DegronMD - P54257(HAP1)

FUNCTION: Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via association with microtubule-dependent transporters can be attenuated by association with mutant HTT. Involved in the axonal transport of BDNF and its activity-dependent secretion; the function seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP trafficking and seems to facilitate APP anterograde transport and membrane insertion thereby possibly reducing processing into amyloid beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptors to synapses; the function is dependent on kinesin motor protein KIF5 and is disrupted by HTT with expanded polyglutamine repeat. Involved in regulation of autophagosome motility by promoting efficient retrograde axonal transport. Seems to be involved in regulation of membrane receptor recycling and degradation, and respective signal transduction, including GABA(A) receptors, tyrosine kinase receptors, EGFR, IP3 receptor and androgen receptor. Among others suggested to be involved in control of feeding behavior (involving hypothalamic GABA(A) receptors), cerebellar and brainstem development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis (involving hypothalamic NTRK2/TrkB), and ITPR1/InsP3R1-mediated Ca(2+) release (involving HTT and possibly the effect of mutant HTT). Via association with DCTN1/dynactin p150-glued and HTT/huntingtin involved in cytoplasmic retention of REST in neurons. May be involved in ciliogenesis. Involved in regulation of exocytosis. Seems to be involved in formation of cytoplasmic inclusion bodies (STBs). In case of anomalous expression of TBP, can sequester a subset of TBP into STBs; sequestration is enhanced by an expanded polyglutamine repeat within TBP. HAP1-containing STBs have been proposed to play a protective role against neurodegeneration in Huntigton disease (HD) and spinocerebellar ataxia 17 (SCA17). {ECO:0000269|PubMed:18922795}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D250N	TCGA-33-4566	LUSC	TCGA	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.25
p.E262K	TCGA-FW-A3R5	SKCM	TCGA	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.2222
p.R257W	DO225337	BRCA	ICGC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.8634
p.Q262H	DO228422	LICA	ICGC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.2222
p.D258N	DO26790	LUSC	ICGC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.6932
p.E245K	DO27074	LUSC	ICGC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.1111
p.E245K	DO220239	SARC	ICGC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.1111
p.A243V	DO220899	MELA	ICGC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.0556
p.Y256S	SIDM01004	Chronic Myelogenous Leukemia	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00216	Colorectal Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00075	Non-Cancerous	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00193	Colorectal Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00267	Biliary Tract Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00590	Oral Cavity Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00293	Small Cell Lung Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00598	Squamous Cell Lung Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00251	Gastric Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00489	Oral Cavity Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00273	Glioblastoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SIDM00171	Colorectal Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SNU-175	large intestine	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	KCL-22	haematopoietic and lymphoid tissue	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.Y256S	SNU-81	large intestine	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation altering degron motif	0.712
p.H244Y	SIDM01219	Non-Small Cell Lung Carcinoma	GDSC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.0833
p.H244Y	LU-99A	lung	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.0833
p.H252Y	LU-99A	lung	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.3056
p.Y264S	SNU-81	large intestine	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.1667
p.Y264S	KCL-22	haematopoietic and lymphoid tissue	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.1667
p.Y264S	SNU-175	large intestine	COSMIC	LQLYSD	LIG_APCC_ABBA_1	253:258	Mutation rewiring degron network	0.1667

Kaplan plot for HAP1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

HAP1

UniProt ID: P54257

Entrez ID: 9001

Protein name: Huntingtin-associated protein 1 (HAP-1) (Neuroan 1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for HAP1 in