SH21B_HUMAN
ID SH21B_HUMAN Reviewed; 132 AA.
AC O14796; B2RBN6; Q5T0L1; Q8NI18; Q969K9;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2002, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=SH2 domain-containing protein 1B;
DE AltName: Full=EWS/FLI1-activated transcript 2;
DE Short=EAT-2;
GN Name=SH2D1B; Synonyms=EAT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=11689425; DOI=10.1093/emboj/20.21.5840;
RA Morra M., Lu J., Poy F., Martin M., Sayos J., Calpe S., Gullo C., Howie D.,
RA Rietdijk S., Thompson A., Coyle A.J., Denny C., Yaffe M.B., Engel P.,
RA Eck M.J., Terhorst C.;
RT "Structural basis for the interaction of the free SH2 domain EAT-2 with
RT SLAM receptors in hematopoietic cells.";
RL EMBO J. 20:5840-5852(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Leukocyte;
RA Colonna M.;
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CD84, AND VARIANT
RP LYS-122.
RX PubMed=12115647;
RX DOI=10.1002/1521-4141(200206)32:6<1640::aid-immu1640>3.0.co;2-s;
RA Tangye S.G., van de Weerdt B.C.M., Avery D.T., Hodgkin P.D.;
RT "CD84 is up-regulated on a major population of human memory B cells and
RT recruits the SH2 domain containing proteins SAP and EAT-2.";
RL Eur. J. Immunol. 32:1640-1649(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Leukocyte, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45.
RX PubMed=9000139;
RA Thompson A.D., Braun B.S., Arvand A., Stewart S.D., May W.A., Chen E.,
RA Korenberg J., Denny C.;
RT "EAT-2 is a novel SH2 domain containing protein that is up regulated by
RT Ewing's sarcoma EWS/FLI1 fusion gene.";
RL Oncogene 13:2649-2658(1996).
RN [9]
RP REVIEW.
RX PubMed=21219180; DOI=10.1146/annurev-immunol-030409-101302;
RA Cannons J.L., Tangye S.G., Schwartzberg P.L.;
RT "SLAM family receptors and SAP adaptors in immunity.";
RL Annu. Rev. Immunol. 29:665-705(2011).
RN [10]
RP FUNCTION, MUTAGENESIS OF TYR-127, INTERACTION WITH PLCG1, AND
RP PHOSPHORYLATION AT TYR-127.
RX PubMed=24687958; DOI=10.1084/jem.20132038;
RA Perez-Quintero L.A., Roncagalli R., Guo H., Latour S., Davidson D.,
RA Veillette A.;
RT "EAT-2, a SAP-like adaptor, controls NK cell activation through
RT phospholipase Cgamma, Ca++, and Erk, leading to granule polarization.";
RL J. Exp. Med. 211:727-742(2014).
CC -!- FUNCTION: Cytoplasmic adapter regulating receptors of the signaling
CC lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9
CC and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with
CC SH2D1A/SAP. Plays a role in regulation of effector functions of natural
CC killer (NK) cells by controlling signal transduction through CD244/2B4
CC without effecting its tyrosine phosphorylation; downstream signaling
CC involves PLCG1 and ERK activation (PubMed:24687958). Activation of
CC SLAMF7-mediated NK cell function does not effect receptor tyrosine
CC phosphorylation but distal signaling (By similarity). In the context of
CC NK cell-mediated cytotoxicity does not enhance conjugate formation with
CC target cells but stimulates polarization of the microtubule-organizing
CC center and cytotoxic granules toward the NK cell synapse
CC (PubMed:24687958). Negatively regulates CD40-induced cytokine
CC production in dendritic cells downstream of SLAM family receptors
CC probably by inducing activation of the PI3K pathway to inhibit p38 MAPK
CC and JNK activation (By similarity). {ECO:0000250|UniProtKB:O35324,
CC ECO:0000269|PubMed:11689425, ECO:0000269|PubMed:24687958,
CC ECO:0000305|PubMed:21219180}.
CC -!- SUBUNIT: Binds to the phosphorylated receptors CD84, SLAMF1, LY9 and
CC CD244. Does not bind to non-phosphorylated SLAMF1 (PubMed:11689425).
