HAP1_HUMAN
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 03-AUG-2022, entry version 171.
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 CCDC113.
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 CCDC113.
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.
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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_177977.2. [P54257-2]
DR AlphaFoldDB; P54257; -.
DR SMR; P54257; -.
DR BioGRID; 114480; 145.
DR CORUM; P54257; -.
DR IntAct; P54257; 75.
DR MINT; P54257; -.
DR STRING; 9606.ENSP00000334002; -.
DR iPTMnet; P54257; -.
DR PhosphoSitePlus; P54257; -.
DR BioMuta; HAP1; -.
DR DMDM; 290457683; -.
DR EPD; P54257; -.
DR MassIVE; P54257; -.
DR PeptideAtlas; P54257; -.
DR PRIDE; P54257; -.
DR Antibodypedia; 80380; 250 antibodies from 35 providers.
DR DNASU; 9001; -.
DR Ensembl; ENST00000310778.5; ENSP00000309392.5; ENSG00000173805.16. [P54257-1]
DR Ensembl; ENST00000341193.9; ENSP00000343170.5; ENSG00000173805.16. [P54257-4]
DR Ensembl; ENST00000347901.9; ENSP00000334002.4; ENSG00000173805.16. [P54257-2]
DR Ensembl; ENST00000393939.6; ENSP00000377513.2; ENSG00000173805.16. [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 CTD; 9001; -.
DR DisGeNET; 9001; -.
DR GeneCards; HAP1; -.
DR HGNC; HGNC:4812; HAP1.
DR HPA; ENSG00000173805; Tissue enriched (brain).
DR MIM; 600947; gene.
DR neXtProt; NX_P54257; -.
DR OpenTargets; ENSG00000173805; -.
DR PharmGKB; PA29188; -.
DR VEuPathDB; HostDB:ENSG00000173805; -.
DR eggNOG; KOG4360; Eukaryota.
DR GeneTree; ENSGT00940000162183; -.
DR HOGENOM; CLU_036493_0_0_1; -.
DR InParanoid; P54257; -.
DR OMA; MERNYEV; -.
DR OrthoDB; 592923at2759; -.
DR PhylomeDB; P54257; -.
DR TreeFam; TF323495; -.
DR PathwayCommons; P54257; -.
DR SignaLink; P54257; -.
DR SIGNOR; P54257; -.
DR BioGRID-ORCS; 9001; 49 hits in 1063 CRISPR screens.
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 136 other tissues.
DR ExpressionAtlas; P54257; baseline and differential.
DR Genevisible; P54257; HS.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
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:0098957; P:anterograde axonal transport of mitochondrion; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0007420; P:brain development; NAS:UniProtKB.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0021979; P:hypothalamus cell differentiation; IEA:Ensembl.
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:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0031587; P:positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; 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:0008104; P:protein localization; IMP: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 Pfam; PF04849; 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; Reference proteome; Synapse;
KW 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 37..65
FT /note="Polar residues"
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
