SLAP2_MOUSE
ID SLAP2_MOUSE Reviewed; 259 AA.
AC Q8R4L0; Q3UU74; Q8C0K2; Q8VI42; Q9D1Z9;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Src-like-adapter 2;
DE AltName: Full=Src-like adapter protein 2;
DE Short=SLAP-2;
GN Name=Sla2;
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] (ISOFORMS 1 AND 2), ALTERNATIVE INITIATION,
RP CHARACTERIZATION, FUNCTION, MYRISTOYLATION AT GLY-2, PHOSPHORYLATION,
RP INTERACTION WITH ZAP70 AND CBL, AND MUTAGENESIS OF GLY-2; MET-27 AND
RP ARG-120.
RX PubMed=12024036; DOI=10.1128/mcb.22.12.4241-4255.2002;
RA Loreto M.P., Berry D.M., McGlade C.J.;
RT "Functional cooperation between c-Cbl and Src-like adaptor protein 2 in the
RT negative regulation of T-cell receptor signaling.";
RL Mol. Cell. Biol. 22:4241-4255(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, MYRISTOYLATION AT
RP GLY-2, INTERACTION WITH CBL; ZAP70 AND CD3Z, AND MUTAGENESIS OF GLY-2;
RP PRO-82 AND ARG-120.
RX PubMed=11891219; DOI=10.1074/jbc.m110318200;
RA Pandey A., Ibarrola N., Kratchmarova I., Fernandez M.M.,
RA Constantinescu S.N., Ohara O., Sawasdikosol S., Lodish H.F., Mann M.;
RT "A novel Src homology 2 domain-containing molecule, Src-like adapter
RT protein-2 (SLAP-2), which negatively regulates T cell receptor signaling.";
RL J. Biol. Chem. 277:19131-19138(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Retina, and Thymus;
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 [4]
RP PHOSPHORYLATION, AND INTERACTION WITH CBL AND CSF1R.
RX PubMed=17353186; DOI=10.1074/jbc.m701182200;
RA Pakuts B., Debonneville C., Liontos L.M., Loreto M.P., McGlade C.J.;
RT "The Src-like adaptor protein 2 regulates colony-stimulating factor-1
RT receptor signaling and down-regulation.";
RL J. Biol. Chem. 282:17953-17963(2007).
CC -!- FUNCTION: Adapter protein, which negatively regulates T-cell receptor
CC (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of
CC nuclear factor of activated T-cells. May act by linking signaling
CC proteins such as ZAP70 with CBL, leading to a CBL dependent degradation
CC of signaling proteins. {ECO:0000269|PubMed:11891219,
CC ECO:0000269|PubMed:12024036}.
CC -!- SUBUNIT: Interacts (via its C-terminal domain) with CBL
CC (phosphorylated). Interacts (via SH2 domain) with ZAP70
CC (phosphorylated) and CD3Z (phosphorylated). Interacts (via SH2 domain)
CC with CSF1R (phosphorylated). {ECO:0000269|PubMed:11891219,
CC ECO:0000269|PubMed:12024036, ECO:0000269|PubMed:17353186}.
CC -!- INTERACTION:
CC Q8R4L0; P36888: FLT3; Xeno; NbExp=14; IntAct=EBI-20766300, EBI-3946257;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Cytoplasmic vesicle.
CC Late endosome. Note=Localized to the plasma membrane and intracellular
CC vesicles, including late endosomal vesicles.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=p28;
CC IsoId=Q8R4L0-1; Sequence=Displayed;
CC Name=2; Synonyms=p25;
CC IsoId=Q8R4L0-2; Sequence=VSP_018795;
CC -!- TISSUE SPECIFICITY: Mainly expressed in immune system. Highly expressed
CC in spleen and thymus and expressed at intermediate levels in lung. Not
CC expressed in liver, heart and brain. Isoform 1 is predominant in lung
CC and spleen, while isoform 2 is predominant in thymus.
CC -!- DOMAIN: The loss of the C-terminal domain partially abolishes the
CC inhibitory function.
CC -!- PTM: Phosphorylated by CSF1R. {ECO:0000269|PubMed:12024036,
CC ECO:0000269|PubMed:17353186}.
CC -!- MISCELLANEOUS: PubMed:12024036 confirmed the alternative initiation by
CC mutating the Met in position 1 to Val, and showed that isoform 1 is
CC abolished in favor of isoform 2.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB32223.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF287467; AAL38196.1; -; mRNA.
DR EMBL; AF434990; AAL86403.1; -; mRNA.
DR EMBL; AK020837; BAB32223.1; ALT_INIT; mRNA.
DR EMBL; AK030877; BAC27168.1; -; mRNA.
DR EMBL; AK088672; BAC40495.1; -; mRNA.
DR EMBL; AK138709; BAE23754.1; -; mRNA.
DR CCDS; CCDS38302.1; -. [Q8R4L0-1]
DR RefSeq; NP_084259.1; NM_029983.5. [Q8R4L0-1]
DR RefSeq; XP_006500468.1; XM_006500405.2.
DR PDB; 6XAR; X-ray; 2.50 A; C/D=237-255.
