ARRB2

Summary

ARRB2 (arrestin beta 2, HGNC:712) is a protein-coding gene on chromosome 17p13.2, encoding Beta-arrestin-2 (P32121). Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes.

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 409 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_004313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:712
Approved symbol	ARRB2
Name	arrestin beta 2
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	BARR2, DKFZp686L0365
Ensembl gene	ENSG00000141480
Ensembl biotype	protein_coding
OMIM	107941
Entrez	409

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 15 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000269260, ENST00000346341, ENST00000381488, ENST00000412477, ENST00000570718, ENST00000570739, ENST00000571206, ENST00000571428, ENST00000571791, ENST00000572457, ENST00000572497, ENST00000572782, ENST00000573886, ENST00000574502, ENST00000574888, ENST00000574954, ENST00000575131, ENST00000575877, ENST00000576235, ENST00000577054, ENST00000855436, ENST00000855439, ENST00000855440, ENST00000855441, ENST00000855442, ENST00000915218

RefSeq mRNA: 7 — MANE Select: NM_004313 NM_001257328, NM_001257329, NM_001257330, NM_001257331, NM_001330064, NM_004313, NM_199004

CCDS: CCDS11050, CCDS11051, CCDS58504, CCDS58505, CCDS59276, CCDS82039

Canonical transcript exons

ENST00000269260 — 15 exons

Exon	Start	End
ENSE00001923103	4710632	4710744
ENSE00002684169	4720946	4721497
ENSE00003333249	4718261	4718345
ENSE00003463230	4717888	4718023
ENSE00003475165	4715973	4716033
ENSE00003478390	4718612	4718684
ENSE00003482546	4720393	4720472
ENSE00003522470	4717217	4717276
ENSE00003527594	4719283	4719420
ENSE00003554419	4716412	4716608
ENSE00003555145	4720216	4720299
ENSE00003560544	4720586	4720640
ENSE00003602228	4717685	4717752
ENSE00003609766	4715013	4715043
ENSE00003663848	4716147	4716191

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.2470 / max 2665.1749, expressed in 1784 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158910	51.8911	1783
158917	1.4250	170
158909	1.1854	325
158908	1.0712	596
158923	0.5847	247
158913	0.4899	38
158912	0.3545	32
158911	0.3539	145
158920	0.3446	80
208033	0.3216	165

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.51	gold quality
monocyte	CL:0000576	99.31	gold quality
leukocyte	CL:0000738	99.21	gold quality
mononuclear cell	CL:0000842	99.20	gold quality
right lung	UBERON:0002167	98.45	gold quality
spleen	UBERON:0002106	98.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.05	gold quality
upper lobe of left lung	UBERON:0008952	98.01	gold quality
blood	UBERON:0000178	97.90	gold quality
cerebellar hemisphere	UBERON:0002245	97.85	gold quality
cerebellar cortex	UBERON:0002129	97.79	gold quality
upper lobe of lung	UBERON:0008948	97.05	gold quality
bone marrow cell	CL:0002092	97.02	gold quality
cerebellum	UBERON:0002037	96.52	gold quality
right frontal lobe	UBERON:0002810	96.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.17	gold quality
omental fat pad	UBERON:0010414	95.91	gold quality
cingulate cortex	UBERON:0003027	95.87	gold quality
peritoneum	UBERON:0002358	95.85	gold quality
anterior cingulate cortex	UBERON:0009835	95.84	gold quality
right coronary artery	UBERON:0001625	95.65	gold quality
left adrenal gland cortex	UBERON:0035825	95.57	gold quality
right adrenal gland	UBERON:0001233	95.56	gold quality
right adrenal gland cortex	UBERON:0035827	95.52	gold quality
left adrenal gland	UBERON:0001234	95.46	gold quality
gall bladder	UBERON:0002110	95.29	gold quality
bone marrow	UBERON:0002371	95.26	gold quality
lymph node	UBERON:0000029	95.18	gold quality
nerve	UBERON:0001021	95.06	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	85.95
E-MTAB-6701	yes	45.00
E-GEOD-135922	yes	44.37
E-MTAB-9221	yes	26.05
E-ANND-3	yes	24.22
E-MTAB-10042	yes	9.05
E-MTAB-5061	yes	4.04

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
GATA4	Activation
MYH6	Activation
TNNT2	Activation

Upstream regulators (CollecTRI, top): AR, NFKB, NFKBIA, TBX1

miRNA regulators (miRDB)

