ARRB1

Summary

ARRB1 (arrestin beta 1, HGNC:711) is a protein-coding gene on chromosome 11q13.4, encoding Beta-arrestin-1 (P49407). 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 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described.

Source: NCBI Gene 408 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 60 total
• Druggable target: yes
• MANE Select transcript: NM_004041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:711
Approved symbol	ARRB1
Name	arrestin beta 1
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137486
Ensembl biotype	protein_coding
OMIM	107940
Entrez	408

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000360025, ENST00000420843, ENST00000524400, ENST00000527385, ENST00000529280, ENST00000529741, ENST00000530086, ENST00000531012, ENST00000532447, ENST00000532525, ENST00000533255, ENST00000533609, ENST00000862392, ENST00000862393, ENST00000862394, ENST00000862395, ENST00000862396, ENST00000862397, ENST00000928507, ENST00000952724, ENST00000952725, ENST00000952726, ENST00000952727

RefSeq mRNA: 2 — MANE Select: NM_004041 NM_004041, NM_020251

CCDS: CCDS31640, CCDS44684

Canonical transcript exons

ENST00000420843 — 16 exons

Exon	Start	End
ENSE00000927589	75267652	75267703
ENSE00000927594	75277364	75277448
ENSE00000927595	75278609	75278744
ENSE00001238499	75268889	75268959
ENSE00001752193	75271701	75271724
ENSE00002189681	75260122	75266274
ENSE00003478208	75283287	75283483
ENSE00003503523	75274074	75274211
ENSE00003524426	75290009	75290039
ENSE00003536482	75287315	75287375
ENSE00003558831	75272895	75272978
ENSE00003566059	75284235	75284279
ENSE00003593647	75281075	75281142
ENSE00003615650	75276839	75276911
ENSE00003621626	75281962	75282021
ENSE00003849621	75351588	75351661

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 96.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.8167 / max 208.0069, expressed in 1683 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121345	9.5323	1426
121347	6.4412	1387
121346	4.1440	1229
121344	2.4128	895
121349	1.3732	326
121338	0.4300	253
121348	0.2334	112
121341	0.0974	52
121350	0.0771	43
121342	0.0753	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.26	gold quality
leukocyte	CL:0000738	95.27	gold quality
mononuclear cell	CL:0000842	95.27	gold quality
granulocyte	CL:0000094	95.07	gold quality
right lung	UBERON:0002167	93.02	gold quality
upper lobe of left lung	UBERON:0008952	92.92	gold quality
adrenal tissue	UBERON:0018303	92.83	gold quality
anterior cingulate cortex	UBERON:0009835	92.74	gold quality
sural nerve	UBERON:0015488	92.61	gold quality
cingulate cortex	UBERON:0003027	92.58	gold quality
upper lobe of lung	UBERON:0008948	92.52	gold quality
cortical plate	UBERON:0005343	92.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.35	gold quality
right frontal lobe	UBERON:0002810	92.15	gold quality
prefrontal cortex	UBERON:0000451	92.09	gold quality
nucleus accumbens	UBERON:0001882	92.09	gold quality
body of stomach	UBERON:0001161	91.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.90	gold quality
mucosa of stomach	UBERON:0001199	91.84	gold quality
lower esophagus	UBERON:0013473	91.82	gold quality
tendon of biceps brachii	UBERON:0008188	91.17	gold quality
stomach	UBERON:0000945	91.12	gold quality
apex of heart	UBERON:0002098	90.83	gold quality
caudate nucleus	UBERON:0001873	90.66	gold quality
amygdala	UBERON:0001876	90.61	gold quality
medial globus pallidus	UBERON:0002477	90.43	gold quality
blood	UBERON:0000178	90.19	gold quality
colonic epithelium	UBERON:0000397	89.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.82	gold quality
transverse colon	UBERON:0001157	89.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.17
E-MTAB-6386	no	13.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

315 targeting ARRB1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4715-3P	99.98	66.03	670
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-507	99.97	70.11	1915
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4525	99.94	64.38	675

Literature-anchored findings (GeneRIF, showing 40)

