General Information of Target

Target ID LDTP04606
Target Name Huntingtin-associated protein 1 (HAP1)
Gene Name HAP1
Gene ID 9001
Synonyms
HAP2; HLP1; Huntingtin-associated protein 1; HAP-1; Neuroan 1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MRPKRLGRCCAGSRLGPGDPAALTCAPSPSASPAPEPSAQPQARGTGQRVGSRATSGSQF
LSEARTGARPASEAGAKAGARRPSAFSAIQGDVRSMPDNSDAPWTRFVFQGPFGSRATGR
GTGKAAGIWKTPAAYVGRRPGVSGPERAAFIRELEEALCPNLPPPVKKITQEDVKVMLYL
LEELLPPVWESVTYGMVLQRERDLNTAARIGQSLVKQNSVLMEENSKLEALLGSAKEEIL
YLRHQVNLRDELLQLYSDSDEEDEDEEEEEEEKEAEEEQEEEEAEEDLQCAHPCDAPKLI
SQEALLHQHHCPQLEALQEKLRLLEEENHQLREEASQLDTLEDEEQMLILECVEQFSEAS
QQMAELSEVLVLRLENYERQQQEVARLQAQVLKLQQRCRMYGAETEKLQKQLASEKEIQM
QLQEESVWVGSQLQDLREKYMDCGGMLIEMQEEVKTLRQQPPVSTGSATHYPYSVPLETL
PGFQETLAEELRTSLRRMISDPVYFMERNYEMPRGDTSSLRYDFRYSEDREQVRGFEAEE
GLMLAADIMRGEDFTPAEEFVPQEELGAAKKVPAEEGVMEEAELVSEETEGWEEVELELD
EATRMNVVTSALEASGLGPSHLDMNYVLQQLANWQDAHYRRQLRWKMLQKGECPHGALPA
ASRTSCRSSCR
Target Bioclass
Other
Subcellular location
Cytoplasm
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).
Uniprot ID
P54257
Ensemble ID
ENST00000310778.5
HGNC ID
HGNC:4812

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
ENE
 Probe Info 
N.A.  LDD0006  [1]
VSF
 Probe Info 
N.A.  LDD0007  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Serine/threonine-protein kinase N1 (PKN1) AGC Ser/Thr protein kinase family Q16512
Cyclin-dependent kinase 18 (CDK18) CMGC Ser/Thr protein kinase family Q07002
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Huntingtin (HTT) Huntingtin family P42858
Sodium channel modifier 1 (SCNM1) . Q9BWG6
Transcription factor
Click To Hide/Show 9 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein Hox-B5 (HOXB5) Antp homeobox family P09067
Zinc finger protein 1 homolog (ZFP1) Krueppel C2H2-type zinc-finger protein family Q6P2D0
Zinc finger protein 124 (ZNF124) Krueppel C2H2-type zinc-finger protein family Q15973
Zinc finger protein 490 (ZNF490) Krueppel C2H2-type zinc-finger protein family Q9ULM2
Zinc finger protein 572 (ZNF572) Krueppel C2H2-type zinc-finger protein family Q7Z3I7
Zinc finger protein 575 (ZNF575) Krueppel C2H2-type zinc-finger protein family Q86XF7
Zinc finger protein 648 (ZNF648) Krueppel C2H2-type zinc-finger protein family Q5T619
Zinc finger protein 835 (ZNF835) Krueppel C2H2-type zinc-finger protein family Q9Y2P0
Mesogenin-1 (MSGN1) . A6NI15
Other
Click To Hide/Show 11 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Gamma-aminobutyric acid receptor-associated protein-like 2 (GABARAPL2) ATG8 family P60520
Protein FAM50B (FAM50B) FAM50 family Q9Y247
U4/U6 small nuclear ribonucleoprotein Prp31 (PRPF31) PRP31 family Q8WWY3
Rhophilin-1 (RHPN1) RHPN family Q8TCX5
UPF0500 protein C1orf216 (C1orf216) UPF0500 family Q8TAB5
Cation channel sperm-associated targeting subunit tau (C2CD6) . Q53TS8
Coiled-coil domain-containing protein 13 (CCDC13) . Q8IYE1
Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) . O14964
Jouberin (AHI1) . Q8N157
Phostensin (PPP1R18) . Q6NYC8
Zinc finger matrin-type protein 2 (ZMAT2) . Q96NC0

References

1 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764