MAP6_RAT
ID MAP6_RAT Reviewed; 952 AA.
AC Q63560; O88748; Q6AYX8;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 117.
DE RecName: Full=Microtubule-associated protein 6;
DE Short=MAP-6;
DE AltName: Full=145-kDa STOP;
DE Short=STOP145;
DE AltName: Full=Stable tubule-only polypeptide;
DE Short=STOP;
GN Name=Map6; Synonyms=Mtap6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP INTERACTION WITH CALMODULIN, AND SUBCELLULAR LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8700896; DOI=10.1073/pnas.93.5.2125;
RA Bosc C., Cronk J.D., Pirollet F., Watterson D.M., Haiech J., Job D.,
RA Margolis R.L.;
RT "Cloning, expression, and properties of the microtubule-stabilizing protein
RT STOP.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2125-2130(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9660871; DOI=10.1083/jcb.142.1.167;
RA Guillaud L., Bosc C., Fourest-Lieuvin A., Denarier E., Pirollet F.,
RA Lafanechere L., Job D.;
RT "STOP proteins are responsible for the high degree of microtubule
RT stabilization observed in neuronal cells.";
RL J. Cell Biol. 142:167-179(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-613 (ISOFORM 2).
RC TISSUE=Testis;
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 [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=3456161; DOI=10.1073/pnas.83.3.639;
RA Margolis R.L., Rauch C.T., Job D.;
RT "Purification and assay of a 145-kDa protein (STOP145) with microtubule-
RT stabilizing and motility behavior.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:639-643(1986).
RN [5]
RP FUNCTION, AND INTERACTION WITH CALMODULIN.
RX PubMed=11413126; DOI=10.1074/jbc.m011614200;
RA Bosc C., Frank R., Denarier E., Ronjat M., Schweitzer A., Wehland J.,
RA Job D.;
RT "Identification of novel bifunctional calmodulin-binding and microtubule-
RT stabilizing motifs in STOP proteins.";
RL J. Biol. Chem. 276:30904-30913(2001).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=14724383; DOI=10.1023/b:neur.0000011334.70648.87;
RA Slaughter T., Black M.M.;
RT "STOP (stable-tubule-only-polypeptide) is preferentially associated with
RT the stable domain of axonal microtubules.";
RL J. Neurocytol. 32:399-413(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185; SER-590; SER-681;
RP SER-736 AND SER-951, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE (ISOFORMS 1 AND 2),
RP PALMITOYLATION AT CYS-5; CYS-10 AND CYS-11, AND MUTAGENESIS OF CYS-5 AND
RP 10-CYS-CYS-11.
RX PubMed=28521134; DOI=10.1016/j.neuron.2017.04.042;
RA Tortosa E., Adolfs Y., Fukata M., Pasterkamp R.J., Kapitein L.C.,
RA Hoogenraad C.C.;
RT "Dynamic palmitoylation targets MAP6 to the axon to promote microtubule
RT stabilization during neuronal polarization.";
RL Neuron 94:809-825(2017).
CC -!- FUNCTION: Involved in microtubule stabilization in many cell types,
CC including neuronal cells (PubMed:8700896, PubMed:9660871,
CC PubMed:3456161, PubMed:11413126, PubMed:28521134). Specifically has
CC microtubule cold stabilizing activity (PubMed:3456161). Involved in
CC dendrite morphogenesis and maintenance by regulating lysosomal
CC trafficking via its interaction with TMEM106B (By similarity).
CC Regulates KIF5A-mediated axonal cargo transport (PubMed:28521134).
CC Regulates axonal growth during neuron polarization (PubMed:28521134).
CC {ECO:0000250|UniProtKB:Q96JE9, ECO:0000269|PubMed:11413126,
CC ECO:0000269|PubMed:28521134, ECO:0000269|PubMed:3456161,
CC ECO:0000269|PubMed:8700896, ECO:0000269|PubMed:9660871}.
CC -!- SUBUNIT: Interacts with calmodulin (via C-terminus); the interaction is
CC dependent on Ca(2+) (PubMed:8700896, PubMed:11413126). Interacts with
CC TMEM106B (By similarity). Interacts with ZDHHC13 (via ANK repeats) (By
CC similarity). Interacts with ZDHHC17 (via ANK repeats) (By similarity).
CC {ECO:0000250|UniProtKB:Q7TSJ2, ECO:0000250|UniProtKB:Q96JE9,
CC ECO:0000269|PubMed:11413126, ECO:0000269|PubMed:8700896}.