43 targeting ARRB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-4635	98.74	67.63	1339

Literature-anchored findings (GeneRIF, showing 40)

• LH/CG R activation is sufficient to expose a conformation in which Asp-564 in the 3i loop confers high affinity binding selectively to arrestin2. (PMID:11867621)
• Phosphorylation of beta-arrestin2 regulates its function in internalization of beta(2)-adrenergic receptors. (PMID:12186555)
• beta-arrestin2 can function not only as a regulator of CXCR4 signaling but also as a mediator of stromal cell-derived factor 1alpha-induced chemotaxis, via the ASK1/p38 MAPK pathway (PMID:12370187)
• role of beta-arrestin, dynamin, and clathrin-dependent pathway in internalization of the complement 5a anaphylatoxin receptor (PMID:12464600)
• this protein functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2. (PMID:12488444)
• examination of desensitization, internalization, and signaling functions demonstrated by RNA interference (PMID:12582207)
• role in angiotensin II activation of extracellular signal-regulated kinases 1 and 2 (PMID:12949261)
• endocytosis of Frizzled 4 (Fz4) in human embryonic kidney 293 cells was dependent on added Wnt5A protein and was accomplished by beta-arrestin 2, which was recruited to Fz4 by binding to phosphorylated Dvl2 (PMID:12958364)
• findings indicate a physiologically significant, unanticipated role for beta arrestin 2 in regulating TGF-beta signaling through internalization and subsequent decreased signaling of TGF-beta receptors (PMID:12958365)
• results suggest that physiological levels of beta-arrestin1 may act as “dominant-negative” inhibitors of beta-arrestin2-mediated extracellular signal-regulated kinases 1 and 2 activation (PMID:14711824)
• arrestin 2 has a role in activating a MAPK pathway that regulates Nur77, which in turn modulates NK(1)R-mediated nonapoptotic programmed cell death (PMID:14769794)
• Beta-arrestin2 mediates a crosstalk between beta-2 adrenergic receptors and NF-kappaB signaling pathways (PMID:15125834)
• Data show how the ability of receptors such as angiotensin type 1A to interact with beta-arrestin 2 determines both the mechanism of extracellular signal-regulated kinase 1 and 2 activation as well as the physiological consequences of this activation. (PMID:15355986)
• Arrestin2 and arrestin3 in striatal homogenates bind to the third cytoplasmic loop of the D2 receptor. (PMID:15361545)
• Arrestin has a role in regulating MAPK activation and preventing NADPH oxidase-dependent death of cells expressing CXCR2 (PMID:15364949)
• protease-activated receptor-2-mediated migration of tumor cells requires both beta-arrestin-1 and -2 (PMID:15489220)
• analysis of the glucagon-like peptide-1 receptor beta-arrestin 2 interaction (PMID:15528268)
• beta-Arrestin 2 and GRK2 are potential mediators of signaling by activated Smoothened (PMID:15618519)
• alpha(1a)-ARs recycle rapidly by an agonist-independent, constitutive, beta-arrestin-dependent process and that this can transport “alpha-blockers” into cells carrying these receptors. (PMID:15626751)
• Agonist-controlled association and dissociation of beta-arrestins from prephosphorylated receptors should permit rapid control of receptor sensitivity. (PMID:15634674)
• beta-arrestin 2 can mediate chemotaxis through mechanisms which may be G-protein-independent (Ang II receptors) or -dependent (LPA receptors). (PMID:15635042)
