ID HAP1_HUMAN Reviewed; 671 AA. AC P54257; A8MQB5; O75358; Q59GK4; Q9H4G3; Q9HA98; Q9NY90; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 02-MAR-2010, sequence version 3. DT 02-SEP-2026, entry version 190. DE RecName: Full=Huntingtin-associated protein 1; DE Short=HAP-1; DE AltName: Full=Neuroan 1; GN Name=HAP1; Synonyms=HAP2, HLP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS ARG-4; THR-58 AND RP LEU-560. RX PubMed=9668110; DOI=10.1074/jbc.273.30.19220; RA Li S.-H., Hosseini S.H., Gutekunst C.-A., Hersch S.M., Ferrante R.J., RA Li X.-J.; RT "A human HAP1 homologue. Cloning, expression, and interaction with RT huntingtin."; RL J. Biol. Chem. 273:19220-19227(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS ARG-4; THR-58 RP AND LEU-560. RX PubMed=10974549; DOI=10.1016/s0378-1119(00)00269-9; RA Nasir J., Lafuente M.-J., Duan K., Colomer V., Engelender S., Ingersoll R., RA Margolis R.L., Ross C.A., Hayden M.R.; RT "Human huntingtin-associated protein (HAP-1) gene: genomic organisation and RT an intragenic polymorphism."; RL Gene 254:181-187(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANTS RP LEU-357; MET-493 AND LEU-560. RC TISSUE=Embryo; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-671 (ISOFORM 3), AND VARIANTS RP ARG-4; THR-58 AND LEU-560. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 96-671 (ISOFORM 1), AND VARIANTS RP LEU-357 AND LEU-560. RA Nasir J., Duan K., Nichol K., Engelender S., Ashworth R., Colomer V., RA Thomas S., Disteche C., Hayden M.R., Ross C.A.; RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 255-626 (ISOFORM 2), AND VARIANT LEU-560. RC TISSUE=Caudate nucleus; RX PubMed=7477378; DOI=10.1038/378398a0; RA Li X.-J., Li S.-H., Sharp A.H., Nucifora F.C. Jr., Schilling G., RA Lanahan A., Worley P., Snyder S.H., Ross C.A.; RT "A huntingtin-associated protein enriched in brain with implications for RT pathology."; RL Nature 378:398-402(1995). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=9742138; DOI=10.1523/jneurosci.18-19-07674.1998; RA Gutekunst C.A., Li S.H., Yi H., Ferrante R.J., Li X.J., Hersch S.M.; RT "The cellular and subcellular localization of huntingtin-associated protein RT 1 (HAP1): comparison with huntingtin in rat and human."; RL J. Neurosci. 18:7674-7686(1998). RN [9] RP FUNCTION. RX PubMed=18922795; DOI=10.1074/jbc.m804183200; RA Shimojo M.; RT "Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive RT silencer factor (REST/NRSF) nuclear trafficking indirectly through a RT complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin RT p150 Glued."; RL J. Biol. Chem. 283:34880-34886(2008). RN [10] RP INTERACTION WITH BDNF. RX PubMed=19996106; DOI=10.1074/jbc.m109.073197; RA Wu L.L., Fan Y., Li S., Li X.J., Zhou X.F.; RT "Huntingtin-associated protein-1 interacts with pro-brain-derived RT neurotrophic factor and mediates its transport and release."; RL J. Biol. Chem. 285:5614-5623(2010). RN [11] RP INTERACTION WITH ATXN3. RX PubMed=21386698; DOI=10.1097/wnr.0b013e32834505f4; RA Takeshita Y., Fujinaga R., Kokubu K., Islam M.N., Jahan M.R., Yanai A., RA Kakizuka A., Shinoda K.; RT "Interaction of ataxin-3 with huntingtin-associated protein 1 through RT Josephin domain."; RL NeuroReport 22:232-238(2011). RN [12] RP INTERACTION WITH APP. RX PubMed=22731248; DOI=10.1111/j.1471-4159.2012.07845.x; RA Yang G.Z., Yang M., Lim Y., Lu J.J., Wang T.H., Qi J.G., Zhong J.H., RA Zhou X.F.; RT "Huntingtin associated protein 1 regulates trafficking of the amyloid RT precursor protein and modulates amyloid beta levels in neurons."; RL J. Neurochem. 