TAU_MACMU
ID TAU_MACMU Reviewed; 459 AA.
AC P57786;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 122.
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 Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TAU-A; TAU-B; TAU-C AND TAU-D).
RC TISSUE=Brain;
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}. Secreted
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. Can be secreted; the secretion is dependent on protein
CC unfolding and facilitated by the cargo receptor TMED10; it results in
CC protein translocation from the cytoplasm into the ERGIC (endoplasmic
CC reticulum-Golgi intermediate compartment) followed by vesicle entry and
CC secretion. {ECO:0000250|UniProtKB:P10636}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist. Isoforms differ from each
CC other by the presence or absence of up to 4 exons. One of these
CC optional exons contains the additional tau/MAP repeat. The sequence
CC shown here is that of the complete isoform not yet characterized.;
CC Name=Tau-A;
CC IsoId=P57786-1; Sequence=Displayed;
CC Name=Tau-B;
CC IsoId=P57786-2; Sequence=VSP_003182, VSP_003184;
CC Name=Tau-C;
CC IsoId=P57786-3; Sequence=VSP_003182, VSP_003183;
CC Name=Tau-D;
CC IsoId=P57786-4; Sequence=VSP_003183;
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 or MARK4), causing detachment
CC from microtubules, and their disassembly (By similarity).
CC Phosphorylation at Ser-280 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}.
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DR RefSeq; XP_014975440.1; XM_015119954.1. [P57786-4]
DR RefSeq; XP_014975443.1; XM_015119957.1. [P57786-3]
DR AlphaFoldDB; P57786; -.
DR BMRB; P57786; -.
DR SMR; P57786; -.
DR PRIDE; P57786; -.
DR ABCD; P57786; 2 sequenced antibodies.
DR Ensembl; ENSMMUT00000005855; ENSMMUP00000005515; ENSMMUG00000004122. [P57786-4]
DR Ensembl; ENSMMUT00000102984; ENSMMUP00000062176; ENSMMUG00000004122. [P57786-3]
DR GeneID; 574327; -.
DR KEGG; mcc:574327; -.
DR CTD; 4137; -.
DR VEuPathDB; HostDB:ENSMMUG00000004122; -.
DR eggNOG; KOG2418; Eukaryota.
DR GeneTree; ENSGT00940000155494; -.
DR InParanoid; P57786; -.
DR Proteomes; UP000006718; Chromosome 16.
DR Bgee; ENSMMUG00000004122; Expressed in dorsolateral prefrontal cortex and 21 other tissues.
DR ExpressionAtlas; P57786; baseline.
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:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0031175; P:neuron projection development; IBA:GO_Central.
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 Secreted; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CHAIN 2..459
FT /note="Microtubule-associated protein tau"
FT /id="PRO_0000072741"
FT REPEAT 262..292
FT /note="Tau/MAP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 293..323
FT /note="Tau/MAP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 324..354
FT /note="Tau/MAP 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REPEAT 355..386
FT /note="Tau/MAP 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00824"
FT REGION 1..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..435
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 132..148
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..435
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:P10636"
FT MOD_RES 29
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 69
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 71
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P19332"
FT MOD_RES 111
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 153
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 155
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 163
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 163
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 169
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 175
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 181
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 215
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 223
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 230
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 235
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 249
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 277
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 277
FT /note="N6-methyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 299
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 308
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 316
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 329
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 329
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 335
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 339
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 349
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 361
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 365
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 367
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 387
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 403
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 412
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 421
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT MOD_RES 445
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT DISULFID 309..340
FT /evidence="ECO:0000250"
FT CROSSLNK 44
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 272
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 277
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 285
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 316
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 329
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 335
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 339
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 349
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 361
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 365
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 371
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10636"
FT CROSSLNK 387
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 393
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P10637"
FT VAR_SEQ 45..102
FT /note="Missing (in isoform Tau-B and isoform Tau-C)"
FT /evidence="ECO:0000303|PubMed:8858947"
FT /id="VSP_003182"
FT VAR_SEQ 186..203
FT /note="Missing (in isoform Tau-C and isoform Tau-D)"
FT /evidence="ECO:0000303|PubMed:8858947"
FT /id="VSP_003183"
FT VAR_SEQ 293..323
FT /note="Missing (in isoform Tau-B)"
FT /evidence="ECO:0000303|PubMed:8858947"
FT /id="VSP_003184"
SQ SEQUENCE 459 AA; 47972 MW; 939CD94ABEDA92D3 CRC64;
MAEPRQEFDV MEDHAGTYGL GDRKDQEGYT MLQDQEGDTD AGLKESPLQT PAEDGSEELG
SETSDAKSTP TAEDVTAPLV DERAPGEQAA AQPHMEIPEG TTAEEAGIGD TPSLEDEAAG
HVTQARMVSK SKDGTGSDDK KAKGADGKTK IATPRGAAPP GQKGQANATR IPAKTPPAPK
TPPSSATKQV QRKPPPAEPT SERGEPPKSG DRSGYSSPGS PGTPGSRSRT PSLPTPPARE
PKKVAVVRTP PKSPSSAKSR LQTAPVPMPD LKNVKSKIGS TENLKHQPGG GKVQIINKKL
DLSNVQSKCG SKDNIKHVPG GGSVQIVYKP VDLSKVTSKC GSLGNIHHKP GGGQVEVKSE
KLDFKDRVQS KIGSLDNITH VPGGGNKKIE THKLTFRENA KAKTDHGAEI VYKSPVVSGD
TSPRHLSNVS STGSIDMVDS PQLATLADEV SASLAKQGL
