CLNK_MOUSE
ID CLNK_MOUSE Reviewed; 435 AA.
AC Q9QZE2; Q8C479; Q9JMJ3;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Cytokine-dependent hematopoietic cell linker {ECO:0000303|PubMed:10562326};
DE AltName: Full=Mast cell immunoreceptor signal transducer {ECO:0000250|UniProtKB:Q7Z7G1};
GN Name=Clnk; Synonyms=Mist;
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] (ISOFORM 1), FUNCTION, SUBUNIT, INDUCTION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Fetal thymus;
RX PubMed=10562326; DOI=10.1084/jem.190.10.1527;
RA Cao M.Y., Davidson D., Yu J., Latour S., Veillette A.;
RT "Clnk, a novel SLP-76-related adaptor molecule expressed in cytokine-
RT stimulated hemopoietic cells.";
RL J. Exp. Med. 190:1527-1534(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION OF ISOFORM 2,
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH PLCG2;
RP FRB2; VAV AND LAT, AND MUTAGENESIS OF TYR-69; TYR-96; TYR-101; TYR-153;
RP TYR-174 AND TYR-188.
RX PubMed=10744659; DOI=10.1093/intimm/12.4.573;
RA Goitsuka R., Kanazashi H., Sasanuma H., Fujimura Y.-C., Hidaka Y.,
RA Tatsuno A., Ra C., Hayashi K., Kitamura D.;
RT "A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-
RT mediated mast cell degranulation.";
RL Int. Immunol. 12:573-580(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 44-435.
RC STRAIN=C57BL/6J;
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 [5]
RP FUNCTION, DOMAIN, PHOSPHORYLATION AT TYR-69 AND TYR-96, INTERACTION WITH
RP GRB2; PLCG1; PLCG2 AND LAT, AND MUTAGENESIS OF TYR-69; TYR-96; TYR-101;
RP TYR-153; TYR-174 AND TYR-188.
RX PubMed=11463797; DOI=10.1074/jbc.m106390200;
RA Goitsuka R., Tatsuno A., Ishiai M., Kurosaki T., Kitamura D.;
RT "MIST functions through distinct domains in immunoreceptor signaling in the
RT presence and absence of LAT.";
RL J. Biol. Chem. 276:36043-36050(2001).
RN [6]
RP FUNCTION, INTERACTION WITH MAP4K1, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP ARG-335.
RX PubMed=11509653; DOI=10.1128/mcb.21.18.6102-6112.2001;
RA Yu J., Riou C., Davidson D., Minhas R., Robson J.D., Julius M., Arnold R.,
RA Kiefer F., Veillette A.;
RT "Synergistic regulation of immunoreceptor signaling by SLP-76-related
RT adaptor Clnk and serine/threonine protein kinase HPK-1.";
RL Mol. Cell. Biol. 21:6102-6112(2001).
RN [7]
RP FUNCTION, INTERACTION WITH FYB1, IDENTIFICATION IN A COMPLEX WITH FYB1 AND
RP SKAP1, PHOSPHORYLATION, AND MUTAGENESIS OF ARG-335.
RX PubMed=12681493; DOI=10.1016/s0014-5793(03)00234-5;
RA Fujii Y., Wakahara S., Nakao T., Hara T., Ohtake H., Komurasaki T.,
RA Kitamura K., Tatsuno A., Fujiwara N., Hozumi N., Ra C., Kitamura D.,
RA Goitsuka R.;
RT "Targeting of MIST to Src-family kinases via SKAP55-SLAP-130 adaptor
RT complex in mast cells(1).";
RL FEBS Lett. 540:111-116(2003).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15199160; DOI=10.1128/mcb.24.13.6067-6075.2004;
RA Utting O., Sedgmen B.J., Watts T.H., Shi X., Rottapel R., Iulianella A.,
RA Lohnes D., Veillette A.;
RT "Immune functions in mice lacking Clnk, an SLP-76-related adaptor expressed
RT in a subset of immune cells.";
RL Mol. Cell. Biol. 24:6067-6075(2004).
RN [9]
RP FUNCTION, INTERACTION WITH FGR, TISSUE SPECIFICITY, INDUCTION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF TYR-69; TYR-96; TYR-101; TYR-153;
RP 160-PRO--PRO-165; TYR-174; 178-PRO--PRO-182; TYR-188 AND ARG-335.
RX PubMed=16439675; DOI=10.1182/blood-2005-10-4102;
RA Sasanuma H., Tatsuno A., Hidano S., Ohshima K., Matsuzaki Y., Hayashi K.,
RA Lowell C.A., Kitamura D., Goitsuka R.;
RT "Dual function for the adaptor MIST in IFN-gamma production by NK and
RT CD4+NKT cells regulated by the Src kinase Fgr.";
RL Blood 107:3647-3655(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-69, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [11]
RP FUNCTION, AND INTERACTION WITH LBR AND AGO2.
