ID   HCLS1_MOUSE             Reviewed;         486 AA.
AC   P49710; Q922I8;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 184.
DE   RecName: Full=Hematopoietic lineage cell-specific protein;
DE   AltName: Full=Hematopoietic cell-specific LYN substrate 1;
DE   AltName: Full=LckBP1;
GN   Name=Hcls1; Synonyms=Hs1;
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=7535527; DOI=10.1006/bbrc.1995.1452;
RA   Kitamura D., Kaneko H., Taniuchi I., Yamamura K., Watanabe T.;
RT   "Molecular cloning and characterization of mouse HS1.";
RL   Biochem. Biophys. Res. Commun. 208:1137-1146(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Thymocyte;
RX   PubMed=7628441; DOI=10.1002/j.1460-2075.1995.tb07346.x;
RA   Takemoto Y., Furuta M., Li X.-K., Strong-Sparks W.J., Hashimoto Y.;
RT   "LckBP1, a proline-rich protein expressed in haematopoietic lineage cells,
RT   directly associates with the SH3 domain of protein tyrosine kinase
RT   p56(lck).";
RL   EMBO J. 14:3403-3414(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   INTERACTION WITH LCK, AND BINDING PATTERN OF SERVERAL SRC KINASES.
RC   STRAIN=BALB/cJ;
RX   PubMed=8943564; DOI=10.1093/intimm/8.11.1699;
RA   Takemoto Y., Sato M., Furuta M., Hashimoto Y.;
RT   "Distinct binding patterns of HS1 to the Src SH2 and SH3 domains reflect
RT   possible mechanisms of recruitment and activation of downstream
RT   molecules.";
RL   Int. Immunol. 8:1699-1705(1996).
RN   [5]
RP   INTERACTION WITH HS1BP3.
RX   PubMed=10590261; DOI=10.1093/intimm/11.12.1957;
RA   Takemoto Y., Furuta M., Sato M., Kubo M., Hashimoto Y.;
RT   "Isolation and characterization of a novel HS1 SH3 domain binding protein,
RT   HS1BP3.";
RL   Int. Immunol. 11:1957-1964(1999).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-140, 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   [7]
RP   INTERACTION WITH ANKRD54.
RX   PubMed=19064729; DOI=10.1182/blood-2008-04-153452;
RA   Samuels A.L., Klinken S.P., Ingley E.;
RT   "Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that
RT   influences erythropoietin-induced differentiation.";
RL   Blood 113:3845-3856(2009).
RN   [8]
RP   INTERACTION WITH FES/FPS, PHOSPHORYLATION AT TYR-388 AND TYR-405, AND
RP   MUTAGENESIS OF TYR-388 AND TYR-405.
RX   PubMed=19001085; DOI=10.1128/mcb.00904-08;
RA   McPherson V.A., Everingham S., Karisch R., Smith J.A., Udell C.M.,
RA   Zheng J., Jia Z., Craig A.W.;
RT   "Contributions of F-BAR and SH2 domains of Fes protein tyrosine kinase for
RT   coupling to the FcepsilonRI pathway in mast cells.";
RL   Mol. Cell. Biol. 29:389-401(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-330 AND SER-333, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Heart, Kidney, 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: Substrate of the antigen receptor-coupled tyrosine kinase.
CC       Plays a role in antigen receptor signaling for both clonal expansion
CC       and deletion in lymphoid cells. May also be involved in the regulation
CC       of gene expression (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts (via SH2 domain) with FGR (By similarity).
CC       Associates with the SH2 and SH3 domains of LCK. Binding to he LCK SH3
CC       domain occurs constitutively, while binding to the LCK SH2 domain
CC       occurs only upon TCR stimulation. A similar binding pattern was
CC       observed with LYN, but not with FYN in which the FYN SH2 region
CC       associates upon TCR stimulation but the FYN SH3 region does not
CC       associate regardless of TCR stimulation. Directly associates with HAX1,
CC       through binding to its C-terminal region. Interacts with HS1BP3.
CC       Interacts with FES/FPS. Forms a multiprotein complex with LYN and
CC       ANKRD54. {ECO:0000250, ECO:0000269|PubMed:10590261,
CC       ECO:0000269|PubMed:19001085, ECO:0000269|PubMed:19064729,
CC       ECO:0000269|PubMed:8943564}.