• filamin A, and beta-arrestin form a signaling complex that is destabilized by agonist- or expression-mediated increases in GRK2/3 activity (PMID:15687500)
• ubiquitination of beta-arrestin directs assembly and targeting of seven-transmembrane receptor signalosomes (PMID:15699045)
• beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform. (PMID:15699339)
• Role in the activation of the P2X(7) receptor. (PMID:15728711)
• GLP-2 receptor C terminus has a role in modulating beta-arrestin-2 association but not ligand-induced desensitization, endocytosis, and G-protein-dependent effector activation (PMID:15817468)
• MKP7 also binds beta-arrestin 2 via amino acids 394-443 of MKP7, the same region that interacts with JIP-1 (PMID:15888437)
• Recruitment of beta-arrestin2 to carboxyl terminal region of beta2AR is important for ERK localization to the nucleus. (PMID:16038799)
• Endogenous beta-arrestin1 functions exclusively in the phosphorylation-dependent receptor internalization, whereas endogenous beta-arrestin2, but not beta-arrestin1, is required for the phosphorylation-independent receptor internalization. (PMID:16181421)
• beta-arrestin2 is identified as a phosphorylation-regulated suppressor of UV induced NF-kappaB activation (PMID:16308565)
• TSH receptor is a member of the class A of G protein-coupled receptors, which have a higher affinity to beta-arrestin 2 than beta-arrestin 1 and do not colocalize with beta-arrestins in endosomes. (PMID:16513835)
• Our results show that PAR1-mediated activation of Src and ERK1/2 in HEK 293 cells was increased with overexpression of beta-arrestin1 or depletion of beta-arrestin2. (PMID:16580177)
• The presence of the alpha(2C)AR within the heterodimer resulted in a marked reduction in the level of GRK2-mediated alpha(2A)AR phosphorylation, which was accompanied by a qualitative attenuation of beta-arrestin recruitment (PMID:16605244)
• RACK1 and beta-arrestin compete to sequester distinct ‘pools’ of PDE4D5. (PMID:16689683)
• Data show that beta-arrestin2, which typically shows a cytoplasmic localization owing to constitutive nuclear export, appears in the nucleus after stimulation of the G-protein-coupled odorant receptor hOR17-4. (PMID:16820410)
• Results suggest that nephrin Y1193 serves as a molecular switch that determines the integrity of the slit diaphragm by functional competition between beta-arrestin2 and podocin. (PMID:16968782)
• Recombinant human beta-arrestin2 is redistributed into the dendritic knobs of mouse olfactory receptor neurons after treatment with a complex odorant mixture. Prolonged odorant exposure results in accumulation of beta-arrestin2 in intracellular vesicles. (PMID:17005854)
• receptor interaction with beta-arrestin to co-precipitate Src and activate ERK1/2 was obviated by expressing a constitutively active c-SrcY527A mutant, suggesting direct binding of activated Src to PTH1R (PMID:17038311)
• This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder. (PMID:17233643)
• Our data suggest that in cirrhosis-induced vasodilation, the AT1-R is desensitized by GRK-2 and beta-arrestin-2 and that changed patterns of phosphorylated Ca(2+) sensitizing proteins decrease Ca(2+) sensitivity. (PMID:17256744)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arrb2b	ENSDARG00000011545
danio_rerio	arrb2a	ENSDARG00000039215
mus_musculus	Arrb2	ENSMUSG00000060216
rattus_norvegicus	Arrb2	ENSRNOG00000019308
drosophila_melanogaster	krz	FBGN0040206
caenorhabditis_elegans		WBGENE00000195