• Determinants in the receptor’s core (Asn-289 and Lys-382) appear to regulate internalization of the receptor/beta-arrestin complex toward early endocytic endosomes during the initial step of endocytosis. (PMID:11726668)
• findings suggest that beta-arrestin 1 acts as an effector for a novel function of PTHrP in cytoplasm (PMID:12220636)
• role of beta-arrestin, dynamin, and clathrin-dependent pathway in internalization of the complement 5a anaphylatoxin receptor (PMID:12464600)
• subcellular localization is determined by their intact N domain and the nuclear export signal at the C terminus (PMID:12538596)
• examination of desensitization, internalization, and signaling functions demonstrated by RNA interference (PMID:12582207)
• both beta-arrestin1 recruitment and the presence of Ser/Thr residues in the distal half of the C-terminal domain were necessary for maximal agonist-induced internalization (PMID:14709160)
• 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)
• D6 is constitutively internalized via a ligand-independent, phosphorylation-independent association with beta-arrestin. (PMID:15084596)
• protease-activated receptor-2-mediated migration of tumor cells requires both beta-arrestin-1 and -2 (PMID:15489220)
• c-Src has a role in regulating the dissociation of AP-2 from agonist-occupied AT1R and beta-arrestin during the clathrin-mediated internalization of receptors (PMID:15498833)
• Mononuclear leukocytes of patients with depression showed significantly reduced immunoreactive quantities of beta-arrestin-1 (PMID:15514408)
• beta-Arrestin 1 and Galphaq/11 have roles in activating RhoA and stress fiber formation following receptor stimulation (PMID:15611106)
• beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+ exchanger NHE5 isoform. (PMID:15699339)
• beta-arrestin has a role in ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase (PMID:15878855)
• 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)
• the beta2 adrenergic receptor has a role in beta-arrestin-dependent, G protein-independent ERK1/2 activation (PMID:16280323)
• results suggest that a GPCR conformation directed by the second intracellular loop, likely using the loop itself as a binding patch, may function as a switch for transitioning beta-arrestin from its inactive form to its active receptor-binding state. (PMID:16319069)
• beta-arrestin 1 is a mediator of cellular migration and metastasis (PMID:16432186)
• beta-arrestin and G proteins activate parathyroid hormone receptor-stimulated ERK1/2 pathways (PMID:16492667)
• 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)
• ERK1/2 is activated by a chimeric neurokinin 1 receptor-beta-arrestin1 fusion protein (PMID:16670094)
• Platelet-activating factor signaling requires beta-arrestin-1 recruitment of a p38 MAP kinase signalosome for transduction before neutrophil endosomal scission. (PMID:16709866)
• analysis of the G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of the angiotensin II type 1A receptor (PMID:17008309)
• results demonstrate the ability of beta-arrestins to recruit diacylglycerol kinases to ligand-activated M1 muscarinic receptors (PMID:17272726)
• Data show that 5-HT(4) receptor stimulation in primary neurons produced a potent but transient activation of the ERK pathway that is dependent on Src tyrosine kinase but totally independent of beta-arrestin. (PMID:17377064)
• MS patients had a greater prevalence of positive T-cell proliferative responses to neuron-specific enolase [NSE], retinal arrestin, and beta-arrestin than healthy controls (p<0.0001). (PMID:17436063)
• ARRB1 and ARRB2 play an important role in biological processes involved in the regulation of smoking urgency (that is time to smoke first cigarette). (PMID:17579607)
• data suggest cells ruffle upon CaSR (calcium sensing receptor)stimulation via a mechanism that involves translocation of beta-arrestin 1 pre-assembled with the CaSR or ARNO (Arf nucleotide binding site opener) (PMID:17623778)
• overexpression of beta-Arr1 promotes matrix metalloproteinase 9 activity and tumor angiogenesis by providing a suitable microenvironment for tumor progression (PMID:17890288)
• Examined interactions between phosphodiesterase 4D5 (PDE4D5) and beta-arrestin and RACK1. (PMID:17900862)
• the AIP4.arrestin-2 complex functions on endosomes to regulate sorting of CXCR4 into the degradative pathway (PMID:17947233)
• beta-arrestins regulate protein synthesis (PMID:18276584)
• beta-arrestins direct the localization of PIP5K Ialpha and PIP(2) production to agonist-activated 7TMRs, thereby regulating receptor internalization (PMID:18534983)
• analysis of the protein kinase A-independent, beta-arrestin-1-dependent signaling pathway for p38 mitogen-activated protein kinase activation by beta2-adrenergic receptors (PMID:18678875)
• Agonist-selective, receptor-specific interaction of human P2Y receptors with beta-arrestin-1 and -2. (PMID:18703513)
• Results identify novel functions of beta-arrestin1 in binding to the beta1gamma2 subunits of heterotrimeric G-proteins and promoting G(betagamma)-mediated Akt signalling for NF-kappaB activation. (PMID:18729826)
• These findings demonstrate that physical interaction of CaM with recombinant and native 5-HT(2C) receptors is critical for G protein-independent, arrestin-dependent receptor signaling. (PMID:18768750)
• Results reveal that nuclear beta-arrestin1, acting as a scaffold for the dephosphorylation of STAT1, is an essential negative regulator of IFN-gamma signaling and participates in the IFN-gamma-induced cellular antiviral response. (PMID:18775329)
• These results show that G(i2) protein is involved in D(2)R-mediated ERK activation but beta-arrestins 1 and 2 are either not involved or play minor role. (PMID:18940181)
• MEK1 binds directly to betaarrestin1, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated internalization (PMID:19153083)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arrb1	ENSDARG00000043241
mus_musculus	Arrb1	ENSMUSG00000018909
rattus_norvegicus	Arrb1	ENSRNOG00000030404
rattus_norvegicus		ENSRNOG00000063241
drosophila_melanogaster	krz	FBGN0040206
caenorhabditis_elegans		WBGENE00000195