RX PubMed=26009488; DOI=10.1016/j.bbrc.2015.05.046;
RA Xu M., Cai C., Sun X., Chen W., Li Q., Zhou H.;
RT "Clnk plays a role in TNF-alpha-induced cell death in murine fibrosarcoma
RT cell line L929.";
RL Biochem. Biophys. Res. Commun. 463:275-279(2015).
CC -!- FUNCTION: An adapter protein which plays a role in the regulation of
CC immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen
CC receptor (BCR) signaling and FC-epsilon R1-mediated mast cell
CC degranulation (PubMed:10562326, PubMed:10744659, PubMed:11509653,
CC PubMed:12681493). Together with FGR, it acts as a negative regulator of
CC natural killer cell-activating receptors and inhibits interferon-gamma
CC production (PubMed:15199160, PubMed:16439675). Acts as a positive
CC regulator of both T-cell receptor and natural killer T (NKT) cell
CC receptor signaling in CD4-positive NKT cells (PubMed:16439675).
CC Together with MAP4K1, it enhances CD3-triggered activation of T-cells
CC and subsequent IL2 production (PubMed:11509653). May be involved in
CC tumor necrosis factor induced cell death by promoting reactive
CC oxidative species generation, and MLKL oligomerization, ultimately
CC leading to necrosis (PubMed:26009488). Involved in phosphorylation of
CC LAT (PubMed:11463797). May be involved in high affinity immunoglobulin
CC epsilon receptor signaling in mast cells (PubMed:12681493).
CC {ECO:0000269|PubMed:10562326, ECO:0000269|PubMed:10744659,
CC ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:11509653,
CC ECO:0000269|PubMed:12681493, ECO:0000269|PubMed:15199160,
CC ECO:0000269|PubMed:16439675, ECO:0000269|PubMed:26009488}.
CC -!- SUBUNIT: When phosphorylated, interacts with PLCG1, PLCG2, GRB2, VAV
CC and LAT (PubMed:10744659, PubMed:11463797). Associated with a tyrosine-
CC phosphorylated polypeptide (p92) in response to immunoreceptor
CC stimulation (PubMed:10562326). Interacts with LBR and AGO2
CC (PubMed:26009488). Interacts with FGR (PubMed:16439675). Part of a
CC complex consisting of CLNK, SKAP1 and FYB1 (PubMed:12681493). Interacts
CC (via SH2 domain) with FYB1; this interaction allows SKAP1 and FYB1 to
CC promote tyrosine phosphorylation of CLNK by LYN (PubMed:26009488).
CC Interacts (via SH2 domain) with MAP4K1 (PubMed:11509653).
CC {ECO:0000269|PubMed:10562326, ECO:0000269|PubMed:10744659,
CC ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:11509653,
CC ECO:0000269|PubMed:12681493, ECO:0000269|PubMed:16439675,
CC ECO:0000269|PubMed:26009488}.
CC -!- INTERACTION:
CC Q9QZE2; P14234: Fgr; NbExp=3; IntAct=EBI-8040679, EBI-7587024;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q7Z7G1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QZE2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QZE2-2; Sequence=VSP_030334;
CC -!- TISSUE SPECIFICITY: Expressed in T-cells, mast cells, natural killer
CC and natural killer T cells (at protein level) (PubMed:10744659,
CC PubMed:15199160, PubMed:16439675, PubMed:11509653). Expressed in
CC cytokine-stimulated hemopoietic cells (PubMed:10562326).
CC {ECO:0000269|PubMed:10562326, ECO:0000269|PubMed:10744659,
CC ECO:0000269|PubMed:11509653, ECO:0000269|PubMed:15199160,
CC ECO:0000269|PubMed:16439675}.
CC -!- INDUCTION: By cytokines such as IL2 and IL3 (PubMed:10562326,
CC PubMed:15199160, PubMed:16439675). In natural killer T cells, by alpha-
CC galactoceramide (PubMed:16439675). {ECO:0000269|PubMed:10562326,
CC ECO:0000269|PubMed:15199160, ECO:0000269|PubMed:16439675}.
CC -!- DOMAIN: The N-terminal proline-rich region interacts with the SH3
CC domain of PLCG1. {ECO:0000269|PubMed:11463797}.
CC -!- DOMAIN: The SH2 domain is important for restoration of BCR-induced
CC calcium response and JNK2 activation in BLNK-deficient DT40 cells
CC expressing LAT. {ECO:0000269|PubMed:11463797}.
