LEUK_RAT
ID LEUK_RAT Reviewed; 378 AA.
AC P13838;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Leukosialin;
DE AltName: Full=Leukocyte sialoglycoprotein;
DE AltName: Full=Sialophorin;
DE AltName: Full=W3/13 antigen;
DE AltName: CD_antigen=CD43;
DE Contains:
DE RecName: Full=CD43 cytoplasmic tail;
DE Short=CD43-ct;
DE Short=CD43ct;
DE Flags: Precursor; Fragment;
GN Name=Spn;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thymocyte;
RX PubMed=2965006; DOI=10.1002/j.1460-2075.1987.tb02747.x;
RA Killeen N., Barclay A.N., Willis A.C., Williams A.F.;
RT "The sequence of rat leukosialin (W3/13 antigen) reveals a molecule with O-
RT linked glycosylation of one third of its extracellular amino acids.";
RL EMBO J. 6:4029-4034(1987).
RN [2]
RP INTERACTION WITH EZR; MSN AND RDX, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 259-LYS--ARG-261.
RX PubMed=9472040; DOI=10.1083/jcb.140.4.885;
RA Yonemura S., Hirao M., Doi Y., Takahashi N., Kondo T., Tsukita S.,
RA Tsukita S.;
RT "Ezrin/radixin/moesin (ERM) proteins bind to a positively charged amino
RT acid cluster in the juxta-membrane cytoplasmic domain of CD44, CD43, and
RT ICAM-2.";
RL J. Cell Biol. 140:885-895(1998).
RN [3]
RP 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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-276; SER-326; SER-330;
RP SER-354 AND THR-361, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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). Negatively regulates Th2 cell
CC differentiation and predisposes the differentiation of T-cells towards
CC a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-
CC 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 Acts as a major E-selectin ligand responsible for Th17 cell rolling on
CC activated vasculature and recruitment during inflammation. Mediates
CC Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell
CC counter-receptor for SIGLEC1. {ECO:0000250|UniProtKB:P15702,
CC ECO:0000250|UniProtKB:P16150}.
CC -!- FUNCTION: [CD43 cytoplasmic tail]: Protects cells from apoptotic
CC signals, promoting cell survival. {ECO:0000250|UniProtKB:P15702}.
CC -!- SUBUNIT: Interacts with SIGLEC1. {ECO:0000269|PubMed:11238599}.
CC -!- SUBUNIT: [CD43 cytoplasmic tail]: Monomer (By similarity). Interacts
CC with CTNNB1 (By similarity). Interacts with EZR, MSN and RDX (via FERM
CC domain) (PubMed:9472040). {ECO:0000250|UniProtKB:P15702,
CC ECO:0000250|UniProtKB:P16150, ECO:0000269|PubMed:9472040}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type I
CC membrane protein {ECO:0000255}. Cell projection, microvillus
CC {ECO:0000269|PubMed:9472040}. Cell projection, uropodium
CC {ECO:0000250|UniProtKB:P15702}. Note=Localizes to the uropodium and
CC microvilli via its interaction with ERM proteins (EZR, RDX and MSN).
CC {ECO:0000250|UniProtKB:P15702, ECO:0000269|PubMed:9472040}.
CC -!- SUBCELLULAR LOCATION: [CD43 cytoplasmic tail]: Nucleus
CC {ECO:0000250|UniProtKB:P15702}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:P15702}. Note=The sumoylated form localizes to
CC the PML body. {ECO:0000250|UniProtKB:P15702}.
CC -!- TISSUE SPECIFICITY: Cell surface of thymocytes, T-lymphocytes,
CC neutrophils, plasma cells and myelomas.
CC -!- PTM: Has a high content of sialic acid and O-linked carbohydrate
CC structures.
CC -!- PTM: Phosphorylation at Ser-330 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:0000250|UniProtKB:P15702}.
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:0000250|UniProtKB:P15702}.
CC -!- PTM: [CD43 cytoplasmic tail]: Sumoylated.
CC {ECO:0000250|UniProtKB:P15702}.
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DR EMBL; Y00090; CAA68281.1; -; mRNA.
DR PIR; S00842; S00842.
DR AlphaFoldDB; P13838; -.
DR SMR; P13838; -.
DR STRING; 10116.ENSRNOP00000051894; -.
DR GlyGen; P13838; 26 sites.
DR iPTMnet; P13838; -.