122:1010-1022(2012). RN [13] RP INTERACTION WITH AHI1. RX PubMed=23532844; DOI=10.1074/jbc.m112.420786; RA Tuz K., Hsiao Y.C., Juarez O., Shi B., Harmon E.Y., Phelps I.G., RA Lennartz M.R., Glass I.A., Doherty D., Ferland R.J.; RT "The Joubert syndrome-associated missense mutation (V443D) in the Abelson- RT helper integration site 1 (AHI1) protein alters its localization and RT protein-protein interactions."; RL J. Biol. Chem. 288:13676-13694(2013). RN [14] RP INTERACTION WITH CFAP263. RX PubMed=25074808; DOI=10.1242/jcs.157008; RA Firat-Karalar E.N., Sante J., Elliott S., Stearns T.; RT "Proteomic analysis of mammalian sperm cells identifies new components of RT the centrosome."; RL J. Cell Sci. 127:4128-4133(2014). RN [15] RP VARIANTS LEU-357; TRP-437 AND MET-493, AND CHARACTERIZATION OF VARIANT RP MET-493. RX PubMed=18192679; DOI=10.1093/hmg/ddn003; RA Metzger S., Rong J., Nguyen H.-P., Cape A., Tomiuk J., Soehn A.S., RA Propping P., Freudenberg-Hua Y., Freudenberg J., Tong L., Li S.-H., RA Li X.-J., Riess O.; RT "Huntingtin-associated protein-1 is a modifier of the age-at-onset of RT Huntington's disease."; RL Hum. Mol. Genet. 17:1137-1146(2008). CC -!- FUNCTION: Originally identified as neuronal protein that specifically CC associates with HTT/huntingtin and the binding is enhanced by an CC expanded polyglutamine repeat within HTT possibly affecting HAP1 CC interaction properties. Both HTT and HAP1 are involved in intracellular CC trafficking and HAP1 is proposed to link HTT to motor proteins and/or CC transport cargos. Seems to play a role in vesicular transport within CC neurons and axons such as from early endosomes to late endocytic CC compartments and to promote neurite outgrowth. The vesicular transport CC function via association with microtubule-dependent transporters can be CC attenuated by association with mutant HTT. Involved in the axonal CC transport of BDNF and its activity-dependent secretion; the function CC seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP CC trafficking and seems to facilitate APP anterograde transport and CC membrane insertion thereby possibly reducing processing into amyloid CC beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) CC receptors to synapses; the function is dependent on kinesin motor CC protein KIF5 and is disrupted by HTT with expanded polyglutamine CC repeat. Involved in regulation of autophagosome motility by promoting CC efficient retrograde axonal transport. Seems to be involved in CC regulation of membrane receptor recycling and degradation, and CC respective signal transduction, including GABA(A) receptors, tyrosine CC kinase receptors, EGFR, IP3 receptor and androgen receptor. Among CC others suggested to be involved in control of feeding behavior CC (involving hypothalamic GABA(A) receptors), cerebellar and brainstem CC development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis CC (involving hypothalamic NTRK2/TrkB), and ITPR1/InsP3R1-mediated Ca(2+) CC release (involving HTT and possibly the effect of mutant HTT). Via CC association with DCTN1/dynactin p150-glued and HTT/huntingtin involved CC in cytoplasmic retention of REST in neurons. May be involved in CC ciliogenesis. Involved in regulation of exocytosis. Seems to be CC involved in formation of cytoplasmic inclusion bodies (STBs). In case CC of anomalous expression of TBP, can sequester a subset of TBP into CC STBs; sequestration is enhanced by an expanded polyglutamine repeat CC within TBP. HAP1-containing STBs have been proposed to play a CC protective role against neurodegeneration in Huntigton disease (HD) and CC spinocerebellar ataxia 17 (SCA17). {ECO:0000269|PubMed:18922795}. CC -!