LEUK_MOUSE
ID LEUK_MOUSE Reviewed; 395 AA.
AC P15702;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Leukosialin;
DE AltName: Full=B-cell differentiation antigen LP-3;
DE AltName: Full=Leukocyte sialoglycoprotein;
DE AltName: Full=Lymphocyte antigen 48;
DE Short=Ly-48;
DE AltName: Full=Sialophorin;
DE AltName: CD_antigen=CD43;
DE Contains:
DE RecName: Full=CD43 cytoplasmic tail {ECO:0000303|PubMed:19696198};
DE Short=CD43-ct {ECO:0000303|PubMed:19696198};
DE Short=CD43ct {ECO:0000303|PubMed:19696198};
DE Flags: Precursor;
GN Name=Spn;
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 [GENOMIC DNA].
RC STRAIN=DBA/2J; TISSUE=Liver;
RX PubMed=2347365; DOI=10.1002/eji.1830200424;
RA Cyster J.G., Somoza C., Killeen N., Williams A.F.;
RT "Protein sequence and gene structure for mouse leukosialin (CD43), a T
RT lymphocyte mucin without introns in the coding sequence.";
RL Eur. J. Immunol. 20:875-881(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=B10.P; TISSUE=Liver;
RX PubMed=2144340; DOI=10.1093/nar/18.16.4932;
RA Dorfman K.S., Litaker K.S., Baecher C.M., Frelinger J.G.;
RT "The nucleotide sequence of Ly 48 (mouse leukosialin, sialophorin): the
RT mouse homolog of CD43.";
RL Nucleic Acids Res. 18:4932-4932(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=7514104; DOI=10.1006/cimm.1994.1133;
RA Shiota J., Nishimura H., Okamoto H., Yu B., Hattori S., Abe M., Okada T.,
RA Nozawa S., Tsurui H., Hirose S.;
RT "A unique murine CD43 epitope Lp-3: distinct distribution from another CD43
RT epitope S7.";
RL Cell. Immunol. 155:402-413(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 345-383.
RC STRAIN=C57BL/6J;
RX PubMed=1973410; DOI=10.1007/bf02115004;
RA Baecher C.M., Dorfman K.S., Mattei M.-G., Frelinger J.G.;
RT "cDNA cloning and localization of the mouse leukosialin gene (Ly48) to
RT chromosome 7.";
RL Immunogenetics 31:307-314(1990).
RN [5]
RP INTERACTION WITH HIPK2.
RX PubMed=11078605; DOI=10.1006/cimm.2000.1716;
RA Wang W., Link V., Green J.M.;
RT "Identification and cloning of a CD43-associated serine/threonine kinase.";
RL Cell. Immunol. 205:34-39(2000).
RN [6]
RP FUNCTION, AND INTERACTION WITH SIGLEC1.
RX PubMed=11238599; DOI=10.4049/jimmunol.166.6.3637;
RA van den Berg T.K., Nath D., Ziltener H.J., Vestweber D., Fukuda M.,
RA van Die I., Crocker P.R.;
RT "CD43 functions as a T cell counterreceptor for the macrophage adhesion
RT receptor sialoadhesin (Siglec-1).";
RL J. Immunol. 166:3637-3640(2001).
RN [7]
RP FUNCTION.
RX PubMed=11728336; DOI=10.1016/s1074-7613(01)00224-2;
RA Allenspach E.J., Cullinan P., Tong J., Tang Q., Tesciuba A.G., Cannon J.L.,
RA Takahashi S.M., Morgan R., Burkhardt J.K., Sperling A.I.;
RT "ERM-dependent movement of CD43 defines a novel protein complex distal to
RT the immunological synapse.";
RL Immunity 15:739-750(2001).
RN [8]
RP FUNCTION, PHOSPHORYLATION AT SER-343 AND SER-347, AND MUTAGENESIS OF
RP SER-343 AND SER-347.
RX PubMed=17638845; DOI=10.1182/blood-2007-01-065276;
RA Mody P.D., Cannon J.L., Bandukwala H.S., Blaine K.M., Schilling A.B.,
RA Swier K., Sperling A.I.;
RT "Signaling through CD43 regulates CD4 T-cell trafficking.";
RL Blood 110:2974-2982(2007).
RN [9]
RP FUNCTION.
RX PubMed=18490738; DOI=10.4049/jimmunol.180.11.7385;
RA Cannon J.L., Collins A., Mody P.D., Balachandran D., Henriksen K.J.,
RA Smith C.E., Tong J., Clay B.S., Miller S.D., Sperling A.I.;
RT "CD43 regulates Th2 differentiation and inflammation.";
RL J. Immunol. 180:7385-7393(2008).
