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Protein

Huntingtin-associated protein 1

Gene

Hap1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 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. Isoform A but not isoform B 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.13 Publications

GO - Molecular functioni

  • brain-derived neurotrophic factor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • ion channel binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • receptor binding Source: RGD

GO - Biological processi

  • anterograde axonal transport Source: UniProtKB
  • autophagy Source: UniProtKB-KW
  • cell projection organization Source: UniProtKB-KW
  • cellular response to growth factor stimulus Source: RGD
  • early endosome to late endosome transport Source: RGD
  • exocytosis Source: UniProtKB-KW
  • negative regulation of beta-amyloid formation Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • neurotrophin TRK receptor signaling pathway Source: UniProtKB
  • positive regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of inclusion body assembly Source: UniProtKB
  • positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity Source: UniProtKB
  • positive regulation of neuron projection development Source: RGD
  • positive regulation of neurotrophin production Source: UniProtKB
  • positive regulation of nonmotile primary cilium assembly Source: UniProtKB
  • positive regulation of synaptic transmission, GABAergic Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of exocytosis Source: UniProtKB
  • regulation of organelle transport along microtubule Source: UniProtKB
  • retrograde axonal transport Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Autophagy, Cilium biogenesis/degradation, Exocytosis, Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Huntingtin-associated protein 1
Short name:
HAP-1
Gene namesi
Name:Hap1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi68327. Hap1.

Subcellular locationi

GO - Cellular componenti

  • autophagosome Source: UniProtKB-SubCell
  • axon cytoplasm Source: GOC
  • axon terminus Source: RGD
  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • cytoskeleton Source: UniProtKB-SubCell
  • cytosol Source: GOC
  • dendrite Source: RGD
  • early endosome Source: RGD
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • growth cone Source: RGD
  • late endosome Source: RGD
  • lysosome Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB-SubCell
  • neuron projection Source: RGD
  • nucleus Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: RGD
  • synaptic vesicle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endoplasmic reticulum, Lysosome, Mitochondrion, Nucleus, Synapse

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 629629Huntingtin-associated protein 1PRO_0000083896Add
BLAST

Post-translational modificationi

Isoform A is phosphorylated on 'Thr-598'.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP54256.
PRIDEiP54256.

Expressioni

Tissue specificityi

In the brain, especially in the olfactory bulb and in the brain stem. No detectable expression in peripheral tissues such as lung, testis, spleen, and small intestine.

Interactioni

Subunit structurei

Self-associates. Interacts with HTT/huntingtin; enhanced by an expanded polyglutamine repeat within HTT. Isoform A interacts with DCTN1; decreased in presence of HTT with expanded polyglutamine repeat; decreased by phosphorylation of Hap1 isoform A at Thr-598. Isoform A interacts with KLC2; decreased by phosphorylation of Hap1 isoform A at Thr-598. Isoform A interacts with ITPR1 and APP. Isoform A interacts with AR; decreased by an expanded polyglutamine repeat within AR. Isoform A interacts with YWHAZ; enhanced by phosphorylation of Hap1 isoform A at Thr-598. Isoform A 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. Interacts with NTRK2; HAP1 stabilizes association of NTRK2 with SORT1 preventing NTRK2 degradation. Interacts with CCDC113.By similarity14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-994539,EBI-994539
DCTN1Q142034EBI-994539,EBI-724352From a different organism.
HgsQ9JJ505EBI-994554,EBI-7092491
HTTP428583EBI-994539,EBI-466029From a different organism.
Itpr1P299944EBI-994554,EBI-8614640
KalrnP979243EBI-994539,EBI-1397166
PCM1Q151543EBI-994539,EBI-741421From a different organism.
YWHAZP631044EBI-994554,EBI-347088From a different organism.

GO - Molecular functioni

  • brain-derived neurotrophic factor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • ion channel binding Source: UniProtKB
  • protein domain specific binding Source: RGD
  • receptor binding Source: RGD

Protein-protein interaction databases

IntActiP54256. 26 interactions.
MINTiMINT-421542.
STRINGi10116.ENSRNOP00000020603.

Structurei

3D structure databases

ProteinModelPortaliP54256.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini80 – 404325HAP1 N-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni153 – 320168Sufficient for interaction with KIF5BAdd
BLAST
Regioni158 – 262105Interaction with TBPBy similarityAdd
BLAST
Regioni277 – 445169Sufficient for self-association and interaction with HDAdd
BLAST
Regioni474 – 583110Interaction with TBPBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili169 – 300132Sequence analysisAdd
BLAST
Coiled coili328 – 36942Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi220 – 529310Glu-richAdd
BLAST
Compositional biasi220 – 23718Poly-GluAdd
BLAST
Compositional biasi468 – 4714Poly-Pro

Sequence similaritiesi

Contains 1 HAP1 N-terminal domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG4360. Eukaryota.
ENOG410XSWD. LUCA.
HOGENOMiHOG000230957.
HOVERGENiHBG031599.
InParanoidiP54256.
KOiK04647.
PhylomeDBiP54256.