- SUBUNIT: Self-associates. Interacts with HTT/huntingtin; enhanced by an CC expanded polyglutamine repeat within HTT. Interacts with DCTN1; CC decreased in presence of HTT with expanded polyglutamine repeat. CC Interacts with KLC2. Interacts with ITPR1 and APP. Interacts with AR; CC decreased by an expanded polyglutamine repeat within AR. Interacts with CC YWHAZ. Interacts with BDNF and SORT1; probably forming a complex CC involved in proBDNF trafficking, degradation and processing. Interacts CC with TBP, AHI1, HGS and KALRN. Interacts with KIF5A, KIF5B, KIF5C and CC GABRB3; indicative for an HAP1:KIF5 complex transporting a GABA(A) CC receptor as cargo. Interacts with ATXN3; in STBs with ATXN3 poly-Gln CC region with 27 repeats (normal population) and 79 repeats CC (spinocerebellar ataxia 3 (SCA3) patients) associating in the same CC strength. Interacts with NTRK2; HAP1 stabilizes association of NTRK2 CC with SORT1 preventing NTRK2 degradation. Interacts with CFAP263. CC {ECO:0000269|PubMed:19996106, ECO:0000269|PubMed:21386698, CC ECO:0000269|PubMed:22731248, ECO:0000269|PubMed:23532844, CC ECO:0000269|PubMed:25074808}. CC -!- INTERACTION: CC P54257; Q8WTP8-2: AEN; NbExp=3; IntAct=EBI-712814, EBI-12119298; CC P54257; Q8N157: AHI1; NbExp=3; IntAct=EBI-712814, EBI-1049056; CC P54257; P54252-1: ATXN3; NbExp=6; IntAct=EBI-712814, EBI-946068; CC P54257; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-712814, EBI-747505; CC P54257; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-712814, EBI-739879; CC P54257; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-712814, EBI-10961312; CC P54257; Q07002: CDK18; NbExp=3; IntAct=EBI-712814, EBI-746238; CC P54257; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-712814, EBI-742802; CC P54257; P60520: GABARAPL2; NbExp=3; IntAct=EBI-712814, EBI-720116; CC P54257; P56524-2: HDAC4; NbExp=3; IntAct=EBI-712814, EBI-11953488; CC P54257; O14964: HGS; NbExp=3; IntAct=EBI-712814, EBI-740220; CC P54257; P09067: HOXB5; NbExp=3; IntAct=EBI-712814, EBI-3893317; CC P54257; A6NI15: MSGN1; NbExp=3; IntAct=EBI-712814, EBI-11991020; CC P54257; Q16512: PKN1; NbExp=3; IntAct=EBI-712814, EBI-602382; CC P54257; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-712814, EBI-2557469; CC P54257; Q8WWY3: PRPF31; NbExp=3; IntAct=EBI-712814, EBI-1567797; CC P54257; Q8TCX5: RHPN1; NbExp=3; IntAct=EBI-712814, EBI-746325; CC P54257; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-712814, EBI-748391; CC P54257; Q6P2D0: ZFP1; NbExp=3; IntAct=EBI-712814, EBI-2555749; CC P54257; Q96NC0: ZMAT2; NbExp=3; IntAct=EBI-712814, EBI-2682299; CC P54257; Q15973: ZNF124; NbExp=3; IntAct=EBI-712814, EBI-2555767; CC P54257; Q9ULM2: ZNF490; NbExp=3; IntAct=EBI-712814, EBI-1105370; CC P54257; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-712814, EBI-10172590; CC P54257; Q86XF7: ZNF575; NbExp=5; IntAct=EBI-712814, EBI-14069183; CC P54257; Q5T619: ZNF648; NbExp=3; IntAct=EBI-712814, EBI-11985915; CC P54257; Q9Y2P0: ZNF835; NbExp=3; IntAct=EBI-712814, EBI-5667516; CC