SLAP1_MOUSE
ID SLAP1_MOUSE Reviewed; 281 AA.
AC Q60898; Q8C9Q8; Q8CAT0; Q8CBE9; Q8QZX8;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Src-like-adapter;
DE AltName: Full=Src-like-adapter protein 1;
DE Short=SLAP-1;
DE Short=mSLAP;
GN Name=Sla; Synonyms=Slap, Slap1;
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), TISSUE SPECIFICITY, AND INTERACTION
RP WITH EPHA2.
RC TISSUE=Embryonic brain;
RX PubMed=7543898; DOI=10.1074/jbc.270.33.19201;
RA Pandey A., Duan H., Dixit V.M.;
RT "Characterization of a novel Src-like adapter protein that associates with
RT the Eck receptor tyrosine kinase.";
RL J. Biol. Chem. 270:19201-19204(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10630289; DOI=10.1007/s002510050601;
RA Carrier A., Nguyen C., Victorero G., Granjeaud S., Rocha D., Bernard K.,
RA Miazek A., Ferrier P., Malissen M., Naquet P., Malissen B., Jordan B.R.;
RT "Differential gene expression in CD3epsilon- and RAG1-deficient thymuses:
RT definition of a set of genes potentially involved in thymocyte
RT maturation.";
RL Immunogenetics 50:255-270(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC STRAIN=ILS, and ISS;
RX PubMed=11471062; DOI=10.1007/s00335-001-1001-x;
RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J.,
RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.;
RT "High-throughput sequence identification of gene coding variants within
RT alcohol-related QTLs.";
RL Mamm. Genome 12:657-663(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
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 [6]
RP INTERACTION WITH PDGFRB.
RX PubMed=9742401; DOI=10.1016/s0960-9822(98)70400-2;
RA Roche S., Alonso G., Kazlauskas A., Dixit V.M., Courtneidge S.A.,
RA Pandey A.;
RT "Src-like adaptor protein (Slap) is a negative regulator of mitogenesis.";
RL Curr. Biol. 8:975-978(1998).
RN [7]
RP CHARACTERIZATION, FUNCTION, INTERACTION WITH ZAP70; CD3Z; VAV1 AND LCP2,
RP AND MUTAGENESIS OF PRO-73 AND ARG-111.
RX PubMed=10662792; DOI=10.1084/jem.191.3.463;
RA Sosinowski T., Pandey A., Dixit V.M., Weiss A.;
RT "Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor
RT signaling.";
RL J. Exp. Med. 191:463-474(2000).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, AND MUTAGENESIS OF
RP GLY-2.
RX PubMed=10779329; DOI=10.1128/mcb.20.10.3396-3406.2000;
RA Manes G., Bello P., Roche S.;
RT "Slap negatively regulates Src mitogenic function but does not revert Src-
RT induced cell morphology changes.";
RL Mol. Cell. Biol. 20:3396-3406(2000).
RN [9]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11567635; DOI=10.1016/s1074-7613(01)00195-9;
RA Sosinowski T., Killeen N., Weiss A.;
RT "The Src-like adaptor protein downregulates the T cell receptor on CD4+CD8+
RT thymocytes and regulates positive selection.";
RL Immunity 15:457-466(2001).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-278, 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. Involved in the negative
CC regulation of positive selection and mitosis of T-cells. May act by
CC linking signaling proteins such as ZAP70 with CBL, leading to a CBL
CC dependent degradation of signaling proteins.
CC {ECO:0000269|PubMed:10662792, ECO:0000269|PubMed:10779329,
CC ECO:0000269|PubMed:11567635}.
CC -!- SUBUNIT: Homodimer. Interacts with phosphorylated CBL, SYK and LAT.
CC Homodimerization and interaction with phosphorylated CBL occurs via its
CC C-terminal domain (By similarity). Interacts with PDGFRB and EPHA2.
CC Interacts with phosphorylated proteins ZAP70; CD3Z; VAV1 and LCP2 via
CC its SH2 domain. {ECO:0000250, ECO:0000269|PubMed:10662792,
CC ECO:0000269|PubMed:7543898, ECO:0000269|PubMed:9742401}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10779329}. Endosome
CC {ECO:0000269|PubMed:10779329}. Note=Colocalizes with endosomes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q60898-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q60898-2; Sequence=VSP_007239;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in lymphoid tissues. Highly
CC expressed in spleen, thymus and lymph nodes. Weakly expressed in lung
CC and brain. Expressed in T-cells and at low level in B-cells.
CC {ECO:0000269|PubMed:7543898}.
CC -!- DEVELOPMENTAL STAGE: Expressed during thymocyte maturation. Weakly
CC expressed in CD4(-) CD8(-) thymocytes, strongly expressed in CD4(+)
CC CD8(+) thymocytes, while expression decreases in more mature cells.
CC {ECO:0000269|PubMed:11567635}.
CC -!- DOMAIN: The C-terminal domain is essential for the homodimerization and
CC the interaction with CBL. While the interaction with CBL is apparently
CC mediated via the hydrophobic region of this domain, the highly charged
CC region is apparently required for the homodimerization (By similarity).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: SLA deficient mice show a strong up-regulation of TCR
CC and CD5 at the CD4(+) CD8(+) stage, and an enhanced positive selection
CC in T-cells.
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DR EMBL; U29056; AAA82756.1; -; mRNA.
DR EMBL; AJ131777; CAB66139.1; -; mRNA.