Family and domain databases

InterProiIPR006933. HAP1_N.
[Graphical view]
PfamiPF04849. HAP1_N. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B (identifier: P54256-1) [UniParc]FASTAAdd to basket
Also known as: Long

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.

« Hide

        10         20         30         40         50
MRPKDQVQSS AGDGTGSGDP ATGTPTTQPA ADPAPEPSAE PKPAPAQGTG
60 70 80 90 100
SGQKSGSRTK TGGSFCRSRI RGDSDAPWTR YIFQGPYGPR ATGLGTGRAE
110 120 130 140 150
GIWKTPAAYI GRRPGVSGPE RAAFIRELQE ALCPNPLPRK KITEDDIKVM
160 170 180 190 200
LYLLEEKERD LNTAARIGQS LVKQNSVLME ENNKLETMLG SAREEILHLR
210 220 230 240 250
KQVNLRDDLL QLYSDSDDDE EDEEDEEEEE GEEEEREGQR DQDQQHDHPY
260 270 280 290 300
GAPKPPPKAE TLHHCPQLEA LKQKLKLLEE ENDHLREEAS HLDNLEDKEQ
310 320 330 340 350
MLILECVEQF SEASQQMAEL SEVLVLRLEG YERQQKEITQ LQAEITKLQQ
360 370 380 390 400
RCQSYGAQTE KLQQQLASEK GVHPESLRAG SHMQDYGSRP RERQEDGKSH
410 420 430 440 450
RQRSSMPAGS VTHYGYSVPL DALPSFPETL AEELRTSLRK FITDPAYFME
460 470 480 490 500
RCDTRCREER KKEQGTMPPP PVQDLKPPED FEAPEELVPE EELGAIEEVG
510 520 530 540 550
TAEDGPAEET EQASEETEAW EEVEPEVDEA TRMNVVVSAL EASGLGPSHL
560 570 580 590 600
DMKYVLQQLS NWQDAHSKRQ QKQKVVPKDS PAPQQQTNMG GGIVEQQPIV
610 620
PTQDSQRLEE DRATHSPSAR EEEGPSGAT
Length:629
Mass (Da):70,213
Last modified:October 1, 1996 - v1
Checksum:iC23C5CB57520B574
GO
Isoform A (identifier: P54256-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     579-629: DSPAPQQQTNMGGGIVEQQPIVPTQDSQRLEEDRATHSPSAREEEGPSGAT → GECSRRGHPPASGTSYRSSTL

Show »
Length:599
Mass (Da):67,004
Checksum:iDA2949D7676C9434
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei579 – 62951DSPAP…PSGAT → GECSRRGHPPASGTSYRSST L in isoform A. 1 PublicationVSP_004280Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U38370 mRNA. Translation: AAC52326.1.
U38373 mRNA. Translation: AAC52327.1.
PIRiS67492.
S67495.
RefSeqiNP_077047.1. NM_024133.2. [P54256-2]
NP_817091.1. NM_177982.1. [P54256-1]
UniGeneiRn.37430.

Genome annotation databases

GeneIDi29430.
KEGGirno:29430.
UCSCiRGD:68327. rat. [P54256-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U38370 mRNA. Translation: AAC52326.1.
U38373 mRNA. Translation: AAC52327.1.
PIRiS67492.
S67495.
RefSeqiNP_077047.1. NM_024133.2. [P54256-2]
NP_817091.1. NM_177982.1. [P54256-1]
UniGeneiRn.37430.

3D structure databases

ProteinModelPortaliP54256.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP54256. 26 interactions.
MINTiMINT-421542.
STRINGi10116.ENSRNOP00000020603.

Proteomic databases

PaxDbiP54256.
PRIDEiP54256.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29430.
KEGGirno:29430.
UCSCiRGD:68327. rat. [P54256-1]

Organism-specific databases

CTDi9001.
RGDi68327. Hap1.

Phylogenomic databases

eggNOGiKOG4360. Eukaryota.
ENOG410XSWD. LUCA.
HOGENOMiHOG000230957.
HOVERGENiHBG031599.
InParanoidiP54256.
KOiK04647.
PhylomeDBiP54256.

Miscellaneous databases

PROiP54256.

Family and domain databases

InterProiIPR006933. HAP1_N.
[Graphical view]
PfamiPF04849. HAP1_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHAP1_RAT
AccessioniPrimary (citable) accession number: P54256
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 7, 2016
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.