P54257-2; P42858: HTT; NbExp=8; IntAct=EBI-9392340, EBI-466029; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9742138}. Cell CC projection, axon {ECO:0000269|PubMed:9742138}. Presynapse CC {ECO:0000250|UniProtKB:P54256}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:P54256}. Cell projection, dendritic spine CC {ECO:0000250|UniProtKB:P54256}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:P54256}. Lysosome CC {ECO:0000250|UniProtKB:P54256}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:P54256}. Mitochondrion CC {ECO:0000305|PubMed:9742138}. Nucleus {ECO:0000250|UniProtKB:P54256}. CC Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:O35668}. CC Early endosome {ECO:0000250|UniProtKB:P54256}. Cell projection, growth CC cone {ECO:0000250|UniProtKB:P54256}. Cell projection, neuron projection CC {ECO:0000250|UniProtKB:P54256}. Cytoplasmic vesicle, secretory vesicle, CC synaptic vesicle {ECO:0000250|UniProtKB:P54256}. Note=Localizes to CC large nonmembrane-bound cytoplasmic bodies found in various types of CC neurons, called stigmoid bodies (STBs). Localization to neuronal CC processes and neurite tips is decreased by YWHAZ. In the nucleus CC localizes to nuclear rods. {ECO:0000250|UniProtKB:P54256}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=P54257-1; Sequence=Displayed; CC Name=2; CC IsoId=P54257-2; Sequence=VSP_004278; CC Name=3; CC IsoId=P54257-3; Sequence=VSP_004277; CC Name=4; CC IsoId=P54257-4; Sequence=VSP_038754, VSP_004277; CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain. Selectively CC expressed in neurons. CC -!- MISCELLANEOUS: Was not found in huntingtin-containing aggregates in CC huntigton disease (HD) tissue. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF040723; AAC39861.1; -; mRNA. DR EMBL; AJ012824; CAC09418.1; -; Genomic_DNA. DR EMBL; AK022007; BAB13952.1; -; mRNA. DR EMBL; AC109319; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB209105; BAD92342.1; -; mRNA. DR EMBL; AJ224877; CAB82785.1; -; Genomic_DNA. DR EMBL; U38371; AAC50297.1; -; mRNA. DR CCDS; CCDS11406.1; -. [P54257-2] DR CCDS; CCDS42338.1; -. [P54257-4] DR CCDS; CCDS42339.1; -. [P54257-3] DR PIR; S72555; S72555. DR RefSeq; NP_001073339.1; NM_001079870.1. [P54257-4] DR RefSeq; NP_001073340.1; NM_001079871.1. [P54257-3] DR RefSeq; NP_817084.2; NM_177977.3. [P54257-2] DR AlphaFoldDB; P54257; -. DR SMR; P54257; -. DR BioGRID; 114480; 146. DR CORUM; P54257; -. DR FunCoup; P54257; 140. DR IntAct; P54257; 86. DR MINT; P54257; -. DR NDEx; IQUERY-CP-HAP1; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000334002; -. DR TCDB; 8.A.266.1.1; the huntingtin-associated protein (hap1) family. DR iPTMnet; P54257; -. DR PhosphoSitePlus; P54257; -. DR BioMuta; HAP1; -. DR DMDM; 290457683; -. DR MassIVE; P54257; -. DR PaxDb; 9606-ENSP00000334002; -. DR PeptideAtlas; P54257; -. DR Antibodypedia; 80380; 247 antibodies from 33 providers. DR DNASU; 9001; -. DR Ensembl; ENST00000310778.5; ENSP00000309392.5; ENSG00000173805.17. [P54257-1] DR Ensembl; ENST00000341193.9; ENSP00000343170.5; ENSG00000173805.17. [P54257-4] DR Ensembl; ENST00000347901.9; ENSP00000334002.4; ENSG00000173805.17. [P54257-2] DR Ensembl; ENST00000393939.6; ENSP00000377513.2; ENSG00000173805.17. [P54257-3] DR GeneID; 9001; -. DR KEGG; hsa:9001; -. DR MANE-Select; ENST00000347901.9; ENSP00000334002.4; NM_177977.3; NP_817084.2. [P54257-2] DR UCSC; uc002hxm.2; human. [P54257-1] DR AGR; HGNC:4812; -. DR