CC   -!- INTERACTION:
CC       P49710; P25911: Lyn; NbExp=10; IntAct=EBI-924601, EBI-643537;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed only in tissues and cells of
CC       hematopoietic origin.
CC   -!- PTM: Phosphorylated by LYN, FYN and FGR after cross-linking of surface
CC       IgM on B-cells. Phosphorylation by LYN, FYN and FGR requires prior
CC       phosphorylation by SYK (By similarity). Binds to LCK in vivo, and is
CC       tyrosine phosphorylated upon TCR stimulation. Phosphorylated by FES.
CC       {ECO:0000250, ECO:0000269|PubMed:19001085}.
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DR   EMBL; D42120; BAA07701.1; -; mRNA.
DR   EMBL; X84797; CAA59265.1; -; mRNA.
DR   EMBL; BC007469; AAH07469.1; -; mRNA.
DR   CCDS; CCDS37336.1; -.
DR   PIR; I49760; I49760.
DR   RefSeq; NP_032251.2; NM_008225.2.
DR   AlphaFoldDB; P49710; -.
DR   SMR; P49710; -.
DR   BioGRID; 200250; 7.
DR   CORUM; P49710; -.
DR   IntAct; P49710; 4.
DR   MINT; P49710; -.
DR   STRING; 10090.ENSMUSP00000023531; -.
DR   MoonDB; P49710; Predicted.
DR   iPTMnet; P49710; -.
DR   PhosphoSitePlus; P49710; -.
DR   SwissPalm; P49710; -.
DR   CPTAC; non-CPTAC-3794; -.
DR   EPD; P49710; -.
DR   jPOST; P49710; -.
DR   MaxQB; P49710; -.
DR   PaxDb; 10090-ENSMUSP00000023531; -.
DR   PeptideAtlas; P49710; -.
DR   ProteomicsDB; 270951; -.
DR   Antibodypedia; 16699; 546 antibodies from 39 providers.
DR   DNASU; 15163; -.
DR   Ensembl; ENSMUST00000023531.15; ENSMUSP00000023531.9; ENSMUSG00000022831.15.
DR   GeneID; 15163; -.
DR   KEGG; mmu:15163; -.
DR   UCSC; uc007zdi.2; mouse.
DR   AGR; MGI:104568; -.
DR   CTD; 3059; -.
DR   MGI; MGI:104568; Hcls1.
DR   VEuPathDB; HostDB:ENSMUSG00000022831; -.
DR   eggNOG; ENOG502QS6C; Eukaryota.
DR   GeneTree; ENSGT00940000158997; -.
DR   HOGENOM; CLU_019379_2_0_1; -.
DR   InParanoid; P49710; -.
DR   OMA; RCRGHFG; -.
DR   OrthoDB; 101008at2759; -.
DR   PhylomeDB; P49710; -.
DR   TreeFam; TF318935; -.
DR   BioGRID-ORCS; 15163; 2 hits in 78 CRISPR screens.
DR   PRO; PR:P49710; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; P49710; Protein.
DR   Bgee; ENSMUSG00000022831; Expressed in granulocyte and 99 other cell types or tissues.
DR   ExpressionAtlas; P49710; baseline and differential.
DR   GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0030427; C:site of polarized growth; IBA:GO_Central.
DR   GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR   GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR   GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:MGI.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR   GO; GO:0017124; F:SH3 domain binding; IDA:MGI.
DR   GO; GO:0035591; F:signaling adaptor activity; ISO:MGI.
DR   GO; GO:0007015; P:actin filament organization; ISO:MGI.
DR   GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI.
DR   GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR   GO; GO:0038158; P:granulocyte colony-stimulating factor signaling pathway; ISO:MGI.
DR   GO; GO:2000107; P:negative regulation of leukocyte apoptotic process; ISO:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0051169; P:nuclear transport; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0030854; P:positive regulation of granulocyte differentiation; IMP:BHF-UCL.
DR   GO; GO:0045651; P:positive regulation of macrophage differentiation; IMP:BHF-UCL.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI.
DR   GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR   GO; GO:0030833; P:regulation of actin filament polymerization; ISO:MGI.
DR   GO; GO:0009725; P:response to hormone; IDA:UniProtKB.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   InterPro; IPR003134; Hs1_Cortactin.
DR   InterPro; IPR036028; SH3-like_dom_sf.