DR PDBsum; 6XAR; -.
DR AlphaFoldDB; Q8R4L0; -.
DR SMR; Q8R4L0; -.
DR BioGRID; 218930; 2.
DR IntAct; Q8R4L0; 1.
DR MINT; Q8R4L0; -.
DR STRING; 10090.ENSMUSP00000029164; -.
DR iPTMnet; Q8R4L0; -.
DR PhosphoSitePlus; Q8R4L0; -.
DR EPD; Q8R4L0; -.
DR jPOST; Q8R4L0; -.
DR MaxQB; Q8R4L0; -.
DR PaxDb; Q8R4L0; -.
DR PRIDE; Q8R4L0; -.
DR ProteomicsDB; 261073; -. [Q8R4L0-1]
DR ProteomicsDB; 261074; -. [Q8R4L0-2]
DR Antibodypedia; 26550; 446 antibodies from 23 providers.
DR Ensembl; ENSMUST00000029164; ENSMUSP00000029164; ENSMUSG00000027636. [Q8R4L0-1]
DR Ensembl; ENSMUST00000109561; ENSMUSP00000105189; ENSMUSG00000027636. [Q8R4L0-1]
DR GeneID; 77799; -.
DR KEGG; mmu:77799; -.
DR UCSC; uc008nod.1; mouse. [Q8R4L0-1]
DR CTD; 84174; -.
DR MGI; MGI:1925049; Sla2.
DR VEuPathDB; HostDB:ENSMUSG00000027636; -.
DR eggNOG; ENOG502QPJN; Eukaryota.
DR GeneTree; ENSGT00940000160331; -.
DR HOGENOM; CLU_084503_1_0_1; -.
DR InParanoid; Q8R4L0; -.
DR OMA; QSRRGCY; -.
DR OrthoDB; 1051480at2759; -.
DR PhylomeDB; Q8R4L0; -.
DR TreeFam; TF354288; -.
DR Reactome; R-MMU-9706369; Negative regulation of FLT3.
DR BioGRID-ORCS; 77799; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q8R4L0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8R4L0; protein.
DR Bgee; ENSMUSG00000027636; Expressed in thymus and 60 other tissues.
DR Genevisible; Q8R4L0; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005770; C:late endosome; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0047485; F:protein N-terminus binding; ISS:UniProtKB.
DR GO; GO:0035591; F:signaling adaptor activity; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; ISO:MGI.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0042110; P:T cell activation; IDA:MGI.
DR CDD; cd10344; SH2_SLAP; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR035054; SLAP2.
DR InterPro; IPR035052; SLAP_SH2.
DR PANTHER; PTHR10155:SF6; PTHR10155:SF6; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative initiation; Cell membrane;
KW Cytoplasm; Cytoplasmic vesicle; Endosome; Immunity; Lipoprotein; Membrane;
KW Myristate; Phosphoprotein; Reference proteome; SH2 domain; SH3 domain.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..259
FT /note="Src-like-adapter 2"
FT /id="PRO_0000022353"
FT DOMAIN 31..91
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 93..190
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 190..259
FT /note="SLA C-terminal"
FT COMPBIAS 1..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:11891219,
FT ECO:0000269|PubMed:12024036"
FT VAR_SEQ 1..26
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11891219,
FT ECO:0000303|PubMed:12024036"
FT /id="VSP_018795"
FT MUTAGEN 2
FT /note="G->A: Abolishes localization to membranes."
FT /evidence="ECO:0000269|PubMed:11891219,
FT ECO:0000269|PubMed:12024036"
FT MUTAGEN 27
FT /note="M->V: Abolishes isoform 2."
FT /evidence="ECO:0000269|PubMed:12024036"
FT MUTAGEN 82
FT /note="P->L: Does not affect its inhibitory function."
FT /evidence="ECO:0000269|PubMed:11891219"
FT MUTAGEN 120
FT /note="R->E: Abolishes interaction with ZAP70, and its
FT inhibitory function."
FT /evidence="ECO:0000269|PubMed:11891219,
FT ECO:0000269|PubMed:12024036"
FT CONFLICT 128
FT /note="C -> Y (in Ref. 3; BAC27168)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="S -> T (in Ref. 3; BAC27168)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="P -> H (in Ref. 2; AAL86403)"
FT /evidence="ECO:0000305"
FT HELIX 241..251
FT /evidence="ECO:0007829|PDB:6XAR"
SQ SEQUENCE 259 AA; 28476 MW; 8270F17CD3FC50A3 CRC64;
MGSLSSRGKT SSPSPSSSGP DQEPVSMQPE RHKVTAVALG SFPAGEQARL SLRLGEPLTI
ISEDGDWWTV QSEVSGREYH MPSVYVAKVA HGWLYEGLSR EKAEELLLLP GNPGGAFLIR
ESQTRRGCYS LSVRLSRPAS WDRIRHYRIQ RLDNGWLYIS PRLTFPSLHA LVEHYSELAD
GICCPLREPC VLQKLGPLPG KDTPPPVTVP TSSLNWKKLD RSLLFLEAPA SGEASLLSEG
LRESLSSYIS LAEDPLDDA
