Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

T-cell surface glycoprotein CD4

Gene

CD4

Organism
Homo sapiens (Human)
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.3 Publications
(Microbial infection) Primary receptor for human immunodeficiency virus-1 (HIV-1) (PubMed:2214026, PubMed:16331979, PubMed:9641677, PubMed:12089508). Down-regulated by HIV-1 Vpu (PubMed:17346169). Acts as a receptor for Human Herpes virus 7/HHV-7 (PubMed:7909607).6 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Receptor
Biological processAdaptive immunity, Host-virus interaction, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-1462054 Alpha-defensins
R-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-173107 Binding and entry of HIV virion
R-HSA-180534 Vpu mediated degradation of CD4
R-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-389948 PD-1 signaling
R-HSA-449836 Other interleukin signaling
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiP01730
SIGNORiP01730

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000010610.9
HGNCiHGNC:1678 CD4
MIMi186940 gene
neXtProtiNX_P01730

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 domaini26 – 396ExtracellularSequence analysisAdd BLAST371
Transmembranei397 – 418HelicalSequence analysisAdd BLAST22
Topological domaini419 – 458CytoplasmicSequence analysisAdd BLAST40

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi432M → T: No effect. 1 Publication1
Mutagenesisi433S → A: About 75% loss of internalization. 1 Publication1
Mutagenesisi433S → A: No effect. 1 Publication1
Mutagenesisi438 – 439LL → AA: Loss of Nef-induced CD4 down-modulation. 1 Publication2
Mutagenesisi440S → L: No effect. 1 Publication1
Mutagenesisi445C → A: Loss of homodimerization; when associated with A-447. 1 Publication1
Mutagenesisi447C → A: Loss of homodimerization; when associated with A-445. 1 Publication1
Mutagenesisi457 – 458Missing : Abolished interaction with SPG21 and induced T-cell activation. 1 Publication2

Organism-specific databases

DisGeNETi920
MalaCardsiCD4
MIMi613949 phenotype
OpenTargetsiENSG00000010610
PharmGKBiPA26220

Chemistry databases

ChEMBLiCHEMBL2754
DrugBankiDB00098 Anti-thymocyte Globulin (Rabbit)

Polymorphism and mutation databases

BioMutaiCD4
DMDMi116013

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 252 PublicationsAdd BLAST25
ChainiPRO_000001462126 – 458T-cell surface glycoprotein CD4Add BLAST433

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi41 ↔ 109PROSITE-ProRule annotation1 Publication
Disulfide bondi155 ↔ 184PROSITE-ProRule annotation1 Publication
GlycosylationiCAR_000053296N-linked (GlcNAc...) asparagine3 Publications1
GlycosylationiCAR_000054325N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi328 ↔ 370PROSITE-ProRule annotation1 Publication
Lipidationi419S-palmitoyl cysteine1 Publication1
Lipidationi422S-palmitoyl cysteine1 Publication1
Modified residuei433Phosphoserine1 Publication1
Modified residuei440Phosphoserine1 Publication1
Modified residuei456Phosphoserine1 Publication1

Post-translational modificationi

Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.1 Publication
Phosphorylated by PKC; phosphorylation at Ser-433 plays an important role for CD4 internalization.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiP01730
PaxDbiP01730
PeptideAtlasiP01730
PRIDEiP01730
ProteomicsDBi51451

PTM databases

GlyConnecti587
iPTMnetiP01730
PhosphoSitePlusiP01730
SwissPalmiP01730
UniCarbKBiP01730

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.3 Publications

Gene expression databases

BgeeiENSG00000010610 Expressed in 189 organ(s), highest expression level in leukocyte
CleanExiHS_CD4
ExpressionAtlasiP01730 baseline and differential
GenevisibleiP01730 HS

