ID AUXI_HUMAN Reviewed; 913 AA. AC O75061; B7Z3V8; D3DQ65; D3DQ66; Q32M66; Q4G0K1; Q5T614; Q5T615; DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 27-JUN-2006, sequence version 3. DT 27-MAR-2024, entry version 189. DE RecName: Full=Auxilin {ECO:0000303|PubMed:18489706}; DE EC=3.1.3.- {ECO:0000305}; DE AltName: Full=DnaJ homolog subfamily C member 6 {ECO:0000312|HGNC:HGNC:15469}; GN Name=DNAJC6 {ECO:0000312|HGNC:HGNC:15469}; GN Synonyms=KIAA0473 {ECO:0000312|EMBL:BAA32318.2}; 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 [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9455484; DOI=10.1093/dnares/4.5.345; RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., RA Nomura N., Ohara O.; RT "Characterization of cDNA clones in size-fractionated cDNA libraries from RT human brain."; RL DNA Res. 4:345-349(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Thalamus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-563 AND SER-570, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] RP FUNCTION. RX PubMed=18489706; DOI=10.1111/j.1600-0854.2008.00764.x; RA Hirst J., Sahlender D.A., Li S., Lubben N.B., Borner G.H., Robinson M.S.; RT "Auxilin depletion causes self-assembly of clathrin into membraneless cages RT in vivo."; RL Traffic 9:1354-1371(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [9] RP INVOLVEMENT IN PARK19A. RX PubMed=22563501; DOI=10.1371/journal.pone.0036458; RA Edvardson S., Cinnamon Y., Ta-Shma A., Shaag A., Yim Y.I., Zenvirt S., RA Jalas C., Lesage S., Brice A., Taraboulos A., Kaestner K.H., Greene L.E., RA Elpeleg O.; RT "A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin- RT uncoating co-chaperone auxilin, is associated with juvenile parkinsonism."; RL PLoS ONE 7:E36458-E36458(2012). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORMS 3 AND 4), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112 AND SER-570, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP TISSUE SPECIFICITY, AND INVOLVEMENT IN PARK19A. RX PubMed=23211418; DOI=10.1016/j.parkreldis.2012.11.006; RA Koroglu C., Baysal L., Cetinkaya M., Karasoy H., Tolun A.; RT "DNAJC6 is responsible for juvenile parkinsonism with phenotypic RT variability."; RL Parkinsonism Relat. Disord. 19:320-324(2013). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-570, RP INTERACTION WITH CLTC, MUTAGENESIS OF SER-570, AND PTM. RX PubMed=29735704; DOI=10.1073/pnas.1717590115; RA Nguyen M., Krainc D.; RT "LRRK2 phosphorylation of auxilin mediates synaptic defects in dopaminergic RT neurons from patients with Parkinson's disease."; RL Proc. Natl. Acad. Sci. U.S.A. 115:5576-5581(2018). RN [15] RP INVOLVEMENT IN PARK19B, VARIANT PARK19B GLY-870, VARIANTS LEU-76; PRO-152; RP VAL-264; SER-441 AND CYS-562, AND CHARACTERIZATION OF VARIANT PARK19B RP GLY-870. RX PubMed=26528954; DOI=10.1002/ana.24553; RG International Parkinsonism Genetics Network; RA Olgiati S., Quadri M., Fang M., Rood J.P., Saute J.A., Chien H.F., RA Bouwkamp C.G., Graafland J., Minneboo M., Breedveld G.J., Zhang J., RA Verheijen F.W., Boon A.J., Kievit A.J., Jardim L.B., Mandemakers W., RA Barbosa E.R., Rieder C.R., Leenders K.L., Wang J., Bonifati V.; RT "DNAJC6 mutations associated with early-onset Parkinson's disease."; RL Ann. Neurol. 79:244-256(2016). RN [16] RP INVOLVEMENT IN PARK19A. RX PubMed=26703368; DOI=10.1002/ana.24591; RA Elsayed L.E., Drouet V., Usenko T., Mohammed I.N., Hamed A.A., Elseed M.A., RA Salih M.A., Koko M.E., Mohamed A.Y., Siddig R.A., Elbashir M.I., RA Ibrahim M.E., Durr A., Stevanin G., Lesage S., Ahmed A.E., Brice A.; RT "A novel nonsense mutation in DNAJC6 expands the phenotype of autosomal- RT recessive juvenile-onset Parkinson's disease."; RL Ann. Neurol. 