MAP6_HUMAN
ID MAP6_HUMAN Reviewed; 813 AA.
AC Q96JE9; A7E2A1; Q6P3T0; Q6ZWB8;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Microtubule-associated protein 6;
DE Short=MAP-6;
DE AltName: Full=Stable tubule-only polypeptide;
DE Short=STOP;
GN Name=MAP6; Synonyms=KIAA1878;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP MET-247.
RC TISSUE=PNS;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 91-813 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14692697; DOI=10.1093/jnen/62.12.1211;
RA Letournel F., Bocquet A., Dubas F., Barthelaix A., Eyer J.;
RT "Stable tubule only polypeptides (STOP) proteins co-aggregate with spheroid
RT neurofilaments in amyotrophic lateral sclerosis.";
RL J. Neuropathol. Exp. Neurol. 62:1211-1219(2003).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=16624526; DOI=10.1016/j.schres.2006.03.017;
RA Shimizu H., Iwayama Y., Yamada K., Toyota T., Minabe Y., Nakamura K.,
RA Nakajima M., Hattori E., Mori N., Osumi N., Yoshikawa T.;
RT "Genetic and expression analyses of the STOP (MAP6) gene in
RT schizophrenia.";
RL Schizophr. Res. 84:244-252(2006).
RN [7]
RP FUNCTION, AND INTERACTION WITH TMEM106B.
RX PubMed=24357581; DOI=10.1002/embj.201385857;
RA Schwenk B.M., Lang C.M., Hogl S., Tahirovic S., Orozco D., Rentzsch K.,
RA Lichtenthaler S.F., Hoogenraad C.C., Capell A., Haass C., Edbauer D.;
RT "The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of
RT lysosomes.";
RL EMBO J. 33:450-467(2014).
RN [8]
RP INTERACTION WITH ZDHHC17 AND ZDHHC13, AND MUTAGENESIS OF PRO-71.
RX PubMed=26198635; DOI=10.1074/jbc.m115.657668;
RA Lemonidis K., Sanchez-Perez M.C., Chamberlain L.H.;
RT "Identification of a novel sequence motif recognized by the ankyrin repeat
RT domain of zDHHC17/13 S-acyltransferases.";
RL J. Biol. Chem. 290:21939-21950(2015).
CC -!- FUNCTION: Involved in microtubule stabilization in many cell types,
CC including neuronal cells (By similarity). Specifically has microtubule
CC cold stabilizing activity (By similarity). Involved in dendrite
CC morphogenesis and maintenance by regulating lysosomal trafficking via
CC its interaction with TMEM106B (PubMed:24357581). Regulates KIF5A-
CC mediated axonal cargo transport (By similarity). Regulates axonal
CC growth during neuron polarization (By similarity).
CC {ECO:0000250|UniProtKB:Q63560, ECO:0000269|PubMed:24357581}.
CC -!- SUBUNIT: Interacts with calmodulin (via C-terminus); the interaction is
CC dependent on Ca(2+) (By similarity). Interacts with TMEM106B
CC (PubMed:24357581). Interacts with ZDHHC17 (via ANK repeats)
CC (PubMed:26198635). Interacts with ZDHHC13 (via ANK repeats)
CC (PubMed:26198635). {ECO:0000250, ECO:0000269|PubMed:24357581,
CC ECO:0000269|PubMed:26198635}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:14692697}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q63560}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q63560}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q63560}. Cytoplasmic vesicle, secretory vesicle
CC membrane {ECO:0000250|UniProtKB:Q63560}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q63560}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q63560}. Note=Localizes predominantly in the
CC proximal part of the axon (By similarity). Preferentially is
CC concentrated on a portion of the microtubule polymer in which tubulin
CC is modified by detyrosination and acetylation and is also resistant to
CC depolymerization induced by both nocodazole and cold (By similarity).
CC In unpolarized neurons, localizes to the Golgi and to secretory
CC vesicles accumulating transiently at the tips of a subset of neurites
CC (By similarity). Following neuronal polarization and during axon
CC outgrowth, accumulates in the axonal growth cone and subsequently
CC localizes throughout the axon (By similarity). Partially localizes to
CC dendrites in mature neurons (By similarity). Colocalizes with
CC neurofilament (NF)-rich inclusions in spinal cord and brain neurons of
CC patients with amyotrophic lateral sclerosis (ALS) (PubMed:14692697).
CC {ECO:0000250|UniProtKB:Q63560, ECO:0000269|PubMed:14692697}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=N-STOP, Neuronal-STOP;
CC IsoId=Q96JE9-1; Sequence=Displayed;
CC Name=2; Synonyms=E-STOP, Early-STOP;
CC IsoId=Q96JE9-2; Sequence=VSP_034723;
CC Name=3;
CC IsoId=Q96JE9-3; Sequence=VSP_054151;
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level). Expressed in
CC spinal cord. Isoform 2 expression is up-regulated in the prefrontal
CC cortex (Brodmann's area 46) of patients with schizophrenia (postmortem
CC brain study). {ECO:0000269|PubMed:14692697,
CC ECO:0000269|PubMed:16624526}.
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:0000250|UniProtKB:Q63560}.
CC -!- SIMILARITY: Belongs to the STOP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH63860.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK123340; BAC85586.1; -; mRNA.
DR EMBL; AP001922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063860; AAH63860.1; ALT_INIT; mRNA.
