa,K., Yamadori,T.,
            Matsushita,M., Baba,Y., Kishimoto,T., Kurosaki,T. and Tsukada,S.
  TITLE     Identification of the SH2 domain binding protein of Bruton's
            tyrosine kinase as BLNK--functional significance of Btk-SH2 domain
            in B-cell antigen receptor-coupled calcium signaling
  JOURNAL   Blood 94 (7), 2357-2364 (1999)
   PUBMED   10498607
REFERENCE   8  (bases 1 to 4344)
  AUTHORS   Wienands,J., Schweikert,J., Wollscheid,B., Jumaa,H., Nielsen,P.J.
            and Reth,M.
  TITLE     SLP-65: a new signaling component in B lymphocytes which requires
            expression of the antigen receptor for phosphorylation
  JOURNAL   J Exp Med 188 (4), 791-795 (1998)
   PUBMED   9705962
REFERENCE   9  (bases 1 to 4344)
  AUTHORS   Fu,C., Turck,C.W., Kurosaki,T. and Chan,A.C.
  TITLE     BLNK: a central linker protein in B cell activation
  JOURNAL   Immunity 9 (1), 93-103 (1998)
   PUBMED   9697839
REFERENCE   10 (bases 1 to 4344)
  AUTHORS   Fu,C. and Chan,A.C.
  TITLE     Identification of two tyrosine phosphoproteins, pp70 and pp68,
            which interact with phospholipase Cgamma, Grb2, and Vav after B
            cell antigen receptor activation
  JOURNAL   J Biol Chem 272 (43), 27362-27368 (1997)
   PUBMED   9341187
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA045252.1, BC018906.2,
            AF068180.1, AI307343.1 and AC021037.6.
            
            On Dec 4, 2019 this sequence version replaced NM_013314.3.
            
            Summary: This gene encodes a cytoplasmic linker or adaptor protein
            that plays a critical role in B cell development. This protein
            bridges B cell receptor-associated kinase activation with
            downstream signaling pathways, thereby affecting various biological
            functions. The phosphorylation of five tyrosine residues is
            necessary for this protein to nucleate distinct signaling effectors
            following B cell receptor activation. Mutations in this gene cause
            hypoglobulinemia and absent B cells, a disease in which the pro- to
            pre-B-cell transition is developmentally blocked. Deficiency in
            this protein has also been shown in some cases of pre-B acute
            lymphoblastic leukemia. Alternatively spliced transcript variants
            have been found for this gene. [provided by RefSeq, May 2012].
            
            Transcript Variant: This variant (1) encodes the longest 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 :: SRR11853563.4101.1, BC018906.2
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000224337.10/ ENSP00000224337.6
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-79                DA045252.1         8-86
            80-354              BC018906.2         1-275
            355-1813            AF068180.1         337-1795
            1814-1816           AI307343.1         7-9                 c
            1817-4344           AC021037.6         87916-90443
FEATURES             Location/Qualifiers
     source          1..4344
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q24.1"
     gene            1..4344
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="B cell linker"
                     /db_xref="GeneID:29760"
                     /db_xref="HGNC:HGNC:14211"
                     /db_xref="MIM:604515"
     exon            1..218
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     CDS             172..1542
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="isoform 1 is encoded by transcript variant 1;
                     B-cell linker protein; B-cell adapter containing a Src
                     homology 2 domain protein; Src homology 2
                     domain-containing leukocyte protein of 65 kDa; B-cell
                     adapter containing a SH2 domain protein; cytoplasmic
                     adapter protein; B-cell activation; B cell adaptor
                     containing SH2 domain; Src homology [SH2]
                     domain-containing leukocyte protein of 65 kD"
                     /codon_start=1
                     /product="B-cell linker protein isoform 1"
                     /protein_id="NP_037446.1"
                     /db_xref="CCDS:CCDS7446.1"
