ASB11

Summary

ASB11 (ankyrin repeat and SOCS box containing 11, HGNC:17186) is a protein-coding gene on chromosome Xp22.2, encoding Ankyrin repeat and SOCS box protein 11 (Q8WXH4). Substrate-recognition component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex, also named CRL5 complex), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as BIK, DIRAS2 and RPN1.

The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 140456 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_080873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17186
Approved symbol	ASB11
Name	ankyrin repeat and SOCS box containing 11
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp779E2460
Ensembl gene	ENSG00000165192
Ensembl biotype	protein_coding
OMIM	300626
Entrez	140456

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000344384, ENST00000380470, ENST00000480796, ENST00000485437, ENST00000964851

RefSeq mRNA: 3 — MANE Select: NM_080873 NM_001012428, NM_001201583, NM_080873

CCDS: CCDS14164, CCDS35209, CCDS56596

Canonical transcript exons

ENST00000480796 — 7 exons

Exon	Start	End
ENSE00001091145	15302728	15302807
ENSE00001091147	15293170	15293320
ENSE00001159152	15297574	15297681
ENSE00001334233	15281697	15283629
ENSE00001894215	15315425	15315640
ENSE00003504396	15287881	15288072
ENSE00003634273	15289504	15289638

Expression profiles

Bgee: expression breadth broad, 65 present calls, max score 92.71.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8355 / max 150.5289, expressed in 66 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198520	0.4134	49
198521	0.3853	47
198519	0.0206	12
198522	0.0161	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	92.71	gold quality
gastrocnemius	UBERON:0001388	89.12	gold quality
muscle of leg	UBERON:0001383	88.38	gold quality
heart left ventricle	UBERON:0002084	85.53	gold quality
cardiac ventricle	UBERON:0002082	84.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.50	gold quality
skeletal muscle tissue	UBERON:0001134	84.04	gold quality
biceps brachii	UBERON:0001507	83.72	gold quality
right atrium auricular region	UBERON:0006631	83.27	gold quality
cardiac atrium	UBERON:0002081	82.32	gold quality
apex of heart	UBERON:0002098	81.62	gold quality
vastus lateralis	UBERON:0001379	79.71	gold quality
quadriceps femoris	UBERON:0001377	79.36	gold quality
heart right ventricle	UBERON:0002080	79.17	gold quality
heart	UBERON:0000948	79.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.83	silver quality
muscle tissue	UBERON:0002385	78.73	gold quality
myocardium	UBERON:0002349	77.88	silver quality
body of tongue	UBERON:0011876	62.38	silver quality
body of stomach	UBERON:0001161	61.38	gold quality
deltoid	UBERON:0001476	60.56	gold quality
stomach	UBERON:0000945	58.96	gold quality
jejunum	UBERON:0002115	51.51	silver quality
islet of Langerhans	UBERON:0000006	49.39	gold quality
fundus of stomach	UBERON:0001160	49.23	gold quality
bone marrow cell	CL:0002092	46.71	gold quality
sural nerve	UBERON:0015488	45.62	gold quality
pharyngeal mucosa	UBERON:0000355	45.43	gold quality
superior surface of tongue	UBERON:0007371	43.68	gold quality
amniotic fluid	UBERON:0000173	43.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting ASB11, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978

Literature-anchored findings (GeneRIF, showing 2)

• ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. (PMID:24337577)
• study reveals that different cellular stresses regulate BIK ubiquitination by ASB11 in opposing directions, which determines whether or not cells survive, and that blocking BIK degradation has the potential to be used as an anti-cancer strategy. (PMID:31387940)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asb11	ENSMUSG00000031382
rattus_norvegicus	Asb11	ENSRNOG00000003452

Paralogs (2): ASB9 (ENSG00000102048), ASB5 (ENSG00000164122)

Protein

Protein identifiers

Ankyrin repeat and SOCS box protein 11 — Q8WXH4 (reviewed: Q8WXH4)

All UniProt accessions (2): Q8WXH4, F8WF31

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex, also named CRL5 complex), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as BIK, DIRAS2 and RPN1. The ECS(ASB11) complex acts as a regulator of the endoplasmic reticulum unfolded protein response by mediating ubiquitination and degradation of BIK.

Subunit / interactions. Substrate-recognition component of the ECS(ASB11) complex, composed of ASB11, CUL5, ELOB, ELOC and RNF7/RBX2.