Paralogs (3): ARR3 (ENSG00000120500), SAG (ENSG00000130561), ARRB2 (ENSG00000141480)

Protein

Protein identifiers

Beta-arrestin-1 — P49407 (reviewed: P49407)

Alternative names: Arrestin beta-1, Non-visual arrestin-2

All UniProt accessions (6): E9PM35, P49407, H0YD81, H0YDS1, H0YEQ2, H0YET9

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. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. 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). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. 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). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as a signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. 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. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. 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. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6). Involved in IL8-mediated granule release in neutrophils. Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3. Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-protein ligase to the receptor. Involved in some MRGPRE-mediated signaling required to improve glucose tolerance: promotes phosphorylation of ALDOA downstream of MRGPRE activation, increasing glycolysis and leading to GLP-1 secretion.

Subunit / interactions. Monomer. Homodimer. Homooligomer; the self-association is mediated by InsP6-binding. Heterooligomer with ARRB2; the association is mediated by InsP6-binding. Interacts with GPR143. Interacts with ADRB2 (phosphorylated). Interacts with CHRM2 (phosphorylated). Interacts with LHCGR. Interacts with CYTH2 and CASR. Interacts with AP2B1 (dephosphorylated at ‘Tyr-737’); phosphorylation of AP2B1 at ‘Tyr-737’ disrupts the interaction. Interacts (dephosphorylated at Ser-412) with CLTC. Interacts with CCR2 and GRK2. Interacts with CRR5. Interacts with PTAFR (phosphorylated on serine residues). Interacts with CLTC and MAP2K3. Interacts with CREB1. Interacts with TRAF6. Interacts with IGF1R and MDM2. Interacts with C5AR1. Interacts with PDE4D. Interacts with SRC (via the SH3 domain and the protein kinase domain); the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with TACR1. Interacts with RAF1. Interacts with CHUK, IKBKB and MAP3K14. Interacts with DVL1; the interaction is enhanced by phosphorylation of DVL1. Interacts with DVL2; the interaction is enhanced by phosphorylation of DVL2. Interacts with IGF1R. Associates with MAP kinase p38. Part of a MAPK signaling complex consisting of TACR1, ARRB1, SRC, MAPK1 (activated) and MAPK3 (activated). Part of a MAPK signaling complex consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and MAPK3 (activated). Interacts with MAP2K4/MKK4. Interacts with HCK and CXCR1 (phosphorylated). Interacts with ACKR3 and ACKR4. Interacts with ARRDC1; the interaction is direct. Interacts with GPR61, GPR62 and GPR135.

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

Post-translational modifications. Constitutively phosphorylated at Ser-412 in the cytoplasm. At the plasma membrane, is rapidly dephosphorylated, a process that is required for clathrin binding and ADRB2 endocytosis but not for ADRB2 binding and desensitization. Once internalized, is rephosphorylated. 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.