                     /db_xref="GeneID:29760"
                     /db_xref="HGNC:HGNC:14211"
                     /db_xref="MIM:604515"
                     /translation="MDKLNKITVPASQKLRQLQKMVHDIKNNEGGIMNKIKKLKVKAP
                     PSVPRRDYASESPADEEEQWSDDFDSDYENPDEHSDSEMYVMPAEENADDSYEPPPVE
                     QETRPVHPALPFARGEYIDNRSSQRHSPPFSKTLPSKPSWPSEKARLTSTLPALTALQ
                     KPQVPPKPKGLLEDEADYVVPVEDNDENYIHPTESSSPPPEKAPMVNRSTKPNSSTPA
                     SPPGTASGRNSGAWETKSPPPAAPSPLPRAGKKPTTPLKTTPVASQQNASSVCEEKPI
                     PAERHRGSSHRQEAVQSPVFPPAQKQIHQKPIPLPRFTEGGNPTVDGPLPSFSSNSTI
                     SEQEAGVLCKPWYAGACDRKSAEEALHRSNKDGSFLIRKSSGHDSKQPYTLVVFFNKR
                     VYNIPVRFIEATKQYALGRKKNGEEYFGSVAEIIRNHQHSPLVLIDSQNNTKDSTRLK
                     YAVKVS"
     exon            219..284
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            285..334
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            335..375
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            376..532
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            533..696
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            697..778
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            779..847
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            848..917
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            918..945
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            946..988
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            989..1073
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            1074..1105
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            1106..1182
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            1183..1266
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            1267..1422
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     exon            1423..4344
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1649..1654
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="hexamer: AATAAA"
     polyA_site      1674
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
     regulatory      1790..1795
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="hexamer: AATAAA"
     polyA_site      1813
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="major polyA site"
     regulatory      2227..2232
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="hexamer: AATAAA"
     polyA_site      2245
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
     regulatory      4268..4273
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="hexamer: AATAAA"
     polyA_site      4299
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
     regulatory      4327..4332
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
                     /note="hexamer: ATTAAA"
     polyA_site      4344
                     /gene="BLNK"
                     /gene_synonym="AGM4; BASH; bca; BLNK-S; LY57; SLP-65;
                     SLP65"
ORIGIN      
        1 acttctccct agagcagggg tgtttgccag cagcctgcac tctcagaaat cagacttgag
       61 tggccggaac ccttgagacc agaggcttac catgctgctc cctaggaggg ccaggaactg
      121 ctgacgtgac cactggacag ttattcgtgt ctcttacaat taccaaacag aatggacaag
      181 cttaataaaa taaccgtccc cgccagtcag aagttgaggc agcttcaaaa gatggtccat
      241 gatattaaaa acaatgaagg tggaataatg aataaaatca aaaagctaaa agtcaaagca
      301 cctccaagtg ttcctcgaag ggactacgct tcagagagcc ctgctgacga agaggagcag
      361 tggtccgatg actttgacag cgactatgaa aatccagatg agcactcgga ctcagagatg
      421 tacgtgatgc ccgccgagga gaacgctgat gacagctacg agccgcctcc agtagagcag
      481 gaaaccaggc cggttcaccc agccctgccc ttcgccagag gcgagtatat agacaatcga
      541 tcaagccaga ggcattcccc acccttcagc aagacacttc ccagtaagcc cagctggcct
      601 tcagagaaag caaggctcac ctccaccctg ccggccctga ctgctttgca gaaacctcaa
      661 gtcccaccca aacccaaagg cctccttgag gatgaggctg attatgtggt ccccgtggaa
      721 gataatgatg aaaactatat tcatcccaca gaaagcagtt cacctccacc tgaaaaagct
      781 cccatggtga atagatcaac caagccaaat tcctcaacgc ccgcctctcc tccaggaaca
      841 gcttcaggtc gaaacagtgg ggcctgggaa accaagtcac ctccaccagc tgcaccatcc
      901 ccgttgccac gggccgggaa aaaaccaacg acaccactga agacaactcc agttgcctct