CC -!- INTERACTION:
CC Q63560; Q6AYA5: Tmem106b; NbExp=6; IntAct=EBI-1638469, EBI-9316198;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:14724383, ECO:0000269|PubMed:28521134,
CC ECO:0000269|PubMed:3456161, ECO:0000269|PubMed:8700896,
CC ECO:0000269|PubMed:9660871}. Golgi apparatus
CC {ECO:0000269|PubMed:28521134}. Cell projection, axon
CC {ECO:0000269|PubMed:28521134, ECO:0000269|PubMed:9660871}. Cell
CC projection, dendrite {ECO:0000269|PubMed:28521134}. Cytoplasmic
CC vesicle, secretory vesicle membrane {ECO:0000269|PubMed:28521134};
CC Lipid-anchor {ECO:0000269|PubMed:28521134}; Cytoplasmic side
CC {ECO:0000269|PubMed:28521134}. Note=Isoform 1 and isoform 2 associate
CC with axonal microtubules in neuronal cells (PubMed:8700896,
CC PubMed:9660871). Localizes predominantly in the proximal part of the
CC axon (PubMed:28521134). Preferentially concentrated on a portion of the
CC microtubule polymer in which tubulin is modified by detyrosination and
CC acetylation and is also resistant to depolymerization induced by both
CC nocodazole and cold (PubMed:9660871, PubMed:14724383, PubMed:28521134).
CC In unpolarized neurons, localizes to the Golgi and to secretory
CC vesicles accumulating transiently at the tips of a subset of neurites
CC (PubMed:28521134). Following neuronal polarization and during axon
CC outgrowth, accumulates in the axonal growth cone and subsequently
CC localizes throughout the axon (PubMed:28521134). Partially localizes to
CC dendrites in mature neurons (PubMed:28521134).
CC {ECO:0000269|PubMed:14724383, ECO:0000269|PubMed:28521134,
CC ECO:0000269|PubMed:8700896, ECO:0000269|PubMed:9660871}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=N-STOP, Neuronal STOP;
CC IsoId=Q63560-1; Sequence=Displayed;
CC Name=2; Synonyms=E-STOP, Early STOP;
CC IsoId=Q63560-2; Sequence=VSP_034728, VSP_034729;
CC -!- TISSUE SPECIFICITY: Isoform 1 is specifically expressed in adult brain.
CC Isoform 2 is predominantly expressed in embryonic brain; expression
CC persists at low levels in the adult brain.
CC {ECO:0000269|PubMed:9660871}.
CC -!- DEVELOPMENTAL STAGE: At E17.5, expressed in brain including hippocampus
CC and corpus callosum (PubMed:28521134). Isoform 1: Expression begins
CC after birth at P1-P5 stages and is maintained in adults
CC (PubMed:9660871, PubMed:28521134). Expressed in mature neurons
CC (PubMed:28521134). Isoform 2: Expressed at E13, E16 and E18 stages
CC (PubMed:9660871, PubMed:28521134). Expression is increased at P1-P5
CC stages and persists at low levels in the adult brain (PubMed:9660871,
CC PubMed:28521134). Expressed in unpolarized hippocampal neurons and
CC throughout neuronal development (PubMed:28521134).
CC {ECO:0000269|PubMed:28521134, ECO:0000269|PubMed:9660871}.
CC -!- PTM: Palmitoylated. Probably depalmitoylated by ABHD17A, ABHD17B and
CC ABHD17C. During neuronal polarization, palmitoylation and
CC depalmitoylation cycles regulate MAP6 shuttling between secretory
CC vesicles and microtubules, and its polarized distribution in the axon.
CC {ECO:0000269|PubMed:28521134}.
CC -!- SIMILARITY: Belongs to the STOP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH78848.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
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DR EMBL; X93495; CAA63762.1; -; mRNA.
DR EMBL; AJ002556; CAA05555.1; -; mRNA.
DR EMBL; BC078848; AAH78848.1; ALT_SEQ; mRNA.
DR RefSeq; NP_058900.1; NM_017204.1. [Q63560-1]
DR AlphaFoldDB; Q63560; -.
DR BioGRID; 248100; 12.
DR IntAct; Q63560; 5.
DR MINT; Q63560; -.
DR STRING; 10116.ENSRNOP00000032018; -.
DR iPTMnet; Q63560; -.
DR PhosphoSitePlus; Q63560; -.
DR SwissPalm; Q63560; -.
DR jPOST; Q63560; -.
DR PaxDb; Q63560; -.
DR PRIDE; Q63560; -.
DR GeneID; 29457; -.
DR KEGG; rno:29457; -.
DR UCSC; RGD:61804; rat. [Q63560-1]
DR CTD; 4135; -.
DR RGD; 61804; Map6.
DR eggNOG; ENOG502QS1F; Eukaryota.
DR InParanoid; Q63560; -.
DR OrthoDB; 577082at2759; -.
DR PhylomeDB; Q63560; -.
DR PRO; PR:Q63560; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005801; C:cis-Golgi network; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005798; C:Golgi-associated vesicle; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0099503; C:secretory vesicle; IDA:UniProtKB.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0019896; P:axonal transport of mitochondrion; IMP:UniProtKB.
DR GO; GO:0030705; P:cytoskeleton-dependent intracellular transport; IBA:GO_Central.
DR GO; GO:0048813; P:dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:InterPro.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IMP:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IMP:UniProtKB.