Domain organisation. The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1. Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface. The N-terminus binds InsP6 with low affinity. The C-terminus binds InsP6 with high affinity.

Similarity. Belongs to the arrestin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49407-1	1A	yes
P49407-2	1B

RefSeq proteins (2): NP_004032, NP_064647 (=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 (64 total): strand 29, sequence conflict 7, helix 7, region of interest 5, binding site 4, mutagenesis site 4, modified residue 2, turn 2, chain 1, splice variant 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8AS4	X-RAY DIFFRACTION	2.3
8ZYT	ELECTRON MICROSCOPY	2.65
8ZYU	ELECTRON MICROSCOPY	2.65
2IV8	X-RAY DIFFRACTION	2.8
8ZYY	ELECTRON MICROSCOPY	2.83
9UYN	ELECTRON MICROSCOPY	2.9
9LXR	ELECTRON MICROSCOPY	3.07
9LY2	ELECTRON MICROSCOPY	3.1
9MBA	ELECTRON MICROSCOPY	3.14
8AS2	X-RAY DIFFRACTION	3.2
9LXP	ELECTRON MICROSCOPY	3.2
9UYI	ELECTRON MICROSCOPY	3.2
9L8L	ELECTRON MICROSCOPY	3.22
6TKO	ELECTRON MICROSCOPY	3.3
7SRS	ELECTRON MICROSCOPY	3.3
8JRV	ELECTRON MICROSCOPY	3.3
9UYH	ELECTRON MICROSCOPY	3.3
9UYJ	ELECTRON MICROSCOPY	3.3
9UYL	ELECTRON MICROSCOPY	3.3
9LY3	ELECTRON MICROSCOPY	3.4
9M0D	ELECTRON MICROSCOPY	3.41
8AS3	X-RAY DIFFRACTION	3.5
9UYM	ELECTRON MICROSCOPY	3.5
8WRZ	ELECTRON MICROSCOPY	3.6
9IJS	ELECTRON MICROSCOPY	3.64
9II2	ELECTRON MICROSCOPY	3.7
9IJR	ELECTRON MICROSCOPY	3.86
9II3	ELECTRON MICROSCOPY	3.9
6UP7	ELECTRON MICROSCOPY	4.2
7R0J	ELECTRON MICROSCOPY	4.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49407-F1	82.44	0.55

Antibody-complex structures (SAbDab): 21 — 6PWC, 6TKO, 7R0C, 7R0J, 7SRS, 8AS2, 8AS3, 8WRZ, 8ZYU, 9II2, 9II3, 9IJR, 9IJS, 9LXR, 9MBA, 9UYH, 9UYI, 9UYJ, 9UYL, 9UYM, 9UYN

Functional residue map

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

Ligand- & substrate-binding residues (4): 324; 326; 250; 255

Post-translational modifications (2): 47, 412

Mutagenesis-validated functional residues (4):

Position	Phenotype
169	constitutive active; enables phosphorylation-independent binding to gpcrs.
388	abolishes interaction with ap2b1.
390	abolishes interaction with ap2b1.
393	abolishes interaction with ap2b1.

Function

Pathways and Gene Ontology

Reactome pathways

41 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-418555	G alpha (s) signalling events
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
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-1980143	Signaling by NOTCH1
R-HSA-199991	Membrane Trafficking
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-392499	Metabolism of proteins
R-HSA-5358351	Signaling by Hedgehog
R-HSA-5632684	Hedgehog ‘on’ state
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 520 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOCC_VACUOLAR_MEMBRANE, PEREZ_TP63_TARGETS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, BIOCARTA_BARRESTIN_SRC_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (25): intracellular glucose homeostasis (GO:0001678), positive regulation of protein phosphorylation (GO:0001934), desensitization of G protein-coupled receptor signaling pathway (GO:0002029), G protein-coupled receptor internalization (GO:0002031), positive regulation of receptor internalization (GO:0002092), regulation of transcription by RNA polymerase II (GO:0006357), ubiquitin-dependent protein catabolic process (GO:0006511), cell surface receptor signaling pathway (GO:0007166), sensory perception (GO:0007600), positive regulation of cardiac muscle hypertrophy (GO:0010613), protein transport (GO:0015031), protein ubiquitination (GO:0016567), negative regulation of protein ubiquitination (GO:0031397), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), negative regulation of interleukin-6 production (GO:0032715), negative regulation of interleukin-8 production (GO:0032717), positive regulation of Rho protein signal transduction (GO:0035025), stress fiber assembly (GO:0043149), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of Notch signaling pathway (GO:0045746), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of ERK1 and ERK2 cascade (GO:0070374), signal transduction (GO:0007165), negative regulation of signal transduction (GO:0009968), positive regulation of intracellular signal transduction (GO:1902533)