79:335-337(2016). CC -!- FUNCTION: May act as a protein phosphatase and/or a lipid phosphatase. CC Co-chaperone that recruits HSPA8/HSC70 to clathrin-coated vesicles CC (CCVs) and promotes the ATP-dependent dissociation of clathrin from CC CCVs and participates in clathrin-mediated endocytosis of synaptic CC vesicles and their recycling and also in intracellular trafficking CC (PubMed:18489706). Firstly, binds tightly to the clathrin cages, at a CC ratio of one DNAJC6 per clathrin triskelion. The HSPA8:ATP complex then CC binds to the clathrin-auxilin cage, initially at a ratio of one HSPA8 CC per triskelion leading to ATP hydrolysis stimulation and causing a CC conformational change in the HSPA8. This cycle is repeated three times CC to drive to a complex containing the clathrin-auxilin cage associated CC to three HSPA8:ADP complex. The ATP hydrolysis of the third HSPA8:ATP CC complex leads to a concerted dismantling of the cage into component CC triskelia. Then, dissociates from the released triskelia and be CC recycled to initiate another cycle of HSPA8's recruitment. Also acts CC during the early steps of clathrin-coated vesicle (CCV) formation CC through its interaction with the GTP bound form of DNM1 (By CC similarity). {ECO:0000250|UniProtKB:Q27974, CC ECO:0000269|PubMed:18489706}. CC -!- SUBUNIT: Forms a complex composed of HSPA8, CLTC and DNAJC6. Interacts CC with HSPA8/HSC70 in an ATP-dependent manner; this interaction CC stimulates the HSPA8's ATPase activity (By similarity). Interacts with CC CLTC; this interaction produces a local change in heavy-chain contacts, CC creating a detectable global distortion of the clathrin coat CC (PubMed:29735704). Interacts with AP2A2. Interacts with DNM1(GTP-bound CC form); this interaction allows clathrin-coated vesicle (CCV) formation CC at the plasma membrane (By similarity). {ECO:0000250|UniProtKB:Q27974, CC ECO:0000269|PubMed:29735704}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, clathrin-coated vesicle CC {ECO:0000250|UniProtKB:Q27974}. Note=Appears on coated vesicles in CC successive transient bursts, immediately after the vesicle release from CC the plasma membrane. Recruitment to clathrin-coated vesicles depends on CC temporal variations in phosphoinositide composition of clathrin-coated CC vesicles. {ECO:0000250|UniProtKB:Q27974}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O75061-1; Sequence=Displayed; CC Name=2; CC IsoId=O75061-2; Sequence=VSP_019580; CC Name=3; CC IsoId=O75061-3; Sequence=VSP_019579, VSP_019581; CC Name=4; CC IsoId=O75061-4; Sequence=VSP_019579; CC -!- TISSUE SPECIFICITY: Expressed in various brain regions, including CC cerebellum, corpus callosum, cortex, striatum, brainstem, pons, CC putamen, spinal cord and substantia nigra. Very low expression in non- CC neural tissues such as leukocytes, liver, adipose tissue, skeletal CC muscle and bone marrow. {ECO:0000269|PubMed:23211418}. CC -!- DOMAIN: The J domain mediates interaction with HSPA8/HSC70 and is CC required for basket dissociation. {ECO:0000250|UniProtKB:Q27974}. CC -!- PTM: Phosphorylation at Ser-570 modulates its ability to bind CLTC and CC therefore the synaptic vesicle endocytosis (SVE). CC {ECO:0000269|PubMed:29735704}. CC -!- PTM: The N-terminus is blocked. {ECO:0000250|UniProtKB:Q27974}. CC -!