TAU_SPECI
ID TAU_SPECI Reviewed; 430 AA.
AC Q6TS35;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Microtubule-associated protein tau;
GN Name=MAPT;
OS Spermophilus citellus (European suslik) (Citellus citellus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; Sciuridae;
OC Xerinae; Marmotini; Spermophilus.
OX NCBI_TaxID=9997;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, PHOSPHORYLATION, AND
RP FUNCTION DURING HIBERNATION.
RX PubMed=12904458; DOI=10.1523/jneurosci.23-18-06972.2003;
RA Arendt T., Stieler J., Strijkstra A.M., Hut R.A., Ruediger J.,
RA Van der Zee E.A., Harkany T., Holzer M., Haertig W.;
RT "Reversible paired helical filament-like phosphorylation of tau is an
RT adaptive process associated with neuronal plasticity in hibernating
RT animals.";
RL J. Neurosci. 23:6972-6981(2003).
CC -!- FUNCTION: Promotes microtubule assembly and stability, and might be
CC involved in the establishment and maintenance of neuronal polarity. The
CC C-terminus binds axonal microtubules while the N-terminus binds neural
CC plasma membrane components, suggesting that tau functions as a linker
CC protein between both. Axonal polarity is predetermined by tau
CC localization (in the neuronal cell) in the domain of the cell body
CC defined by the centrosome. The short isoforms allow plasticity of the
CC cytoskeleton whereas the longer isoforms may preferentially play a role
CC in its stabilization. {ECO:0000269|PubMed:12904458}.
CC -!- SUBUNIT: Interacts with MARK1, MARK2, MARK3 AND MARK4 (By similarity).
CC Interacts with SQSTM1 when polyubiquitinated (By similarity). Interacts
CC with PSMC2 through SQSTM1 (By similarity). Interacts with FKBP4 (By
CC similarity). Binds to CSNK1D (By similarity). Interacts with SGK1 (By
CC similarity). Interacts with PIN1 (By similarity). Interacts with LRRK2
CC (By similarity). Interacts with LRP1, leading to endocytosis; this
CC interaction is reduced in the presence of LRPAP1/RAP (By similarity).
CC {ECO:0000250|UniProtKB:P10636, ECO:0000250|UniProtKB:P10637,
CC ECO:0000250|UniProtKB:P19332}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P10636}. Cell membrane
CC {ECO:0000250|UniProtKB:P10636}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P10636}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P10636}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P10636}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P10636}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P10636}. Note=Mostly found in the axons of
CC neurons, in the cytosol and in association with plasma membrane
CC components. {ECO:0000250|UniProtKB:P10636}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=A number of isoforms are produced. 6 isoforms have been
CC detected in the adult brain. The pattern of isoforms and their
CC relative expression levels are unaffected during hibernation cycle.;
CC Name=1;
CC IsoId=Q6TS35-1; Sequence=Displayed;
CC -!- DOMAIN: The tau/MAP repeat binds to tubulin. {ECO:0000250}.
CC -!- PTM: Polyubiquitinated. Requires functional TRAF6 and may provoke
CC SQSTM1-dependent degradation by the proteasome (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at various serine and threonine residues in S-P or
CC T-P motifs by proline-directed protein kinases (PDPK1, CDK1, CDK5,
CC GSK3, MAPK) (a few sites per protein in interphase, more in mitosis),
CC and at serine residues in K-X-G-S motifs by MAP/microtubule affinity-
CC regulating kinase (MARK1, MARK2, MARK3 or MARK4), causing detachment
CC from microtubules, and their disassembly (By similarity).
CC Phosphorylation at Ser-345 by BRSK1 and BRSK2 in neurons affects
CC ability to bind microtubules and plays a role in neuron polarization.
CC Phosphorylated by PHK. Dephosphorylation at several serine and
CC threonine residues by the serine/threonine phosphatase PPP5C (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P10636}.
CC -!- PTM: Hyperphosphorylated (in particular at Thr-170, Ser-191, Thr-194,
CC Ser-251, and Ser-345) during hibernation. Phosphorylation is fully
CC reversible after arousal. Highly phosphorylated tau contains a number
CC of paired helical filaments (PHFs)-like epitopes. PHF-like
CC phosphorylation is not associated with fibril formation. Distribution
CC of PHF-like tau is more intense in the entorhinal cortex, hippocampus
CC and isocortical areas. PHF-like phosphorylation-dephosphorylation
CC during hibernation cycle is synchronized with regression-re-
CC establishment of afferentation. It may reflect a protective mechanism
CC in an unfavorable environment. {ECO:0000269|PubMed:12904458}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Vita minima - Issue 68 of
CC March 2006;
CC URL="https://web.expasy.org/spotlight/back_issues/068";
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DR EMBL; AY388477; AAQ92319.1; -; mRNA.
DR AlphaFoldDB; Q6TS35; -.
DR SMR; Q6TS35; -.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008017; F:microtubule binding; IEA:InterPro.
DR GO; GO:0042750; P:hibernation; IEA:UniProtKB-KW.
DR InterPro; IPR001084; MAP_tubulin-bd_rpt.
DR InterPro; IPR002955; Tau.
DR Pfam; PF00418; Tubulin-binding; 4.
DR PRINTS; PR01261; TAUPROTEIN.
DR PROSITE; PS00229; TAU_MAP_1; 4.
DR PROSITE; PS51491; TAU_MAP_2; 4.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Cytoskeleton; Disulfide bond; Hibernation; Isopeptide bond;
KW Membrane; Methylation; Microtubule; Phosphoprotein; Repeat;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CHAIN 2..430
FT /note="Microtubule-associated protein tau"
FT /id="PRO_0000232454"
FT REPEAT 233..263
FT /note="Tau/MAP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 264..294
FT /note="Tau/MAP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 295..325
FT /note="Tau/MAP 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 326..357
FT /note="Tau/MAP 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REGION 1..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..134
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..164
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..200
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 18
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 56
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 98
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 142
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 144
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 152
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 152
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 158
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 164
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 165
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 186
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 194
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 201
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 206
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 214
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 220
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 248
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 248
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 270
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 279
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 287
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 300
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 300
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 306
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 310
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 320
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 332
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 336
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 338
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 358
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 374
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 383
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 392
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 416
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT DISULFID 280..311
FT /evidence="ECO:0000250"
FT CROSSLNK 31
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 243
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 248
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 256
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 287
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 300
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 306
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 310
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 320
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 332
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 336
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 342
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 358
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 364
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 374
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
SQ SEQUENCE 430 AA; 44803 MW; 5ED2B0EB0DFADAF0 CRC64;
MAEPRQEFDT AEDHAEGYAL LQDQEGEHGL KASPLQTPAD DGPEEPVSET SDAKSTPTAE
DVTAPLVDER TPGEQAATQP PTDIPEGTTA EEAGIGDTPN MEDQAAGHVT QARMVSKGKE
GTGSEDRKAK GADSKTGTKI ATPRGTAPPG QKGTANATRI PAKTTPSPKT PPGTGEPAKS
GDRSGYSSPG SPGTPGSRSR TPSLPTPPTR EPKKVAVVRT PPKSPSSTKS RLQTAPVPMP
DLKNVRSKIG STENLKHQPG GGKVQIINKK LDLSNVQSKC GSKDNIKHVP GGGSVQIVYK
PVDLSKVTSK CGSLGNIHHK PGGGQVEVKS EKLDFKDRVQ SKIGSLDNIT HVPGGGNKKI
ETHKLTFREN AKAKTDHGAE IVYKSPVVSG DTSPRHLSNV SSTGSINMVD SPQLATLADE
VSASLAKQGL