ClinPGx; PA29188; -. DR CTD; 9001; -. DR DisGeNET; 9001; -. DR GeneCards; HAP1; -. DR HGNC; HGNC:4812; HAP1. DR HPA; ENSG00000173805; Tissue enhanced (brain). DR MalaCards; HAP1; -. DR MIM; 600947; gene. DR OpenTargets; ENSG00000173805; -. DR VEuPathDB; HostDB:ENSG00000173805; -. DR eggNOG; KOG4360; Eukaryota. DR GeneTree; ENSGT00940000162183; -. DR HOGENOM; CLU_036493_0_0_1; -. DR InParanoid; P54257; -. DR OMA; RNYEVTP; -. DR OrthoDB; 10067624at2759; -. DR PAN-GO; P54257; 10 GO annotations based on evolutionary models. DR PhylomeDB; P54257; -. DR PathwayCommons; P54257; -. DR SignaLink; P54257; -. DR SIGNOR; P54257; -. DR Agora; ENSG00000173805; -. DR BioGRID-ORCS; 9001; 50 hits in 1141 CRISPR screens. DR CD-CODE; 8C2F96ED; Centrosome. DR ChiTaRS; HAP1; human. DR GenomeRNAi; 9001; -. DR Pharos; P54257; Tbio. DR PRO; PR:P54257; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P54257; protein. DR Bgee; ENSG00000173805; Expressed in hypothalamus and 137 other cell types or tissues. DR ExpressionAtlas; P54257; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc. DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0005814; C:centriole; IEA:Ensembl. DR GO; GO:0005813; C:centrosome; IEA:Ensembl. DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central. DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0005769; C:early endosome; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0098793; C:presynapse; ISS:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0048403; F:brain-derived neurotrophic factor binding; ISS:UniProtKB. DR GO; GO:0017022; F:myosin binding; IBA:GO_Central. DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central. DR GO; GO:0044325; F:transmembrane transporter binding; ISS:UniProtKB. DR GO; GO:0008089; P:anterograde axonal transport; ISS:UniProtKB. DR GO; GO:0007420; P:brain development; NAS:UniProtKB. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0021979; P:hypothalamus cell differentiation; IEA:Ensembl. DR GO; GO:0008104; P:intracellular protein localization; IMP:UniProtKB. DR GO; GO:0048311; P:mitochondrion distribution; IBA:GO_Central. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:UniProtKB. DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISS:UniProtKB. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl. DR GO; GO:0032901; P:positive regulation of neurotrophin production; ISS:UniProtKB. DR GO; GO:1902857; P:positive regulation of non-motile cilium assembly; ISS:UniProtKB. DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; ISS:UniProtKB. DR GO; GO:0006605; P:protein targeting; IBA:GO_Central. DR GO; GO:0017157; P:regulation of exocytosis; ISS:UniProtKB. DR GO; GO:1902513; P:regulation of organelle transport along microtubule; ISS:UniProtKB. DR GO; GO:0008090; P:retrograde axonal transport; ISS:UniProtKB. DR GO; GO:0047496; P:vesicle transport along microtubule; IBA:GO_Central. DR InterPro; IPR006933; HAP1_N. DR InterPro; IPR051946; Intracell_Traff-Reg. DR PANTHER; PTHR15751:SF14; HUNTINGTIN-ASSOCIATED PROTEIN 1; 1. DR PANTHER; PTHR15751; TRAFFICKING KINESIN-BINDING PROTEIN; 1. DR Pfam; PF04849; HAP1_N; 1. DR SMART; SM01424; HAP1_N; 1. PE 1: Evidence at protein level; KW Alternative splicing; Autophagy; Cell projection; KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoplasmic vesicle; KW Cytoskeleton; Endoplasmic reticulum; Endosome; Exocytosis; Lysosome; KW Mitochondrion; Nucleus; Protein transport; Proteomics