P54257 · HAP1_HUMAN
- ProteinHuntingtin-associated protein 1
- GeneHAP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids671 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 Ca2+ 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).
Miscellaneous
Was not found in huntingtin-containing aggregates in huntigton disease (HD) tissue.
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHuntingtin-associated protein 1
- Short namesHAP-1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP54257
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_046736 | 4 | in dbSNP:rs4796604 | |||
Sequence: K → R | ||||||
Natural variant | VAR_046737 | 58 | in dbSNP:rs4796603 | |||
Sequence: S → T | ||||||
Natural variant | VAR_046738 | 357 | in dbSNP:rs4796693 | |||
Sequence: S → L | ||||||
Natural variant | VAR_056906 | 408 | in dbSNP:rs35612698 | |||
Sequence: L → F | ||||||
Natural variant | VAR_046739 | 437 | in dbSNP:rs11867808 | |||
Sequence: R → W | ||||||
Natural variant | VAR_046741 | 483 | in dbSNP:rs8075017 | |||
Sequence: F → L | ||||||
Natural variant | VAR_046742 | 488 | in dbSNP:rs34853043 | |||
Sequence: A → V | ||||||
Natural variant | VAR_056907 | 493 | may influence the age-at-onset of Huntington disease; increases binding to mutated HTT; influences HTT degradation; dbSNP:rs4523977 | |||
Sequence: T → M | ||||||
Natural variant | VAR_056908 | 557 | in dbSNP:rs34853043 | |||
Sequence: A → V | ||||||
Natural variant | VAR_062817 | 560 | in dbSNP:rs8075017 | |||
Sequence: F → L | ||||||
Natural variant | VAR_056909 | 656 | in dbSNP:rs34044330 | |||
Sequence: G → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 999 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000083894 | 1-671 | Huntingtin-associated protein 1 | |||
Sequence: MRPKRLGRCCAGSRLGPGDPAALTCAPSPSASPAPEPSAQPQARGTGQRVGSRATSGSQFLSEARTGARPASEAGAKAGARRPSAFSAIQGDVRSMPDNSDAPWTRFVFQGPFGSRATGRGTGKAAGIWKTPAAYVGRRPGVSGPERAAFIRELEEALCPNLPPPVKKITQEDVKVMLYLLEELLPPVWESVTYGMVLQRERDLNTAARIGQSLVKQNSVLMEENSKLEALLGSAKEEILYLRHQVNLRDELLQLYSDSDEEDEDEEEEEEEKEAEEEQEEEEAEEDLQCAHPCDAPKLISQEALLHQHHCPQLEALQEKLRLLEEENHQLREEASQLDTLEDEEQMLILECVEQFSEASQQMAELSEVLVLRLENYERQQQEVARLQAQVLKLQQRCRMYGAETEKLQKQLASEKEIQMQLQEESVWVGSQLQDLREKYMDCGGMLIEMQEEVKTLRQQPPVSTGSATHYPYSVPLETLPGFQETLAEELRTSLRRMISDPVYFMERNYEMPRGDTSSLRYDFRYSEDREQVRGFEAEEGLMLAADIMRGEDFTPAEEFVPQEELGAAKKVPAEEGVMEEAELVSEETEGWEEVELELDEATRMNVVTSALEASGLGPSHLDMNYVLQQLANWQDAHYRRQLRWKMLQKGECPHGALPAASRTSCRSSCR |
Proteomic databases
PTM databases
Expression
Tissue specificity
Predominantly expressed in brain. Selectively expressed in neurons.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Self-associates. Interacts with HTT/huntingtin; enhanced by an expanded polyglutamine repeat within HTT. Interacts with DCTN1; decreased in presence of HTT with expanded polyglutamine repeat. Interacts with KLC2. Interacts with ITPR1 and APP. Interacts with AR; decreased by an expanded polyglutamine repeat within AR. Interacts with YWHAZ. Interacts with BDNF and SORT1; probably forming a complex involved in proBDNF trafficking, degradation and processing. Interacts with TBP, AHI1, HGS and KALRN. Interacts with KIF5A, KIF5B, KIF5C and GABRB3; indicative for an HAP1:KIF5 complex transporting a GABA(A) receptor as cargo. Interacts with ATXN3; in STBs with ATXN3 poly-Gln region with 27 repeats (normal population) and 79 repeats (spinocerebellar ataxia 3 (SCA3) patients) associating in the same strength. Interacts with NTRK2; HAP1 stabilizes association of NTRK2 with SORT1 preventing NTRK2 degradation. Interacts with CFAP263.
