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CD4 molecule
250px Crystallographic structure of the V-set and C2 domains of human CD4.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1CDH, 1CDI, 1CDJ, 1CDU, 1CDY, 1G9M, 1G9N, 1GC1, 1JL4, 1Q68, 1RZJ, 1RZK, 1WBR, 1WIO, 1WIP, 1WIQ, 2B4C, 2JKR, 2JKT, 2KLU, 2NXY, 2NXZ, 2NY0, 2NY1, 2NY2, 2NY3, 2NY4, 2NY5, 2NY6, 2QAD, 3B71, 3CD4, 3JWD, 3JWO, 3LQA, 3O2D, 3S4S, 3S5L, 3T0E
Identifiers
Symbols	CD4; CD4mut
External IDs	OMIM: 186940 MGI: 88335 HomoloGene: 513 ChEMBL: 2754 GeneCards: CD4 Gene
Gene Ontology Molecular function • glycoprotein binding • receptor activity • transmembrane signaling receptor activity • extracellular matrix structural constituent • protein binding • zinc ion binding • coreceptor activity • enzyme binding • protein kinase binding • MHC class II protein binding • protein homodimerization activity Cellular component • early endosome • endoplasmic reticulum lumen • endoplasmic reticulum membrane • plasma membrane • plasma membrane • external side of plasma membrane • integral to membrane • T cell receptor complex • membrane raft Biological process • cytokine production • induction by virus of host cell-cell fusion • immune response • cell adhesion • signal transduction • cell surface receptor signaling pathway • enzyme linked receptor protein signaling pathway • transmembrane receptor protein tyrosine kinase signaling pathway • viral reproduction • initiation of viral infection • T cell differentiation • entry into host cell • T cell costimulation • maintenance of protein location in cell • interspecies interaction between organisms • T cell selection • positive regulation of interleukin-2 biosynthetic process • innate immune response • protein palmitoleylation • positive regulation of protein kinase activity • regulation of defense response to virus by virus • positive regulation of peptidyl-tyrosine phosphorylation • positive regulation of calcium-mediated signaling • T cell receptor signaling pathway • regulation of T cell activation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	920	12504
Ensembl	ENSG00000010610	ENSMUSG00000023274
UniProt	P01730	P06332
RefSeq (mRNA)	NM_000616.4	NM_013488.2
RefSeq (protein)	NP_000607.1	NP_038516.1
Location (UCSC)	Chr 12: 6.9 – 6.93 Mb	Chr 6: 124.81 – 124.84 Mb
PubMed search	[1]	[2]
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CD4, extracellular

structure of t-cell surface glycoprotein cd4, monoclinic crystal form
Identifiers
Symbol	CD4-extracel
Pfam	PF09191
InterPro	IPR015274
SCOP	1cid
SUPERFAMILY	1cid
OPM superfamily	230
OPM protein	2klu
CDD	cd07695
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

CD4 (cluster of differentiation 4) is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named CD4 in 1984.^[2] In humans, the CD4 protein is encoded by the CD4 gene.^[3][4]

Structure[link]

Schematic representation of CD4 receptor.

Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily.

It has four immunoglobulin domains (D₁ to D₄) that are exposed on the extracellular surface of the cell:

• D₁ and D₃ resemble immunoglobulin variable (IgV) domains.
• D₂ and D₄ resemble immunoglobulin constant (IgC) domains.

CD4 uses its D₁ domain to interact with the β₂-domain of MHC class II molecules. T cells expressing CD4 molecules (and not CD8) on their surface, therefore, are specific for antigens presented by MHC II and not by MHC class I (they are MHC class II-restricted).

The short cytoplasmic/intracellular tail (C) of CD4 contains a special sequence of amino acids that allow it to interact with the lck molecule described above.

Function[link]

CD4 is a co-receptor that assists the T cell receptor (TCR) with an antigen-presenting cell. Using its portion that resides inside the T cell, CD4 amplifies the signal generated by the TCR by recruiting an enzyme, known as the tyrosine kinase lck, which is essential for activating many molecules involved in the signaling cascade of an activated T cell. CD4 also interacts directly with MHC class II molecules on the surface of the antigen-presenting cell using its extracellular domain. The extracellular domain adopts an immunoglobulin-like beta-sandwich with seven strands in 2 beta sheets, in a Greek key topology.^[5]

Other Interactions[link]

CD4 has also been shown to interact with SPG21,^[6] Lck^{[7][8][9][10][11]} and Protein unc-119 homolog.^[12]

Disease[link]

HIV infection[link]

HIV-1 uses CD4 to gain entry into host T-cells and achieves this by binding of the viral envelope protein known as gp120 to CD4.^[13] The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host cell. These co-receptors are chemokine receptors CCR5 or CXCR4, which of these co-receptor is used during infection is dependent on whether the virus is infecting a macrophage or T-helper cell^{[citation needed]}. Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane.