Paralogs (3): ARR3 (ENSG00000120500), SAG (ENSG00000130561), ARRB1 (ENSG00000137486)

Protein

Protein identifiers

Beta-arrestin-2 — P32121 (reviewed: P32121)

Alternative names: Arrestin beta-2, Non-visual arrestin-3

All UniProt accessions (7): P32121, I3L0V6, I3L1M6, I3L412, K7EL17, K7ENA6, Q68DZ5

UniProt curated annotations — full annotation on UniProt →

Function. Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as a signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as a signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in IL8-mediated granule release in neutrophils. Involved in the internalization of the atypical chemokine receptor ACKR3. Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis. During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release and inhibition of inflammation.

Subunit / interactions. Homooligomer; the self-association is mediated by InsP6-binding. Heterooligomer with ARRB1; the association is mediated by InsP6-binding. Interacts with ADRB2 and CHRM2. Interacts with PDE4A. Interacts with PDE4D. Interacts with MAPK10, MAPK1 and MAPK3. Interacts with DRD2. Interacts with FSHR. Interacts with CLTC. Interacts with HTR2C. Interacts with CCR5. Interacts with CXCR4. Interacts with SRC. Interacts with DUSP16; the interaction is interrupted by stimulation of AGTR1 and activation of MAPK10. Interacts with CHUK; the interaction is enhanced stimulation of ADRB2. Interacts with RELA. Interacts with MDM2; the interaction is enhanced by activation of GPCRs. Interacts with SLC9A5. Interacts with TRAF6. Interacts with IGF1R. Interacts with ENG. Interacts with KIR2DL1, KIR2DL3 and KIR2DL4. Interacts with LDLR. Interacts with AP2B1. Interacts with C5AR1. Interacts with RAF1. Interacts with MAP2K1. Interacts with MAPK1. Interacts with MAPK10; the interaction enhances MAPK10 activation by MAP3K5. Interacts with MAP2K4; the interaction is enhanced by presence of MAP3K5 and MAPK10. Interacts with MAP3K5. Interacts with AKT1. Interacts with IKBKB and MAP3K14. Interacts with SMO (activated). Interacts with GSK3A and GSK3B. Associates with protein phosphatase 2A (PP2A). Interacts with DHX8; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with GAPDHS; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with H2AFX; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with KIF14; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with RCC1; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with CXCR4; the interaction is dependent on C-terminal phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with GPR143. Interacts with HCK and CXCR1 (phosphorylated). Interacts with ACKR3 and ACKR4. Interacts with ARRDC1; the interaction is direct. Interacts with GPR61, GPR62 and GPR135. Interacts (via NACHT and LRR domains) with NLRP3; this interaction is direct and inducible by omega-3 polyunsaturated fatty acids (PUFAs). Interacts with FFAR4 (via C-terminus); this interaction is stimulated by long-chain fatty acids (LCFAs). Interacts with GPR35. Interacts with GPR84. Interacts with TIGIT; this interaction inhibits the NF-kappa-B pathway. Interacts with TGFBR3.

Subcellular location. Cytoplasm. Nucleus. Cell membrane. Membrane. Clathrin-coated pit. Cytoplasmic vesicle.

Post-translational modifications. Phosphorylated at Thr-382 in the cytoplasm; probably dephosphorylated at the plasma membrane. The phosphorylation does not regulate internalization and recycling of ADRB2, interaction with clathrin or AP2B1. The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and signaling. Ubiquitination appears to occur GPCR-specific. Ubiquitinated by MDM2; the ubiquitination is required for rapid internalization of ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a dissociation of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such as ADRB2, induces transient ubiquitination and subsequently promotes association with USP33. Stimulation of a class B GPCR promotes a sustained ubiquitination. Deubiquitinated by USP20; allowing USP20 to deubiquitinate TRAF6 leading to inhibition of NF-kappa-B signaling. Hydroxylation by PHD2 modulates the rate of internalization by slowing down recruitment to the plasma membrane and inhibiting subsequent co-internalization with class A receptors.

Domain organisation. The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1.

Similarity. Belongs to the arrestin family.

Isoforms (5)

UniProt ID	Names	Canonical?
P32121-1	1	yes
P32121-3	2
P32121-2	3
P32121-4	4
P32121-5	5

RefSeq proteins (7): NP_001244257, NP_001244258, NP_001244259, NP_001244260, NP_001316993, NP_004304, NP_945355 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000698	Arrestin	Family
IPR011021	Arrestin-like_N	Domain
IPR011022	Arrestin-like_C	Domain
IPR014752	Arrestin-like_C_sf	Homologous_superfamily
IPR014753	Arrestin_N	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR017864	Arrestin_CS	Conserved_site

Pfam: PF00339, PF02752

UniProt features (25 total): mutagenesis site 8, sequence conflict 5, modified residue 5, splice variant 3, region of interest 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9UYM	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32121-F1	83.97	0.59

Antibody-complex structures (SAbDab): 1 — 9UYM

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 48, 176, 181, 360, 382

Mutagenesis-validated functional residues (8):

Position	Phenotype
11	abolishes interaction with chuk; when associated with a-12; a-230 and a-231.
12	abolishes interaction with chuk; when associated with a-11; a-230 and a-231.
54	inhibits internalization of cxcr4; no effect on interaction with cxcr4.
230	abolishes interaction with chuk; when associated with a-11; a-12 and a-231.
231	abolishes interaction with chuk; when associated with a-11; a-12 and a-230.
360	reduces interaction with chuk; when associated with a-382.
382	reduces interaction with chuk; when associated with a-360.
382	loss of phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-418555	G alpha (s) signalling events
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-5099900	WNT5A-dependent internalization of FZD4
R-HSA-5635838	Activation of SMO
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-5689880	Ub-specific processing proteases
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-9839389	TGFBR3 regulates TGF-beta signaling
R-HSA-109582	Hemostasis
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-195721	Signaling by WNT
R-HSA-1980143	Signaling by NOTCH1
R-HSA-199991	Membrane Trafficking
R-HSA-372790	Signaling by GPCR
R-HSA-3858494	Beta-catenin independent WNT signaling
R-HSA-388396	GPCR downstream signalling
R-HSA-392499	Metabolism of proteins
R-HSA-4086400	PCP/CE pathway
R-HSA-5358351	Signaling by Hedgehog
R-HSA-5632684	Hedgehog ‘on’ state