Organism-specific databases

HPAiCAB000011
CAB068180
HPA004252
HPA004472

Interactioni

Subunit structurei

Forms disulfide-linked homo-dimers at the cell surface. Interacts with LCK (PubMed:16888650). Interacts with PTK2/FAK1. Binds to P4HB/PDI. Interacts with IL16; this interaction induces a CD4-dependent signaling in lymphocytes.5 Publications
(Microbial infection) Interacts with HIV-1 Envelope polyprotein gp160 and protein Vpu (PubMed:2214026, PubMed:16331979, PubMed:9641677).3 Publications
(Microbial infection) Interacts with Human Herpes virus 7 surface proteins.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107358, 94 interactors
DIPiDIP-617N
ELMiP01730
IntActiP01730, 21 interactors
MINTiP01730
STRINGi9606.ENSP00000011653

Chemistry databases

BindingDBiP01730

Structurei

Secondary structure

1458
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00123
ProteinModelPortaliP01730
SMRiP01730
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01730

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 125Ig-like V-typeAdd BLAST100
Domaini126 – 203Ig-like C2-type 1Add BLAST78
Domaini204 – 317Ig-like C2-type 2Add BLAST114
Domaini318 – 374Ig-like C2-type 3Add BLAST57

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni427 – 455HIV-1 Vpu-susceptibility domainAdd BLAST29

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IK9F Eukaryota
ENOG410YWI4 LUCA
GeneTreeiENSGT00390000001745
HOGENOMiHOG000008696
HOVERGENiHBG005281
InParanoidiP01730
KOiK06454
OMAiCEVWGPT
OrthoDBiEOG091G0AZL
PhylomeDBiP01730
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
IPR003598 Ig_sub2
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
SM00408 IGc2, 2 hits
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 4 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P01730-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNRGVPFRHL LLVLQLALLP AATQGKKVVL GKKGDTVELT CTASQKKSIQ
60 70 80 90 100
FHWKNSNQIK ILGNQGSFLT KGPSKLNDRA DSRRSLWDQG NFPLIIKNLK
110 120 130 140 150
IEDSDTYICE VEDQKEEVQL LVFGLTANSD THLLQGQSLT LTLESPPGSS
160 170 180 190 200
PSVQCRSPRG KNIQGGKTLS VSQLELQDSG TWTCTVLQNQ KKVEFKIDIV
210 220 230 240 250
VLAFQKASSI VYKKEGEQVE FSFPLAFTVE KLTGSGELWW QAERASSSKS
260 270 280 290 300
WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA
310 320 330 340 350
LEAKTGKLHQ EVNLVVMRAT QLQKNLTCEV WGPTSPKLML SLKLENKEAK
360 370 380 390 400
VSKREKAVWV LNPEAGMWQC LLSDSGQVLL ESNIKVLPTW STPVQPMALI
410 420 430 440 450
VLGGVAGLLL FIGLGIFFCV RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR

FQKTCSPI
Length:458
Mass (Da):51,111
Last modified:November 1, 1988 - v1
Checksum:i20ED893F9E56D236
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5GYA9F5GYA9_HUMAN
T-cell surface glycoprotein CD4
CD4
45Annotation score:
F5H480F5H480_HUMAN
T-cell surface glycoprotein CD4
CD4
148Annotation score:

Polymorphismi

The OKT monoclonal antibodies are widely used for the analysis of human peripheral blood T-lymphocytes. OKT4 reacts with T-helper/inducer lymphocytes. The OKT4 epitope of the CD4 cell-surface protein is polymorphic in white, black, and Japanese populations. The variable phenotypic expression is due a CD4 polymorphism. OKT4 positive individuals carry Arg-265 and OKT4 negative individuals carry Trp-265 [MIMi:613949].2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023459191K → E1 PublicationCorresponds to variant dbSNP:rs28917504Ensembl.1
Natural variantiVAR_023460227F → S1 PublicationCorresponds to variant dbSNP:rs11064419Ensembl.1
Natural variantiVAR_003906265R → W in OKT4-negative populations. 3 PublicationsCorresponds to variant dbSNP:rs28919570EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12807 mRNA Translation: AAA35572.1
U47924 Genomic DNA Translation: AAB51309.1
M35160 mRNA Translation: AAA16069.1
BT019791 mRNA Translation: AAV38594.1
BT019811 mRNA Translation: AAV38614.1
DQ012936 Genomic DNA Translation: AAY22175.1
AK312828 mRNA Translation: BAG35684.1
CH471116 Genomic DNA Translation: EAW88738.1
CH471116 Genomic DNA Translation: EAW88739.1
BC025782 mRNA Translation: AAH25782.1
CCDSiCCDS8562.1
PIRiA90872 RWHUT4
RefSeqiNP_000607.1, NM_000616.4
UniGeneiHs.631659

Genome annotation databases

EnsembliENST00000011653; ENSP00000011653; ENSG00000010610
GeneIDi920
KEGGihsa:920
UCSCiuc001qqv.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

CD4 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12807 mRNA Translation: AAA35572.1
U47924 Genomic DNA Translation: AAB51309.1
M35160 mRNA Translation: AAA16069.1
BT019791 mRNA Translation: AAV38594.1
BT019811 mRNA Translation: AAV38614.1
DQ012936 Genomic DNA Translation: AAY22175.1
AK312828 mRNA Translation: BAG35684.1
CH471116 Genomic DNA Translation: EAW88738.1
CH471116 Genomic DNA Translation: EAW88739.1
BC025782 mRNA Translation: AAH25782.1
CCDSiCCDS8562.1
PIRiA90872 RWHUT4
RefSeqiNP_000607.1, NM_000616.4
UniGeneiHs.631659

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CDHX-ray2.30A26-203[»]
1CDIX-ray2.90A26-203[»]
1CDJX-ray2.50A26-203[»]
1CDUX-ray2.70A26-203[»]
1CDYX-ray2.00A26-203[»]
1G9MX-ray2.20C26-208[»]
1G9NX-ray2.90C26-208[»]
1GC1X-ray2.50C26-206[»]
1JL4X-ray4.30D26-203[»]
1OPNmodel-C26-206[»]
1OPTmodel-C26-206[»]
1OPWmodel-C26-206[»]
1Q68NMR-A421-458[»]
1RZJX-ray2.20C26-208[»]
1RZKX-ray2.90C26-208[»]
1WBRNMR-A428-444[»]
1WIOX-ray3.90A/B26-388[»]
1WIPX-ray4.00A/B26-388[»]
1WIQX-ray5.00A/B26-388[»]
2B4CX-ray3.30C26-206[»]
2JKRX-ray2.98P/Q431-441[»]
2JKTX-ray3.40P/Q435-441[»]
2KLUNMR-A397-458[»]
2NXYX-ray2.00B26-208[»]
2NXZX-ray2.04B26-208[»]
2NY0X-ray2.20B26-208[»]
2NY1X-ray1.99B26-208[»]
2NY2X-ray2.00B26-208[»]
2NY3X-ray2.00B26-208[»]
2NY4X-ray2.00B26-208[»]
2NY5X-ray2.50C26-208[»]
2NY6X-ray2.80B26-208[»]
2QADX-ray3.30B/F26-206[»]
3B71X-ray2.82D/E/F428-450[»]
3CD4X-ray2.20A26-207[»]
3J70electron microscopy-C/O/T26-208[»]
3JCBelectron microscopy-D26-200[»]
3JCCelectron microscopy-D26-200[»]
3JWDX-ray2.61C/D26-208[»]
3JWOX-ray3.51C26-208[»]
3LQAX-ray3.40C26-207[»]
3O2DX-ray2.19A26-207[»]
3S4SX-ray2.40G/H26-203[»]
3S5LX-ray2.10G/H26-203[»]
3T0EX-ray4.00E26-388[»]
4H8WX-ray1.85C26-208[»]
4JM2X-ray3.10F26-208[»]
4P9HX-ray3.00C26-207[»]
4Q6IX-ray3.65C/I/J/K1-208[»]
4R2GX-ray3.28B/F/H/L26-208[»]
4R4HX-ray4.28B26-203[»]
4RQSX-ray4.49B26-208[»]
5A7Xelectron microscopy17.00B/F/J26-206[»]
5A8Helectron microscopy23.00B/H/N26-208[»]
5CAYX-ray3.00B26-208[»]
5THRelectron microscopy8.90G/H/I26-207[»]
5U1Felectron microscopy6.80M26-388[»]
5VN3electron microscopy3.70C/E/F26-208[»]
DisProtiDP00123
ProteinModelPortaliP01730
SMRiP01730
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107358, 94 interactors
DIPiDIP-617N
ELMiP01730
IntActiP01730, 21 interactors
MINTiP01730
STRINGi9606.ENSP00000011653

