AUXI_MOUSE
ID AUXI_MOUSE Reviewed; 938 AA.
AC Q80TZ3; B1B0B9; Q6P2K9; Q8C7L9;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Putative tyrosine-protein phosphatase auxilin {ECO:0000305};
DE EC=3.1.3.48;
DE AltName: Full=DnaJ homolog subfamily C member 6 {ECO:0000312|MGI:MGI:1919935};
GN Name=Dnajc6 {ECO:0000312|MGI:MGI:1919935};
GN Synonyms=Kiaa0473 {ECO:0000312|EMBL:BAC65575.1};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, Hippocampus, and Medulla oblongata;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-478; SER-481 AND SER-595, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, 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 [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20160091; DOI=10.1073/pnas.1000738107;
RA Yim Y.I., Sun T., Wu L.G., Raimondi A., De Camilli P., Eisenberg E.,
RA Greene L.E.;
RT "Endocytosis and clathrin-uncoating defects at synapses of auxilin knockout
RT mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4412-4417(2010).
CC -!- FUNCTION: Recruits HSPA8/HSC70 to clathrin-coated vesicles and promotes
CC uncoating of clathrin-coated vesicles. Plays a role in clathrin-
CC mediated endocytosis in neurons. {ECO:0000269|PubMed:20160091}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC -!- SUBUNIT: Interacts with HSPA8/HSC70. Interacts with CLTC. Interacts
CC with AP2A2 (By similarity). {ECO:0000250|UniProtKB:Q27974}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q80TZ3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80TZ3-2; Sequence=VSP_019582;
CC Name=3;
CC IsoId=Q80TZ3-3; Sequence=VSP_019583;
CC -!- DISRUPTION PHENOTYPE: Mice have a high rate of early postnatal
CC mortality, although surviving pups have a normal life span despite
CC decreased body weight. Knockout animals have impaired synaptic vesicle
CC recycling, with an increased number of clathrin-coated vesicles, and
CC impaired clathrin-mediated endocytosis of synaptic vesicles in neuronal
CC culture. There is an up-regulation of Gak, but this does not fully
CC compensate for the lack of the protein. The brains from mutant mice do
CC not display alterations in substantia nigra morphology or dopamine
CC transporter abundance or distribution, in agreement with the lack of
CC gait or movement abnormalities in the mutant animals.
CC {ECO:0000269|PubMed:20160091}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH60734.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK122293; BAC65575.1; -; mRNA.
DR EMBL; AK049935; BAC33992.1; -; mRNA.
DR EMBL; AK147570; BAE28000.1; -; mRNA.
DR EMBL; AK147637; BAE28039.1; -; mRNA.
DR EMBL; AK163657; BAE37443.1; -; mRNA.
DR EMBL; BX323551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC060734; AAH60734.1; ALT_INIT; mRNA.
DR EMBL; BC064460; AAH64460.1; -; mRNA.
DR CCDS; CCDS18395.1; -. [Q80TZ3-2]
DR CCDS; CCDS51237.1; -. [Q80TZ3-1]
DR CCDS; CCDS51238.1; -. [Q80TZ3-3]
DR RefSeq; NP_001158055.1; NM_001164583.1. [Q80TZ3-3]
DR RefSeq; NP_001158056.1; NM_001164584.1. [Q80TZ3-1]
DR RefSeq; NP_001158057.1; NM_001164585.1. [Q80TZ3-2]
DR RefSeq; NP_940804.1; NM_198412.2. [Q80TZ3-2]
DR RefSeq; XP_017175882.1; XM_017320393.1.
DR AlphaFoldDB; Q80TZ3; -.
DR SMR; Q80TZ3; -.
DR BioGRID; 215514; 6.
DR IntAct; Q80TZ3; 5.
DR MINT; Q80TZ3; -.
DR STRING; 10090.ENSMUSP00000044251; -.
DR iPTMnet; Q80TZ3; -.
DR PhosphoSitePlus; Q80TZ3; -.
DR SwissPalm; Q80TZ3; -.
DR EPD; Q80TZ3; -.
DR jPOST; Q80TZ3; -.
DR MaxQB; Q80TZ3; -.
DR PaxDb; Q80TZ3; -.
DR PeptideAtlas; Q80TZ3; -.
DR PRIDE; Q80TZ3; -.
DR ProteomicsDB; 273635; -. [Q80TZ3-1]
DR ProteomicsDB; 273636; -. [Q80TZ3-2]
DR ProteomicsDB; 273637; -. [Q80TZ3-3]
DR Antibodypedia; 33368; 134 antibodies from 26 providers.
DR DNASU; 72685; -.
DR Ensembl; ENSMUST00000038207; ENSMUSP00000044251; ENSMUSG00000028528. [Q80TZ3-1]
DR Ensembl; ENSMUST00000094953; ENSMUSP00000092560; ENSMUSG00000028528. [Q80TZ3-2]
DR Ensembl; ENSMUST00000106929; ENSMUSP00000102542; ENSMUSG00000028528. [Q80TZ3-2]
DR Ensembl; ENSMUST00000106930; ENSMUSP00000102543; ENSMUSG00000028528. [Q80TZ3-2]
DR Ensembl; ENSMUST00000106933; ENSMUSP00000102546; ENSMUSG00000028528. [Q80TZ3-3]
DR GeneID; 72685; -.
DR KEGG; mmu:72685; -.