Subcellular location. Endoplasmic reticulum.

Induction. Expression is induced by XBP1 in response to endoplasmic reticulum stress.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the ankyrin SOCS box (ASB) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WXH4-1	1	yes
Q8WXH4-2	2
Q8WXH4-3	3

RefSeq proteins (3): NP_001012428, NP_001188512, NP_543149* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001496	SOCS_box	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR036036	SOCS_box-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037333	ASB9/11_SOCS	Domain
IPR051573	Ankyrin-SOCS_box_domain	Family

Pfam: PF07525, PF12796

UniProt features (28 total): helix 14, repeat 6, sequence variant 3, splice variant 2, chain 1, turn 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4UUC	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXH4-F1	87.28	0.58

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8951664	Neddylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 109 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_PROTEIN_K11_LINKED_UBIQUITINATION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, BRN2_01, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, TGACATY_UNKNOWN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION

GO Biological Process (6): protein ubiquitination (GO:0016567), endoplasmic reticulum unfolded protein response (GO:0030968), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of protein catabolic process (GO:0045732), protein K11-linked ubiquitination (GO:0070979), intracellular signal transduction (GO:0035556)

GO Molecular Function (2): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), Cul5-RING ubiquitin ligase complex (GO:0031466), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Post-translational protein modification	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
protein modification by small protein conjugation	1
cellular response to unfolded protein	1
response to endoplasmic reticulum stress	1
intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
protein polyubiquitination	1
intracellular anatomical structure	1
signal transduction	1
enzyme-substrate adaptor activity	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

1592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASB11	RPN1	P04843	748
ASB11	CISH	Q9NSE2	659
ASB11	ANKRD9	Q96BM1	650
ASB11	NEUROG1	Q92886	636
ASB11	SOX3	P35714	591
ASB11	ASB17	Q8WXJ9	568
ASB11	KLHL21	Q9UJP4	536
ASB11	B7Z1P2	B7Z1P2	533
ASB11	TRIM63	Q969Q1	515
ASB11	FBXO32	Q969P5	511
ASB11	ASB6	Q9NWX5	508
ASB11	FBXO40	Q9UH90	453
ASB11	ZBTB16	Q05516	431
ASB11	SOX2	P48431	427
ASB11	LRRC30	A6NM36	426

IntAct

0 interactions, top by confidence:

BioGRID (262): CUL5 (Co-localization), RPN1 (Co-localization), ASB11 (PCA), CUL5 (Reconstituted Complex), RNF7 (Reconstituted Complex), TCEB1 (Reconstituted Complex), TCEB2 (Reconstituted Complex), BIK (Affinity Capture-Western), BIK (Reconstituted Complex), ASB11 (Affinity Capture-MS), BIK (Biochemical Activity), PAICS (Proximity Label-MS), HSPA4L (Proximity Label-MS), ABCA10 (Proximity Label-MS), ACBD3 (Proximity Label-MS)

ESM2 similar proteins: A2AS55, B2RXR6, O15084, O75832, P0C927, Q08DV6, Q0P5B9, Q29RM5, Q2TB02, Q3SX45, Q495B1, Q499M5, Q4V890, Q502K3, Q505D1, Q53RE8, Q5F478, Q5RFS1, Q5U2S6, Q5ZLC8, Q6GPE5, Q6P6B7, Q6P9Z4, Q70X92, Q7T3P8, Q810B6, Q8BTI7, Q8C0T1, Q8C6Y6, Q8K0L0, Q8N8A2, Q8NB46, Q8NI38, Q8WXH4, Q91ZT8, Q96AX9, Q96DX5, Q96NS5, Q96Q27, Q9BSK4

Diamond homologs: Q02989, Q17QS6, Q3SZE4, Q5RFS1, Q70X92, Q810B6, Q862Z2, Q8VBX0, Q8WWX0, Q8WXH4, Q8WXK3, Q91ZT8, Q91ZU0, Q96DX5, Q9BSK4, Q9CQ31, Q9D1A4, Q9J4Z6, Q9WV74, Q9XZC0, Q9Y576, O90760, Q18297, Q21209, Q96NS5, A2ARS0, A2AS55, C9JTQ0, H9JD76, O75179, P58223, Q05823, Q21920, Q5XJ13, Q60J38, Q6GQX6, Q8IWZ3, Q99NH0, Q9VCA8, A2AQH4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ASB11	“down-regulates quantity by destabilization”	RPN1	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1432 predictions. Top by Δscore:

Variant	Effect	Δscore
X:15287868:AGC:A	donor_gain	1.0000
X:15287877:TTA:T	donor_loss	1.0000
X:15287878:TA:T	donor_loss	1.0000
X:15287879:ACC:A	donor_loss	1.0000
X:15287880:C:CA	donor_loss	1.0000
X:15288074:T:C	acceptor_gain	1.0000
X:15293169:CCT:C	donor_gain	1.0000
X:15293169:CCTCT:C	donor_gain	1.0000
X:15297572:A:AC	donor_gain	1.0000
X:15297573:C:CC	donor_gain	1.0000
X:15283627:GGCC:G	acceptor_loss	0.9900
X:15283628:GCC:G	acceptor_loss	0.9900
X:15283629:CCTG:C	acceptor_loss	0.9900
X:15283630:C:CC	acceptor_gain	0.9900
X:15283631:T:C	acceptor_loss	0.9900
X:15287880:CCT:C	donor_gain	0.9900
X:15288070:CTC:C	acceptor_gain	0.9900
X:15288072:CCT:C	acceptor_gain	0.9900
X:15288073:C:CC	acceptor_gain	0.9900
X:15288073:CTT:C	acceptor_loss	0.9900
X:15288074:T:A	acceptor_loss	0.9900
X:15289638:CCT:C	acceptor_loss	0.9900
X:15289639:C:CC	acceptor_gain	0.9900
X:15289639:C:CG	acceptor_loss	0.9900
X:15289650:CAAGA:C	acceptor_loss	0.9900
X:15290334:AAAC:A	donor_gain	0.9900
X:15293167:TA:T	donor_loss	0.9900
X:15293168:A:AT	donor_loss	0.9900
X:15293169:C:T	donor_loss	0.9900
X:15293320:CC:C	acceptor_loss	0.9900

AlphaMissense

2092 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:15297627:A:G	C106R	0.996
X:15297625:G:C	C106W	0.994
X:15297630:C:G	A105P	0.994
X:15302763:C:A	G76W	0.994
X:15302775:C:G	A72P	0.993
X:15293275:A:G	C139R	0.992
X:15293278:C:G	A138P	0.992
X:15297593:A:G	L117S	0.992
X:15302772:C:G	A73P	0.992
X:15297638:A:T	L102H	0.991
X:15302747:A:G	L81P	0.991
X:15302771:G:T	A73E	0.991
X:15297604:A:C	C113W	0.990
X:15297626:C:T	C106Y	0.990
X:15293273:G:C	C139W	0.989
X:15297629:G:T	A105E	0.989
X:15297606:A:G	C113R	0.988
X:15289515:A:G	L215P	0.987
X:15302762:C:A	G76V	0.987
X:15293277:G:T	A138D	0.986
X:15297638:A:G	L102P	0.985
X:15302747:A:T	L81H	0.985
X:15315454:A:T	I51K	0.985
X:15315464:C:G	A48P	0.985
X:15293289:G:T	P134H	0.984
X:15293289:G:C	P134R	0.983
X:15315452:C:G	A52P	0.983
X:15315454:A:G	I51T	0.983
X:15289549:A:G	C204R	0.982
X:15293182:C:G	A170P	0.982

dbSNP variants (sampled 300 via entrez): RS1000060589 (X:15282199 A>C,G), RS1000129205 (X:15289171 C>T), RS1000244218 (X:15289589 G>A), RS1000599872 (X:15286871 A>T), RS1000718222 (X:15305715 A>T), RS1000740223 (X:15298080 C>G,T), RS1000968791 (X:15310367 G>A), RS1000978561 (X:15305330 G>A), RS1001096254 (X:15298461 C>A), RS1001118112 (X:15290824 C>T), RS1001275095 (X:15291320 C>G,T), RS1001366969 (X:15300490 T>C), RS1001535485 (X:15309105 C>A,T), RS1001589311 (X:15309492 A>G), RS1001592768 (X:15305420 C>T)

Disease associations

OMIM: gene MIM:300626 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009571_1	vascular endothelial growth factor D levels	1.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010575	vascular endothelial growth factor D measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Doxorubicin	decreases expression	2
4-aminophenylarsenoxide	affects binding, decreases reaction	1
clothianidin	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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