GO Molecular Function (11): G protein-coupled receptor binding (GO:0001664), transcription coactivator activity (GO:0003713), enzyme inhibitor activity (GO:0004857), GTPase activator activity (GO:0005096), insulin-like growth factor receptor binding (GO:0005159), ubiquitin protein ligase binding (GO:0031625), angiotensin receptor binding (GO:0031701), molecular adaptor activity (GO:0060090), arrestin family protein binding (GO:1990763), protein binding (GO:0005515), enzyme binding (GO:0019899)

GO Cellular Component (16): Golgi membrane (GO:0000139), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), nuclear body (GO:0016604), cytoplasmic vesicle membrane (GO:0030659), endocytic vesicle membrane (GO:0030666), pseudopodium (GO:0031143), cytoplasmic vesicle (GO:0031410), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Oncogenic MAPK signaling	5
trans-Golgi Network Vesicle Budding	2
Signaling by NOTCH1	1
GPCR downstream signalling	1
Platelet activation, signaling and aggregation	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	6
receptor internalization	2
protein ubiquitination	2
negative regulation of cytokine production	2
signaling receptor binding	2
binding	2
protein binding	2
bounding membrane of organelle	2
cytoplasm	2
membrane	2
glucose homeostasis	1
intracellular chemical homeostasis	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
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
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
modification-dependent protein catabolic process	1
signal transduction	1
nervous system process	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein modification by small protein conjugation	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
Rho protein signal transduction	1

Protein interactions and networks

STRING

3779 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARRB1	ADRB2	P07550	999
ARRB1	SRC	P12931	995
ARRB1	AKT1	P31749	985
ARRB1	GRK2	P25098	982
ARRB1	AVPR2	P30518	982
ARRB1	NTSR1	P30989	968
ARRB1	AP2B1	P21851	959
ARRB1	PDE4A	P27815	949
ARRB1	RAPGEF4	Q8WZA2	945
ARRB1	RHO	P08100	944
ARRB1	RAPGEF3	O95398	942
ARRB1	MDM2	Q00987	935
ARRB1	ADRB1	P08588	929
ARRB1	TACR1	P25103	918
ARRB1	CXCR4	P30991	918

IntAct

204 interactions, top by confidence:

A	B	Type	Score
GNMT	ARRB1	psi-mi:“MI:0915”(physical association)	0.890
ARRB1	GNMT	psi-mi:“MI:0915”(physical association)	0.890
ARRB1	GNMT	psi-mi:“MI:0403”(colocalization)	0.890
MAPK9	ARRB1	psi-mi:“MI:0915”(physical association)	0.840
ARRB1	MAPK9	psi-mi:“MI:0915”(physical association)	0.840
ANKRD44	PPP6C	psi-mi:“MI:0914”(association)	0.790
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
ARRB1	ZBTB43	psi-mi:“MI:0915”(physical association)	0.740
ZBTB43	ARRB1	psi-mi:“MI:0915”(physical association)	0.740
ARRB1	ARRB2	psi-mi:“MI:0914”(association)	0.740
ARRB2	ARRB2	psi-mi:“MI:0914”(association)	0.670
EGFR	ARRB1	psi-mi:“MI:0915”(physical association)	0.650
ARRB1	EGFR	psi-mi:“MI:2364”(proximity)	0.650
ARRB1	MDM2	psi-mi:“MI:0915”(physical association)	0.640
ZRANB2	ARRB1	psi-mi:“MI:0915”(physical association)	0.640
MDM2	ARRB1	psi-mi:“MI:0915”(physical association)	0.640
ARRB1	GNAS	psi-mi:“MI:0915”(physical association)	0.640