DR UCSC; uc008tvq.2; mouse. [Q80TZ3-1]
DR UCSC; uc008tvt.1; mouse. [Q80TZ3-3]
DR CTD; 9829; -.
DR MGI; MGI:1919935; Dnajc6.
DR VEuPathDB; HostDB:ENSMUSG00000028528; -.
DR eggNOG; KOG0431; Eukaryota.
DR eggNOG; KOG2283; Eukaryota.
DR GeneTree; ENSGT00940000158755; -.
DR HOGENOM; CLU_007537_1_0_1; -.
DR InParanoid; Q80TZ3; -.
DR OrthoDB; 826336at2759; -.
DR PhylomeDB; Q80TZ3; -.
DR TreeFam; TF105165; -.
DR Reactome; R-MMU-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 72685; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Dnajc6; mouse.
DR PRO; PR:Q80TZ3; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q80TZ3; protein.
DR Bgee; ENSMUSG00000028528; Expressed in medial dorsal nucleus of thalamus and 192 other tissues.
DR ExpressionAtlas; Q80TZ3; baseline and differential.
DR Genevisible; Q80TZ3; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0045202; C:synapse; IMP:MGI.
DR GO; GO:0031982; C:vesicle; IBA:GO_Central.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
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; IMP:MGI.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; IBA:GO_Central.
DR GO; GO:0016311; P:dephosphorylation; IEA:InterPro.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; IMP:MGI.
DR GO; GO:0016191; P:synaptic vesicle uncoating; IDA:SynGO.
DR CDD; cd06257; DnaJ; 1.
DR Gene3D; 1.10.287.110; -; 1.
DR Gene3D; 3.90.190.10; -; 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 Pfam; PF10409; PTEN_C2; 1.
DR SMART; SM00271; DnaJ; 1.
DR SMART; SM01326; PTEN_C2; 1.
DR SUPFAM; SSF46565; SSF46565; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS51182; C2_TENSIN; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS51181; PPASE_TENSIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chaperone; Hydrolase; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Repeat; SH3-binding.
FT CHAIN 1..938
FT /note="Putative tyrosine-protein phosphatase auxilin"
FT /id="PRO_0000244517"
FT REPEAT 61..64
FT /note="1"
FT REPEAT 65..68
FT /note="2"
FT REPEAT 69..72
FT /note="3"
FT DOMAIN 80..247
FT /note="Phosphatase tensin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT DOMAIN 253..391
FT /note="C2 tensin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00589"
FT DOMAIN 874..938
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT REGION 19..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..72
FT /note="3 X 4 AA approximate tandem repeats"
FT REGION 467..801
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 434..442
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 530..545
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 577..598
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 621..656
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 678..721
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 750..795
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 189
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75061"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 595
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..38
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_019582"
FT VAR_SEQ 1..32
FT /note="MTNPKSGVAESAGLACSRAAAGENRMKDSENK -> MSLLGSYRKKTSSDGY
FT ESLQLVDSHGDSSARGAAAGTQRATAGAVRSPARQPPHRASTTDSS (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_019583"
FT CONFLICT 442
FT /note="P -> T (in Ref. 1; BAC65575)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 938 AA; 102299 MW; 3DFB7D9275BEF3F6 CRC64;
MTNPKSGVAE SAGLACSRAA AGENRMKDSE NKGASSPDME PSYGGGLFDM VKGGAGRLFS
NLKDNLKDTL KDTSSRVIQS VSSYTKGDLD FTYVTSRIIV MSFPVDSVDI GFRNQVDDIR
SFLDSRHLDH YTVYNLSPKS YRTAKFHSRV SECSWPIRQA PSLHNLFAVC RNMYNWLLQN
PKNVCVVHCL DGRAASSILV GAMFIFCNLY STPGPAVRLL YAKRPGIGLS PSHRRYLGYM
CDLLADKPYR PHFKPLTIKA ITVSPVPFFN KQRNGCRPYC DVLIGETKIY STCTDFERMK
EYRVQDGKIF IPLNITVQGD VIVSMYHLRS TIGSRLQAKV TNTQIFQLQF HSGFIPLDTT
VLKFTKPELD ACDVPEKYPQ LFQVTLDIEV QPQDKVIDLT PPWEHYCTKD VNPSILFSSQ
QEHQDTLALG GQAPADLPPD HPRNLGQGGF FASLCWQDQK SEKSRCEEDH AALVNQESEQ
SDDELLTLSS PHGNAEGDKP HGAKKPGKKQ QEPAAPPPPE EVDLLGLEGS DVSTNFSSLA
APPSNSELLS DLFGGVGATG PAQAGQAGVE DVFHPSGPVS AQSTPRRTAT SASASPTLRV
GEGATFDPFG APAKPPGQDL LGSFLNTSSA SSDPFLQPTR SPSPTVHASS TPAVNIQPDI
AGGWDWHTKP GGFGMGSKSA ATSPTGSSHG TPTHQSKPQT LDPFADLGTL GSSSFASKPT
TPTGLGGGFP PLSSPQKASP QPMGGGWQQP AGYNWQQTQS KPQSSMPHSS PQNRPNYNVS
FSAMPAGQSE RGKGSTNLEG KQKAADFEDL LSSQGFNAHK DKKGPRTIAE MRKEEMAKEM
DPEKLKILEW IEGKERNIRA LLSTMHTVLW AGETKWKPVG MADLVTPEQV KKVYRRAVLV
VHPDKATGQP YEQYAKMIFM ELNDAWSEFE NQGQKPLY
