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Protein

T-cell surface glycoprotein CD4

Gene

CD4

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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 similarity

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cell adhesion Source: InterPro
  • T cell differentiation Source: UniProtKB
  • T cell selection Source: UniProtKB

Keywordsi

Biological processAdaptive immunity, Immunity

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD4
Alternative name(s):
T-cell surface antigen T4/Leu-3
CD_antigen: CD4
Gene namesi
Name:CD4
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

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 domaini25 – 401ExtracellularSequence analysisAdd BLAST377
Transmembranei402 – 423HelicalSequence analysisAdd BLAST22
Topological domaini424 – 463CytoplasmicSequence analysisAdd BLAST40

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001461925 – 463T-cell surface glycoprotein CD4Add BLAST439

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi41 ↔ 109PROSITE-ProRule annotation
Glycosylationi123N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi168N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi176N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi324N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi329N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi332 ↔ 374PROSITE-ProRule annotation
Glycosylationi389N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi424S-palmitoyl cysteineBy similarity1
Lipidationi427S-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.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Expressioni

Tissue specificityi

Expressed in macrophages and a subset of T lymphocytes.1 Publication

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

Structurei

3D structure databases

ProteinModelPortaliP33705.
SMRiP33705.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 124Ig-like V-typeAdd BLAST99
Domaini125 – 211Ig-like C2-type 1Add BLAST87
Domaini212 – 321Ig-like C2-type 2Add BLAST110
Domaini322 – 378Ig-like C2-type 3Add BLAST57

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

HOGENOMiHOG000008696.
HOVERGENiHBG005281.
InParanoidiP33705.
KOiK06454.

Family and domain databases

Gene3Di2.60.40.10. 3 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. 4 hits.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P33705-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNQEAAFRHL LLMLQLVMLP AVTPVREVVL GKAGDAVELP CQTSQKKNIH
60 70 80 90 100
FNWRDSSMVQ ILGNQGSFWT VGSSRLKHRV ESKKNLWDQG SFPLVIKDLE
110 120 130 140 150
VADSGIYFCD TDKRQEVELL VFNLTAKWDS GSSSGSSNIR LLQGQQLTLT
160 170 180 190 200
LENPSGSSPS VQWKGPGNKS KHGGQNLSLS WPELQDGGTW TCIISQSQKT
210 220 230 240 250
VEFNINVLVL AFQKVSNTFY AREGDQVEFS FPLSFEDENL VGELRWQAQG
260 270 280 290 300
ASSSLLWISF TLENRKLSMK EAHAPLKLQM KESLPLRFTL PQVLSRYAGS
310 320 330 340 350
GILTLNLAKG TLYQEVNLVV MRANSSQNNL TCEVLGPTSP ELTLSLNLKE
360 370 380 390 400
QAAKVSKQQK LVWVVDPEGG TWQCLLSDKD KVLLASSLNV SSPVVIKSWP
410 420 430 440 450
KFLAITLGGI LGLLLLIGLC VFCCVKCWRR RRQAERMSQI KRLLSEKKTC
460
QCSHRIQKTC SLI
Length:463
Mass (Da):51,640
Last modified:February 1, 1994 - v1
Checksum:i95805170CB44A833
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X68565 mRNA. No translation available.
L06130 mRNA. Translation: AAB02295.1.
RefSeqiNP_001003252.1. NM_001003252.1.
UniGeneiCfa.3673.

Genome annotation databases

GeneIDi403931.
KEGGicfa:403931.

Similar proteinsi

Entry informationi

Entry nameiCD4_CANLF
AccessioniPrimary (citable) accession number: P33705
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: October 25, 2017
This is version 119 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, Reference proteome