BioGRID (430): USP33 (Affinity Capture-Western), MAPK9 (Two-hybrid), HGS (Affinity Capture-Western), ARRB1 (Two-hybrid), ARRB1 (Two-hybrid), ZBTB43 (Two-hybrid), GNMT (Two-hybrid), ARRB1 (Reconstituted Complex), ARRB1 (Affinity Capture-Western), ARRB1 (Affinity Capture-Western), ARRB1 (Affinity Capture-Western), ARRB1 (Reconstituted Complex), MDM2 (Affinity Capture-Western), ARRB1 (Reconstituted Complex), ARRB1 (Affinity Capture-Western)

ESM2 similar proteins: A0JN27, A0PJN4, A1L167, A2VEA3, B1H1E4, F1LTR1, G1TGF1, O95164, P49407, P61201, P61202, P61203, P83868, Q07G17, Q13888, Q15185, Q2KJ29, Q2TA46, Q2TBV5, Q32NS4, Q3KNV8, Q3ZBF7, Q5BJT2, Q5F398, Q5NVM4, Q5NVP9, Q5RBN9, Q5SP67, Q5TDH0, Q5XIT1, Q6AYU1, Q6IQT4, Q6IR75, Q6NW85, Q6P1K8, Q6PER3, Q6PFJ9, Q6PWL5, Q86TJ2, Q8BTQ0

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

14 interactions.

A	Effect	B	Mechanism
MAPK1	down-regulates	ARRB1	phosphorylation
MAPK3	down-regulates	ARRB1	phosphorylation
SMO	up-regulates	ARRB1	binding
SRC	down-regulates	ARRB1	phosphorylation
ARRB1	up-regulates	KIF3A	binding
Gbeta	down-regulates	ARRB1	phosphorylation
ERK1/2	down-regulates	ARRB1	phosphorylation
PRKCA	“up-regulates activity”	ARRB1	phosphorylation
ARRB1	“down-regulates activity”	SLC9A5	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	5	29.2×	4e-05
Fc epsilon receptor (FCERI) signaling	8	24.4×	8e-07
MAP kinase activation	5	17.3×	3e-04
MyD88 cascade initiated on plasma membrane	7	16.0×	3e-05
Toll Like Receptor TLR6:TLR2 Cascade	8	15.8×	8e-06
RHOU GTPase cycle	5	15.7×	5e-04
Toll Like Receptor 2 (TLR2) Cascade	8	15.6×	8e-06
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	9	15.4×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
Fc-epsilon receptor signaling pathway	6	40.0×	9e-06
positive regulation of miRNA transcription	6	15.8×	1e-03
tumor necrosis factor-mediated signaling pathway	5	15.0×	5e-03
JNK cascade	6	14.8×	1e-03
cellular senescence	5	13.4×	5e-03
positive regulation of cell growth	6	10.0×	5e-03
transforming growth factor beta receptor signaling pathway	6	8.7×	7e-03
positive regulation of ERK1 and ERK2 cascade	8	6.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3269 predictions. Top by Δscore:

Variant	Effect	Δscore
11:75266166:T:C	donor_gain	1.0000
11:75266206:T:TA	donor_gain	1.0000
11:75266270:CATCA:C	acceptor_gain	1.0000
11:75266272:TCA:T	acceptor_gain	1.0000
11:75266273:CA:C	acceptor_gain	1.0000
11:75266273:CAC:C	acceptor_gain	1.0000
11:75266275:C:CC	acceptor_gain	1.0000
11:75267650:A:AC	donor_gain	1.0000
11:75267651:C:CC	donor_gain	1.0000
11:75271769:C:CT	acceptor_gain	1.0000
11:75271770:A:T	acceptor_gain	1.0000
11:75274067:T:TA	donor_gain	1.0000
11:75274072:A:AC	donor_gain	1.0000
11:75274073:C:CC	donor_gain	1.0000
11:75274073:CAGG:C	donor_gain	1.0000
11:75274101:T:TA	donor_gain	1.0000
11:75274114:T:TA	donor_gain	1.0000
11:75274212:C:CC	acceptor_gain	1.0000
11:75276833:A:AC	donor_gain	1.0000
11:75276834:C:CC	donor_gain	1.0000
11:75276835:TTACT:T	donor_loss	1.0000
11:75276836:TACTC:T	donor_loss	1.0000
11:75276837:A:AC	donor_gain	1.0000
11:75276837:A:C	donor_loss	1.0000
11:75276838:C:CA	donor_gain	1.0000
11:75276838:CT:C	donor_gain	1.0000
11:75276838:CTCAG:C	donor_gain	1.0000
11:75276841:AG:A	donor_gain	1.0000
11:75276842:G:C	donor_gain	1.0000
11:75276908:CGCA:C	acceptor_gain	1.0000

