dbPTM

CD4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CD4_HUMAN
UniProt AC	P01730
Protein Name	T-cell surface glycoprotein CD4
Gene Name	CD4
Organism	Homo sapiens (Human).
Sequence Length	458
Subcellular Localization	Cell membrane Single-pass type I membrane protein . Localizes to lipid rafts (PubMed:12517957, PubMed:9168119). Removed from plasma membrane by HIV-1 Nef protein that increases clathrin-dependent endocytosis of this antigen to target it to lysosoma
Protein Description	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.; (Microbial infection) Primary receptor for human immunodeficiency virus-1 (HIV-1). [PubMed: 2214026]
Protein Sequence	MNRGVPFRHLLLVLQLALLPAATQGKKVVLGKKGDTVELTCTASQKKSIQFHWKNSNQIKILGNQGSFLTKGPSKLNDRADSRRSLWDQGNFPLIIKNLKIEDSDTYICEVEDQKEEVQLLVFGLTANSDTHLLQGQSLTLTLESPPGSSPSVQCRSPRGKNIQGGKTLSVSQLELQDSGTWTCTVLQNQKKVEFKIDIVVLAFQKASSIVYKKEGEQVEFSFPLAFTVEKLTGSGELWWQAERASSSKSWITFDLKNKEVSVKRVTQDPKLQMGKKLPLHLTLPQALPQYAGSGNLTLALEAKTGKLHQEVNLVVMRATQLQKNLTCEVWGPTSPKLMLSLKLENKEAKVSKREKAVWVLNPEAGMWQCLLSDSGQVLLESNIKVLPTWSTPVQPMALIVLGGVAGLLLFIGLGIFFCVRCRHRRRQAERMSQIKRLLSEKKTCQCPHRFQKTCSPI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
67	Phosphorylation	KILGNQGSFLTKGPS EEECCCCCCCCCCCC	13.81	23401153
70	Phosphorylation	GNQGSFLTKGPSKLN CCCCCCCCCCCCCCC	31.76	26074081
74	Phosphorylation	SFLTKGPSKLNDRAD CCCCCCCCCCCCCHH	59.45	22617229
296	N-linked_Glycosylation	PQYAGSGNLTLALEA CCCCCCCCEEEEEEE	31.39	UniProtKB CARBOHYD
325	N-linked_Glycosylation	RATQLQKNLTCEVWG EHHHHHHCCEEEEEC	27.85	2592374
419	S-palmitoylation	IGLGIFFCVRCRHRR HHHHHHHHHHHHHHH	1.00	12517957
422	S-palmitoylation	GIFFCVRCRHRRRQA HHHHHHHHHHHHHHH	1.83	12517957
433	Phosphorylation	RRQAERMSQIKRLLS HHHHHHHHHHHHHHH	34.67	22817900
436	Ubiquitination	AERMSQIKRLLSEKK HHHHHHHHHHHHHCC	29.38	-
440	Phosphorylation	SQIKRLLSEKKTCQC HHHHHHHHHCCCCCC	52.54	22817900
453	Ubiquitination	QCPHRFQKTCSPI-- CCCCCCCCCCCCC--	49.11	-
456	Phosphorylation	HRFQKTCSPI----- CCCCCCCCCC-----	30.75	9168119

