Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000728
UniProt IDP61073
Primary gene name(s)CXCR4
Synonym gene name(s)unknown
Protein nameC-X-C chemokine receptor type 4
Protein functionReceptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. {ECO:0000269|PubMed:10074102, ECO:0000269|PubMed:10644702, ECO:0000269|PubMed:10825158, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:17197449, ECO:0000269|PubMed:20048153, ECO:0000269|PubMed:20228059, ECO:0000269|PubMed:20505072, ECO:0000269|PubMed:8752280, ECO:0000269|PubMed:8752281}.; FUNCTION:, Microbial infection Acts as a coreceptor, CD4 being the primary receptor for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus, PubMed:9427609, PubMed:10074122, PubMed:10756055. Binds bacterial lipopolysaccharide, LPS et mediates LPS-induced inflammatory response, including TNF secretion by monocytes, PubMed:11276205. {ECO:0000269|PubMed:10074122, ECO:0000269|PubMed:10756055, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:9427609}.
Subcellular locationCell membrane;
Multi-pass membrane protein. Cell junction. Early endosome. Late endosome. Lysosome. Note=In unstimulated cells, diffuse pattern on plasma membrane. On agonist stimulation, colocalizes with ITCH at the plasma membrane where it becomes ubiquitinated. In the presence of antigen, distributes to the immunological synapse forming at the T-cell-APC contact area, where it localizes at the peripheral and distal supramolecular activation cluster, SMAC.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P61073
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
apoptotic process [GO:0006915];
calcium-mediated signaling [GO:0019722];
cellular response to cytokine stimulus [GO:0071345];
dendritic cell chemotaxis [GO:0002407];
entry into host cell [GO:0030260];
fusion of virus membrane with host plasma membrane [GO:0019064];
G-protein coupled receptor signaling pathway [GO:0007186];
inflammatory response [GO:0006954];
myelin maintenance [GO:0043217];
positive regulation of cytosolic calcium ion concentration [GO:0007204];
positive regulation of oligodendrocyte differentiation [GO:0048714];
regulation of cell migration [GO:0030334];
regulation of chemotaxis [GO:0050920];
response to hypoxia [GO:0001666];
response to virus [GO:0009615]
Gene Ontology
(Molecular Function)
Complete annatation
actin binding [GO:0003779];
coreceptor activity [GO:0015026];
C-X-C chemokine receptor activity [GO:0016494];
drug binding [GO:0008144];
G-protein coupled receptor activity [GO:0004930];
myosin light chain binding [GO:0032027];
ubiquitin binding [GO:0043130];
ubiquitin protein ligase binding [GO:0031625];
virus receptor activity [GO:0001618]
Gene Ontology
(Cellular Component)
Complete annatation
cell junction [GO:0030054];
cell leading edge [GO:0031252];
cell surface [GO:0009986];
cytoplasm [GO:0005737];
cytoplasmic, membrane-bounded vesicle [GO:0016023];
cytoplasmic vesicle [GO:0031410];
early endosome [GO:0005769];
extracellular exosome [GO:0070062];
integral component of membrane [GO:0016021];
late endosome [GO:0005770];
lysosome [GO:0005764];
plasma membrane [GO:0005886]
Protein-protein interaction113607
Phylogenetic treeP61073
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is not observed
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.7008281339643410.06585425949569120.12499123524985
AZA vs. DISU1.102617585778710.003404278281860520.150889895597489
AZA vs. IL71.346093165125770.0002980154036296150.0336820378567591
AZA vs. SAHA0.02358361052587760.9622921225035560.990779256780515
DISU vs. CD30.3887179995996730.286759572771130.416999208947714
DISU vs. IL70.2331410723727050.356821600041810.735675740472717
DISU vs. SAHA-1.074533151691370.01048998580849550.106903380837384
DMSO vs. AZA-0.1282422731083350.7800201666988611
DMSO vs. CD3-0.8340672576701560.03176627289973850.0658174805713879
DMSO vs. DISU-1.230776944897770.00114207738893690.0685701444274068
DMSO vs. IL71.480641424669136.27452474851742e-050.00858758310347383
DMSO vs. SAHA0.146633988919480.7679353165195040.933692888384032
HIV vs. Mock in Activation0.1383009513202680.8245810176236860.999983755607037
HIV vs. Mock in Latency1.010810182924481.45576539711811e-097.31473586538615e-07
IL7 vs. CD30.648777906296660.04393360509192730.098558004100405
SAHA vs. CD3-0.6980908505366730.09545400513267670.167656393630471
SAHA vs. IL7-1.32119648890230.001529592150943950.0162602765044634
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
0.4345 0.0258

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.625567 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.981 1.484 0.719 0.324 1.93
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
209201_x_at 1.36 No downregulated in CD8+ cells
211919_s_at 1.41 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00452 Framycetin approved unknown antagonist
DB05501 AMD-070 investigational unknown unknown
DB06809 Plerixafor approved yes antagonist

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2K03 NMR - B/D=1-38.
