4RWS, 2K03, 2K04, 2K05, 3ODU, 3OE0, 3OE6, 3OE8, 3OE9, 2N55785212767ENSG00000121966ENSMUSG00000045382P61073P70658NM_003467NM_001008540NM_001348056NM_001348059NM_001348060NM_009911NM_001356509NP_001008540NP_003458NP_001334985NP_001334988NP_001334989NP_034041NP_001343438C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene.

[7] CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes.

[citation needed] CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.

It is best known for its intracellular role in targeting ubiquitylated proteins for degradation via the ubiquitin proteasome system.

Evidence in numerous animal models suggests ubiquitin is anti-inflammatory immune modulator and endogenous opponent of proinflammatory damage associated molecular pattern molecules.

[16] The presence of CXCR4 WHIM mutations has been associated with clinical resistance to ibrutinib in patients with Waldenström's macroglobulinemia.

Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow.

CXCL12 (over-)expressing cancers might not sense the CXCL12 gradient released from the metastasis target tissues since the receptor, CXCR4, is saturated with the ligand produced in an autocrine manner.