MSigDB gene sets: 465 (showing top): GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, WANG_CLIM2_TARGETS_UP, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_ADULT_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY

GO Biological Process (37): desensitization of G protein-coupled receptor signaling pathway (GO:0002029), G protein-coupled receptor internalization (GO:0002031), positive regulation of receptor internalization (GO:0002092), transcription by RNA polymerase II (GO:0006366), transforming growth factor beta receptor signaling pathway (GO:0007179), adult walking behavior (GO:0007628), positive regulation of cardiac muscle hypertrophy (GO:0010613), positive regulation of gene expression (GO:0010628), protein transport (GO:0015031), protein ubiquitination (GO:0016567), sensory perception of pain (GO:0019233), negative regulation of protein ubiquitination (GO:0031397), receptor internalization (GO:0031623), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), positive regulation of synaptic transmission, dopaminergic (GO:0032226), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of interleukin-12 production (GO:0032695), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of toll-like receptor signaling pathway (GO:0034122), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of natural killer cell mediated cytotoxicity (GO:0045953), modulation of chemical synaptic transmission (GO:0050804), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), excitatory postsynaptic potential (GO:0060079), cell chemotaxis (GO:0060326), positive regulation of ERK1 and ERK2 cascade (GO:0070374), postsynaptic signal transduction (GO:0098926), beta-arrestin-dependent dopamine receptor signaling pathway (GO:0160213), positive regulation of cardiac muscle cell differentiation (GO:2000727), signal transduction (GO:0007165), canonical NF-kappaB signal transduction (GO:0007249), regulation of G protein-coupled receptor signaling pathway (GO:0008277), negative regulation of signal transduction (GO:0009968), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (10): G protein-coupled receptor binding (GO:0001664), signaling receptor binding (GO:0005102), enzyme binding (GO:0019899), protein-macromolecule adaptor activity (GO:0030674), ubiquitin protein ligase binding (GO:0031625), angiotensin receptor binding (GO:0031701), D1 dopamine receptor binding (GO:0031748), protein kinase B binding (GO:0043422), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), endocytic vesicle (GO:0030139), endocytic vesicle membrane (GO:0030666), cytoplasmic vesicle (GO:0031410), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Oncogenic MAPK signaling	5
Signaling by NOTCH1	1
GPCR downstream signalling	1
Platelet activation, signaling and aggregation	1
PCP/CE pathway	1
Hedgehog ‘on’ state	1
RAF/MAP kinase cascade	1
Deubiquitination	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Signaling by RAS mutants	1
Signaling by TGFBR3	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein binding	3
receptor internalization	2
negative regulation of cytokine production	2
binding	2
cytoplasm	2
membrane	2
synapse	2
negative adaptation of signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
desensitization of G protein-coupled receptor signaling pathway	1
regulation of receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
DNA-templated transcription	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
adult locomotory behavior	1
walking behavior	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein modification by small protein conjugation	1
sensory perception	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
receptor-mediated endocytosis	1
synaptic transmission, dopaminergic	1
regulation of synaptic transmission, dopaminergic	1
positive regulation of synaptic transmission	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
interleukin-12 production	1

Protein interactions and networks

STRING

4155 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARRB2	ADRB2	P07550	998
ARRB2	AKT1	P31749	993
ARRB2	GRK2	P25098	991
ARRB2	SRC	P12931	989
ARRB2	TAB1	Q15750	979
ARRB2	MAP2K4	P45985	971
ARRB2	NFKBIA	P25963	970
ARRB2	MAP3K5	Q99683	969
ARRB2	DRD2	P14416	963
ARRB2	AP2B1	P21851	960
ARRB2	SMO	Q99835	959
ARRB2	RAPGEF4	Q8WZA2	945
ARRB2	RAPGEF3	O95398	944
ARRB2	MAP2K1	Q02750	934
ARRB2	PDE4A	P27815	934