identification; KW Reference proteome; Synapse; Transport. FT CHAIN 1..671 FT /note="Huntingtin-associated protein 1" FT /id="PRO_0000083894" FT DOMAIN 106..461 FT /note="HAP1 N-terminal" FT REGION 1..83 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 258..289 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 212..427 FT /evidence="ECO:0000255" FT COMPBIAS 20..29 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 258..288 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 183 FT /note="E -> EVCTAFLIQ (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038754" FT VAR_SEQ 401..477 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.5" FT /id="VSP_004277" FT VAR_SEQ 426..477 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7477378, FT ECO:0000303|PubMed:9668110" FT /id="VSP_004278" FT VARIANT 4 FT /note="K -> R (in dbSNP:rs4796604)" FT /evidence="ECO:0000269|PubMed:10974549, FT ECO:0000269|PubMed:9668110, ECO:0000269|Ref.5" FT /id="VAR_046736" FT VARIANT 58 FT /note="S -> T (in dbSNP:rs4796603)" FT /evidence="ECO:0000269|PubMed:10974549, FT ECO:0000269|PubMed:9668110, ECO:0000269|Ref.5" FT /id="VAR_046737" FT VARIANT 357 FT /note="S -> L (in dbSNP:rs4796693)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:18192679, ECO:0000269|Ref.6" FT /id="VAR_046738" FT VARIANT 408 FT /note="L -> F (in dbSNP:rs35612698)" FT /id="VAR_056906" FT VARIANT 437 FT /note="R -> W (in dbSNP:rs11867808)" FT /evidence="ECO:0000269|PubMed:18192679" FT /id="VAR_046739" FT VARIANT 483 FT /note="F -> L (in dbSNP:rs8075017)" FT /id="VAR_046741" FT VARIANT 488 FT /note="A -> V (in dbSNP:rs34853043)" FT /id="VAR_046742" FT VARIANT 493 FT /note="T -> M (may influence the age-at-onset of Huntington FT disease; increases binding to mutated HTT; influences HTT FT degradation; dbSNP:rs4523977)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:18192679" FT /id="VAR_056907" FT VARIANT 557 FT /note="A -> V (in dbSNP:rs34853043)" FT /id="VAR_056908" FT VARIANT 560 FT /note="F -> L (in dbSNP:rs8075017)" FT /evidence="ECO:0000269|PubMed:10974549, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:7477378, FT ECO:0000269|PubMed:9668110, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_062817" FT VARIANT 656 FT /note="G -> R (in dbSNP:rs34044330)" FT /id="VAR_056909" FT CONFLICT 184..199 FT /note="Missing (in Ref. 6; CAB82785)" FT /evidence="ECO:0000305" FT CONFLICT 573 FT /note="P -> L (in Ref. 3; BAB13952)" FT /evidence="ECO:0000305" FT CONFLICT 579 FT /note="M -> V (in Ref. 1; AAC39861)" FT /evidence="ECO:0000305" FT CONFLICT 611 FT /note="A -> T (in Ref. 7; AAC50297)" FT /evidence="ECO:0000305" SQ SEQUENCE 671 AA; 75506 MW; 10971B807941B4EE CRC64; MRPKRLGRCC AGSRLGPGDP AALTCAPSPS ASPAPEPSAQ PQARGTGQRV GSRATSGSQF LSEARTGARP ASEAGAKAGA RRPSAFSAIQ GDVRSMPDNS DAPWTRFVFQ GPFGSRATGR GTGKAAGIWK TPAAYVGRRP GVSGPERAAF IRELEEALCP NLPPPVKKIT QEDVKVMLYL LEELLPPVWE SVTYGMVLQR ERDLNTAARI GQSLVKQNSV LMEENSKLEA LLGSAKEEIL YLRHQVNLRD ELLQLYSDSD EEDEDEEEEE EEKEAEEEQE EEEAEEDLQC AHPCDAPKLI SQEALLHQHH CPQLEALQEK LRLLEEENHQ LREEASQLDT LEDEEQMLIL ECVEQFSEAS QQMAELSEVL VLRLENYERQ QQEVARLQAQ VLKLQQRCRM YGAETEKLQK QLASEKEIQM QLQEESVWVG SQLQDLREKY MDCGGMLIEM QEEVKTLRQQ PPVSTGSATH YPYSVPLETL PGFQETLAEE LRTSLRRMIS DPVYFMERNY EMPRGDTSSL RYDFRYSEDR EQVRGFEAEE GLMLAADIMR GEDFTPAEEF VPQEELGAAK KVPAEEGVME EAELVSEETE GWEEVELELD EATRMNVVTS ALEASGLGPS HLDMNYVLQQ LANWQDAHYR RQLRWKMLQK GECPHGALPA ASRTSCRSSC R //