CC -!- PTM: Tyrosine-phosphorylated upon BCR cross-linking (PubMed:10744659,
CC PubMed:11463797). Tyrosine phosphorylation at both Tyr-69 and Tyr-96
CC are required for BCR-induced calcium response and are essential to
CC restore PLCG2-mediated signaling in BLNK-deficient DT40 cells, but this
CC phosphorylation is dispensable in cells expressing LAT
CC (PubMed:10744659, PubMed:11463797). Interacts with the SH2 domain of
CC PLCG1 via phosphorylated Tyr-96 (PubMed:10744659, PubMed:11463797).
CC Tyrosine phosphorylation is increased when complexed with SKAP1 and
CC FYB1 (PubMed:12681493). {ECO:0000269|PubMed:10744659,
CC ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:12681493}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype.
CC {ECO:0000269|PubMed:15199160, ECO:0000269|PubMed:16439675}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC38640.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF187819; AAF14299.1; -; mRNA.
DR EMBL; AB021220; BAA96240.1; -; mRNA.
DR EMBL; BC125637; AAI25638.1; -; mRNA.
DR EMBL; BC125639; AAI25640.1; -; mRNA.
DR EMBL; AK082826; BAC38640.2; ALT_INIT; mRNA.
DR CCDS; CCDS51486.1; -. [Q9QZE2-1]
DR RefSeq; NP_038776.3; NM_013748.3. [Q9QZE2-1]
DR RefSeq; XP_006504037.1; XM_006503974.2. [Q9QZE2-1]
DR RefSeq; XP_011239036.1; XM_011240734.1. [Q9QZE2-2]
DR AlphaFoldDB; Q9QZE2; -.
DR SMR; Q9QZE2; -.
DR BioGRID; 205158; 1.
DR IntAct; Q9QZE2; 1.
DR MINT; Q9QZE2; -.
DR STRING; 10090.ENSMUSP00000132779; -.
DR iPTMnet; Q9QZE2; -.
DR PhosphoSitePlus; Q9QZE2; -.
DR jPOST; Q9QZE2; -.
DR MaxQB; Q9QZE2; -.
DR PaxDb; Q9QZE2; -.
DR PRIDE; Q9QZE2; -.
DR ProteomicsDB; 279116; -. [Q9QZE2-1]
DR ProteomicsDB; 279117; -. [Q9QZE2-2]
DR TopDownProteomics; Q9QZE2-1; -. [Q9QZE2-1]
DR Antibodypedia; 50006; 72 antibodies from 12 providers.
DR Ensembl; ENSMUST00000169819; ENSMUSP00000128473; ENSMUSG00000039315. [Q9QZE2-1]
DR GeneID; 27278; -.
DR KEGG; mmu:27278; -.
DR UCSC; uc008xgv.2; mouse. [Q9QZE2-1]
DR CTD; 116449; -.
DR MGI; MGI:1351468; Clnk.
DR VEuPathDB; HostDB:ENSMUSG00000039315; -.
DR eggNOG; ENOG502S0EU; Eukaryota.
DR GeneTree; ENSGT00940000161846; -.
DR HOGENOM; CLU_052668_0_0_1; -.
DR InParanoid; Q9QZE2; -.
DR OMA; SRCFSPW; -.
DR OrthoDB; 744111at2759; -.
DR PhylomeDB; Q9QZE2; -.
DR BioGRID-ORCS; 27278; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Clnk; mouse.
DR PRO; PR:Q9QZE2; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9QZE2; protein.
DR Bgee; ENSMUSG00000039315; Expressed in spermatid and 9 other tissues.
DR ExpressionAtlas; Q9QZE2; baseline and differential.
DR Genevisible; Q9QZE2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0042629; C:mast cell granule; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0043303; P:mast cell degranulation; IMP:UniProtKB.
DR GO; GO:0032815; P:negative regulation of natural killer cell activation; IMP:UniProtKB.
DR GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; IMP:UniProtKB.
DR GO; GO:0010941; P:regulation of cell death; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:MGI.
DR Gene3D; 3.30.505.10; -; 1.
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 Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome;
KW SH2 domain.
FT CHAIN 1..435
FT /note="Cytokine-dependent hematopoietic cell linker"
FT /id="PRO_0000314598"
FT DOMAIN 309..418
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 155..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 160..165
FT /note="Mediates interaction with PLCG1; essential for BCR
FT signaling; involved in restoration of BCR-induced calcium
FT response and ERK2 and JNK2 activation in BLNK-deficient
FT cells expressing LAT"
FT /evidence="ECO:0000269|PubMed:11463797"
FT REGION 178..182
FT /note="Mediates interaction with LAT, GRB2, and FGR;
FT involved in translocation to the glycolipid-enriched
FT microdomain and restoration of BCR-induced calcium response
FT in BLNK-deficient DT40 cells expressing LAT"
FT /evidence="ECO:0000269|PubMed:11463797,
FT ECO:0000269|PubMed:16439675"
FT COMPBIAS 159..186
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 202..225
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..273
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 335
FT /note="Interaction with FYB1"
FT /evidence="ECO:0000269|PubMed:12681493"
FT MOD_RES 69
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:11463797,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 96
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:11463797"
FT VAR_SEQ 5..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_030334"
FT MUTAGEN 69
FT /note="Y->F: Loss of phosphorylation and loss of
FT interaction with PLCG1, PLCG2 and VAV. No effect on the
FT suppression of natural killer cell activation and
FT suppression of interferon-gamma production; when associated
FT with F-96, F-101, F-153, F-174 and F-188."