RN [10]
RP FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND SUMOYLATION.
RX PubMed=19696198; DOI=10.1182/blood-2009-06-228791;
RA Seo W., Ziltener H.J.;
RT "CD43 processing and nuclear translocation of CD43 cytoplasmic tail are
RT required for cell homeostasis.";
RL Blood 114:3567-3577(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-339; SER-343; SER-347;
RP SER-371 AND THR-378, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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).
RN [12]
RP FUNCTION, PHOSPHORYLATION AT SER-347, MUTAGENESIS OF SER-347 AND
RP 276-LYS--ARG-278, SUBCELLULAR LOCATION, AND INTERACTION WITH EZR.
RX PubMed=21289089; DOI=10.1091/mbc.e10-07-0586;
RA Cannon J.L., Mody P.D., Blaine K.M., Chen E.J., Nelson A.D., Sayles L.J.,
RA Moore T.V., Clay B.S., Dulin N.O., Shilling R.A., Burkhardt J.K.,
RA Sperling A.I.;
RT "CD43 interaction with ezrin-radixin-moesin (ERM) proteins regulates T-cell
RT trafficking and CD43 phosphorylation.";
RL Mol. Biol. Cell 22:954-963(2011).
RN [13]
RP FUNCTION.
RX PubMed=26700769; DOI=10.4049/jimmunol.1501171;
RA Velazquez F., Grodecki-Pena A., Knapp A., Salvador A.M., Nevers T.,
RA Croce K., Alcaide P.;
RT "CD43 functions as an E-selectin ligand for Th17 cells in vitro and is
RT required for rolling on the vascular endothelium and Th17 cell recruitment
RT during inflammation in vivo.";
RL J. Immunol. 196:1305-1316(2016).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 272-291 IN COMPLEX WITH RDX,
RP SUBUNIT, AND MUTAGENESIS OF ARG-278; THR-279; LEU-282 AND LEU-284.
RX PubMed=18614175; DOI=10.1016/j.jmb.2008.05.085;
RA Takai Y., Kitano K., Terawaki S., Maesaki R., Hakoshima T.;
RT "Structural basis of the cytoplasmic tail of adhesion molecule CD43 and its
RT binding to ERM proteins.";
RL J. Mol. Biol. 381:634-644(2008).
CC -!- FUNCTION: Predominant cell surface sialoprotein of leukocytes which
CC regulates multiple T-cell functions, including T-cell activation,
CC proliferation, differentiation, trafficking and migration. Positively
CC regulates T-cell trafficking to lymph-nodes via its association with
CC ERM proteins (EZR, RDX and MSN) (PubMed:17638845, PubMed:21289089,
CC PubMed:11728336). Negatively regulates Th2 cell differentiation and
CC predisposes the differentiation of T-cells towards a Th1 lineage
CC commitment (PubMed:18490738). Promotes the expression of IFN-gamma by
CC T-cells during T-cell receptor (TCR) activation of naive cells and
CC induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser
CC extent by CD8(+) T-cells. Plays a role in preparing T-cells for
CC cytokine sensing and differentiation into effector cells by inducing
CC the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR
CC and IL4R signaling and by mediating the clustering of IFNGR with TCR
CC (By similarity). Acts as a major E-selectin ligand responsible for Th17
CC cell rolling on activated vasculature and recruitment during
CC inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-
CC selectin (PubMed:26700769). Acts as a T-cell counter-receptor for
CC SIGLEC1 (PubMed:11238599). {ECO:0000250|UniProtKB:P16150,
CC ECO:0000269|PubMed:11238599, ECO:0000269|PubMed:11728336,
CC ECO:0000269|PubMed:17638845, ECO:0000269|PubMed:18490738,
CC ECO:0000269|PubMed:21289089, ECO:0000269|PubMed:26700769}.
CC -!- FUNCTION: [CD43 cytoplasmic tail]: Protects cells from apoptotic
CC signals, promoting cell survival. {ECO:0000269|PubMed:19696198}.
CC -!- SUBUNIT: Interacts with SIGLEC1. {ECO:0000269|PubMed:11238599}.
CC -!- SUBUNIT: [CD43 cytoplasmic tail]: Interacts with isoform 2 of HIPK2
CC (PubMed:11078605). Interacts with CTNNB1 (By similarity). Interacts
CC with RDX (via FERM domain) (PubMed:18614175). Interacts with EZR
CC (PubMed:21289089). Interacts with MSN (By similarity) (PubMed:18614175,
CC PubMed:21289089). {ECO:0000250|UniProtKB:P13838,
CC ECO:0000250|UniProtKB:P16150, ECO:0000269|PubMed:11078605,
CC ECO:0000269|PubMed:18614175, ECO:0000269|PubMed:21289089}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type I
CC membrane protein {ECO:0000255}. Cell projection, microvillus
CC {ECO:0000250|UniProtKB:P13838}. Cell projection, uropodium
CC {ECO:0000269|PubMed:21289089}. Note=Localizes to the uropodium and
CC microvilli via its interaction with ERM proteins (EZR, RDX and MSN).