DR PhosphoSitePlus; P13838; -.
DR PaxDb; P13838; -.
DR PRIDE; P13838; -.
DR UCSC; RGD:3750; rat.
DR RGD; 3750; Spn.
DR eggNOG; ENOG502SBHY; Eukaryota.
DR InParanoid; P13838; -.
DR PhylomeDB; P13838; -.
DR TreeFam; TF337688; -.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-210991; Basigin interactions.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005604; C:basement membrane; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0032154; C:cleavage furrow; IDA:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005902; C:microvillus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0001931; C:uropod; ISS:UniProtKB.
DR GO; GO:0031072; F:heat shock protein binding; ISO:RGD.
DR GO; GO:0030544; F:Hsp70 protein binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:0002544; P:chronic inflammatory response; IEP:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR GO; GO:0050901; P:leukocyte tethering or rolling; ISS:UniProtKB.
DR GO; GO:0042117; P:monocyte activation; IEP:RGD.
DR GO; GO:0007162; P:negative regulation of cell adhesion; ISO:RGD.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISO:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0001808; P:negative regulation of type IV hypersensitivity; ISO:RGD.
DR GO; GO:0045060; P:negative thymic T cell selection; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0050688; P:regulation of defense response to virus; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; IGI:ARUK-UCL.
DR GO; GO:0050776; P:regulation of immune response; ISO:RGD.
DR GO; GO:2000404; P:regulation of T cell migration; ISS:UniProtKB.
DR GO; GO:0001562; P:response to protozoan; ISO:RGD.
DR GO; GO:0031295; P:T cell costimulation; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0002296; P:T-helper 1 cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0071594; P:thymocyte aggregation; IMP:RGD.
DR InterPro; IPR038829; Leukosialin.
DR PANTHER; PTHR35265; PTHR35265; 1.
PE 1: Evidence at protein level;
KW Cell projection; Glycoprotein; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL <1..7
FT CHAIN 8..378
FT /note="Leukosialin"
FT /id="PRO_0000021590"
FT CHAIN 255..378
FT /note="CD43 cytoplasmic tail"
FT /evidence="ECO:0000250|UniProtKB:P15702"
FT /id="PRO_0000443408"
FT TOPO_DOM 8..231
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 13..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 255..285
FT /note="Required for interaction with EZR, MSN and RDX and
FT for co-localization to microvilli"
FT /evidence="ECO:0000269|PubMed:9472040"
FT REGION 265..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 259..273
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT COMPBIAS 293..326
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT MOD_RES 276
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT MOD_RES 316
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16150"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15702"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 330
FT /note="Phosphoserine; by PKC/PRKCQ"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 361
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 13
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 15
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 20
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 23
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 25
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 27
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 28
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 29
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 33
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 34
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 36
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 37
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 40
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 108
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 113
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 118
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 120
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 124
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 125
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 126
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 174
FT /note="O-linked (GalNAc...) threonine"
FT CARBOHYD 176
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 180
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 183
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="O-linked (GalNAc...) serine"
FT CARBOHYD 189
FT /note="O-linked (GalNAc...) threonine"
FT MUTAGEN 259..261
FT /note="KRR->NGG: Loss of interaction with EZR, MSN and RDX
FT and co-localization to microvilli."
FT /evidence="ECO:0000269|PubMed:9472040"
FT NON_TER 1
SQ SEQUENCE 378 AA; 38426 MW; 231CC80E8A8A257C CRC64;
WAQVVSQENL PNTMTMLPFT PNSESPSTSE ALSTYSSIAT VPVTEDPKES ISPWGQTTAP
ASSIPLGTPE LSSFFFTSAG ASGNTPVPEL TTSQEVSTEA SLVLFPKSSG VASDPPVTIT
NPATSSAVAS TSLETFKGTS APPVTVTSST MTSGPFVATT VSSETSGPPV TMATGSLGPS
KETHGLSATI ATSSGESSSV AGGTPVFSTK ISTTSTPNPI TTVPPRPGSS GMLLVSMLIA
LTVVLVLVAL LLLWRQRQKR RTGALTLSRG GKRNGTVDAW AGPARVPDEE ATTASGSGGN
KSSGAPETDG SGQRPTLTTF FSRRKSRQGS VALEELKPGT GPNLKGEEEP LVGSEDEAVE
TPTSDGPQAK DGAAPQSL