      961 caacagaatg cttcaagtgt ttgtgaagaa aaacctatac ctgctgaacg ccaccgaggg
     1021 tcaagtcaca gacaagaagc tgtgcagtca ccagtgtttc ctcctgccca gaaacaaatc
     1081 caccaaaaac ccatacctct gccaagattt acagaagggg gaaacccaac tgtggatggg
     1141 cccctaccca gcttttcatc taattccact atttcagaac aggaagctgg cgttctctgc
     1201 aagccatggt atgctggagc ctgtgatcga aagtctgctg aagaggcatt gcacagatca
     1261 aacaaggatg gatcatttct tattcggaaa agctctggcc atgattccaa acaaccatat
     1321 acactagttg tattctttaa taagcgagta tataatattc ctgtgcgatt tattgaagca
     1381 acaaaacaat atgccttggg cagaaagaaa aatggtgaag agtactttgg aagtgttgct
     1441 gaaatcatca ggaatcatca acatagtcct ttggttctta ttgacagtca gaataacaca
     1501 aaagattcca ccagactgaa gtatgcagtt aaagtttcat aaagggggaa aaaaaagatc
     1561 aataccattg cttcagacac tttcccaaag tttctccttt tgagaaaaag tcccaaaact
     1621 tcatattttg gattatgaat catccagtaa taaaatggaa gatggagtca gctattgaag
     1681 tggtcatcca tttcttttta agaagctcat gtggacttgt tctattgcct gacctgatga
     1741 actgttaata tctggtgagg ttgagttatc atgctactaa tattttccaa ataaatattt
     1801 ttatttttaa aaataagtgt aaagtatatt atcaaaataa gaaaataatg ctcttgcata
     1861 aaacaaagtg gctggaaatt taaacctcca caatgatcat tggtacacta atgtagctgg
     1921 gctctccact gccaatgctt gacaattaag tcttggttaa aattttaatt tgtagaaaat
     1981 aaggtattaa aggtaatgta tgatatctgt aagtataggc aagaaggatg taatggttcc
     2041 tttttgtgag cactctcaac catgggatat atatatatat ggatatgaac tttctataag
     2101 ttcttgtcta ggattatgct gttagttttg cttactaaag ataattatac cctctttgat
     2161 ctacatgtct atcaaataga acctaaactt gatatgaggt ttgtattagt ccattatcac
     2221 gctgctaata aagacatact caagactggg tgatttacat aaaaaaaaaa aaaaaaaaag
     2281 aggtttaatg gactcacagt tccacatggt tggggaggcc tcacaatcat ggcagaaggc
     2341 aaagaagaag caaaggcatg ttttacatgg tggcaggcaa gagagcatgt gcaggggaac
     2401 tgccctttat aaaaccatca gatctcatga gacttactca ctatcacaac aacatgggaa
     2461 aacctgcccg cgtgattcag ttacctccca ccaggtccct cccatggcac gtggggatta
     2521 tgggagctac aattcaagat gagatttggg tgaggacaca gccaaaccat atcaagtttc
     2581 aaagtggaat gacagcaaag ctagactaaa agccagttcc tagagaaata tcccacaaaa
     2641 caagagcaga aaagcagaca ttggtgaaca ccaaggaata aaagagatac catcgtggag
     2701 aatcaggtcc aaggtcttag atcatcccag aaatgtatca tactttgtca tatatttcta
     2761 ctgtgtactt cagacagcag tgaagtgata aagcagctaa ttaagtctaa taattaaatg
     2821 gggaacacac ttggccactg cataagatag caatctatga aagtatgttg aaaggccaga
     2881 aggtaataat ttcagggtaa ctcatgactc acttctaaag ataattgtat atttaaatgt
     2941 cataaacttt cataattgcc acctatgtta cagattgaac tgtggtcccc tcaaaaagat
     3001 atgttgaagt cctaatccat aaggccacat atctcagaat gtgaccttat ttgggaatga
     3061 ggtctttaca gatatagtca aggtaagatg aggtcagtag ggtgggcctt aatacaatgg
     3121 ctggtgtcct tataaaatta ggaaatttgg atgcaggcac agagagaaga ctatatgaag
     3181 agacacacag gaacaatact actggcgtga ttccatcctg tatggctgtt ctcttgagca
     3241 gtggtcgttt atctccgtct gctttctctc ccacctaagt gtgtgccgcc acctgatgga
     3301 agattcgatg gacatggacg tgagccccct gaggcccaga actatctttt cagttgtgaa
     3361 ctaaaggccg acaaagatga tcactttaag gtggataatg atgaaaatga gcaccagtta
     3421 tccttaagaa cggtcagttt aggggctggt gcaaaggatg aactgcacat tgttgaagca
     3481 gaggcaatga attatgaagg cagtccaatt aaataacact ggcacctttg aaaatgtctg
     3541 tacagccaac agtttccctt ggggtctttg aaataacacc accagtgctt ttatggttga
     3601 agtgtggttc agggccagtg catattagtg gacagcattt agtagctgtg gaggaagatg
     3661 cagagtcaga agatgaagag gaggaggatg tgaaactctt aaggatatct ggaaagtgat
     3721 ctgtccctgg aggtggtagc aagattccag agaataaaag taaaacttgc tgctgatgaa
     3781 gatgatgatg atgatgatga tgatgatgat gatgattttg atgatgagga aactgaagaa
     3841 aaagcaccat tgaagaaatc tacatactcc agccaaaaat gcacaaaagt caaatcagaa
     3901 tagaaaacac tcaaacccat catcaacacc aagattaaaa ggacaagaat ccttcaaaaa
     3961 acaggaaaaa actcgtaaaa caccaaaagg gcctagttct gtagaagaca ttaaatcaaa
     4021 aatgcaagca agtatagaaa aaggtggttc tcttcccaaa gtggaagcca agttcatcaa
     4081 ttatgtgaag aattgcttcc ggacaactga ccaggagact attcaagatc ctggcagtgg
     4141 aggaagtctc tttagaaaat agtttaaaca atttgttaac atttttccat cttatttcat
     4201 ttctctaaca gtcaatatct ggctgtcctt tctataatgc agagtgagaa ctttccctac
     4261 tgtgtttaat aaatgttgtc caggttccat tgccaagaat gtgttgtcca aaatgcctgt
     4321 ttcattatta aagatggaac ttca
//
