CD4_CANLF
ID CD4_CANLF Reviewed; 463 AA.
AC P33705;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=T-cell surface glycoprotein CD4;
DE AltName: Full=T-cell surface antigen T4/Leu-3;
DE AltName: CD_antigen=CD4;
DE Flags: Precursor;
GN Name=CD4;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Beagle; TISSUE=Thymus;
RX PubMed=8091416; DOI=10.1111/j.1399-0039.1994.tb02320.x;
RA Gorman S.D., Frewin M.R., Cobbold S.P., Waldmann H.;
RT "Isolation and expression of cDNA encoding the canine CD4 and CD8 alpha
RT antigens.";
RL Tissue Antigens 43:184-188(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-463.
RC STRAIN=Beagle; TISSUE=Thymus;
RX PubMed=7916632; DOI=10.1016/0167-4781(93)90220-8;
RA Milde K.F., Conner G.E., Minz D.H., Alejandro R.;
RT "Primary structure of the canine CD4 antigen.";
RL Biochim. Biophys. Acta 1172:315-318(1993).
CC -!- FUNCTION: Integral membrane glycoprotein that plays an essential role
CC in the immune response and serves multiple functions in responses
CC against both external and internal offenses. In T-cells, functions
CC primarily as a coreceptor for MHC class II molecule:peptide complex.
CC The antigens presented by class II peptides are derived from
CC extracellular proteins while class I peptides are derived from
CC cytosolic proteins. Interacts simultaneously with the T-cell receptor
CC (TCR) and the MHC class II presented by antigen presenting cells
CC (APCs). In turn, recruits the Src kinase LCK to the vicinity of the
CC TCR-CD3 complex. LCK then initiates different intracellular signaling
CC pathways by phosphorylating various substrates ultimately leading to
CC lymphokine production, motility, adhesion and activation of T-helper
CC cells. In other cells such as macrophages or NK cells, plays a role in
CC differentiation/activation, cytokine expression and cell migration in a
CC TCR/LCK-independent pathway. Participates in the development of T-
CC helper cells in the thymus and triggers the differentiation of
CC monocytes into functional mature macrophages.
CC {ECO:0000250|UniProtKB:P01730}.
CC -!- SUBUNIT: Forms disulfide-linked homodimers at the cell surface.
CC Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI.
CC Interacts with IL16; this interaction induces a CD4-dependent signaling
CC in lymphocytes. Interacts (via Ig-like V-type domain) with MHCII alpha
CC chain (via alpha-2 domain) and beta chain (via beta-2 domain); this
CC interaction increases the affinity of TCR for peptide-MHCII. CD4
CC oligomerization via Ig-like C2-type 2 and 3 domains appears to be
CC required for stable binding to MHCII and adhesion between T cells and
CC APCs. {ECO:0000250|UniProtKB:P01730}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01730};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P01730}.
CC Note=Localizes to lipid rafts. {ECO:0000250|UniProtKB:P01730}.
CC -!- TISSUE SPECIFICITY: Expressed in macrophages and a subset of T
CC lymphocytes. {ECO:0000269|PubMed:8091416}.
CC -!- DOMAIN: The Ig-like V-type domain mediates the interaction with MHCII.
CC {ECO:0000250|UniProtKB:P01730}.
CC -!- PTM: Palmitoylation and association with LCK contribute to the
CC enrichment of CD4 in lipid rafts. {ECO:0000250|UniProtKB:P01730}.
CC -!- PTM: Phosphorylated by PKC; phosphorylation plays an important role for
CC CD4 internalization. {ECO:0000250|UniProtKB:P01730}.
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DR EMBL; X68565; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L06130; AAB02295.1; -; mRNA.
DR RefSeq; NP_001003252.1; NM_001003252.1.
DR AlphaFoldDB; P33705; -.
DR SMR; P33705; -.
DR STRING; 9615.ENSCAFP00000063394; -.