CC {ECO:0000250|UniProtKB:P13838, ECO:0000269|PubMed:21289089}.
CC -!- SUBCELLULAR LOCATION: [CD43 cytoplasmic tail]: Nucleus
CC {ECO:0000269|PubMed:19696198}. Nucleus, PML body
CC {ECO:0000269|PubMed:19696198}. Note=The sumoylated form localizes to
CC the PML body. {ECO:0000269|PubMed:19696198}.
CC -!- TISSUE SPECIFICITY: Cell surface of thymocytes, T-lymphocytes,
CC neutrophils, plasma cells and myelomas.
CC -!- PTM: Phosphorylation at Ser-347 is regulated by chemokines, requires
CC its association with ERM proteins (EZR, RDX and MSN) and is essential
CC for its function in the regulation of T-cell trafficking to lymph
CC nodes. {ECO:0000269|PubMed:17638845, ECO:0000269|PubMed:21289089}.
CC -!- PTM: Has a high content of sialic acid and O-linked carbohydrate
CC structures.
CC -!- PTM: Cleavage by CTSG releases its extracellular domain and triggers
CC its intramembrane proteolysis by gamma-secretase releasing the CD43
CC cytoplasmic tail chain (CD43-ct) which translocates to the nucleus.
CC {ECO:0000269|PubMed:19696198}.
CC -!- PTM: [CD43 cytoplasmic tail]: Sumoylated.
CC {ECO:0000269|PubMed:19696198}.
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DR EMBL; X17018; CAA34884.1; -; Genomic_DNA.
DR EMBL; X52609; CAA36840.1; -; Genomic_DNA.
DR EMBL; S70677; AAB30765.1; -; mRNA.
DR EMBL; M30693; AAA39457.1; -; mRNA.
DR CCDS; CCDS21858.1; -.
DR PIR; A43545; A43545.
DR RefSeq; NP_001032899.1; NM_001037810.2.
DR RefSeq; NP_033285.1; NM_009259.5.
DR RefSeq; XP_006507585.1; XM_006507522.3.
DR PDB; 2EMS; X-ray; 2.90 A; B=272-291.
DR PDBsum; 2EMS; -.
DR AlphaFoldDB; P15702; -.
DR SMR; P15702; -.
DR STRING; 10090.ENSMUSP00000049534; -.
DR GlyGen; P15702; 1 site.
DR iPTMnet; P15702; -.
DR PhosphoSitePlus; P15702; -.
DR EPD; P15702; -.
DR jPOST; P15702; -.
DR PaxDb; P15702; -.
DR PeptideAtlas; P15702; -.
DR PRIDE; P15702; -.
DR ProteomicsDB; 265062; -.
DR Antibodypedia; 3627; 2231 antibodies from 46 providers.
DR DNASU; 20737; -.
DR Ensembl; ENSMUST00000049931; ENSMUSP00000049534; ENSMUSG00000051457.
DR Ensembl; ENSMUST00000143713; ENSMUSP00000122787; ENSMUSG00000051457.
DR GeneID; 20737; -.
DR KEGG; mmu:20737; -.
DR UCSC; uc009juh.2; mouse.
DR CTD; 6693; -.
DR MGI; MGI:98384; Spn.
DR VEuPathDB; HostDB:ENSMUSG00000051457; -.
DR eggNOG; ENOG502SBHY; Eukaryota.
DR GeneTree; ENSGT00390000017626; -.
DR HOGENOM; CLU_038831_0_1_1; -.
DR InParanoid; P15702; -.
DR OMA; GVSVMKP; -.
DR OrthoDB; 1178463at2759; -.
DR PhylomeDB; P15702; -.
DR TreeFam; TF337688; -.
DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-MMU-210991; Basigin interactions.
DR BioGRID-ORCS; 20737; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Spn; mouse.
DR EvolutionaryTrace; P15702; -.
DR PRO; PR:P15702; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P15702; protein.
DR Bgee; ENSMUSG00000051457; Expressed in ectoplacental cone and 157 other tissues.
DR ExpressionAtlas; P15702; baseline and differential.
DR Genevisible; P15702; MM.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0032154; C:cleavage furrow; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0001931; C:uropod; IDA:UniProtKB.
DR GO; GO:0031072; F:heat shock protein binding; IPI:CAFA.