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
433	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
440	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	MARCHF4	Q9P2E8	PMID:14722266
-	K	Ubiquitination	E3 ubiquitin ligase	MARCHF1	Q8TCQ1	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	MARCHF9	Q86YJ5	PMID:17174307
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:11893391
-	K	Ubiquitination	E3 ubiquitin ligase	MARCHF11	A6NNE9	PMID:17604280
-	K	Ubiquitination	E3 ubiquitin ligase	5L	Q9DHV7	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
433	S	Phosphorylation		2105883
Phosphorylated by PKC; phosphorylation at Ser-433 plays an important role for CD4 internalization.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of CD4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
U119A_HUMAN	UNC119	physical	14757743
SPG21_HUMAN	SPG21	physical	11113139
PIP_HUMAN	PIP	physical	10820003
CCR5_HUMAN	CCR5	physical	10816381
CXCR4_HUMAN	CXCR4	physical	10816381
LCK_HUMAN	LCK	physical	12007789
IL16_HUMAN	IL16	physical	7910967
CD81_HUMAN	CD81	physical	7636191
CD82_HUMAN	CD82	physical	7636191
LCK_HUMAN	LCK	physical	11854499
KSYK_HUMAN	SYK	physical	7539035
ZAP70_HUMAN	ZAP70	physical	7539035
EPS15_HUMAN	EPS15	physical	16497223
ENV_HV1H2	env	physical	2076345
ENV_HV1H2	env	physical	1605591
NEF_HV1H2	nef	physical	20179761
NEF_HV1H2	nef	physical	8599760
LPPRC_HUMAN	LRPPRC	physical	15047060
EIF3C_HUMAN	EIF3C	physical	15047060
TNPO1_HUMAN	TNPO1	physical	15047060
IMB1_HUMAN	KPNB1	physical	15047060
EIF3B_HUMAN	EIF3B	physical	15047060
HS90A_HUMAN	HSP90AA1	physical	15047060
NEP_HUMAN	MME	physical	15047060
HS90B_HUMAN	HSP90AB1	physical	15047060
SSRP1_HUMAN	SSRP1	physical	15047060
ANXA6_HUMAN	ANXA6	physical	15047060
NUCL_HUMAN	NCL	physical	15047060
DDX3X_HUMAN	DDX3X	physical	15047060
HSP7C_HUMAN	HSPA8	physical	15047060
DDX5_HUMAN	DDX5	physical	15047060
SYFB_HUMAN	FARSB	physical	15047060
EIF3D_HUMAN	EIF3D	physical	15047060
CH60_HUMAN	HSPD1	physical	15047060
LCK_HUMAN	LCK	physical	15047060
ATPA_HUMAN	ATP5A1	physical	15047060
CD4_HUMAN	CD4	physical	15047060
VIME_HUMAN	VIM	physical	15047060
TBB5_HUMAN	TUBB	physical	15047060
HNRH1_HUMAN	HNRNPH1	physical	15047060
ENOA_HUMAN	ENO1	physical	15047060
IF4A2_HUMAN	EIF4A2	physical	15047060
GNAI2_HUMAN	GNAI2	physical	15047060
ANXA1_HUMAN	ANXA1	physical	15047060
ROA1_HUMAN	HNRNPA1	physical	15047060
ANXA2_HUMAN	ANXA2	physical	15047060
HNRPD_HUMAN	HNRNPD	physical	15047060
VDAC2_HUMAN	VDAC2	physical	15047060
ROA2_HUMAN	HNRNPA2B1	physical	15047060
EIF3I_HUMAN	EIF3I	physical	15047060
G3P_HUMAN	GAPDH	physical	15047060
RLA0_HUMAN	RPLP0	physical	15047060
RSSA_HUMAN	RPSA	physical	15047060
NPM_HUMAN	NPM1	physical	15047060
VDAC1_HUMAN	VDAC1	physical	15047060
VDAC3_HUMAN	VDAC3	physical	15047060
PHB_HUMAN	PHB	physical	15047060
RL7_HUMAN	RPL7	physical	15047060
DHRS2_HUMAN	DHRS2	physical	15047060
EF1B_HUMAN	EEF1B2	physical	15047060
RS9_HUMAN	RPS9	physical	15047060
RL18_HUMAN	RPL18	physical	15047060
ML12A_HUMAN	MYL12A	physical	15047060
RS10_HUMAN	RPS10	physical	15047060
RS19_HUMAN	RPS19	physical	15047060
RL22_HUMAN	RPL22	physical	15047060
RS12_HUMAN	RPS12	physical	15047060
RLA1_HUMAN	RPLP1	physical	15047060
CHIP_HUMAN	STUB1	physical	20974815
GCR_HUMAN	NR3C1	physical	16888650
LCK_HUMAN	LCK	physical	16888650
ENV_HV1H2	env	physical	2461565
HGS_HUMAN	HGS	physical	17686993
TERA_HUMAN	VCP	physical	22090097
UBL7_HUMAN	UBL7	physical	21988832
SHIP2_HUMAN	INPPL1	physical	21988832
RANB9_HUMAN	RANBP9	physical	14722085
ENV_HV1H2	env	physical	24156545
SIVA_HUMAN	SIVA1	physical	17653867
LCK_HUMAN	LCK	physical	17653867
K319L_HUMAN	KIAA0319L	physical	28514442
POGZ_HUMAN	POGZ	physical	28514442
TMM11_HUMAN	TMEM11	physical	28514442
VPP2_HUMAN	ATP6V0A2	physical	28514442
CC85C_HUMAN	CCDC85C	physical	28514442
ARV1_HUMAN	ARV1	physical	28514442
VAMP3_HUMAN	VAMP3	physical	28514442
VPP1_HUMAN	ATP6V0A1	physical	28514442
EI2BG_HUMAN	EIF2B3	physical	28514442
SAAL1_HUMAN	SAAL1	physical	28514442
CD320_HUMAN	CD320	physical	28514442
EI2BD_HUMAN	EIF2B4	physical	28514442

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D03420	Cedelizumab (USAN/INN)
D05610	Priliximab (USAN/INN)
D06356	Zanolimumab (USAN/INN)
D09575	Ibalizumab (USAN/INN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of CD4_HUMAN

Related Literatures of Post-Translational Modification

N-linked Glycosylation
Reference	PubMed
"Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry."; Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; J. Proteome Res. 8:651-661(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-296, AND MASSSPECTROMETRY.	19159218 [Abstract]
Palmitoylation
Reference	PubMed
"Identification of palmitoylation sites on CD4, the humanimmunodeficiency virus receptor."; Crise B., Rose J.K.; J. Biol. Chem. 267:13593-13597(1992). Cited for: PALMITOYLATION AT CYS-419 AND CYS-422.	1618861 [Abstract]

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