CC Interacts with SLAMF7 (via ITSM phosphorylated on 'Tyr-304'). Interacts
CC with Src kinases HCK, LYN, FYN, FGR and LCK (via kinase domains) (By
CC similarity). Interacts (phosphorylated at Tyr-127) with PLCG1.
CC {ECO:0000250|UniProtKB:O35324, ECO:0000269|PubMed:11689425,
CC ECO:0000269|PubMed:24687958}.
CC -!- INTERACTION:
CC O14796; O95994: AGR2; NbExp=3; IntAct=EBI-3923013, EBI-712648;
CC O14796; P10275: AR; NbExp=3; IntAct=EBI-3923013, EBI-608057;
CC O14796; P51451: BLK; NbExp=3; IntAct=EBI-3923013, EBI-2105445;
CC O14796; Q9BZW8: CD244; NbExp=7; IntAct=EBI-3923013, EBI-1580565;
CC O14796; Q9UIB8: CD84; NbExp=3; IntAct=EBI-3923013, EBI-6691679;
CC O14796; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-3923013, EBI-742054;
CC O14796; P01100: FOS; NbExp=3; IntAct=EBI-3923013, EBI-852851;
CC O14796; Q13480: GAB1; NbExp=8; IntAct=EBI-3923013, EBI-517684;
CC O14796; P10721: KIT; NbExp=8; IntAct=EBI-3923013, EBI-1379503;
CC O14796; O15481: MAGEB4; NbExp=3; IntAct=EBI-3923013, EBI-751857;
CC O14796; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-3923013, EBI-16439278;
CC O14796; P08581: MET; NbExp=6; IntAct=EBI-3923013, EBI-1039152;
CC O14796; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-3923013, EBI-10271199;
CC O14796; Q8TAK6: OLIG1; NbExp=2; IntAct=EBI-3923013, EBI-3867416;
CC O14796; P19174: PLCG1; NbExp=2; IntAct=EBI-3923013, EBI-79387;
CC O14796; P16885: PLCG2; NbExp=2; IntAct=EBI-3923013, EBI-617403;
CC O14796; Q96DU3: SLAMF6; NbExp=4; IntAct=EBI-3923013, EBI-14058448;
CC O14796; P12931: SRC; NbExp=3; IntAct=EBI-3923013, EBI-621482;
CC O14796; Q99081-3: TCF12; NbExp=3; IntAct=EBI-3923013, EBI-11952764;
CC O14796; Q07912-2: TNK2; NbExp=3; IntAct=EBI-3923013, EBI-11994780;
CC O14796; Q9BYV2: TRIM54; NbExp=6; IntAct=EBI-3923013, EBI-2130429;
CC O14796; Q53HF2; NbExp=3; IntAct=EBI-3923013, EBI-877761;
CC O14796-2; O76024: WFS1; NbExp=3; IntAct=EBI-25899828, EBI-720609;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14796-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14796-2; Sequence=VSP_010341;
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DR EMBL; AF256653; AAL26000.1; -; mRNA.
DR EMBL; AF403479; AAL27357.1; -; mRNA.
DR EMBL; AF484964; AAM28522.1; -; mRNA.
DR EMBL; AK097162; BAC04968.1; -; mRNA.
DR EMBL; AK314743; BAG37283.1; -; mRNA.
DR EMBL; AL512785; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW90703.1; -; Genomic_DNA.
DR EMBL; BC022407; AAH22407.1; -; mRNA.
DR EMBL; BC066595; AAH66595.1; -; mRNA.
DR EMBL; AF020264; AAB70927.1; -; Genomic_DNA.
DR CCDS; CCDS30928.1; -. [O14796-1]
DR RefSeq; NP_444512.2; NM_053282.4. [O14796-1]
DR PDB; 5KAZ; X-ray; 1.70 A; A=1-104.
DR PDBsum; 5KAZ; -.
DR AlphaFoldDB; O14796; -.
DR SMR; O14796; -.
DR BioGRID; 125563; 29.
DR IntAct; O14796; 37.
DR MINT; O14796; -.
DR STRING; 9606.ENSP00000356906; -.
DR iPTMnet; O14796; -.
DR PhosphoSitePlus; O14796; -.
DR BioMuta; SH2D1B; -.
DR MassIVE; O14796; -.
