HAP40_MOUSE
ID HAP40_MOUSE Reviewed; 381 AA.
AC Q00558; Q3TLS9; Q9JJQ6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=40-kDa huntingtin-associated protein {ECO:0000303|PubMed:11035034};
DE AltName: Full=CpG island protein;
DE AltName: Full=Factor VIII intron 22 protein;
GN Name=F8a1; Synonyms=F8a, Hap40;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CBA/J;
RX PubMed=1639415; DOI=10.1016/0888-7543(92)90170-w;
RA Levinson B., Bermingham J.R. Jr., Metzenberg A., Kenwrick S., Chapman V.,
RA Gitschier J.;
RT "Sequence of the human factor VIII-associated gene is conserved in mouse.";
RL Genomics 13:862-865(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH HTT, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 34-LYS--ARG-36.
RC STRAIN=C57BL/6J;
RX PubMed=11035034; DOI=10.1074/jbc.m008099200;
RA Peters M.F., Ross C.A.;
RT "Isolation of a 40-kDa Huntingtin-associated protein.";
RL J. Biol. Chem. 276:3188-3194(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, Mammary gland, and Oviduct;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION.
RX PubMed=16476778; DOI=10.1083/jcb.200509091;
RA Pal A., Severin F., Lommer B., Shevchenko A., Zerial M.;
RT "Huntingtin-HAP40 complex is a novel Rab5 effector that regulates early
RT endosome motility and is up-regulated in Huntington's disease.";
RL J. Cell Biol. 172:605-618(2006).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=23749422; DOI=10.1002/cne.23381;
RA Milman P., Woulfe J.;
RT "Novel variant of neuronal intranuclear rodlet immunoreactive for 40 kDa
RT huntingtin associated protein and ubiquitin in the mouse brain.";
RL J. Comp. Neurol. 521:3832-3846(2013).
CC -!- FUNCTION: RAB5A effector molecule that is involved in vesicular
CC trafficking of early endosomes. Mediates the recruitment of HTT by
CC RAB5A onto early endosomes (By similarity). The HTT-F8A1/F8A2/F8A3-
CC RAB5A complex stimulates early endosomal interaction with actin
CC filaments and inhibits interaction with microtubules, leading to the
CC reduction of endosome motility (PubMed:16476778).
CC {ECO:0000250|UniProtKB:P23610, ECO:0000269|PubMed:16476778}.
CC -!- SUBUNIT: Interacts with HTT (via C-terminus) (PubMed:11035034).
CC Interacts with RAB5A (By similarity). Found in a complex with
CC F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A
CC onto early endosomes (By similarity). {ECO:0000250|UniProtKB:M0RDU0,
CC ECO:0000269|PubMed:11035034}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11035034,
CC ECO:0000269|PubMed:23749422}. Nucleus {ECO:0000269|PubMed:11035034,
CC ECO:0000269|PubMed:23749422}. Early endosome
CC {ECO:0000250|UniProtKB:P23610}. Nucleus, nuclear body
CC {ECO:0000269|PubMed:23749422}. Note=Diffuse presence in the cytoplasm
CC and accumulation in the nucleus (By similarity). In absence of HTT,
CC F8A1/F8A2/F8A3 is concentred in cytoplasm (PubMed:11035034).
CC Colocalized with HTT in endosomes (By similarity). In neuron found in
CC intranuclear structures, the intranuclear rodlets (INRs), also known as
CC rodlets of Roncoroni, in association with ubiquitin (PubMed:23749422).
CC {ECO:0000250|UniProtKB:P23610, ECO:0000269|PubMed:11035034,
CC ECO:0000269|PubMed:23749422}.
CC -!- TISSUE SPECIFICITY: Produced abundantly in a wide variety of cell
CC types.
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; M83118; AAA37588.1; -; mRNA.
DR EMBL; AF299331; AAG17919.1; -; mRNA.
DR EMBL; AL136328; CAB88074.1; -; Genomic_DNA.