DR InterPro; IPR007882; MAP6.
DR PANTHER; PTHR14759; PTHR14759; 7.
PE 1: Evidence at protein level;
KW Alternative splicing; Calmodulin-binding; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Direct protein sequencing;
KW Golgi apparatus; Lipoprotein; Membrane; Microtubule; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; Transport.
FT CHAIN 1..952
FT /note="Microtubule-associated protein 6"
FT /id="PRO_0000344046"
FT REPEAT 222..267
FT /note="Mc-1"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REPEAT 268..313
FT /note="Mc-2"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REPEAT 314..359
FT /note="Mc-3"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REPEAT 360..405
FT /note="Mc-4"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REPEAT 406..451
FT /note="Mc-5"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 1..15
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 37..457
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 116..139
FT /note="Mn 1"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 124..138
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 151..174
FT /note="Mn 2"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 160..174
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 187..201
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 222..451
FT /note="5 X approximate tandem repeat Mc"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 235..249
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 280..294
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 325..339
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 373..387
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 421..435
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 473..496
FT /note="Mn 3"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 481..495
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 486..952
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 532..546
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT REGION 559..573
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11413126"
FT COMPBIAS 40..56
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 150..164
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..191
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..429
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 525..548
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..620
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 763..779
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 897..919
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSJ2"
FT MOD_RES 141
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSJ2"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSJ2"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 736
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 951
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:28521134"
FT LIPID 10
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:28521134"
FT LIPID 11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:28521134"
FT VAR_SEQ 325
FT /note="R -> RDTRRKAGPAWMVTRTEGHEEKPLPPAQSQTQEGGPAAGKASGADQR
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9660871"
FT /id="VSP_034728"
FT VAR_SEQ 615..952
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9660871"
FT /id="VSP_034729"
FT MUTAGEN 5
FT /note="C->G: Loss of palmitoylation. Loss of Golgi and
FT secretory vesicle localization; when associated with G-10
FT and G-11. Loss of axonal polarization; when associated with
FT G-10 and G-11. Increased dendrite localization without
FT affecting association with microtubules; when associated
FT with G-10 and G-11."
FT /evidence="ECO:0000269|PubMed:28521134"
FT MUTAGEN 10..11
FT /note="CC->GG: Loss of Golgi and secretory vesicle
FT localization; when associated with G-5. Loss of axonal
FT polarization; when associated with G-5. Increased dendrite
FT localization without affecting association with
FT microtubules; when associated with G-5."
FT /evidence="ECO:0000269|PubMed:28521134"
SQ SEQUENCE 952 AA; 100485 MW; 3599A5069096FA73 CRC64;
MAWPCITRAC CIARFWNQLD KADIAVPLVF TKYSEATEHP GAPPQPPAPP QPGLAPPSRA
VAIETQPAQG ESDAVARATG PAPGPSGDRE TAAAPGRSGL GLGAASGSTS GSGPADSVMR
QDYRAWKVQR PEPSCRPRSE YQPSDAPFER ETQYQKDFRA WPLPRRGDHP WIPKPVQIPA
TSQPSPPVLG MPKRRPQSQE RGPIQLSADA RDPEGAGGAG VPAAGKASGA DQRDTRRKAG
PAWMVTRTEG HEEKPLPPAQ SQTQEGGPAA GKASGADQRD TRRKAGPAWM VTRTEGHEEK
PLPPAQSQTQ EGGPAAGKAS GADQRDTRRK AGPAWMVTRT EGHEETPLPP AQSQTQEGGP
AAGKASGADQ RDTRRKAGPA WMVTRTEGHE ETPLPPAQSQ TQEGGPAAGK ASGADERDTR
RKAGPAWMVR RSEGHEQTTA AHAQGTGPEG GKGRAVADAL NRQIREEVTS TVSSSYRNEF
RAWTDIKPVK PIKAKPQYKP PDDKMVHETS YSAQFKGEAS KPTTADNKVV DRRRIRSLYS
EPFKESPKVE KPSVQSSKPK KTSTSQKPLR KAKDKQVASG QAAKKKTTES PSATKPDDKE
QSKEMNNKLA EAKESRVKPT SDKNQGPVAK EPHKDQGPVA PGLPKGQGPA VQEPLKDQGP
MVPGLPKDQA PVVPGSLKGQ SPTAPGPPKD QGAVLLGPMK DLGPVAPASV KDQDHMASEL
LKNKDSVPLA PAKAQSPLLP EPLKNQSPVV PARAKDQSFP APAPTPLKDP GPVIPEPEKD
GAPMVPERRK DQNASIMASL KNEAPVASES VKNQGLGGPE PAKDTGTDLK GHGSVFVAPV
KSQGPVVPEP TKGQDPIIPA LAKDQGPILP EPPKNQGPPV VLGPIKNQDP VIPVPLKGQD
PVVPAPTKDP GPTAPDPLKS QGPRGPQLPT VSPSPPVMIP TVPHAEYIEG SP