AlphaMissense

2734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:75266243:G:T	R393S	1.000
11:75266247:A:C	F391L	1.000
11:75266247:A:T	F391L	1.000
11:75266248:A:C	F391C	1.000
11:75266248:A:G	F391S	1.000
11:75266249:A:G	F391L	1.000
11:75268930:A:G	L351P	1.000
11:75268942:A:G	L347P	1.000
11:75272932:A:C	Y321D	1.000
11:75272932:A:G	Y321H	1.000
11:75272937:A:T	V319D	1.000
11:75272943:A:G	I317T	1.000
11:75272943:A:T	I317N	1.000
11:75272946:C:T	G316E	1.000
11:75272947:C:A	G316W	1.000
11:75272947:C:G	G316R	1.000
11:75272947:C:T	G316R	1.000
11:75274079:G:C	S303R	1.000
11:75274079:G:T	S303R	1.000
11:75274080:C:A	S303I	1.000
11:75274081:T:G	S303R	1.000
11:75274083:G:A	S302F	1.000
11:75274086:G:T	A301D	1.000
11:75274089:A:C	L300W	1.000
11:75274089:A:G	L300S	1.000
11:75274099:C:G	D297H	1.000
11:75274116:C:A	G291V	1.000
11:75274116:C:T	G291E	1.000
11:75274117:C:A	G291W	1.000
11:75274117:C:G	G291R	1.000

dbSNP variants (sampled 300 via entrez): RS1000016372 (11:75317176 T>C), RS1000024352 (11:75293609 C>A), RS1000049904 (11:75313620 C>G,T), RS1000071742 (11:75288346 C>A,T), RS1000106291 (11:75278535 A>G), RS1000124370 (11:75334200 T>A,C), RS1000135488 (11:75342716 C>T), RS1000160283 (11:75278269 G>A), RS1000208877 (11:75319092 C>T), RS1000218115 (11:75325263 C>T), RS1000270445 (11:75325470 T>C), RS1000280692 (11:75283951 T>C), RS1000297525 (11:75307932 C>T), RS1000334280 (11:75299253 T>C), RS1000336896 (11:75352430 G>A,T)

Disease associations

OMIM: gene MIM:107940 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001859_55	Thiazide-induced adverse metabolic effects in hypertensive patients	6.000000e-06
GCST003675_7	Obstructive sleep apnea trait (average respiratory event duration)	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007817	sleep apnea measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795088 (SINGLE PROTEIN)

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs140226575	ARRB1		0.00	0
rs78979036	ARRB1		0.00	0
rs58428187	ARRB1		0.00	0
rs78052828	ARRB1		0.00	0

ChEMBL bioactivities

21 potent at pChembl≥5 of 22 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.31	EC50	0.4898	nM	CHEMBL5417669
8.03	EC50	9.333	nM	CHEMBL5414487
7.69	EC50	20.42	nM	UROTENSIN-II
7.34	Kd	45.21	nM	CHEMBL5653589
7.34	ED50	45.21	nM	CHEMBL5653589
7.22	EC50	60	nM	CHEMBL5739600
7.02	EC50	95.5	nM	CHEMBL5421473
6.93	EC50	117.5	nM	CHEMBL5401911
6.76	EC50	173.8	nM	CHEMBL5421352
6.57	EC50	270	nM	CHEMBL5905642
6.51	EC50	310	nM	CHEMBL5665374
6.08	EC50	830	nM	CHEMBL5977166
6.07	EC50	851.1	nM	CHEMBL5422077
6.03	EC50	933.2	nM	CHEMBL5416714
5.92	EC50	1202	nM	CHEMBL5396036
5.91	EC50	1230	nM	CHEMBL5423896
5.75	EC50	1778	nM	CHEMBL5406651
5.59	EC50	2560	nM	CHEMBL5895874
5.51	EC50	3100	nM	CHEMBL5946750
5.50	EC50	3170	nM	CHEMBL6052956
5.43	EC50	3670	nM	CHEMBL5806020