DR EMBL; AK046459; BAC32739.1; -; mRNA.
DR EMBL; AK054140; BAC35668.1; -; mRNA.
DR EMBL; AK166334; BAE38713.1; -; mRNA.
DR EMBL; BC131938; AAI31939.1; -; mRNA.
DR EMBL; BC131940; AAI31941.1; -; mRNA.
DR CCDS; CCDS41011.1; -.
DR PIR; A42832; A42832.
DR RefSeq; NP_032004.2; NM_007978.3.
DR AlphaFoldDB; Q00558; -.
DR SMR; Q00558; -.
DR STRING; 10090.ENSMUSP00000100743; -.
DR PhosphoSitePlus; Q00558; -.
DR EPD; Q00558; -.
DR MaxQB; Q00558; -.
DR PaxDb; Q00558; -.
DR PeptideAtlas; Q00558; -.
DR PRIDE; Q00558; -.
DR ProteomicsDB; 343229; -.
DR DNASU; 14070; -.
DR Ensembl; ENSMUST00000105111; ENSMUSP00000100743; ENSMUSG00000078317.
DR GeneID; 14070; -.
DR KEGG; mmu:14070; -.
DR UCSC; uc009tlk.1; mouse.
DR CTD; 14070; -.
DR MGI; MGI:95474; F8a.
DR VEuPathDB; HostDB:ENSMUSG00000078317; -.
DR eggNOG; ENOG502QQQW; Eukaryota.
DR GeneTree; ENSGT00390000016992; -.
DR HOGENOM; CLU_076185_0_0_1; -.
DR InParanoid; Q00558; -.
DR OMA; YCWEAPE; -.
DR OrthoDB; 1141704at2759; -.
DR TreeFam; TF313929; -.
DR BioGRID-ORCS; 14070; 11 hits in 71 CRISPR screens.
DR PRO; PR:Q00558; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q00558; protein.
DR Bgee; ENSMUSG00000078317; Expressed in primary oocyte and 156 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0099518; P:vesicle cytoskeletal trafficking; ISS:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR039494; F8A.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR16797; PTHR16797; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Endosome; Nucleus; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P23610"
FT CHAIN 2..381
FT /note="40-kDa huntingtin-associated protein"
FT /id="PRO_0000087160"
FT REGION 221..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 34..36
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:11035034"
FT COMPBIAS 225..261
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P23610"
FT MUTAGEN 34..36
FT /note="KKR->STS: Not detected in nucleus. Redistributed in
FT cytoplasm."
FT /evidence="ECO:0000269|PubMed:11035034"
FT CONFLICT 124
FT /note="Missing (in Ref. 1; AAA37588)"
FT /evidence="ECO:0000305"
FT CONFLICT 127
FT /note="A -> D (in Ref. 1; AAA37588)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="L -> H (in Ref. 3; BAE38713)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="L -> R (in Ref. 1; AAA37588)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 381 AA; 40474 MW; AA58467EB676B628 CRC64;
MAAGSASSLG GGAWPGSEAG DFLARYRQVS NKLKKRFLRK PNVAEAGEQF AQLARELRAQ
ECLPYAAWCQ LAVARCQQAL FHGPGEALAL TEAARLFLRQ ECDARQRLGC PAAYGEPLQA
AASALGAAVR LHLELGQPAA AAALCLELAA ALRAVGQPAA AAGHFQRAAQ LHLPLMPLAA
LQALGDAASC QLLARDYTGA LALFTRMQRL AREHGGHPVQ QLELLPQPPS GPQPPLSGPQ
PRPVLGSTLP LPQPPDHAPG SVAPSPGTLG AFADVLVRCE VSRVLLLLLL QPPPAKLLPE
HAQTLEKYSW EAFDGHGQDT SGQLPEELFL LLQSLVMAAQ EKDTEGIKKL QVEMWPLLTA
EQNHLLHLVL QETISPSGQG V