2K04 NMR - B/D=1-38.
2K05 NMR - B/D=1-38.
2N55 NMR - B=1-38.
3ODU X-ray 2.5Å A/B=2-319.
3OE0 X-ray 2.9Å A=2-319.
3OE6 X-ray 3.2Å A=2-325.
3OE8 X-ray 3.1Å A/B/C=2-319.
3OE9 X-ray 3.1Å A/B=2-319.
4RWS X-ray 3.1Å A=2-228# A=231-319.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 induces rearrangement of 23575248
Envelope surface glycoprotein gp120 stimulates 23177198
Envelope surface glycoprotein gp120 interacts with 10758170
11698270
12857973
12960231
15710459
1618896910941932
11278567
11356952
11390601
11529558
11679153
11689632
11709091
11711617
12368322
16188969
16227248
16966601
17202224
17329448
17411375
17507467
17977968
19232661
19339951
20923564
21071054
21152581
21295814
21513481
21525208
21569409
23446039
23672855
25313689
2532217011591370
11602639
12873764
1600563812843275
15972662
16005638
16375941
2290819116524887
17010165
18288973
18775311
18808680
2477823419906780
21573951
21835796
2404800222292949
22313935
22657741
22954962
24027570
24048002
24090041
2532217024155926
24318111
24778234
25231990
25313689
25688986
25688986
8976200
9031325
9359702
9632631
9653051
9653130
9658081
9770524
10393974
10602722
10651866
11162626
11595336
11877445
12713058
12832058
12834106
12871111
12873764
12873765
12963807
14576059
14990703
15113900
15183061
15279544
15351504
15585836
15710459
15748209
15992849
16005638
16188969
16306611
17346946
18242797
19057930
19339953
19540208
19885584
20018238
20842205
21188555
21459858
22101518
23692808
257856109151868
9653051
10074122
10329539
10825158
10860877
11551942
12502809
161889699184207
9261451
9600268
9653051
10329539
10357469
10544150
10801487
11069996
11118068
11153675
11278567
12368322
12490404
15890935
16378977
16942785
17328229
17329448
17582634
17640743
18480460
18753930
18815295
19692474
20921899
20923564
21152581
21188555
21513481
21555814
21676905
21760891
21835796
21994672
22157596
22292949
22313935
22657741
22728273
22732432
22830600
22954962
23297034
23341955
23369572
23446039
23672855
23745959
23925152
24027570
24048002
24148007
24215935
24763408
252651949614108
9696823
9721247
10801487
11333905
11356952
16702010
16966601
17202224
17507467
17507486
21071054
233419559744279
Envelope surface glycoprotein gp160; precursor co-localizes with 18190699
Rev inhibits 20580677
Nef inhibits 12354773
19149577
Pr55(Gag) co-localizes with 25031337
Tat upregulates 9765440
9973525
12605695
15857508
16179731
23842123
Envelope surface glycoprotein gp120 inhibits 9601645
9653130
9658081
10393974
10446313
10651866
11333905
11413305
11414813
11551942
16784459
21188555
Envelope surface glycoprotein gp160; precursor binds 17888880
Nef modulates 18707241
Envelope surface glycoprotein gp120 modulates 18784079
Envelope surface glycoprotein gp120 relocalizes 11278278
11799176
Tat cooperates with 20661303
Nef downregulates 16928758
18438604
19149577
19449444
20465832
20594957
22103833
22103834
22175768
22537596
22980333
24489825
2527512720465832
22808111
2580704922537596
24489825
24489825
Envelope surface glycoprotein gp120 binds 10229873
10339592
10438870
10559349
10864687
1133390510623764
10704341
10942389
11141237
11462036
11602639
15327899
15719026
1745708411119612
11390582
11468147
11698270
12857973
12960231
1895862611931835
15183061
15509740
16631222
17457084
19366992
21931863
24778234
25801155
9362541
11698270
12857973
12960231
Envelope surface glycoprotein gp120 upregulates 19414793
24162774
25688986
Tat downregulates 18760839
Envelope surface glycoprotein gp120 regulated by 22479424
Envelope surface glycoprotein gp120 enhances 24778234
Envelope transmembrane glycoprotein gp41 complexes with 12871111
14505910
14694113
15047829
15258189
15308751
15479838
18500445
18977142
21760891
22732432
23043103
23043104
2523199018925934
Envelope surface glycoprotein gp120 downregulates 10438703
1134241511877445
9780207
Nef interacts with 14990729
15452229
18438604
1944944415452229
16978607
1843860423224761
Envelope transmembrane glycoprotein gp41 interacts with 11591141
18500445
18925934
2304310425231990
8629022
8640552
9710449
12871111
14505910
14640682
14694113
15161081
15258189
17959679
18468560
18500445
18991615
19540208
22226668
22297516
Envelope surface glycoprotein gp120 regulates 26083631
HIV-1 virus replication enhanced by expression of human gene 18976975