IntAct

200 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
ARRB2	MAPK9	psi-mi:“MI:0915”(physical association)	0.840
MAPK9	ARRB2	psi-mi:“MI:0915”(physical association)	0.840
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
ARRB2	NOLC1	psi-mi:“MI:0915”(physical association)	0.760
ARRB1	ARRB2	psi-mi:“MI:0914”(association)	0.740
MDM2	ARRB2	psi-mi:“MI:0915”(physical association)	0.710
ARRB2	MDM2	psi-mi:“MI:0915”(physical association)	0.710
ARRB2	MDM2	psi-mi:“MI:0407”(direct interaction)	0.710
MDM2	ARRB2	psi-mi:“MI:0220”(ubiquitination reaction)	0.710
ARRB2	AKT1	psi-mi:“MI:0915”(physical association)	0.700
AKT1	ARRB2	psi-mi:“MI:0915”(physical association)	0.700
ARRB2	AKT1	psi-mi:“MI:2364”(proximity)	0.700
CLTC	ARRB2	psi-mi:“MI:0407”(direct interaction)	0.680
ARRB2	CLTC	psi-mi:“MI:0915”(physical association)	0.680
ARRB2	ARRB2	psi-mi:“MI:0915”(physical association)	0.670
ARRB2	ARRB2	psi-mi:“MI:0914”(association)	0.670
EGFR	ARRB2	psi-mi:“MI:0915”(physical association)	0.650
EGFR	ARRB2	psi-mi:“MI:2364”(proximity)	0.650
ARRB2	EGFR	psi-mi:“MI:0915”(physical association)	0.650

BioGRID (629): USP33 (Two-hybrid), USP33 (Affinity Capture-Western), ARRB2 (Biochemical Activity), ARRB2 (Affinity Capture-Western), ARRB2 (Affinity Capture-Western), ARRB2 (Affinity Capture-Western), MAPK9 (Two-hybrid), HGS (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), ARRDC3 (Affinity Capture-Western), ARRB2 (Two-hybrid), ARRB2 (Two-hybrid), ARRB2 (Affinity Capture-MS), ARRB2 (Affinity Capture-MS), ARRB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A2AIG8, A7Z026, B0BNL6, B2RYF1, D4ABL6, E9PV86, O35393, O54804, O73884, O75078, O75864, P20417, P29067, P32120, P32121, P35790, P35821, P51467, Q00961, Q01098, Q01134, Q14957, Q5E9H2, Q5RCR4, Q642A6, Q6AZB0, Q6DN14, Q6IA17, Q8BHT7, Q8BKR5, Q8CIW5, Q8N431, Q8N5I2, Q8N5X7, Q8NBA8, Q8NCT1, Q8R2Z5, Q91YI4, Q92546

Diamond homologs: P08168, P10523, P15372, P15887, P17870, P19107, P19108, P20443, P29066, P29067, P32120, P32121, P32122, P36575, P36576, P49407, P51466, P51467, P51468, P51477, P51478, P51479, P51481, P51482, P51483, P51484, P51485, P51486, P51487, P55274, P79260, Q28281, Q4R562, Q5DRQ4, Q5RCR4, Q7YS78, Q8BWG8, Q91YI4, Q95223, Q9EQP6

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
SMO	up-regulates	ARRB2	binding
ARRB2	up-regulates	KIF3A	binding
MAP2K1	“up-regulates activity”	ARRB2	phosphorylation
ARRB2	“up-regulates activity”	INPP5D	binding
TIGIT	“up-regulates activity”	ARRB2	binding
ARRB2	“up-regulates quantity by stabilization”	MDM2	binding
CCR7	“up-regulates activity”	ARRB2	relocalization
MDM2	“down-regulates quantity”	ARRB2	ubiquitination
ERK1/2	“up-regulates activity”	ARRB2	phosphorylation
CSNK2A1	unknown	ARRB2	phosphorylation
CSNK2A2	unknown	ARRB2	phosphorylation
ARRB2	“down-regulates activity”	ADRB2	binding
ARRB2	“down-regulates activity”	ADRB1	binding
ARRB2	“down-regulates activity”	SLC9A5	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Spry regulation of FGF signaling	5	31.6×	9e-06
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	6	27.6×	3e-06
Fc epsilon receptor (FCERI) signaling	10	24.1×	6e-09
Signaling by RAS mutants	6	22.5×	7e-06
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	5	19.4×	8e-05
MAP kinase activation	7	19.1×	3e-06
FCERI mediated MAPK activation	6	18.4×	2e-05
VEGFR2 mediated vascular permeability	5	18.1×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
Fc-epsilon receptor signaling pathway	6	29.3×	6e-05
stress-activated MAPK cascade	5	23.4×	9e-04
regulation of heart rate	6	18.7×	6e-04
lipopolysaccharide-mediated signaling pathway	5	17.6×	3e-03
epidermal growth factor receptor signaling pathway	7	11.6×	9e-04
JNK cascade	6	10.9×	4e-03
insulin receptor signaling pathway	6	8.9×	7e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	8.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