- DISEASE: Parkinson disease 19A, juvenile-onset (PARK19A) [MIM:615528]: CC A juvenile form of Parkinson disease, a complex neurodegenerative CC disorder characterized by bradykinesia, resting tremor, muscular CC rigidity and postural instability, as well as by a clinically CC significant response to treatment with levodopa. The pathology involves CC the loss of dopaminergic neurons in the substantia nigra and the CC presence of Lewy bodies (intraneuronal accumulations of aggregated CC proteins), in surviving neurons in various areas of the brain. PARK19A CC is characterized by onset of parkinsonian symptoms in the first or CC second decade of life. Some patients may have additional neurologic CC features, including intellectual disability and seizures. CC {ECO:0000269|PubMed:22563501, ECO:0000269|PubMed:23211418, CC ECO:0000269|PubMed:26703368}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Parkinson disease 19B, early-onset (PARK19B) [MIM:615528]: An CC early-onset form of Parkinson disease, a complex neurodegenerative CC disorder characterized by bradykinesia, resting tremor, muscular CC rigidity and postural instability, as well as by a clinically CC significant response to treatment with levodopa. The pathology involves CC the loss of dopaminergic neurons in the substantia nigra and the CC presence of Lewy bodies (intraneuronal accumulations of aggregated CC proteins), in surviving neurons in various areas of the brain. PARK19B CC is characterized by symptoms onset in the third-to-fifth decade, slow CC disease progression, and prominent. response to dopaminergic therapies. CC Inheritance is autosomal recessive. {ECO:0000269|PubMed:26528954}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAA32318.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AB007942; BAA32318.2; ALT_INIT; mRNA. DR EMBL; AK296408; BAH12344.1; -; mRNA. DR EMBL; AC119800; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL139294; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL355487; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356212; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX06533.1; -; Genomic_DNA. DR EMBL; CH471059; EAX06534.1; -; Genomic_DNA. DR EMBL; CH471059; EAX06536.1; -; Genomic_DNA. DR EMBL; CH471059; EAX06537.1; -; Genomic_DNA. DR EMBL; BC051722; AAH51722.1; -; mRNA. DR EMBL; BC109279; AAI09280.2; -; mRNA. DR EMBL; BC109280; AAI09281.2; -; mRNA. DR CCDS; CCDS30739.1; -. [O75061-1] DR CCDS; CCDS58004.1; -. [O75061-2] DR CCDS; CCDS58005.1; -. [O75061-4] DR RefSeq; NP_001243793.1; NM_001256864.1. [O75061-2] DR RefSeq; NP_001243794.1; NM_001256865.1. [O75061-4] DR RefSeq; NP_055602.1; NM_014787.3. [O75061-1] DR AlphaFoldDB; O75061; -. DR BMRB; O75061; -. DR SMR; O75061; -. DR BioGRID; 115167; 62. DR IntAct; O75061; 9. DR MINT; O75061; -. DR STRING; 9606.ENSP00000360108; -. DR DEPOD; DNAJC6; -. DR iPTMnet; O75061; -. DR PhosphoSitePlus; O75061; -. DR BioMuta; DNAJC6; -. DR EPD; O75061; -. DR jPOST; O75061; -. DR MassIVE; O75061; -. DR MaxQB; O75061; -. DR PaxDb; 9606-ENSP00000360108; -. DR PeptideAtlas; O75061; -. DR ProteomicsDB; 12747; -. DR ProteomicsDB; 49731; -. [O75061-1] DR ProteomicsDB; 49732; -. [O75061-2] DR ProteomicsDB; 49733; -. [O75061-3] DR Pumba; O75061; -. DR Antibodypedia; 33368; 140 antibodies from 26 providers. DR DNASU; 9829; -. DR Ensembl; ENST00000263441.11; ENSP00000263441.7; ENSG00000116675.16. [O75061-4] DR Ensembl; ENST00000371069.5; ENSP00000360108.4; ENSG00000116675.16. [O75061-2] DR Ensembl; ENST00000395325.7; ENSP00000378735.3; ENSG00000116675.16. [O75061-1] DR GeneID; 9829; -. DR KEGG; hsa:9829; -. DR MANE-Select; ENST00000371069.5; ENSP00000360108.4; NM_001256864.2; NP_001243793.1. [O75061-2] DR UCSC; uc001dcd.3; human. [O75061-1] DR AGR; HGNC:15469; -. DR CTD; 9829; -. DR DisGeNET; 9829; -. DR GeneCards; DNAJC6; -. DR GeneReviews; DNAJC6; -. DR HGNC; HGNC:15469; DNAJC6. DR HPA; ENSG00000116675; Group enriched (brain, retina). DR MalaCards; DNAJC6; -. DR MIM; 608375; gene. DR MIM; 615528; phenotype. DR neXtProt; NX_O75061; -. DR OpenTargets; ENSG00000116675; -. DR Orphanet; 