InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HAP1

Summary

InnateDB Protein

IDBP-49701.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HAP1

Protein Name

huntingtin-associated protein 1

Synonyms

HAP2; hHLP1; HIP5; HLP;

Species

Homo sapiens

Ensembl Protein

ENSP00000309392

InnateDB Gene

IDBG-49695 (HAP1)

Protein Structure

UniProt Annotation

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 faciltate 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:0000269PubMed:18922795}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:9742138}. Cell projection, axon {ECO:0000269PubMed:9742138}. Cytoplasm, cytoskeleton {ECO:0000250}. Lysosome {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle {ECO:0000250}. Mitochondrion {ECO:0000305PubMed:9742138}. Nucleus {ECO:0000250}. Cytoplasmic vesicle, autophagosome {ECO:0000250}. Note=Localizes to large nonmembrane-bound cytoplasmic bodies found in various types of neurons, called stigmoid bodies (STBs). Localization to neuronal processes and neurite tips is decreased by YWHAZ. In the nucleus localizes to nuclear rods (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Predominantly expressed in brain. Selectively expressed in neurons.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 82 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	82 [view]
Protein-Protein	82 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding

Biological Process

GO:0007268	synaptic transmission
GO:0007420	brain development
GO:0008104	protein localization

Cellular Component

GO:0005856	cytoskeleton
GO:0015629	actin cytoskeleton

Protein Structure and Domains

PDB ID

InterPro

IPR006933 HAP1, N-terminal

PFAM

PF04849

PRINTS

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P54257

PhosphoSite

PhosphoSite-P54257

TrEMBL

UniProt Splice Variant

Entrez Gene

9001

UniGene

Hs.669865

RefSeq

HUGO

HGNC:4812

OMIM

600947

CCDS

HPRD

02972

IMGT

EMBL

AB209105 AC109319 AF040723 AJ012824 AJ224877 AK022007 U38371

GenPept

AAC39861 AAC50297 BAB13952 BAD92342 CAB82785 CAC09418