HCLS1_MOUSE
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 03-AUG-2022, entry version 176.
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; 6.
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; P49710; -.
DR PeptideAtlas; P49710; -.
DR PRIDE; P49710; -.
DR ProteomicsDB; 270951; -.
DR Antibodypedia; 16699; 501 antibodies from 39 providers.
DR DNASU; 15163; -.
DR Ensembl; ENSMUST00000023531; ENSMUSP00000023531; ENSMUSG00000022831.
DR GeneID; 15163; -.
DR KEGG; mmu:15163; -.
DR UCSC; uc007zdi.2; mouse.
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; 1243441at2759; -.
DR PhylomeDB; P49710; -.
DR TreeFam; TF318935; -.
DR BioGRID-ORCS; 15163; 2 hits in 73 CRISPR screens.
DR PRO; PR:P49710; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P49710; protein.
DR Bgee; ENSMUSG00000022831; Expressed in granulocyte and 97 other tissues.
DR ExpressionAtlas; P49710; baseline and differential.
DR Genevisible; P49710; MM.
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:0030041; P:actin filament polymerization; IEA:InterPro.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
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:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
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:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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 InterPro; IPR028534; HS1.
DR InterPro; IPR003134; Hs1_Cortactin.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10829:SF5; PTHR10829:SF5; 2.
DR Pfam; PF02218; HS1_rep; 4.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51090; CORTACTIN; 4.
DR PROSITE; PS50002; SH3; 1.
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 F-
FT 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 F-
FT 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