391411; Atypical juvenile parkinsonism. DR Orphanet; 2828; Young-onset Parkinson disease. DR PharmGKB; PA27423; -. DR VEuPathDB; HostDB:ENSG00000116675; -. DR eggNOG; KOG0431; Eukaryota. DR eggNOG; KOG2283; Eukaryota. DR GeneTree; ENSGT00940000158755; -. DR HOGENOM; CLU_007537_1_0_1; -. DR InParanoid; O75061; -. DR OMA; XPELDAC; -. DR OrthoDB; 103262at2759; -. DR PhylomeDB; O75061; -. DR TreeFam; TF105165; -. DR PathwayCommons; O75061; -. DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis. DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR SignaLink; O75061; -. DR SIGNOR; O75061; -. DR BioGRID-ORCS; 9829; 12 hits in 1157 CRISPR screens. DR ChiTaRS; DNAJC6; human. DR GeneWiki; Auxilin; -. DR GenomeRNAi; 9829; -. DR Pharos; O75061; Tbio. DR PRO; PR:O75061; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O75061; Protein. DR Bgee; ENSG00000116675; Expressed in endothelial cell and 153 other cell types or tissues. DR ExpressionAtlas; O75061; baseline and differential. DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0098894; C:extrinsic component of presynaptic endocytic zone membrane; IEA:Ensembl. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0014069; C:postsynaptic density; IBA:GO_Central. DR GO; GO:0031982; C:vesicle; IBA:GO_Central. DR GO; GO:0030276; F:clathrin binding; ISS:UniProtKB. DR GO; GO:0032050; F:clathrin heavy chain binding; ISS:UniProtKB. DR GO; GO:0031072; F:heat shock protein binding; ISS:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0072318; P:clathrin coat disassembly; ISS:UniProtKB. DR GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:UniProtKB. DR GO; GO:0016311; P:dephosphorylation; IEA:InterPro. DR GO; GO:0046907; P:intracellular transport; IMP:UniProtKB. DR GO; GO:1905443; P:regulation of clathrin coat assembly; IMP:UniProtKB. DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; IEA:Ensembl. DR GO; GO:0036465; P:synaptic vesicle recycling; ISS:UniProtKB. DR GO; GO:0016191; P:synaptic vesicle uncoating; ISS:BHF-UCL. DR CDD; cd06257; DnaJ; 1. DR CDD; cd14563; PTP_auxilin_N; 1. DR Gene3D; 2.60.40.1110; -; 1. DR Gene3D; 1.10.287.110; DnaJ domain; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR001623; DnaJ_domain. DR InterPro; IPR036869; J_dom_sf. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR014020; Tensin_C2-dom. DR InterPro; IPR029023; Tensin_phosphatase. DR InterPro; IPR000387; Tyr_Pase_dom. DR PANTHER; PTHR23172; AUXILIN/CYCLIN G-ASSOCIATED KINASE-RELATED; 1. DR PANTHER; PTHR23172:SF4; TYROSINE-PROTEIN PHOSPHATASE AUXILIN-RELATED; 1. DR Pfam; PF10409; PTEN_C2; 1. DR SMART; SM00271; DnaJ; 1. DR SMART; SM01326; PTEN_C2; 1. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF46565; Chaperone J-domain; 1. DR PROSITE; PS51182; C2_TENSIN; 1. DR PROSITE; PS50076; DNAJ_2; 1. DR PROSITE; PS51181; PPASE_TENSIN; 1. DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1. DR Genevisible; O75061; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Chaperone; Cytoplasmic vesicle; KW Disease variant; Hydrolase; Neurodegeneration; Parkinson disease; KW Parkinsonism; Phosphoprotein; Protein phosphatase; Reference proteome; KW Repeat; SH3-binding. FT CHAIN 1..913 FT /note="Auxilin" FT /id="PRO_0000244516" FT REPEAT 36..39 FT /note="1" FT REPEAT 40..43 FT /note="2" FT REPEAT 44..47 FT /note="3" FT DOMAIN 55..222 FT /note="Phosphatase tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT DOMAIN 228..366 FT /note="C2 tensin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589" FT DOMAIN 849..913 FT /note="J" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286" FT REGION 36..47 FT /note="3 X 4 AA approximate tandem repeats" FT REGION 451..776 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 