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Protein

T-cell surface glycoprotein CD4

Gene

Cd4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages.By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-MMU-202424 Downstream TCR signaling
R-MMU-202427 Phosphorylation of CD3 and TCR zeta chains
R-MMU-202430 Translocation of ZAP-70 to Immunological synapse
R-MMU-202433 Generation of second messenger molecules
R-MMU-389948 PD-1 signaling
R-MMU-449836 Other interleukin signaling
R-MMU-8856825 Cargo recognition for clathrin-mediated endocytosis
R-MMU-8856828 Clathrin-mediated endocytosis

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD4
Alternative name(s):
T-cell differentiation antigen L3T4
T-cell surface antigen T4/Leu-3
CD_antigen: CD4
Gene namesi
Name:Cd4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:88335 Cd4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 394ExtracellularSequence analysisAdd BLAST368
Transmembranei395 – 417HelicalSequence analysisAdd BLAST23
Topological domaini418 – 457CytoplasmicSequence analysisAdd BLAST40

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice lacking Cd4 display markedly decreased T-helper cell activity.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 261 PublicationAdd BLAST26
ChainiPRO_000001462727 – 457T-cell surface glycoprotein CD4Add BLAST431

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 112PROSITE-ProRule annotation1 Publication
Disulfide bondi159 ↔ 188PROSITE-ProRule annotation1 Publication
Glycosylationi187N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi298N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi323N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi328 ↔ 370PROSITE-ProRule annotation1 Publication
Glycosylationi392N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi418S-palmitoyl cysteineBy similarity1
Lipidationi421S-palmitoyl cysteineBy similarity1
Modified residuei432PhosphoserineBy similarity1
Modified residuei439PhosphoserineBy similarity1

Post-translational modificationi

Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.By similarity
Phosphorylated by PKC; phosphorylation plays an important role for CD4 internalization.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP06332
PRIDEiP06332

PTM databases

iPTMnetiP06332
PhosphoSitePlusiP06332

Expressioni

Tissue specificityi

Highly expressed in T-helper cells. The presence of CD4 is a hallmark of T-helper cells which are specialized in the activation and growth of cytotoxic T-cells, regulation of B cells, or activation of phagocytes. CD4 is also present in other immune cells such as macrophages, dendritic cells or NK cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000023274 Expressed in 192 organ(s), highest expression level in thymus
CleanExiMM_CD4
ExpressionAtlasiP06332 baseline and differential
GenevisibleiP06332 MM

Interactioni

Subunit structurei

Forms disulfide-linked homo-dimers at the cell surface. Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI. Interacts with IL16; this interaction induces a CD4-dependent signaling in lymphocytes.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
LckP062403EBI-1404,EBI-1401

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198599, 1 interactor
IntActiP06332, 5 interactors
MINTiP06332
STRINGi10090.ENSMUSP00000024044

Structurei

3D structure databases

ProteinModelPortaliP06332
SMRiP06332
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 128Ig-like V-typeAdd BLAST102
Domaini129 – 207Ig-like C2-type 1Add BLAST79
Domaini208 – 317Ig-like C2-type 2Add BLAST110
Domaini318 – 374Ig-like C2-type 3Add BLAST57

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IK9F Eukaryota
ENOG410YWI4 LUCA
GeneTreeiENSGT00390000001745
HOGENOMiHOG000008696
HOVERGENiHBG005281
InParanoidiP06332
KOiK06454
OMAiCEVWGPT
OrthoDBiEOG091G0AZL
PhylomeDBiP06332
TreeFamiTF335974

Family and domain databases

Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR000973 CD4
IPR015274 CD4-extracel
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR008424 Ig_C2-set
IPR003599 Ig_sub
IPR013106 Ig_V-set
IPR013151 Immunoglobulin
IPR021963 Tcell_CD4_Cterm
PANTHERiPTHR11422:SF0 PTHR11422:SF0, 1 hit
PfamiView protein in Pfam
PF05790 C2-set, 2 hits
PF09191 CD4-extracel, 1 hit
PF00047 ig, 1 hit
PF12104 Tcell_CD4_C, 1 hit
PRINTSiPR00692 CD4TCANTIGEN
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P06332-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MCRAISLRRL LLLLLQLSQL LAVTQGKTLV LGKEGESAEL PCESSQKKIT
60 70 80 90 100
VFTWKFSDQR KILGQHGKGV LIRGGSPSQF DRFDSKKGAW EKGSFPLIIN
110 120 130 140 150
KLKMEDSQTY ICELENRKEE VELWVFKVTF SPGTSLLQGQ SLTLTLDSNS
160 170 180 190 200
KVSNPLTECK HKKGKVVSGS KVLSMSNLRV QDSDFWNCTV TLDQKKNWFG
210 220 230 240 250
MTLSVLGFQS TAITAYKSEG ESAEFSFPLN FAEENGWGEL MWKAEKDSFF
260 270 280 290 300
QPWISFSIKN KEVSVQKSTK DLKLQLKETL PLTLKIPQVS LQFAGSGNLT
310 320 330 340 350
LTLDKGTLHQ EVNLVVMKVA QLNNTLTCEV MGPTSPKMRL TLKQENQEAR
360 370 380 390 400
VSEEQKVVQV VAPETGLWQC LLSEGDKVKM DSRIQVLSRG VNQTVFLACV
410 420 430 440 450
LGGSFGFLGF LGLCILCCVR CRHQQRQAAR MSQIKRLLSE KKTCQCPHRM

QKSHNLI
Length:457
Mass (Da):51,297
Last modified:January 1, 1988 - v1
Checksum:i1B1DA7527CB00F33
GO
Isoform 2 (identifier: P06332-2) [UniParc]FASTAAdd to basket
Also known as: Brain-specific

The sequence of this isoform differs from the canonical sequence as follows:
     1-240: Missing.