18187620
25985398
Envelope surface glycoprotein gp120 mediated by 12551992
12960231
15585836
2084220516841089
2084220517011204
17121788
20842205
Envelope surface glycoprotein gp120 induces phosphorylation of 10358157
Pr55(Gag) upregulates 18267010
Nef co-localizes with 24489825
Envelope surface glycoprotein gp120 complexes with 11069996
11162839
11533159
17331556
17507486
20018238
21264298
21760891
21994672
24119449
2447095911711593
19066282
8629022
8805353
8849450
8898753
8976200
8995603
9020356
9024623
9031325
9151868
9261451
9300725
9302439
9359702
9362541
9499113
9499115
9600268
9601645
9614108
9632631
9653051
9696823
9721247
9736741
9770524
9780207
9826718
9882290
10029247
10074122
10089882
10229873
10329539
10339592
10357469
10364484
10370370
10371171
10393974
10430052
10438870
10446313
10449282
10482576
10487781
10505675
10544150
10555208
10559349
10582593
10585143
10590105
10590121
10600606
10602722
10623764
10651866
10669334
10704341
10738970
10816381
10825158
10860877
10864687
10875613
10877489
10903911
10903920
10941932
10942389
11005830
11024154
11069996
11086073
11115360
11118068
11119612
11141237
11162626
11162839
11264367
11265761
11278278
11278567
11313374
11333905
11342415
11356952
11356967
11390582
11397808
11408611
11413305
11414813
11426226
11464139
11468147
11489906
11517394
11529558
11533159
11551942
11591141
11591370
11595336
11602639
11602715
11679153
11689632
11698270
11709091
11752220
11799176
11861874
11876757
11877445
11878912
11884536
11931835
11967288
12120995
12163558
12190962
12368322
12402167
12429712
12429730
12502809
12614324
12634405
12713058
12832058
12834106
12843275
12845769
12857973
12864967
12871111
12873764
12873765
12953261
12960231
12963807
14576059
14585219
14592831
14689450
14990703
15014135
15018709
15045488
15113900
15113923
15183061
15215692
15258189
15279544
15279586
15327899
15351504
15509740
15585836
15710459
15719026
15737612
15748209
15784911
15890935
15972662
16005638
16047221
16188969
16227248
16306611
16314403
16375941
16386774
16400660
16437164
16553776
16672549
16685256
16702010
16855325
16886053
16886061
16934308
16942785
17010165
17011204
17041228
17121788
17144914
17151939
17187670
17201668
17292399
17328229
17346946
17457084
17507467
17507486
17640743
17933717
17933721
17947541
17959679
17977968
18036244
18090388
18160142
18187620
18197116
18242797
18288973
18377645
18468560
18480460
18500445
18577234
18614865
18624812
18775311
18784079
18788913
18808680
18815295
18850076
18925934
18930512
18958626
18976462
18976975
18977142
18991615
19020816
19020832
19047650
19055831
19057930
19066282
19178925
19180188
19232661
19339951
19339953
19401538
19414793
19457995
19540208
19556424
19661992
19695656
19837465
19906780
20007245
20015684
20041213
20051874
20299967
20530226
20639728
20678176
20686090
20697919
20797755
20842205
20861743
20921899
20923564
20942936
20947116
20967243
20981786
21071054
21106747
21128884
21152581
21165786
21179547
21188555
21284900
21284902
21284907
21295814
21310296
21346189
21349294
21373976
21474836
21555814
21569409
21569838
21663455
21676905
21760891
21835796
21902590
21914280
21948112
21994458
21994672
22084248
22086059
22101471
22101518
22124968
22147793
22147802
22157596
22219640
22226668
22237899
22286875
22291694
22297516
22313935
22332354
22470838
22513895
22657741
22692798
22732432
22842622
22897429
22908191
22954962
23043103
23043104
23143844
23202514
23330719
23343425
23350534
23389465
23446039
23449229
23672855
23692808
23774428
23804632
23884589
23925152
23989454
24158961
24205895
24215935
24312095
24312168
24461764
24465884
24480462
24635642
24731927
24778234
24990163
25072615
25193376
25231990
25313689
25387392
25595802
25636314
25880110
Tat inhibits 14630801
18760839
Nef enhances 24489825
Tat binds 10772939
11027346
16697675
19526283
20380698
21951552
Vpu downregulates 25275127
Envelope surface glycoprotein gp120 activates 21670103
22084248
24086760
Envelope transmembrane glycoprotein gp41 modulates 18353956
Nef upregulates 21668366

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04670 Leukocyte transendothelial migration - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
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