HIV pathology[link]

HIV infection leads to a progressive reduction in the number of T cells expressing CD4. Medical professionals refer to the CD4 count to decide when to begin treatment during HIV infection. Normal blood values are 500-1200x10⁶/L.^[14] CD4 count test measures the number of T cells expressing CD4. Results are usually expressed in the number of cells per microliter (or cubic millimeter, mm³) of blood. While CD4 tests are not a direct HIV test e.g. does not check the presence of viral DNA, or specific antibodies against HIV, the CD4 count is used to assess the immune system of patients. Patients often undergo treatments when the CD4 count reach a level of 350 cells per microliter; less than 200 cells per microliter in an HIV positive individual is diagnosed as AIDS. Medical professionals also refer to CD4 tests to determine efficacy of treatment.

Reference ranges for blood tests of white blood cells, comparing CD4+ cell amount (shown in green-yellow) with other cells.

Other diseases[link]

CD4 continues to be expressed in most neoplasms derived from T helper cells. It is therefore possible to use CD4 immunohistochemistry on tissue biopsy samples to identify most forms of peripheral T cell lymphoma and related malignant conditions.^[15] The antigen has also been associated with a number of autoimmune diseases such as vitiligo and type I diabetes mellitus.^[16]

References[link]

Further reading[link]

External links[link]

• CD1+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• Mouse CD Antigen Chart
• Human CD Antigen Chart
• *Human Immunodeficiency Virus Glycoprotein 120

v t e PDB gallery 1cdh: STRUCTURES OF AN HIV AND MHC BINDING FRAGMENT FROM HUMAN CD4 AS REFINED IN TWO CRYSTAL LATTICES   1cdi: STRUCTURES OF AN HIV AND MHC BINDING FRAGMENT FROM HUMAN CD4 AS REFINED IN TWO CRYSTAL LATTICES   1cdj: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4   1cdu: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH PHE 43 REPLACED BY VAL   1cdy: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4 MUTANT WITH GLY 47 REPLACED BY SER   1g9m: HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1g9n: HIV-1 YU2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1gc1: HIV-1 GP120 CORE COMPLEXED WITH CD4 AND A NEUTRALIZING HUMAN ANTIBODY   1jl4: CRYSTAL STRUCTURE OF THE HUMAN CD4 N-TERMINAL TWO DOMAIN FRAGMENT COMPLEXED TO A CLASS II MHC MOLECULE   1q68: Solution structure of T-cell surface glycoprotein CD4 and Proto-oncogene tyrosine-protein kinase LCK fragments   1rzj: HIV-1 HXBC2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1rzk: HIV-1 YU2 GP120 ENVELOPE GLYCOPROTEIN COMPLEXED WITH CD4 AND INDUCED NEUTRALIZING ANTIBODY 17B   1wio: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4, TETRAGONAL CRYSTAL FORM   1wip: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4, MONOCLINIC CRYSTAL FORM   1wiq: STRUCTURE OF T-CELL SURFACE GLYCOPROTEIN CD4, TRIGONAL CRYSTAL FORM   2b4c: Crystal structure of HIV-1 JR-FL gp120 core protein containing the third variable region (V3) complexed with CD4 and the X5 antibody   2nxy: HIV-1 gp120 Envelope Glycoprotein(S334A) Complexed with CD4 and Antibody 17b   2nxz: HIV-1 gp120 Envelope Glycoprotein (T257S, S334A, S375W) Complexed with CD4 and Antibody 17b   2ny0: HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, T257S, V275C, S334A, S375W, A433M) Complexed with CD4 and Antibody 17b   2ny1: HIV-1 gp120 Envelope Glycoprotein (I109C, T257S, S334A, S375W, Q428C) Complexed with CD4 and Antibody 17b   2ny2: HIV-1 gp120 Envelope Glycoprotein (T123C, T257S, S334A, S375W, G431C) Complexed with CD4 and Antibody 17b   2ny3: HIV-1 gp120 Envelope Glycoprotein (K231C, T257S, E267C, S334A, S375W) Complexed with CD4 and Antibody 17b   2ny4: HIV-1 gp120 Envelope Glycoprotein (K231C, T257S, E268C, S334A, S375W) Complexed with CD4 and Antibody 17b   2ny5: HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, I109C, T257S, V275C, S334A, S375W, Q428C, A433M) Complexed with CD4 and Antibody 17b   2ny6: HIV-1 gp120 Envelope Glycoprotein (M95W, W96C, I109C, T123C, T257S, V275C,S334A, S375W, Q428C, G431C) Complexed with CD4 and Antibody 17b   3cd4: REFINEMENT AND ANALYSIS OF THE FIRST TWO DOMAINS OF HUMAN CD4

This article incorporates text from the public domain Pfam and InterPro IPR015274

Craig David
Craig David, 2009
Background information
Birth name	Craig Ashley David
Born	(1981-05-05) 5 May 1981 (age 31) Southampton, Hampshire, England
Genres	R&B, UK garage, hip hop, dance
Occupations	Singer-songwriter, MC
Years active	1999–present
Labels	Universal (2009–2010) Warner / Atlantic (1999–2009) Sire (1999–2009)
Website	craigdavid.com

Craig Ashley David (born 5 May 1981) is an English singer and songwriter.^[1] He has released five studio albums: Born to Do It, Slicker Than Your Average, The Story Goes..., Trust Me, Signed Sealed Delivered and a Greatest Hits album. Craig David has sold over 13 million albums worldwide.

