TABLE 2

CXCR4- and ACKR3-interacting proteins described in the literature.

Protein	Method of Identification	Cellular Context	Direct	Constitutive/Induced	Site of Interaction	Role	Reference
CXCR4-interacting proteins
Filamin A	Pull-down	HEK293 cells	Yes	Constitutive and CXCL12-induced The ROCK inhibitor Y27632 reverses CXCL12-induced increased interaction	C-terminal tail and third loop of CXCR4	Stabilize CXCR4 at the surface	Gómez-Moutón et al. (2015)
Filamin A	Co-IP	Recombinant protein	Yes		C-terminal tail and third loop of CXCR4	Stabilize CXCR4 at the surface	Gómez-Moutón et al. (2015)
AIP4	Pull Down	HEK293 cells	Yes	Constitutive and CXCL12-induced	CXCR4 C-tail serines and WW domains of AIP4. Serine 324 and 325 when phosphorylated increase interaction	Increase CXCR4 degradation	Bhandari et al. (2009)
	Co-IP
	FRET
RTN3	Y2H	HEK293 cells	NA	Constitutive, induction not tested	Carboxyl terminal of RTN3	Increase cytoplasmic localization of CXCR4	Li et al. (2016)
RTN3	Co-IP	HEK293 cells	NA	Constitutive, induction not tested	Carboxyl terminal of RTN3	Increase cytoplasmic localization of CXCR4	Li et al. (2016)
CD74	Co-IP	HEK293 and MonoMac6 cells	NA	Constitutive, induction not tested	NA	Phosphorylation of AKT	Schwartz et al. (2009)
CD74	Colocalization	HEK293 and MonoMac6 cells	NA	Constitutive, induction not tested	NA	Phosphorylation of AKT	Schwartz et al. (2009)
TLR2	FRET	Human monocyte and HEK293 cells	NA	Induced by Pg-fimbria	NA	CXCR4 inhibits TLR2-induced NF- κB activation. In addition, CXCR4 found to be receptor of the pattern-recognition receptor complex	Hajishengallis et al. (2008), Triantafilou et al. (2008)
TLR2	Co-IP	Human monocyte and HEK293 cells	NA	Induced by Pg-fimbria	NA		Hajishengallis et al. (2008), Triantafilou et al. (2008)
NMMHC	Pull-down	Jurkat T and Peer T cells lymphocytes	NA	Constitutive and not induced by CXCL12	CXCR4 C-terminus	Lymphocytes migration	Rey et al. (2002)
	Co-IP
	Colocalization
Drebrin	Pull Down	J77 T,	YES	Constitutive and induced by superantigen E, which also relocalizes the interaction to the leading edge of migrating lymphocytes	Drebrin	Drebrin affects key physiologic processes during antigen presentation in HIV entry	Pérez-Martínez et al. (2010), Gordón-Alonso et al. (2013)
	Co-IP	HEK293T and			N-terminus positively regulates interaction whereas the C-terminus seems to negatively regulate it
	FRET	HIV-infected T cells
CD164	Co-IP	Jurkat and	NA	Only induced when CXCL12 is presented on fibronectin	NA	CD164 participates to the CXCL12 mediated AKT and PKC-ζ phosphorylation	Forde et al. (2007), Huang et al. (2013)
CD164	Colocalization	Ovarian surface epithelial cells	NA	Only induced when CXCL12 is presented on fibronectin	NA		Forde et al. (2007), Huang et al. (2013)
mDIA2	Co-IP	MDA-MB-231 cells	NA	Constitutive (very weak) and CXCL12 induced	NA	Cytoskeletal rearrangement necessary for nonapoptotic blebbing	Wyse et al. (2017)
mDIA2	Colocalization	MDA-MB-231 cells	NA	Constitutive (very weak) and CXCL12 induced	NA		Wyse et al. (2017)
ATP13A2	MYTH	Yeast	YES	Constitutive	NA	NA	Usenovic et al. (2012)
PI3Kγ	Co-IP	Human myeloid cells	NA	Only CXCL12 induced	NA	Integrin activation and chemotaxis	Schmid et al. (2011)
PECAM-1	PLA	Human coronary artery endothelial cells	NO	Constitutive  Induction not studied	NA	CXCR4 part of a junctional mechano-sensitive complex	dela Paz et al. (2014)
MYBL2	2HY	Yeast	Yes	NA	NA	NA	Wang et al. (2011)
KCNK1	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
TMEM63B	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
GOLT1B	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
eIFB2	Co-IP	Pre-B NALM6 cells	NA	Constitutive and negatively regulated by CXCL12	NA	NA	Palmesino et al. (2016)
eIFB2	Colocalization	Pre-B NALM6 cells	NA	Constitutive and negatively regulated by CXCL12	NA	NA	Palmesino et al. (2016)
CDC73	Co-IP	Pre-B NALM6 cells	NA	Constitutive Induction not studied	NA	NA	Palmesino et al. (2016)
CTR9	Co-IP	Pre-B NALM6 cells	NA	Constitutive Induction not studied	NA	NA	Palmesino et al. (2016)
PAF1	Co-IP	Pre-B NALM6 cells	NA	Constitutive Induction not studied	NA	NA	Palmesino et al. (2016)
NPM	Co-IP	Pre-B NALM6 cells	NA	Constitutive Induction not studied	NA	NA	Palmesino et al. (2016)
CD11B	Co-IP	Pre-B NALM6 cells	NA	Constitutive Induction not studied	NA	NA	Palmesino et al. (2016)
PTPRS	Co-IP	Pre-B NALM6 cells	NA	Constitutive Induction not studied	NA	NA	Palmesino et al. (2016)
LGALS8	Co-IP	Pre-B NALM6 cells	NA	Constitutive Induction not studied	NA	NA	Palmesino et al. (2016)