409..417 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 453..469 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 505..519 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 551..574 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 594..632 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 653..696 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 745..770 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 164 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590" FT MOD_RES 112 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 453 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80TZ3" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q80TZ3" FT MOD_RES 563 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 570 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:29735704, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..13 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_019579" FT VAR_SEQ 1..7 FT /note="MKDSENK -> MSLLGSYRKKTSNDGYESLQLVDSNGDLSAGSGGVGGKQRV FT NAGAAARSPARQPPDRASTMDSS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019580" FT VAR_SEQ 456..913 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_019581" FT VARIANT 76 FT /note="M -> L (in dbSNP:rs61757223)" FT /evidence="ECO:0000269|PubMed:26528954" FT /id="VAR_077924" FT VARIANT 152 FT /note="L -> P" FT /evidence="ECO:0000269|PubMed:26528954" FT /id="VAR_077925" FT VARIANT 264 FT /note="I -> V" FT /evidence="ECO:0000269|PubMed:26528954" FT /id="VAR_077926" FT VARIANT 441 FT /note="C -> S (in dbSNP:rs145329294)" FT /evidence="ECO:0000269|PubMed:26528954" FT /id="VAR_077927" FT VARIANT 562 FT /note="R -> C (in dbSNP:rs770127313)" FT /evidence="ECO:0000269|PubMed:26528954" FT /id="VAR_077928" FT VARIANT 671 FT /note="S -> N (in dbSNP:rs4915691)" FT /id="VAR_026908" FT VARIANT 870 FT /note="R -> G (in PARK19B; patient fibroblasts show FT decreased levels of the protein; dbSNP:rs879255630)" FT /evidence="ECO:0000269|PubMed:26528954" FT /id="VAR_077929" FT MUTAGEN 570 FT /note="S->A: Increase interaction with CLTC. Does not FT affect interaction with HSPA8." FT /evidence="ECO:0000269|PubMed:29735704" FT MUTAGEN 570 FT /note="S->D: Does not affect interaction with CLTC. Does FT not affect interaction with HSPA8." FT /evidence="ECO:0000269|PubMed:29735704" FT CONFLICT 178 FT /note="M -> V (in Ref. 2; BAH12344)" FT /evidence="ECO:0000305" FT CONFLICT 425 FT /note="F -> S (in Ref. 5; AAH51722)" FT /evidence="ECO:0000305" FT MOD_RES O75061-3:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES O75061-4:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" SQ SEQUENCE 913 AA; 99997 MW; 7B7187AAC8ADF2E4 CRC64; MKDSENKGAS SPDMEPSYGG GLFDMVKGGA GRLFSNLKDN LKDTLKDTSS RVIQSVTSYT KGDLDFTYVT SRIIVMSFPL DNVDIGFRNQ VDDIRSFLDS RHLDHYTVYN LSPKSYRTAK FHSRVSECSW PIRQAPSLHN LFAVCRNMYN WLLQNPKNVC VVHCLDGRAA SSILVGAMFI FCNLYSTPGP AIRLLYAKRP GIGLSPSHRR YLGYMCDLLA DKPYRPHFKP LTIKSITVSP IPFFNKQRNG CRPYCDVLIG ETKIYSTCTD FERMKEYRVQ DGKIFIPLNI TVQGDVVVSM YHLRSTIGSR LQAKVTNTQI FQLQFHTGFI PLDTTVLKFT KPELDACDVP EKYPQLFQVT LDVELQPHDK VIDLTPPWEH YCTKDVNPSI LFSSHQEHQD TLALGGQAPI DIPPDNPRHY GQSGFFASLC WQDQKSEKSF CEEDHAALVN QESEQSDDEL LTLSSPHGNA NGDKPHGVKK PSKKQQEPAA PPPPEDVDLL GLEGSAMSNS FSPPAAPPTN SELLSDLFGG GGAAGPTQAG QSGVEDVFHP SGPASTQSTP RRSATSTSAS PTLRVGEGAT FDPFGAPSKP SGQDLLGSFL NTSSASSDPF LQPTRSPSPT VHASSTPAVN IQPDVSGGWD WHAKPGGFGM GSKSAATSPT GSSHGTPTHQ SKPQTLDPFA DLGTLGSSSF ASKPTTPTGL GGGFPPLSSP QKASPQPMGG GWQQGGAYNW QQPQPKPQPS MPHSSPQNRP NYNVSFSAMP GGQNERGKGS SNLEGKQKAA DFEDLLSGQG FNAHKDKKGP RTIAEMRKEE MAKEMDPEKL KILEWIEGKE RNIRALLSTM HTVLWAGETK WKPVGMADLV TPEQVKKVYR KAVLVVHPDK ATGQPYEQYA KMIFMELNDA WSEFENQGQK PLY //