PubChem BioAssay actives

12 with measured affinity, of 23 total; 12 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-(4-aminobutyl)-5-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxo-N-(2-phenoxyethyl)-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.0005	uM
3-(4-aminobutyl)-N-benzyl-5-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.0093	uM
(4S)-4-amino-5-[[(2S,3R)-1-[(2S)-2-[[(2S)-1-[[(4R,7S,10S,13S,16S,19R)-10-(4-aminobutyl)-16-benzyl-4-[[(1S)-1-carboxy-2-methylpropyl]carbamoyl]-7-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl]amino]-3-carboxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxopentanoic acid	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.0204	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147895: Binding affinity to human ARRB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0452	uM
3-(4-aminobutyl)-N-(2,2-diphenylethyl)-5-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.0955	uM
3-(4-aminobutyl)-N-benzyl-5-[(E)-2-(4-hydroxyphenyl)ethenyl]-N-methyl-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.1175	uM
3-(4-aminobutyl)-5-[2-(4-hydroxyphenyl)ethyl]-2-oxo-1-[(4-phenylphenyl)methyl]-N-(3-phenylpropyl)-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.1738	uM
3-(4-aminobutyl)-5-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-N-(3-phenylpropyl)-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.8511	uM
3-(4-aminobutyl)-N-benzyl-5-[2-(4-hydroxyphenyl)ethyl]-N-methyl-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	0.9333	uM
3-(4-aminobutyl)-5-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-N-(3-phenylpropyl)-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	1.2023	uM
3-(4-aminobutyl)-N-benzyl-5-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxo-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	1.2303	uM
3-(4-aminobutyl)-5-[2-(4-hydroxyphenyl)ethyl]-2-oxo-N-(2-phenoxyethyl)-1-[(4-phenylphenyl)methyl]-1,3,4-benzotriazepine-8-carboxamide;hydrochloride	2019496: Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	ec50	1.7783	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
bisphenol A	decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol	affects localization, affects reaction, increases reaction, increases phosphorylation	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Carvedilol	increases phosphorylation, increases reaction, increases expression, affects binding, decreases reaction (+1 more)	2
Panobinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance	2
Alprenolol	increases expression, affects binding, increases reaction, increases phosphorylation, affects cotreatment	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Copper	affects binding, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects localization, increases reaction, increases expression (+1 more)	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
methyleugenol	increases expression	1
propionaldehyde	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
benzo(e)pyrene	increases methylation	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1794493	Functional	PUBCHEM_BIOASSAY: Dose Response Assay for Inhibitors of the beta-Arrestin-Adaptor Protein 2 Interaction for Cherry Pick 1. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504490, AID504493, AID504541]	PubChem BioAssay data set
CHEMBL5373404	Binding	Agonist activity at RLucII/GFP10-tagged beta-arrestin-1 (unknown origin) recruitment expressed in HEK293 cells co-expressing human UT assessed as beta-arrestin recruitment by BRET assay	Urotensin II Receptor Modulation with 1,3,4-Benzotriazepin-2-one Tetrapeptide Mimics. — J Med Chem

Cellosaurus cell lines

23 cell lines: 13 cancer cell line, 7 spontaneously immortalized cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B9DM	Abcam A-549 ARRB1 KO	Cancer cell line	Male
CVCL_D7KG	Ubigene A-549 ARRB1 KO	Cancer cell line	Male
CVCL_D8HH	Ubigene HCT 116 ARRB1 KO	Cancer cell line	Male
CVCL_D8ZG	Ubigene HEK293 ARRB1 KO	Transformed cell line	Female
CVCL_D9XU	Ubigene HeLa ARRB1 KO	Cancer cell line	Female
CVCL_KW33	PathHunter CHO-K1 AGTRL1 beta-arrestin-1	Spontaneously immortalized cell line	Female
CVCL_KW42	PathHunter CHO-K1 beta-arrestin1-EA Parental	Spontaneously immortalized cell line	Female
CVCL_KX12	PathHunter CHO-K1 GCGR beta-arrestin-1	Spontaneously immortalized cell line	Female
CVCL_KX16	PathHunter CHO-K1 GLP1R beta-arrestin-1	Spontaneously immortalized cell line	Female
CVCL_KX27	PathHunter CHO-K1 GPR120S beta-arrestin-1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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