Show »
Length:217
Mass (Da):24,473
Checksum:i53589C44281646C5
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0024891 – 240Missing in isoform 2. CuratedAdd BLAST240

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36850 mRNA Translation: AAA39401.1
M13816 mRNA Translation: AAA37267.1
X04836 mRNA Translation: CAA28539.1
M36851 Genomic DNA Translation: AAA39402.1
M17080, M17078, M17079 Genomic DNA Translation: AAA37403.1
AC002397 Genomic DNA Translation: AAC36010.1
BC039137 mRNA Translation: AAH39137.1
CCDSiCCDS20535.1 [P06332-1]
PIRiA02110 RWMST4
RefSeqiNP_038516.1, NM_013488.2 [P06332-1]
UniGeneiMm.2209

Genome annotation databases

EnsembliENSMUST00000024044; ENSMUSP00000024044; ENSMUSG00000023274 [P06332-1]
GeneIDi12504
KEGGimmu:12504
UCSCiuc009dsi.1 mouse [P06332-1]
uc012esr.1 mouse [P06332-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36850 mRNA Translation: AAA39401.1
M13816 mRNA Translation: AAA37267.1
X04836 mRNA Translation: CAA28539.1
M36851 Genomic DNA Translation: AAA39402.1
M17080, M17078, M17079 Genomic DNA Translation: AAA37403.1
AC002397 Genomic DNA Translation: AAC36010.1
BC039137 mRNA Translation: AAH39137.1
CCDSiCCDS20535.1 [P06332-1]
PIRiA02110 RWMST4
RefSeqiNP_038516.1, NM_013488.2 [P06332-1]
UniGeneiMm.2209

3D structure databases

ProteinModelPortaliP06332
SMRiP06332
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198599, 1 interactor
IntActiP06332, 5 interactors
MINTiP06332
STRINGi10090.ENSMUSP00000024044

PTM databases

iPTMnetiP06332
PhosphoSitePlusiP06332

Proteomic databases

PaxDbiP06332
PRIDEiP06332

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024044; ENSMUSP00000024044; ENSMUSG00000023274 [P06332-1]
GeneIDi12504
KEGGimmu:12504
UCSCiuc009dsi.1 mouse [P06332-1]
uc012esr.1 mouse [P06332-2]

Organism-specific databases

CTDi920
MGIiMGI:88335 Cd4

Phylogenomic databases

eggNOGiENOG410IK9F Eukaryota
ENOG410YWI4 LUCA
GeneTreeiENSGT00390000001745
HOGENOMiHOG000008696
HOVERGENiHBG005281
InParanoidiP06332
KOiK06454
OMAiCEVWGPT
OrthoDBiEOG091G0AZL
PhylomeDBiP06332
TreeFamiTF335974

Enzyme and pathway databases

ReactomeiR-MMU-202424 Downstream TCR signaling
R-MMU-202427 Phosphorylation of CD3 and TCR zeta chains
R-MMU-202430 Translocation of ZAP-70 to Immunological synapse
R-MMU-202433 Generation of second messenger molecules
R-MMU-389948 PD-1 signaling
R-MMU-449836 Other interleukin signaling
R-MMU-8856825 Cargo recognition for clathrin-mediated endocytosis
R-MMU-8856828 Clathrin-mediated endocytosis

Miscellaneous databases

PROiPR:P06332
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023274 Expressed in 192 organ(s), highest expression level in thymus
CleanExiMM_CD4
ExpressionAtlasiP06332 baseline and differential
GenevisibleiP06332 MM

Family and domain databases

Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR000973 CD4
IPR015274 CD4-extracel
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR008424 Ig_C2-set
IPR003599 Ig_sub
IPR013106 Ig_V-set
IPR013151 Immunoglobulin
IPR021963 Tcell_CD4_Cterm
PANTHERiPTHR11422:SF0 PTHR11422:SF0, 1 hit
PfamiView protein in Pfam
PF05790 C2-set, 2 hits
PF09191 CD4-extracel, 1 hit
PF00047 ig, 1 hit
PF12104 Tcell_CD4_C, 1 hit
PRINTSiPR00692 CD4TCANTIGEN
SMARTiView protein in SMART
SM00409 IG, 3 hits
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 3 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCD4_MOUSE
AccessioniPrimary (citable) accession number: P06332
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: November 7, 2018
This is version 181 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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