SH21B_MOUSE
ID SH21B_MOUSE Reviewed; 132 AA.
AC O35324; Q8C268;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 131.
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, Eat2a, Sh2d1b1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Dendritic cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH CD244, PHOSPHORYLATION, AND
RP MUTAGENESIS OF TYR-120 AND TYR-127.
RC STRAIN=129/Sv;
RX PubMed=16127454; DOI=10.1038/ni1242;
RA Roncagalli R., Taylor J.E., Zhang S., Shi X., Chen R., Cruz-Munoz M.E.,
RA Yin L., Latour S., Veillette A.;
RT "Negative regulation of natural killer cell function by EAT-2, a SAP-
RT related adaptor.";
RL Nat. Immunol. 6:1002-1010(2005).
RN [4]
RP TISSUE SPECIFICITY, AND INTERACTION WITH SLAMF1; HCK; LYN; FYN; FGR AND
RP LCK.
RC STRAIN=129/Sv, and C57BL/6J;
RX PubMed=16425036; DOI=10.1007/s00251-005-0056-3;
RA Calpe S., Erdos E., Liao G., Wang N., Rietdijk S., Simarro M., Scholtz B.,
RA Mooney J., Lee C.H., Shin M.S., Rajnavoelgyi E., Schatzle J.,
RA Morse H.C. III, Terhorst C., Lanyi A.;
RT "Identification and characterization of two related murine genes, Eat2a and
RT Eat2b, encoding single SH2-domain adapters.";
RL Immunogenetics 58:15-25(2006).
RN [5]
RP FUNCTION, INTERACTION WITH SLAMF7, AND MUTAGENESIS OF TYR-120 AND TYR-127.
RX PubMed=19151721; DOI=10.1038/ni.1693;
RA Cruz-Munoz M.E., Dong Z., Shi X., Zhang S., Veillette A.;
RT "Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2,
RT on natural killer cell function.";
RL Nat. Immunol. 10:297-305(2009).
RN [6]
RP FUNCTION.
RX PubMed=20962259; DOI=10.4049/jimmunol.1001974;
RA Wang N., Calpe S., Westcott J., Castro W., Ma C., Engel P., Schatzle J.D.,
RA Terhorst C.;
RT "The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-
RT dependent NK cell functions in the C57BL/6 mouse.";
RL J. Immunol. 185:5683-5687(2010).
RN [7]
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 [8]
RP FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF TYR-120 AND TYR-127,
RP INTERACTION WITH PLCG2, AND 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).
RN [9]
RP FUNCTION.
RX PubMed=26432891; DOI=10.4049/jimmunol.1500552;
RA Talaei N., Yu T., Manion K., Bremner R., Wither J.E.;
RT "Identification of the SLAM adapter molecule EAT-2 as a lupus-
RT susceptibility gene that acts through impaired negative regulation of
RT dendritic cell signaling.";
RL J. Immunol. 195:4623-4631(2015).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-103 IN COMPLEX WITH SLAMF1, AND
RP INTERACTION WITH SLAMF1 AND CD84.
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).
CC -!- FUNCTION: Cytoplasmic adapter regulating receptors of the signaling
CC lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9
CC and CD244. In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays
CC a role in regulation of effector functions of natural killer (NK) cells
CC by controlling signal transduction through CD244/2B4. However,
CC conflicting results are reported which may reflect the use of different
CC strain backgrounds. Proposed to act as an inhibitor of CD244-mediated
CC NK cell function including cytotoxicity and IFN-gamma production, the
CC latter found also by triggering KLRA4 and KLRK1 next to CD244
CC (PubMed:16127454). Seems to positively regulate CD244- and CD84-
CC dependent NK cell functions implicating CD244-mediated phosphorylation
CC of VAV1. Activation of SLAMF7-mediated NK cell function does not effect
CC receptor tyrosine phosphorylation but distal signaling
CC (PubMed:19151721, PubMed:20962259, PubMed:24687958). 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 (PubMed:26432891). {ECO:0000250|UniProtKB:O14796,
CC ECO:0000269|PubMed:16127454, ECO:0000269|PubMed:19151721,
CC ECO:0000269|PubMed:20962259, ECO:0000269|PubMed:24687958,
CC ECO:0000269|PubMed:26432891}.
CC -!- SUBUNIT: Binds to the phosphorylated receptors CD84, SLAMF1, LY9 and
CC CD244. Does not bind to non-phosphorylated SLAMF1 (By similarity).
CC Interacts with SLAMF7 (via ITSM phosphorylated on 'Tyr-302'). Interacts
CC with Src kinases HCK, LYN, FYN, FGR and LCK (via kinase domains).
CC Interacts (phosphorylated at Tyr-127) with PLCG2.
CC {ECO:0000250|UniProtKB:O14796, ECO:0000269|PubMed:11689425,
CC ECO:0000269|PubMed:16425036, ECO:0000269|PubMed:19151721,
CC ECO:0000269|PubMed:24687958, ECO:0000305|PubMed:21219180}.