DR PRIDE; P33705; -.
DR Ensembl; ENSCAFT00000077975; ENSCAFP00000063394; ENSCAFG00000041713.
DR Ensembl; ENSCAFT00030040954; ENSCAFP00030035742; ENSCAFG00030022291.
DR Ensembl; ENSCAFT00040044806; ENSCAFP00040039142; ENSCAFG00040024046.
DR Ensembl; ENSCAFT00845048936; ENSCAFP00845038388; ENSCAFG00845027739.
DR GeneID; 403931; -.
DR KEGG; cfa:403931; -.
DR CTD; 920; -.
DR VEuPathDB; HostDB:ENSCAFG00845027739; -.
DR GeneTree; ENSGT00390000001745; -.
DR InParanoid; P33705; -.
DR OrthoDB; 652984at2759; -.
DR Proteomes; UP000002254; Chromosome 27.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro.
DR GO; GO:0042011; F:interleukin-16 binding; IEA:Ensembl.
DR GO; GO:0042012; F:interleukin-16 receptor activity; IEA:Ensembl.
DR GO; GO:0042289; F:MHC class II protein binding; IBA:GO_Central.
DR GO; GO:0023026; F:MHC class II protein complex binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:1990782; F:protein tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:InterPro.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IEA:Ensembl.
DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl.
DR GO; GO:0032507; P:maintenance of protein location in cell; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0050863; P:regulation of T cell activation; IEA:Ensembl.
DR GO; GO:0042110; P:T cell activation; IBA:GO_Central.
DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR GO; GO:0045058; P:T cell selection; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR000973; CD4.
DR InterPro; IPR015274; CD4-extracel.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR008424; Ig_C2-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR021963; Tcell_CD4_Cterm.
DR PANTHER; PTHR11422:SF0; PTHR11422:SF0; 1.
DR Pfam; PF05790; C2-set; 2.
DR Pfam; PF09191; CD4-extracel; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF12104; Tcell_CD4_C; 1.
DR PRINTS; PR00692; CD4TCANTIGEN.
DR SMART; SM00409; IG; 3.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 2: Evidence at transcript level;
KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..463
FT /note="T-cell surface glycoprotein CD4"
FT /id="PRO_0000014619"
FT TOPO_DOM 25..401
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 402..423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..463
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..124
FT /note="Ig-like V-type"
FT DOMAIN 125..211
FT /note="Ig-like C2-type 1"
FT DOMAIN 212..321
FT /note="Ig-like C2-type 2"
FT DOMAIN 322..378
FT /note="Ig-like C2-type 3"
FT REGION 153..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01730"
FT LIPID 424
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 427
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 332..374
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 463 AA; 51640 MW; 95805170CB44A833 CRC64;
MNQEAAFRHL LLMLQLVMLP AVTPVREVVL GKAGDAVELP CQTSQKKNIH FNWRDSSMVQ
ILGNQGSFWT VGSSRLKHRV ESKKNLWDQG SFPLVIKDLE VADSGIYFCD TDKRQEVELL
VFNLTAKWDS GSSSGSSNIR LLQGQQLTLT LENPSGSSPS VQWKGPGNKS KHGGQNLSLS
WPELQDGGTW TCIISQSQKT VEFNINVLVL AFQKVSNTFY AREGDQVEFS FPLSFEDENL
VGELRWQAQG ASSSLLWISF TLENRKLSMK EAHAPLKLQM KESLPLRFTL PQVLSRYAGS
GILTLNLAKG TLYQEVNLVV MRANSSQNNL TCEVLGPTSP ELTLSLNLKE QAAKVSKQQK
LVWVVDPEGG TWQCLLSDKD KVLLASSLNV SSPVVIKSWP KFLAITLGGI LGLLLLIGLC
VFCCVKCWRR RRQAERMSQI KRLLSEKKTC QCSHRIQKTC SLI