DR GO; GO:0030544; F:Hsp70 protein binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IMP:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:MGI.
DR GO; GO:0050868; P:negative regulation of T cell activation; IMP:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:UniProtKB.
DR GO; GO:0001808; P:negative regulation of type IV hypersensitivity; IMP:MGI.
DR GO; GO:0045060; P:negative thymic T cell selection; IMP:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:2000406; P:positive regulation of T cell migration; IMP:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IGI:MGI.
DR GO; GO:0050688; P:regulation of defense response to virus; IMP:MGI.
DR GO; GO:0050776; P:regulation of immune response; IMP:MGI.
DR GO; GO:2000404; P:regulation of T cell migration; IMP:UniProtKB.
DR GO; GO:0001562; P:response to protozoan; IDA:MGI.
DR GO; GO:0031295; P:T cell costimulation; IDA:MGI.
DR GO; GO:0042098; P:T cell proliferation; IDA:MGI.
DR GO; GO:0002296; P:T-helper 1 cell lineage commitment; ISS:UniProtKB.
DR IDEAL; IID50200; -.
DR InterPro; IPR038829; Leukosialin.
DR PANTHER; PTHR35265; PTHR35265; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell projection; Direct protein sequencing; Glycoprotein;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..19
FT CHAIN 20..395
FT /note="Leukosialin"
FT /id="PRO_0000021589"
FT CHAIN 272..395
FT /note="CD43 cytoplasmic tail"
FT /evidence="ECO:0000305|PubMed:19696198"
FT /id="PRO_0000443407"
FT TOPO_DOM 20..248
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 27..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..302
FT /note="Required for interaction with EZR, MSN and RDX and
FT for co-localization to microvilli"
FT /evidence="ECO:0000250|UniProtKB:P13838"
FT REGION 303..395
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..290
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT COMPBIAS 27..117
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 142..245
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..343
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT MOD_RES 333
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17638845,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 347
FT /note="Phosphoserine; by PKC/PRKCQ"
FT /evidence="ECO:0000269|PubMed:21289089,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 378
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 276..278
FT /note="KRR->NGG: Loss of phosphorylation, interaction with
FT EZR and localization to the uropodium."
FT /evidence="ECO:0000269|PubMed:21289089"
FT MUTAGEN 278
FT /note="R->A: Significant reduction in interaction with
FT RDX."
FT /evidence="ECO:0000269|PubMed:18614175"
FT MUTAGEN 279
FT /note="T->A: No effect on its interaction with RDX."
FT /evidence="ECO:0000269|PubMed:18614175"
FT MUTAGEN 282
FT /note="L->A: Significant reduction in interaction with
FT RDX."
FT /evidence="ECO:0000269|PubMed:18614175"
FT MUTAGEN 284
FT /note="L->A: Significant reduction in interaction with
FT RDX."
FT /evidence="ECO:0000269|PubMed:18614175"
FT MUTAGEN 343
FT /note="S->A: Reduced phosphorylation. Significant loss of
FT phosphorylation; when associated with A-347."
FT /evidence="ECO:0000269|PubMed:17638845"
FT MUTAGEN 347
FT /note="S->A: Reduced phosphorylation. Significant loss of
FT phosphorylation; when associated with A-343."
FT /evidence="ECO:0000269|PubMed:17638845,
FT ECO:0000269|PubMed:21289089"
FT MUTAGEN 347
FT /note="S->D: No loss of phosphorylation or localization to
FT the uropodium. Loss of interaction with EZR."
FT /evidence="ECO:0000269|PubMed:21289089"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:2EMS"
FT TURN 285..288
FT /evidence="ECO:0007829|PDB:2EMS"
SQ SEQUENCE 395 AA; 40038 MW; 369F201B04DBC055 CRC64;
MALHLLLLFG ACWVQVASPD SLQRTTMLPS TPHITAPSTS EAQNASPSVS VGSGTVDSKE
TISPWGQTTI PVSLTPLETT ELSSLETSAG ASMSTPVPEP TASQEVSSKT SALLPEPSNV
ASDPPVTAAN PVTDGPAANP VTDGTAASTS ISKGTSAPPT TVTTSSNETS GPSVATTVSS
KTSGPPVTTA TGSLGPSSEM HGLPATTATS SVESSSVARG TSVSSRKTST TSTQDPITTR
SPSQESSGML LVPMLIALVV VLALVALLLL WRQRQKRRTG ALTLSGGGKR NGVVDAWAGP
ARVPDEEATT TSGAGGNKGS EVLETEGSGQ RPTLTTFFSR RKSRQGSLVL EELKPGSGPN
LKGEEEPLVG SEDEAVETPT SDGPQAKDEA APQSL