CC -!- INTERACTION:
CC O35324; Q8BHK6: Slamf7; NbExp=3; IntAct=EBI-8022357, EBI-11463802;
CC -!- TISSUE SPECIFICITY: Expressed in spleen, thymus, lung, kidney, heart,
CC colon and small bowel. Expressed in NK cells (all stages of cell
CC maturation), macrophages and dendritic cells.
CC {ECO:0000269|PubMed:16127454, ECO:0000269|PubMed:16425036,
CC ECO:0000269|PubMed:24687958}.
CC -!- PTM: Phosphorylated on tyrosine residues; probably at Tyr-120 and/or
CC Tyr-127. {ECO:0000269|PubMed:16127454}.
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DR EMBL; AF020263; AAB70923.1; -; mRNA.
DR EMBL; AK089191; BAC40784.1; -; mRNA.
DR CCDS; CCDS35767.1; -.
DR PDB; 1I3Z; X-ray; 2.15 A; A=1-103.
DR PDBsum; 1I3Z; -.
DR AlphaFoldDB; O35324; -.
DR SMR; O35324; -.
DR IntAct; O35324; 2.
DR MINT; O35324; -.
DR iPTMnet; O35324; -.
DR PhosphoSitePlus; O35324; -.
DR MaxQB; O35324; -.
DR PaxDb; O35324; -.
DR PRIDE; O35324; -.
DR MGI; MGI:1349420; Sh2d1b1.
DR InParanoid; O35324; -.
DR PhylomeDB; O35324; -.
DR EvolutionaryTrace; O35324; -.
DR PRO; PR:O35324; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O35324; protein.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IDA:MGI.
DR GO; GO:0035591; F:signaling adaptor activity; NAS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0002366; P:leukocyte activation involved in immune response; IDA:UniProtKB.
DR GO; GO:0002769; P:natural killer cell inhibitory signaling pathway; IMP:MGI.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IMP:MGI.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:MGI.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IMP:MGI.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0045089; P:positive regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IGI:MGI.
DR GO; GO:0002717; P:positive regulation of natural killer cell mediated immunity; IMP:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0009967; P:positive regulation of signal transduction; NAS:UniProtKB.
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; Immunity; Innate immunity; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..132
FT /note="SH2 domain-containing protein 1B"
FT /id="PRO_0000097725"
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 MUTAGEN 120
FT /note="Y->F: Abolishes tyrosine phosphorylation, no effect
FT on interaction with SLAMF7 and CD244, abolishes SLAMF7-,
FT CD244-, LY9- and CD8 mediated NK cell activation, fails to
FT inhibit natural cytotoxicity and to suppress IFN-gamma
FT secretion in response to ligation with CD244, FCGR3 or
FT KLRB1C; when associated with F-127."
FT /evidence="ECO:0000269|PubMed:16127454,
FT ECO:0000269|PubMed:19151721, ECO:0000269|PubMed:24687958"
FT MUTAGEN 127
FT /note="Y->F: Abolishes tyrosine phosphorylation, no effect
FT on interaction with SLAMF7 and CD244, abolishes SLAMF7-,
FT CD244-, LY9- and CD84-mediated NK cell activation, fails to
FT inhibit natural cytotoxicity and to suppress IFN-gamma
FT secretion in response to ligation with CD244, FCGR3 or
FT KLRB1C; when associated with F-120."
FT /evidence="ECO:0000269|PubMed:16127454,
FT ECO:0000269|PubMed:19151721, ECO:0000269|PubMed:24687958"
FT MUTAGEN 127
FT /note="Y->F: No stimulation of granule polarization during
FT NK-mediated cytotoxicity."
FT /evidence="ECO:0000269|PubMed:24687958"
FT CONFLICT 71
FT /note="T -> S (in Ref. 2; BAC40784)"
FT /evidence="ECO:0000305"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:1I3Z"
FT HELIX 12..20
FT /evidence="ECO:0007829|PDB:1I3Z"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:1I3Z"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1I3Z"
FT STRAND 40..45
FT /evidence="ECO:0007829|PDB:1I3Z"
FT STRAND 47..57
FT /evidence="ECO:0007829|PDB:1I3Z"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:1I3Z"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:1I3Z"
FT HELIX 80..85
FT /evidence="ECO:0007829|PDB:1I3Z"
FT STRAND 88..95
FT /evidence="ECO:0007829|PDB:1I3Z"
SQ SEQUENCE 132 AA; 15259 MW; 7B8201836026C02D CRC64;
MDLPYYHGCL TKRECEALLL KGGVDGNFLI RDSESVPGAL CLCVSFKKLV YSYRIFREKH
GYYRIETDAH TPRTIFPNLQ ELVSKYGKPG QGLVVHLSNP IMRNNLCQRG RRMELELNVY
ENTDEEYVDV LP