FT /evidence="ECO:0000269|PubMed:10744659,
FT ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:16439675"
FT MUTAGEN 96
FT /note="Y->F: Loss of phosphorylation and loss of
FT interaction with PLCG1, PLCG2 and VAV. No effect on the
FT suppression of natural killer cell activation and
FT suppression of interferon-gamma production; when associated
FT with F-69, F-101, F-153, F-174 and F-188."
FT /evidence="ECO:0000269|PubMed:10744659,
FT ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:16439675"
FT MUTAGEN 101
FT /note="Y->F: Loss of phosphorylation and loss of
FT interaction with PLCG1, PLCG2 and VAV. No effect on the
FT suppression of natural killer cell activation and
FT suppression of interferon-gamma production; when associated
FT with F-69, F-96, F-153, F-174 and F-188."
FT /evidence="ECO:0000269|PubMed:10744659,
FT ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:16439675"
FT MUTAGEN 153
FT /note="Y->F: Loss of phosphorylation and loss of
FT interaction with PLCG1, PLCG2 and VAV. No effect on the
FT suppression of natural killer cell activation and
FT suppression of interferon-gamma production; when associated
FT with F-69, F-96, F-101, F-174 and F-188."
FT /evidence="ECO:0000269|PubMed:10744659,
FT ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:16439675"
FT MUTAGEN 160..165
FT /note="Missing: Slightly increases natural killer cell
FT activation and interferon-gamma production."
FT /evidence="ECO:0000269|PubMed:16439675"
FT MUTAGEN 174
FT /note="Y->F: Loss of phosphorylation and loss of
FT interaction with PLCG1, PLCG2 and VAV. No effect on the
FT suppression of natural killer cell activation and
FT suppression of interferon-gamma production; when associated
FT with F-69, F-96, F-101, F-153 and F-188."
FT /evidence="ECO:0000269|PubMed:10744659,
FT ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:16439675"
FT MUTAGEN 178..182
FT /note="Missing: Increases natural killer cell activation
FT and interferon-gamma production. Loss of FGR binding."
FT /evidence="ECO:0000269|PubMed:16439675"
FT MUTAGEN 188
FT /note="Y->F: Loss of phosphorylation and loss of
FT interaction with PLCG1, PLCG2 and VAV. No effect on the
FT suppression of natural killer cell activation and
FT suppression of interferon-gamma production; when associated
FT with F-69, F-96, F-101, F-153 and F-174."
FT /evidence="ECO:0000269|PubMed:10744659,
FT ECO:0000269|PubMed:11463797, ECO:0000269|PubMed:16439675"
FT MUTAGEN 335
FT /note="R->K: Loss of binding to FYB1 and MAP4K1. Reduced
FT tyrosine phosphorylation. No effect on the suppression of
FT natural killer cell activation and suppression of
FT interferon-gamma production."
FT /evidence="ECO:0000269|PubMed:12681493,
FT ECO:0000269|PubMed:16439675"
FT CONFLICT 105
FT /note="T -> M (in Ref. 2; BAA96240 and 3; AAI25638)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="H -> Q (in Ref. 2; BAA96240 and 3; AAI25638)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="C -> R (in Ref. 4; BAC38640)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 435 AA; 49492 MW; 5CD27EC971FC0EA5 CRC64;
MTSQGNKRTT KEGFGDLRFQ NVSLLKNRSW PSLSSAKGRC RAVLEPLPDH RRNLAGVPGG
EKCNSNNDYE DPEFQLLKAW PSMKILPARP IQESEYADTR YFQDTMEAPL LLPPKASVST
ERQTRDVRMT HLEEVDKPTF KDVRSQRFKG FKYTKINKTP LPPPRPAITL PKKYQPLPPA
PPEESSAYFA PKPTFPEVQR GPRQRSAKDF SRVLGAEEES HHQTKPESSC PSSNQNTQKS
PPAIASSSYM PGKHSIQARD HTGSMQHCPA QRCQAAASHS PRMLPYENTN SEKPDPTKPD
EKDVWQNEWY IGEYSRQAVE DVLMKENKDG TFLVRDCSTK SKAEPYVLVV FYGNKVYNVK
IRFLESNQQF ALGTGLRGNE MFDSVEDIIE HYTYFPILLI DGKDKAARRK QCYLTQPLPL
ARLLLTQYSS QALHE