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-83 | Disordered | ||||
Sequence: MRPKRLGRCCAGSRLGPGDPAALTCAPSPSASPAPEPSAQPQARGTGQRVGSRATSGSQFLSEARTGARPASEAGAKAGARRP | ||||||
Compositional bias | 37-65 | Polar residues | ||||
Sequence: PSAQPQARGTGQRVGSRATSGSQFLSEAR | ||||||
Domain | 106-461 | HAP1 N-terminal | ||||
Sequence: RFVFQGPFGSRATGRGTGKAAGIWKTPAAYVGRRPGVSGPERAAFIRELEEALCPNLPPPVKKITQEDVKVMLYLLEELLPPVWESVTYGMVLQRERDLNTAARIGQSLVKQNSVLMEENSKLEALLGSAKEEILYLRHQVNLRDELLQLYSDSDEEDEDEEEEEEEKEAEEEQEEEEAEEDLQCAHPCDAPKLISQEALLHQHHCPQLEALQEKLRLLEEENHQLREEASQLDTLEDEEQMLILECVEQFSEASQQMAELSEVLVLRLENYERQQQEVARLQAQVLKLQQRCRMYGAETEKLQKQLASEKEIQMQLQEESVWVGSQLQDLREKYMDCGGMLIEMQEEVKTLRQQP | ||||||
Coiled coil | 212-427 | |||||
Sequence: QSLVKQNSVLMEENSKLEALLGSAKEEILYLRHQVNLRDELLQLYSDSDEEDEDEEEEEEEKEAEEEQEEEEAEEDLQCAHPCDAPKLISQEALLHQHHCPQLEALQEKLRLLEEENHQLREEASQLDTLEDEEQMLILECVEQFSEASQQMAELSEVLVLRLENYERQQQEVARLQAQVLKLQQRCRMYGAETEKLQKQLASEKEIQMQLQEESV | ||||||
Compositional bias | 258-288 | Acidic residues | ||||
Sequence: DSDEEDEDEEEEEEEKEAEEEQEEEEAEEDL | ||||||
Region | 258-289 | Disordered | ||||
Sequence: DSDEEDEDEEEEEEEKEAEEEQEEEEAEEDLQ |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing. Additional isoforms seem to exist.
P54257-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length671
- Mass (Da)75,506
- Last updated2010-03-02 v3
- Checksum10971B807941B4EE
P54257-2
- Name2
- Differences from canonical
- 426-477: Missing
P54257-3
- Name3
- Differences from canonical
- 401-477: Missing
P54257-4
- Name4
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 37-65 | Polar residues | ||||
Sequence: PSAQPQARGTGQRVGSRATSGSQFLSEAR | ||||||
Alternative sequence | VSP_038754 | 183 | in isoform 4 | |||
Sequence: E → EVCTAFLIQ | ||||||
Sequence conflict | 184-199 | in Ref. 6; CAB82785 | ||||
Sequence: Missing | ||||||
Compositional bias | 258-288 | Acidic residues | ||||
Sequence: DSDEEDEDEEEEEEEKEAEEEQEEEEAEEDL | ||||||
Alternative sequence | VSP_004277 | 401-477 | in isoform 3 and isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_004278 | 426-477 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 573 | in Ref. 3; BAB13952 | ||||
Sequence: P → L | ||||||
Sequence conflict | 579 | in Ref. 1; AAC39861 | ||||
Sequence: M → V | ||||||
Sequence conflict | 611 | in Ref. 7; AAC50297 | ||||
Sequence: A → T |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF040723 EMBL· GenBank· DDBJ | AAC39861.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ012824 EMBL· GenBank· DDBJ | CAC09418.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK022007 EMBL· GenBank· DDBJ | BAB13952.1 EMBL· GenBank· DDBJ | mRNA | ||
AC109319 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AB209105 EMBL· GenBank· DDBJ | BAD92342.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ224877 EMBL· GenBank· DDBJ | CAB82785.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U38371 EMBL· GenBank· DDBJ | AAC50297.1 EMBL· GenBank· DDBJ | mRNA |