DR PaxDb; O14796; -.
DR PeptideAtlas; O14796; -.
DR PRIDE; O14796; -.
DR ProteomicsDB; 48245; -. [O14796-1]
DR ProteomicsDB; 48246; -. [O14796-2]
DR Antibodypedia; 34320; 247 antibodies from 33 providers.
DR DNASU; 117157; -.
DR Ensembl; ENST00000367929.3; ENSP00000356906.2; ENSG00000198574.6. [O14796-1]
DR GeneID; 117157; -.
DR KEGG; hsa:117157; -.
DR MANE-Select; ENST00000367929.3; ENSP00000356906.2; NM_053282.5; NP_444512.2.
DR UCSC; uc001gbz.2; human. [O14796-1]
DR CTD; 117157; -.
DR DisGeNET; 117157; -.
DR GeneCards; SH2D1B; -.
DR HGNC; HGNC:30416; SH2D1B.
DR HPA; ENSG00000198574; Tissue enhanced (lymphoid tissue, skeletal muscle, tongue).
DR MIM; 608510; gene.
DR neXtProt; NX_O14796; -.
DR OpenTargets; ENSG00000198574; -.
DR PharmGKB; PA142670926; -.
DR VEuPathDB; HostDB:ENSG00000198574; -.
DR eggNOG; KOG0565; Eukaryota.
DR GeneTree; ENSGT00940000163577; -.
DR HOGENOM; CLU_125532_0_0_1; -.
DR InParanoid; O14796; -.
DR OMA; GFYNIQT; -.
DR OrthoDB; 1417830at2759; -.
DR PhylomeDB; O14796; -.
DR TreeFam; TF343096; -.
DR PathwayCommons; O14796; -.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR SignaLink; O14796; -.
DR BioGRID-ORCS; 117157; 14 hits in 1073 CRISPR screens.
DR GeneWiki; SH2D1B; -.
DR GenomeRNAi; 117157; -.
DR Pharos; O14796; Tbio.
DR PRO; PR:O14796; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O14796; protein.
DR Bgee; ENSG00000198574; Expressed in granulocyte and 102 other tissues.
DR Genevisible; O14796; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; TAS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002366; P:leukocyte activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0002717; P:positive regulation of natural killer cell mediated immunity; ISS:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IBA:GO_Central.
DR GO; GO:0050776; P:regulation of immune response; IBA:GO_Central.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR CDD; cd10342; SH2_SAP1; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035049; EAT2_SH2.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Immunity;
KW Innate immunity; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..132
FT /note="SH2 domain-containing protein 1B"
FT /id="PRO_0000097724"
FT DOMAIN 5..101
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT MOD_RES 127
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:24687958"
FT VAR_SEQ 67..121
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_010341"
FT VARIANT 36
FT /note="I -> T (in dbSNP:rs35688243)"
FT /id="VAR_051347"
FT VARIANT 122
FT /note="N -> K (in dbSNP:rs34001279)"
FT /evidence="ECO:0000269|PubMed:12115647"
FT /id="VAR_051348"
FT MUTAGEN 127
FT /note="Y->F: No stimulation of granule polarization during
FT NK-mediated cytotoxicity, abolishes activation of
FT CD244/2B4-mediated cytotoxicity, abolishes augmentation of
FT CD244/2B4-triggered PLCG1 phosphorylation and ERK
FT activation."
FT /evidence="ECO:0000269|PubMed:24687958"
FT HELIX 12..20
FT /evidence="ECO:0007829|PDB:5KAZ"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:5KAZ"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:5KAZ"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:5KAZ"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:5KAZ"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:5KAZ"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:5KAZ"
FT HELIX 79..87
FT /evidence="ECO:0007829|PDB:5KAZ"
FT STRAND 88..95
FT /evidence="ECO:0007829|PDB:5KAZ"
SQ SEQUENCE 132 AA; 15297 MW; BC9FEA398B6B27DE CRC64;
MDLPYYHGRL TKQDCETLLL KEGVDGNFLL RDSESIPGVL CLCVSFKNIV YTYRIFREKH
GYYRIQTAEG SPKQVFPSLK ELISKFEKPN QGMVVHLLKP IKRTSPSLRW RGLKLELETF
VNSNSDYVDV LP
