TAU_CAPHI
ID TAU_CAPHI Reviewed; 403 AA.
AC O02828;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Microtubule-associated protein tau;
DE AltName: Full=Neurofibrillary tangle protein;
DE AltName: Full=Paired helical filament-tau;
DE Short=PHF-tau;
GN Name=MAPT; Synonyms=TAU;
OS Capra hircus (Goat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Capra.
OX NCBI_TaxID=9925;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TAU-A AND TAU-B).
RC TISSUE=Brain cortex;
RX PubMed=8858947; DOI=10.1046/j.1471-4159.1996.67041622.x;
RA Nelson P.T., Stefansson K., Gulcher J., Saper C.B.;
RT "Molecular evolution of tau protein: implications for Alzheimer's
RT disease.";
RL J. Neurochem. 67:1622-1632(1996).
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.
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=2;
CC Comment=Additional isoforms seem to exist. Isoforms differ from each
CC other by the presence or absence of two exons. One of these optional
CC exons contains the additional tau/MAP repeat.;
CC Name=Tau-A;
CC IsoId=O02828-1; Sequence=Displayed;
CC Name=Tau-B;
CC IsoId=O02828-2; Sequence=VSP_003173, VSP_003174;
CC -!- TISSUE SPECIFICITY: Expressed in neurons.
CC -!- DOMAIN: The tau/MAP repeat binds to tubulin. Type I isoforms contain 3
CC repeats while type II isoforms contain 4 repeats.
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, MARK4), causing detachment from
CC microtubules, and their disassembly (By similarity). Phosphorylation at
CC Ser-224 by BRSK1 and BRSK2 in neurons affects ability to bind
CC microtubules and plays a role in neuron polarization. Phosphorylated by
CC PHK. Dephosphorylation at several serine and threonine residues by the
CC serine/threonine phosphatase PPP5C (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P10636}.
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DR EMBL; S83347; AAB50785.1; -; mRNA.
DR RefSeq; XP_017920784.1; XM_018065295.1. [O02828-1]
DR RefSeq; XP_017920788.1; XM_018065299.1. [O02828-2]
DR AlphaFoldDB; O02828; -.
DR BMRB; O02828; -.
DR SMR; O02828; -.
DR Ensembl; ENSCHIT00000040079; ENSCHIP00000032204; ENSCHIG00000026221. [O02828-1]
DR GeneID; 100860820; -.
DR CTD; 4137; -.
DR GeneTree; ENSGT00940000155494; -.
DR OrthoDB; 716848at2759; -.
DR Proteomes; UP000291000; Chromosome 19.
DR Bgee; ENSCHIG00000026221; Expressed in frontal cortex and 16 other tissues.
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 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 2: Evidence at transcript level;
KW Acetylation; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Cytoskeleton; Disulfide bond; Isopeptide bond; Membrane;
KW Methylation; Microtubule; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CHAIN 2..403
FT /note="Microtubule-associated protein tau"
FT /id="PRO_0000072737"
FT REPEAT 206..236
FT /note="Tau/MAP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 237..267
FT /note="Tau/MAP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 268..298
FT /note="Tau/MAP 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 299..330
FT /note="Tau/MAP 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REGION 1..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..31
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 92..107
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..173
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 364..379
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 19
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 60
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 71
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 115
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 117
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 125
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 125
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 131
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 137
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 138
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 143
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 159
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 167
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 174
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 179
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 187
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 193
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 221
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 221
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 243
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 252
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 260
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 273
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 273
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 279
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 283
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 293
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 305
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 309
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 311
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 331
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 347
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 356
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 365
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 389
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT DISULFID 253..284
FT /evidence="ECO:0000250"
FT CROSSLNK 33
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 216
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 221
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 229
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); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 260
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 273
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 279
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 283
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 293
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 305
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 309
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 315
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 331
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 337
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 347
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT VAR_SEQ 34..62
FT /note="Missing (in isoform Tau-B)"
FT /evidence="ECO:0000303|PubMed:8858947"
FT /id="VSP_003173"
FT VAR_SEQ 237..267
FT /note="Missing (in isoform Tau-B)"
FT /evidence="ECO:0000303|PubMed:8858947"
FT /id="VSP_003174"
SQ SEQUENCE 403 AA; 41848 MW; 259D0302E1A339C7 CRC64;
MAEPRQEFDV MEDHAQGDYT LQDHEGDMEP GLKESPLQTP ADDGSEEPGS ETSDAKSTPT
AEAEEAGIGD TSNLEDQAAG HVTQARMVSK GKDGTGPDDK KAKGADGKPG TKIATPRGAA
PPGQKGQANA TRIPAKTTPT PKTSPGTGES GKSGDRSGYS SPGSPGTPGS RSRTPSLPTP
PTREPKKVAV VRTPPKSPSA AKSRLQAAPG PMPDLKNVKS KIGSTENLKH QPGGGKVQII
NKKLDLSNVQ SKCGSKDNIK HVPGGGSVQI VYKPVDLSKV TSKCGSLGNI HHKPGGGQVE
VKSEKLDFKD RVQSKIGSLD NITHVPGGGN KKIETHKLTF RENAKAKTDH GAEIVYKSPV
VSGDTSPRHL SNVSSTGSID MVDSPQLATL ADEVSASLAK QGL