73 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2478 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4715953:T:TA	acceptor_gain	1.0000
17:4716029:TGTAG:T	donor_loss	1.0000
17:4716033:GGTA:G	donor_loss	1.0000
17:4716034:GTA:G	donor_loss	1.0000
17:4716407:GCCAG:G	acceptor_loss	1.0000
17:4716408:CCA:C	acceptor_loss	1.0000
17:4716409:CAG:C	acceptor_loss	1.0000
17:4716410:A:AG	acceptor_gain	1.0000
17:4716410:A:AT	acceptor_loss	1.0000
17:4716410:AGT:A	acceptor_gain	1.0000
17:4716411:G:GG	acceptor_gain	1.0000
17:4716411:GT:G	acceptor_gain	1.0000
17:4716411:GTG:G	acceptor_gain	1.0000
17:4716411:GTGT:G	acceptor_gain	1.0000
17:4716411:GTGTT:G	acceptor_gain	1.0000
17:4716572:G:GT	donor_gain	1.0000
17:4716576:C:G	donor_gain	1.0000
17:4716609:G:GG	donor_gain	1.0000
17:4716614:G:GT	donor_gain	1.0000
17:4717273:A:T	donor_gain	1.0000
17:4717681:C:CA	acceptor_gain	1.0000
17:4717684:G:A	acceptor_gain	1.0000
17:4717752:GGTA:G	donor_loss	1.0000
17:4717754:T:A	donor_loss	1.0000
17:4717879:T:TA	acceptor_gain	1.0000
17:4717885:CAG:C	acceptor_loss	1.0000
17:4717886:A:AG	acceptor_gain	1.0000
17:4717886:AG:A	acceptor_gain	1.0000
17:4717886:AGGAA:A	acceptor_loss	1.0000
17:4717887:G:A	acceptor_loss	1.0000

AlphaMissense

2676 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4715017:T:C	F10L	1.000
17:4715018:T:C	F10S	1.000
17:4715019:C:A	F10L	1.000
17:4715019:C:G	F10L	1.000
17:4715022:G:C	K11N	1.000
17:4715022:G:T	K11N	1.000
17:4715023:A:G	K12E	1.000
17:4715025:G:C	K12N	1.000
17:4715025:G:T	K12N	1.000
17:4715029:A:C	S14R	1.000
17:4715031:C:A	S14R	1.000
17:4715031:C:G	S14R	1.000
17:4715982:T:C	Y22H	1.000
17:4715982:T:G	Y22D	1.000
17:4715995:G:C	R26P	1.000
17:4715995:G:T	R26L	1.000
17:4715997:G:C	D27H	1.000
17:4716000:T:C	F28L	1.000
17:4716001:T:C	F28S	1.000
17:4716002:C:A	F28L	1.000
17:4716002:C:G	F28L	1.000
17:4716149:G:C	G40R	1.000
17:4716150:G:A	G40D	1.000
17:4716424:T:C	L58P	1.000
17:4716430:G:A	C60Y	1.000
17:4716431:C:G	C60W	1.000
17:4716435:T:A	F62I	1.000
17:4716435:T:C	F62L	1.000
17:4716436:T:C	F62S	1.000
17:4716436:T:G	F62C	1.000

dbSNP variants (sampled 300 via entrez): RS1000043712 (17:4714546 G>A,T), RS1000332019 (17:4711471 G>A,C,T), RS1000384693 (17:4710473 G>A), RS1000417378 (17:4710347 G>A), RS1000642937 (17:4716026 C>T), RS1001405312 (17:4711640 C>A,T), RS1001613212 (17:4717559 C>A,G,T), RS1001835175 (17:4721223 C>T), RS1002333217 (17:4719140 G>A), RS1002489836 (17:4712941 T>C), RS1002616138 (17:4718955 A>G), RS1003182118 (17:4714921 C>A), RS1003241067 (17:4719903 G>A), RS1003278103 (17:4709028 G>T), RS1003310865 (17:4708817 G>A)