DR   InterPro; IPR001452; SH3_domain.
DR   PANTHER; PTHR10829; CORTACTIN AND DREBRIN; 1.
DR   PANTHER; PTHR10829:SF5; HEMATOPOIETIC LINEAGE CELL-SPECIFIC PROTEIN; 1.
DR   Pfam; PF02218; HS1_rep; 4.
DR   Pfam; PF00018; SH3_1; 1.
DR   PRINTS; PR00499; P67PHOX.
DR   PRINTS; PR00452; SH3DOMAIN.
DR   SMART; SM00326; SH3; 1.
DR   SUPFAM; SSF50044; SH3-domain; 1.
DR   PROSITE; PS51090; CORTACTIN; 4.
DR   PROSITE; PS50002; SH3; 1.
DR   Genevisible; P49710; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Mitochondrion; Phosphoprotein; Reference proteome; Repeat;
KW   SH3 domain.
FT   CHAIN           1..486
FT                   /note="Hematopoietic lineage cell-specific protein"
FT                   /id="PRO_0000083922"
FT   REPEAT          79..115
FT                   /note="Cortactin 1"
FT   REPEAT          116..152
FT                   /note="Cortactin 2"
FT   REPEAT          153..189
FT                   /note="Cortactin 3"
FT   REPEAT          190..212
FT                   /note="Cortactin 4; truncated"
FT   DOMAIN          429..486
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   REGION          27..66
FT                   /note="Involved in HAX-1 binding"
FT                   /evidence="ECO:0000250"
FT   REGION          226..430
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        241..274
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        366..411
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         41
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P14317"
FT   MOD_RES         123
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P14317"
FT   MOD_RES         140
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:17947660"
FT   MOD_RES         192
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P14317"
FT   MOD_RES         198
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P14317"
FT   MOD_RES         222
FT                   /note="Phosphotyrosine; by FGR"
FT                   /evidence="ECO:0000250|UniProtKB:P14317"
FT   MOD_RES         241
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P14317"
FT   MOD_RES         275
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P14317"
FT   MOD_RES         330
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         333
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         388
FT                   /note="Phosphotyrosine; by SYK and FES"
FT                   /evidence="ECO:0000305|PubMed:19001085"
FT   MOD_RES         405
FT                   /note="Phosphotyrosine; by SYK and FES"
FT                   /evidence="ECO:0000305|PubMed:19001085"
FT   MUTAGEN         388
FT                   /note="Y->F: Strongly reduces phosphorylation by FES.
FT                   Abolishes phosphorylation by FES; when associated with
FT                   F-405."
FT                   /evidence="ECO:0000269|PubMed:19001085"
FT   MUTAGEN         405
FT                   /note="Y->F: Minor effect on phosphorylation by FES.
FT                   Abolishes phosphorylation by FES; when associated with
FT                   F-388."
FT                   /evidence="ECO:0000269|PubMed:19001085"
FT   CONFLICT        86
FT                   /note="R -> Q (in Ref. 1; BAA07701 and 2; CAA59265)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   486 AA;  54240 MW;  0EE14FEFA0A31412 CRC64;
     MWKSVVGHDV SVSVETQGDD WDTDPDFVND ISEKEQRWGA KTIEGSGRTE HINIHQLRNK
     VSEEHDILKK KELESGPKAS HGYGGRFGVE RDRMDKSAVG HEYVADVEKH SSQTDAARGF
     GGKYGVERDR ADKSAVGFDY KGEVEKHASQ KDYSHGFGGR YGVEKDKRDK AALGYDYKGE
     TEKHESQRDY AKGFGGQYGI QKDRVDKSAV GFNEMEAPTT AYKKTTPIEA ASSGARGLKA
     KFESLAEEKR KREEEEKAQQ MARQQQERKA VVKMSREVQQ PSMPVEEPAA PAQLPKKISS
     EVWPPAESHL PPESQPVRSR REYPVPSLPT RQSPLQNHLE DNEEPPALPP RTPEGLQVVE
     EPVYEAAPEL EPEPEPDYEP EPETEPDYED VGELDRQDED AEGDYEDVLE PEDTPSLSYQ
     AGPSAGAGGA GISAIALYDY QGEGSDELSF DPDDIITDIE MVDEGWWRGQ CRGHFGLFPA
     NYVKLL
//