Early life[link]

David was born in Southampton, Hampshire,^[2] the son of Tina (née Loftus), a retail assistant at Superdrug, and George David, a carpenter,^[3][4] and grew up in the Holyrood estate.^[5] David's father is Grenadian and David's mother is English and related to the founders of the Accurist watch-making company; David's maternal grandfather was an Orthodox Jew and his maternal grandmother a convert to Judaism.^[6] David's parents separated when he was eight and he was raised by his mother.^[7] He attended Bellemoor School and Southampton City College.

David's father played bass in a reggae band called Ebony Rockers. As a teen, David began accompanying his father to local dance clubs, where DJs let him take the microphone.

Career[link]

David's earliest exposure came when he worked on a b-side to British group Damage's cover of "Wonderful Tonight". He then started doing vocals for a few tracks with garage act Artful Dodger.

Wildstar Records first became aware of Craig David when the artist's then manager Paul Widger met the label's co-owner Colin Lester and played some of his music.^[8] Lester later told HitQuarters that he was particularly impressed by the first song he heard, "Walking Away", saying "That was an absolute stand out ... It struck me that any seventeen year-old that could write a song like this had huge potential."^[8] The Wildstar boss was further won over when, on later visiting the artist's home in Southampton, he found that David's tiny bedroom stacked from floor to ceiling with 12" vinyl records, commenting: "That convinced me he was the real deal and not just some kid acting out the part."^[8] At that point Lester offered him a development deal with his label. When Lester later heard the song "7 Days", he said he immediately heard a #1 record and promoted the contract to an album deal the same day.^[8]

The song "Re-Rewind", from the Artful Dodger album It's All About the Stragglers, hit Number 2 on the UK charts in 1999; thus, paving the way for a solo career. David's first single, "Fill Me In", released on Colin Lester's and Ian McAndrew's Wildstar Records, made him the youngest solo male artist ever to reach Number 1 in the United Kingdom (he was 18 years old at the time). This was the first of a string of four Top 10 singles from his debut album Born To Do It, which eventually sold more than seven million units worldwide, earning multi-platinum status in more than 20 countries.^[9][10] The song "Key To My Heart", taken from the US version of the album, was also featured on the award-winning Warner Brothers animated film Osmosis Jones.#

[edit] 2000–2001: Born to Do It

The success of David's debut, which was written almost entirely by David and Mark Hill of Artful Dodger, led to the United States release of "Fill Me In" in May 2001. It reached Number 15 on the Billboard Hot 100. Born to Do It was released in the United States on 17 July 2001, peaking at Number 11 on the Billboard 200 and sold over one million copies. The single "7 Days" hit the Top 10 in the U.S.; although "Walking Away", which had reached Number 3 in the UK and Number 5 in Australia, missed the Top 40 in the U.S. and was the last of his singles to chart there.

In April 2009, MTV viewers voted Born To Do It as Number 2 on their "Greatest Album of All-Time" poll, behind Michael Jackson's Thriller.^[11]

[edit] 2002–2003: Slicker Than Your Average

The follow-up album, Slicker Than Your Average, was released in 2002. The albums' first four singles continued his streak of Top 10 hits in the UK, bringing a total of nine consecutive Top 10 hits until "World Filled with Love" peaked at Number 15 in 2003. None of the six singles released from the album charted in the U.S.. Although "What's Your Flava?" and "Rise & Fall" (duet with Sting) received airplay on the Urban Contemporary and Soft AC formats, they did not make the Hot R&B/Hip-Hop Singles Tracks chart or the Adult Contemporary chart. However, "What's Your Flava?" made the Rhythmic Top 40 (Number 32), Top 40 Mainstream (Number 24) and the Top 40 Tracks (Number 37). According to the RIAA Slicker Than Your Average reached Gold Status in the USA.

David also commented that the album title could be looked at in two different ways: "On the one hand, it's coming across like I'm arrogant. On the other hand, it's saying I have a lot more composure on the album." "^[12]

The album was leaked onto the internet prior to its official release but David was not too bothered as he feels it "spreads the word".

[edit] 2005–2006: The Story Goes...

David later signed on with Warner Music and put together his third album, The Story Goes..., which was released worldwide in August 2005 (excluding the U.S. where it was never released). The first single, "All The Way", returned him to the Top 3. The second single, "Don't Love You No More (I'm Sorry)", tied with "7 Days" as his longest running single in the charts since "Re-Rewind", spending 15 weeks inside the UK Top 75. The album's third single, "Unbelievable", debuted at Number 18 in March 2006.

[edit] 2007–2008: Trust Me

In 2007, David collaborated with UK rapper Kano on his album London Town, for the single "This is the Girl". The track was released on 27 August 2007 and debuted at Number 18 on the UK charts.

The first single "Hot Stuff" from his album Trust Me, was released on 5 November 2007 . The single was a top ten hit, whilst the album charted at Number 18 on the UK Albums Chart. "6 of 1 Thing", the second single to be taken from Trust Me, charted at number 39 on the UK Singles Chart, becoming his third-lowest charting single to date.