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Protein

T-cell surface glycoprotein CD4

Gene

Cd4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

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.By similarity1 Publication

Gene expression databases

BgeeiENSMUSG00000023274.
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.
MINTiMINT-5024918.
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.
OMAiPEAGMWQ.
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.
IPR013783. Ig-like_fold.
IPR008424. Ig_C2-set.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR013151. Immunoglobulin.
IPR021963. Tcell_CD4_Cterm.
PANTHERiPTHR11422:SF3. PTHR11422:SF3. 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

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: September 27, 2017
This is version 173 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