NEF_HV1H2 - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NEF_HV1H2
• UniProt AC: P04601
• Protein Name: Protein Nef {ECO:0000255|HAMAP-Rule:MF_04078}
• Gene Name: nef {ECO:0000255|HAMAP-Rule:MF_04078}
• Organism: Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1).
• Sequence Length: 206
• Subcellular Localization: Host cell membrane ; Lipid-anchor ; Cytoplasmic side . Virion . Secreted . Host Golgi apparatus membrane . TGN localization requires PACS1. Associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the
• Protein Description: Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocytes function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells.; In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection). Down-regulates host SERINC3 and SERINC5 thereby excluding these proteins from the viral particles. Virion infectivity is drastically higher when SERINC3 or SERINC5 are excluded from the viral envelope, because these host antiviral proteins impare the membrane fusion event necessary for subsequent virion penetration.; Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis.; Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of Bad.; Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors..
• Protein Sequence: MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAITSSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGYFPDWQNYTPGPGVRYPLTFGWCYKLVPVEPDKIEEANKGENTSLLHPVSLHGMDDPEREVLEWRFDSRLAFHHVARELHPEYFKNC

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Myristoylation	------MGGKWSKSS ------CCCCCCHHH	46.52	-
6	Phosphorylation	--MGGKWSKSSVIGW --CCCCCCHHHCCCC	26.58	-

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

Oops, there are no upstream regulatory protein records of NEF_HV1H2 !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of NEF_HV1H2 !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of NEF_HV1H2 !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
AP1M1_HUMAN	AP1M1	physical	10814565
AP3M1_HUMAN	AP3M1	physical	10814565
HCK_HUMAN	HCK	physical	18042718
HCK_HUMAN	HCK	physical	12076760
PAK2_HUMAN	PAK2	physical	15047825
TFR1_HUMAN	TFRC	physical	15047825
SAP_HUMAN	PSAP	physical	15047825
ARF1_HUMAN	ARF1	physical	15202998
CD4_HUMAN	CD4	physical	11264384
AP2M1_HUMAN	AP2M1	physical	10814565
PSB4_HUMAN	PSMB4	physical	9344905
TNIP1_HUMAN	TNIP1	physical	9923610
GNAI2_HUMAN	GNAI2	physical	23071112
ITCH_HUMAN	ITCH	physical	23071112
HCK_HUMAN	HCK	physical	16374509
LCK_HUMAN	LCK	physical	16374509
SRC_HUMAN	SRC	physical	16374509
LYN_HUMAN	LYN	physical	16374509
YES_HUMAN	YES1	physical	16374509
FYN_HUMAN	FYN	physical	16374509
ARHG7_HUMAN	ARHGEF7	physical	16374509
ARHG6_HUMAN	ARHGEF6	physical	16374509
NCK1_HUMAN	NCK1	physical	16374509
SRBS2_HUMAN	SORBS2	physical	16374509
VINEX_HUMAN	SORBS3	physical	16374509
SRBS1_HUMAN	SORBS1	physical	16374509
SH3R3_HUMAN	SH3RF3	physical	16374509
RBX2_HUMAN	RNF7	physical	22190037
SQSTM_HUMAN	SQSTM1	physical	22190037
HCK_HUMAN	HCK	physical	21886773
TRAF2_HUMAN	TRAF2	physical	21886773
GPM6A_HUMAN	GPM6A	physical	23284715
GPM6B_HUMAN	GPM6B	physical	23284715
PEBP1_HUMAN	PEBP1	physical	23284715
P4HTM_HUMAN	P4HTM	physical	23284715
CYB5B_HUMAN	CYB5B	physical	23284715
BAP31_HUMAN	BCAP31	physical	23284715
CHIN_HUMAN	CHN1	physical	23284715
ITB1_HUMAN	ITGB1	physical	23284715
CD320_HUMAN	CD320	physical	23284715
TSN7_HUMAN	TSPAN7	physical	23284715
ARAID_HUMAN	ATRAID	physical	23284715
B4GA1_HUMAN	B4GAT1	physical	23284715
CLD10_HUMAN	CLDN10	physical	23284715
GRP75_HUMAN	HSPA9	physical	23284715
OCAD1_HUMAN	OCIAD1	physical	23284715
PMEPA_HUMAN	PMEPA1	physical	23284715
VSIG4_HUMAN	VSIG4	physical	23284715
VKORL_HUMAN	VKORC1L1	physical	23284715
AT132_HUMAN	ATP13A2	physical	23284715
VAS1_HUMAN	ATP6AP1	physical	23284715
COPT2_HUMAN	SLC31A2	physical	23284715
ACOT8_HUMAN	ACOT8	physical	22190034
NMT1_HUMAN	NMT1	physical	22190034
MTDC_HUMAN	MTHFD2	physical	22190034
ERGI1_HUMAN	ERGIC1	physical	22190034
EXOC4_HUMAN	EXOC4	physical	22190034
CDN2A_HUMAN	CDKN2A	physical	22190034
ARF_HUMAN	CDKN2A	physical	22190034
SDHA_HUMAN	SDHA	physical	22190034
MTCH1_HUMAN	MTCH1	physical	22190034
ACOT8_HUMAN	ACOT8	physical	9153233
ACOT8_HUMAN	ACOT8	physical	9299485
CXCR4_HUMAN	CXCR4	physical	24489825
TRAF2_HUMAN	TRAF2	physical	23774506
TRAF5_HUMAN	TRAF5	physical	23774506
TRAF6_HUMAN	TRAF6	physical	23774506
UBP15_HUMAN	USP15	physical	27460547

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.