Chemistry databases

BindingDBiP01730
ChEMBLiCHEMBL2754
DrugBankiDB00098 Anti-thymocyte Globulin (Rabbit)

PTM databases

GlyConnecti587
iPTMnetiP01730
PhosphoSitePlusiP01730
SwissPalmiP01730
UniCarbKBiP01730

Polymorphism and mutation databases

BioMutaiCD4
DMDMi116013

Proteomic databases

MaxQBiP01730
PaxDbiP01730
PeptideAtlasiP01730
PRIDEiP01730
ProteomicsDBi51451

Protocols and materials databases

DNASUi920
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000011653; ENSP00000011653; ENSG00000010610
GeneIDi920
KEGGihsa:920
UCSCiuc001qqv.3 human

Organism-specific databases

CTDi920
DisGeNETi920
EuPathDBiHostDB:ENSG00000010610.9
GeneCardsiCD4
HGNCiHGNC:1678 CD4
HPAiCAB000011
CAB068180
HPA004252
HPA004472
MalaCardsiCD4
MIMi186940 gene
613949 phenotype
neXtProtiNX_P01730
OpenTargetsiENSG00000010610
PharmGKBiPA26220
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IK9F Eukaryota
ENOG410YWI4 LUCA
GeneTreeiENSGT00390000001745
HOGENOMiHOG000008696
HOVERGENiHBG005281
InParanoidiP01730
KOiK06454
OMAiCEVWGPT
OrthoDBiEOG091G0AZL
PhylomeDBiP01730
TreeFamiTF335974

Enzyme and pathway databases

ReactomeiR-HSA-1462054 Alpha-defensins
R-HSA-167590 Nef Mediated CD4 Down-regulation
R-HSA-173107 Binding and entry of HIV virion
R-HSA-180534 Vpu mediated degradation of CD4
R-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-389948 PD-1 signaling
R-HSA-449836 Other interleukin signaling
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiP01730
SIGNORiP01730

Miscellaneous databases

ChiTaRSiCD4 human
EvolutionaryTraceiP01730
GeneWikiiCD4
GenomeRNAii920
PROiPR:P01730
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000010610 Expressed in 189 organ(s), highest expression level in leukocyte
CleanExiHS_CD4
ExpressionAtlasiP01730 baseline and differential
GenevisibleiP01730 HS

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
IPR003598 Ig_sub2
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
SM00408 IGc2, 2 hits
SM00406 IGv, 1 hit
SUPFAMiSSF48726 SSF48726, 4 hits
PROSITEiView protein in PROSITE
PS50835 IG_LIKE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCD4_HUMAN
AccessioniPrimary (citable) accession number: P01730
Secondary accession number(s): B2R737
, D3DUS5, Q4ZGK2, Q5U066, Q9UDE5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: November 1, 1988
Last modified: November 7, 2018
This is version 217 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  6. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again