DR EMBL; AY079449; AAL87537.1; -; Genomic_DNA.
DR EMBL; AY079450; AAL87538.1; -; Genomic_DNA.
DR EMBL; AK036167; BAC29328.1; -; mRNA.
DR EMBL; AK037901; BAC29896.1; -; mRNA.
DR EMBL; AK041565; BAC30988.1; -; mRNA.
DR EMBL; BC032922; AAH32922.1; -; mRNA.
DR CCDS; CCDS27509.1; -. [Q60898-1]
DR PIR; A57152; A57152.
DR RefSeq; NP_001025012.1; NM_001029841.4.
DR RefSeq; NP_033218.1; NM_009192.3. [Q60898-1]
DR RefSeq; XP_011243832.1; XM_011245530.2. [Q60898-1]
DR AlphaFoldDB; Q60898; -.
DR SMR; Q60898; -.
DR BioGRID; 203272; 3.
DR DIP; DIP-292N; -.
DR IntAct; Q60898; 1.
DR STRING; 10090.ENSMUSP00000131865; -.
DR iPTMnet; Q60898; -.
DR PhosphoSitePlus; Q60898; -.
DR jPOST; Q60898; -.
DR MaxQB; Q60898; -.
DR PaxDb; Q60898; -.
DR PRIDE; Q60898; -.
DR ProteomicsDB; 258687; -. [Q60898-1]
DR ProteomicsDB; 258688; -. [Q60898-2]
DR Antibodypedia; 1995; 133 antibodies from 28 providers.
DR DNASU; 20491; -.
DR Ensembl; ENSMUST00000100572; ENSMUSP00000098138; ENSMUSG00000022372. [Q60898-1]
DR Ensembl; ENSMUST00000164163; ENSMUSP00000127901; ENSMUSG00000022372. [Q60898-1]
DR Ensembl; ENSMUST00000168589; ENSMUSP00000130222; ENSMUSG00000022372. [Q60898-1]
DR GeneID; 20491; -.
DR KEGG; mmu:20491; -.
DR UCSC; uc007war.2; mouse. [Q60898-1]
DR CTD; 6503; -.
DR MGI; MGI:104295; Sla.
DR VEuPathDB; HostDB:ENSMUSG00000022372; -.
DR eggNOG; ENOG502QPWY; Eukaryota.
DR GeneTree; ENSGT00940000159104; -.
DR HOGENOM; CLU_084503_1_0_1; -.
DR InParanoid; Q60898; -.
DR OMA; GMCVAKV; -.
DR OrthoDB; 1051480at2759; -.
DR PhylomeDB; Q60898; -.
DR TreeFam; TF354288; -.
DR Reactome; R-MMU-9706369; Negative regulation of FLT3.
DR BioGRID-ORCS; 20491; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Sla; mouse.
DR PRO; PR:Q60898; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q60898; protein.
DR Bgee; ENSMUSG00000022372; Expressed in cortical plate and 132 other tissues.
DR ExpressionAtlas; Q60898; baseline and differential.
DR Genevisible; Q60898; MM.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005925; C:focal adhesion; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10344; SH2_SLAP; 1.
DR CDD; cd12010; SH3_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; IPR035055; SLAP.
DR InterPro; IPR035052; SLAP_SH2.
DR InterPro; IPR035596; SLAP_SH3.
DR PANTHER; PTHR24418:SF293; PTHR24418:SF293; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 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 Alternative splicing; Cytoplasm; Endosome; Lipoprotein; Myristate;
KW Phosphoprotein; Reference proteome; SH2 domain; SH3 domain.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..281
FT /note="Src-like-adapter"
FT /id="PRO_0000071947"
FT DOMAIN 22..82
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 84..175
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 190..281
FT /note="SLA C-terminal"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59622"
FT MOD_RES 278
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:10779329"
FT VAR_SEQ 1..2
FT /note="MG -> MLCRLRVPSTAQGEKEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_007239"
FT MUTAGEN 2
FT /note="G->A: Abolishes myristoylation and localization to
FT endosomes."
FT /evidence="ECO:0000269|PubMed:10779329"
FT MUTAGEN 73
FT /note="P->L: Slightly affects inhibitory function.
FT Abolishes inhibitory function; when associated with E-111."
FT /evidence="ECO:0000269|PubMed:10662792"
FT MUTAGEN 111
FT /note="R->E: Abolishes localization to endosomes. Strongly
FT affects inhibitory function. Abolishes inhibitory function;
FT when associated with L-73."
FT /evidence="ECO:0000269|PubMed:10662792"
FT CONFLICT 162
FT /note="Missing (in Ref. 4; BAC29896)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="N -> S (in Ref. 4; BAC30988)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 281 AA; 31681 MW; B347921656A74DA1 CRC64;
MGNSMKSTSP PSERPLSSSE GLESDFLAVL TDYPSPDISP PIFRRGEKLR VISDEGGWWK
AISLSTGRES YIPGICVARV YHGWLFEGLG RDKAEELLQL PDTKIGSFMI RESETKKGFY
SLSVRHRQVK HYRIFRLPNN WYYISPRLTF QCLEDLVTHY SEVADGLCCV LTTPCLAQNI
PAPTSHPSPC TSPGSPVTLR QKTFDWKRVS RLQEGSEGAE NPLRVDESLF SYGLRESIAS
YLSLTGDDSS SFDRKKKSLS LMYTGSKRKS SFFSAPQYFE D