Disease associations

OMIM: gene MIM:107941 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004627_166	Lymphocyte count	4.000000e-15
GCST012073_21	Behcet’s disease	2.000000e-07
GCST90002388_482	Lymphocyte count	2.000000e-32
GCST90002389_218	Lymphocyte percentage of white cells	5.000000e-17
GCST90002407_569	White blood cell count	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1045280	Other	3	methamphetamine	Substance-Related Disorders
rs1045280	Toxicity	3	buprenorphine;fentanyl;tramadol	adverse events;Opioid-Related Disorders
rs2036657	Toxicity	3	methamphetamine	Substance-Related Disorders
rs4790694	Toxicity	3	methamphetamine	Substance-Related Disorders

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1045280	ARRB2	3	2.25	2	buprenorphine;fentanyl;tramadol;methamphetamine
rs2036657	ARRB2	3	0.00	1	methamphetamine
rs3786047	ARRB2		0.00	0
rs4790694	ARRB2	3	1.50	1	methamphetamine
rs34230287	ARRB2		0.00	0
rs4790693	ARRB2		0.00	0
rs7208257	ARRB2		0.00	0
rs2271167	ARRB2		0.00	0
rs4522461	ARRB2		0.00	0

CTD chemical–gene interactions

77 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Morphine	increases activity, affects response to substance, decreases expression, decreases reaction, affects cotreatment	4
Isoproterenol	affects binding, decreases reaction, increases phosphorylation, increases reaction, affects localization	3
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-	affects localization, affects reaction, affects cotreatment, decreases reaction, increases activity	3
Particulate Matter	increases abundance, increases expression, affects localization, increases reaction, increases secretion	3
bisphenol A	affects expression, decreases expression	2
(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone	affects cotreatment, affects localization, increases reaction	2
1-pentyl-3-(1-naphthoyl)indole	affects binding, increases reaction, decreases reaction	2
Resveratrol	affects reaction, decreases expression, affects response to substance, affects cotreatment	2
Carvedilol	decreases reaction, affects cotreatment, increases phosphorylation, increases reaction, affects binding	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases oxidation, increases expression, affects cotreatment	2
Estradiol	decreases expression, affects cotreatment	2
Tretinoin	decreases expression, increases expression	2
1-pentyl-1H-indole-3-carboxylic acid 8-quinolinyl ester	affects binding, increases reaction	1
1-(5-fluoropentyl)-3-(4-methyl-1-naphthoyl)indole	affects binding, increases reaction	1
(4-ethyl-1-naphthalenyl)(1-(5-fluoropentyl)-1H-indol-3-yl)methanone	affects binding, increases reaction	1
methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate	affects binding, increases reaction	1
1-pentyfluoro-1H-indole-3-carboxylic acid 8-quinolinyl ester	affects binding, increases reaction	1
5F-APP-PICA	affects binding, affects reaction, increases reaction	1
pamoic acid	affects binding, increases reaction	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
zinc chloride	affects localization	1
sodium arsenite	decreases expression	1
S-nitrosocysteine	affects localization, decreases reaction	1
nickel chloride	affects localization	1
benzo(e)pyrene	decreases methylation	1
ICI 118551	decreases reaction, increases reaction, affects binding	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1

Cellosaurus cell lines

512 cell lines: 287 spontaneously immortalized cell line, 194 cancer cell line, 31 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B0ZI	Abcam Hep-G2 ARRB2 KO	Cancer cell line	Male
CVCL_B2S9	Abcam HEK293T ARRB2 KO	Transformed cell line	Female
CVCL_B9DN	Abcam A-549 ARRB2 KO	Cancer cell line	Male
CVCL_D7KH	Ubigene A-549 ARRB2 KO	Cancer cell line	Male
CVCL_D8HI	Ubigene HCT 116 ARRB2 KO	Cancer cell line	Male
CVCL_D8ZH	Ubigene HEK293 ARRB2 KO	Transformed cell line	Female
CVCL_D9XV	Ubigene HeLa ARRB2 KO	Cancer cell line	Female
CVCL_KW17	PathHunter BHK-21 rPTGER4 beta-arrestin	Spontaneously immortalized cell line	Male
CVCL_KW18	PathHunter C2C12 CXCR4 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KW19	PathHunter C2C12 CXCR5 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.