ACKR3-interacting proteins
EGFR	PLA	MCF7 cells, breast cancer tissues, CaP cells	Mediated by β-arrestin2	Interaction constitutive and induced by the epidermal growth factor.	NA	ACKR3 mediates phosphorylation of EGFR at tyrosine1110 after EGF-stimulation and phosphorylation of ERK1/2 with consequences on tumor proliferation.	Singh and Lokeshwar (2011), Salazar et al. (2014), Kallifatidis et al. (2016)
	Colocalization
	Co-IP
CD74	Co-IP	NIH/3T3 cells and human B cells	NA	Constitutive, induction not investigated.	NA	ACKR3 is involved in MIF-mediated ERK-1/2 and ζ-chain-associated protein kinase activation in addition to MIF-mediated chemotaxis.	Alampour-Rajabi et al. (2015)
	Colocalization
	PLA
PECAM-1	PLA	HCAECs cells	NA	Constitutive	NA	NA	dela Paz et al. (2014)
ATP13A2	MYTH	Yeast	Yes	NA	NA	NA	Usenovic et al. (2012)
GJB2	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
MRPL4	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
ATP5H	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
ATP5B	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
ATP5A1	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
ATP5O	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
ACKR3	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
ESPL1	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
HECTD2	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)
UBR7	Co-IP	HeLa cells	NA	NA	NA	NA	Hein et al. (2015)

ATP13A2, cation-transporting ATPase 13A2; ATP5H/ATP5B/ATP5A1/ATP5O, ATP synthase subunit d/beta/alpha/O, mitochondrial; CAP, human prostate cancer cells; CD11B, cyclin-dependent kinase 11B; CD164, endolyn; CDC73, parafibromin; CTR9, SH2 domain binding protein; eIF2B, eukaryotic translation initiation factor 2B; EGFR, epidermal growth factor receptor; ESPL1, HCAEC, Human Coronary Artery Endothelial Cells; HECTD2, probable E3 ubiquitin-protein ligase; GJB2, gap junction β-2 protein; GOLT1B, vesicle transport protein GOT1B; KCNK1, potassium channel subfamily K member 1; LGALS8, galectin; mDIA2, diaphanous-related formin-2; MYBL2, myb-related protein B; MRPL4, 54S ribosomal protein L4, mitochondrial; MYTH, membrane yeast two-hybrid assay; NA, not applicable; NF, nuclear factor; NMMHC, motor protein nonmuscle myosin H chain; NPM, nucleophosmin; PAF1, hypothetical protein PD2; PECAM-1, platelet endothelial cell adhesion molecule; PI3Kγ, PI3-kinase isoform p110γ; PLA, proximity ligation assay; PTPRS, receptor-type tyrosine-protein phosphatase S; RTN3, reticulon3; TLR2, Toll-like receptor 2; TMEM63B, CSC1-like protein 2; UBR7, putative E3 ubiquitin-protein ligase; Y2H, yeast two-hybrid assay.