DR EMBL; BC139780; AAI39781.1; -; mRNA.
DR EMBL; BC150254; AAI50255.1; -; mRNA.
DR EMBL; AB058781; BAB47507.1; -; mRNA.
DR CCDS; CCDS31641.1; -. [Q96JE9-1]
DR CCDS; CCDS44686.1; -. [Q96JE9-2]
DR RefSeq; NP_149052.1; NM_033063.1. [Q96JE9-1]
DR RefSeq; NP_997460.1; NM_207577.1. [Q96JE9-2]
DR AlphaFoldDB; Q96JE9; -.
DR BioGRID; 110307; 7.
DR IntAct; Q96JE9; 2.
DR MINT; Q96JE9; -.
DR STRING; 9606.ENSP00000307093; -.
DR GlyGen; Q96JE9; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q96JE9; -.
DR PhosphoSitePlus; Q96JE9; -.
DR SwissPalm; Q96JE9; -.
DR BioMuta; MAP6; -.
DR DMDM; 205830862; -.
DR EPD; Q96JE9; -.
DR jPOST; Q96JE9; -.
DR MassIVE; Q96JE9; -.
DR PaxDb; Q96JE9; -.
DR PeptideAtlas; Q96JE9; -.
DR PRIDE; Q96JE9; -.
DR ProteomicsDB; 68473; -.
DR ProteomicsDB; 76951; -. [Q96JE9-1]
DR ProteomicsDB; 76952; -. [Q96JE9-2]
DR Antibodypedia; 17382; 60 antibodies from 18 providers.
DR DNASU; 4135; -.
DR Ensembl; ENST00000304771.8; ENSP00000307093.3; ENSG00000171533.12. [Q96JE9-1]
DR Ensembl; ENST00000434603.2; ENSP00000415108.2; ENSG00000171533.12. [Q96JE9-2]
DR Ensembl; ENST00000526740.3; ENSP00000434278.1; ENSG00000171533.12. [Q96JE9-3]
DR GeneID; 4135; -.
DR KEGG; hsa:4135; -.
DR MANE-Select; ENST00000304771.8; ENSP00000307093.3; NM_033063.2; NP_149052.1.
DR UCSC; uc001owu.4; human. [Q96JE9-1]
DR CTD; 4135; -.
DR DisGeNET; 4135; -.
DR GeneCards; MAP6; -.
DR HGNC; HGNC:6868; MAP6.
DR HPA; ENSG00000171533; Tissue enhanced (brain, pituitary gland, retina).
DR MIM; 601783; gene.
DR neXtProt; NX_Q96JE9; -.
DR OpenTargets; ENSG00000171533; -.
DR PharmGKB; PA30614; -.
DR VEuPathDB; HostDB:ENSG00000171533; -.
DR eggNOG; ENOG502QS1F; Eukaryota.
DR GeneTree; ENSGT00530000063947; -.
DR HOGENOM; CLU_018049_1_0_1; -.
DR InParanoid; Q96JE9; -.
DR OMA; KKPGPAW; -.
DR OrthoDB; 577082at2759; -.
DR PhylomeDB; Q96JE9; -.
DR TreeFam; TF338320; -.
DR PathwayCommons; Q96JE9; -.
DR SignaLink; Q96JE9; -.
DR BioGRID-ORCS; 4135; 13 hits in 1075 CRISPR screens.
DR ChiTaRS; MAP6; human.
DR GeneWiki; MAP6; -.
DR GenomeRNAi; 4135; -.
DR Pharos; Q96JE9; Tbio.
DR PRO; PR:Q96JE9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96JE9; protein.
DR Bgee; ENSG00000171533; Expressed in cortical plate and 155 other tissues.
DR Genevisible; Q96JE9; HS.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005801; C:cis-Golgi network; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005798; C:Golgi-associated vesicle; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; 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; IBA:GO_Central.
DR GO; GO:0030705; P:cytoskeleton-dependent intracellular transport; IBA:GO_Central.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IMP:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:InterPro.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IBA:GO_Central.
DR InterPro; IPR007882; MAP6.
DR PANTHER; PTHR14759; PTHR14759; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Calmodulin-binding; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Golgi apparatus; Lipoprotein; Membrane;
KW Microtubule; Palmitate; Phosphoprotein; Reference proteome; Transport.
FT CHAIN 1..813
FT /note="Microtubule-associated protein 6"
FT /id="PRO_0000344044"
FT REGION 36..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..141
FT /note="Mn 1"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 126..140
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 153..176
FT /note="Mn 2"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 162..176
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 189..203
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 298..321
FT /note="Mn 3"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 306..320
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 314..651
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 357..371
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 384..398
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT REGION 756..813
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..55
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..166
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 232..246
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..373
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..435
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSJ2"
FT MOD_RES 143
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSJ2"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT MOD_RES 812
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSJ2"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT LIPID 10
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT LIPID 11
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q63560"
FT VAR_SEQ 1..329
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_054151"
FT VAR_SEQ 440..813
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_034723"
FT VARIANT 247
FT /note="I -> M (in dbSNP:rs12225010)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_044542"
FT MUTAGEN 71
FT /note="P->A: Inhibits interaction with ZDHHC13 and
FT ZDHHC17."
FT /evidence="ECO:0000269|PubMed:26198635"
SQ SEQUENCE 813 AA; 86505 MW; 9680ACAFDB5694D1 CRC64;
MAWPCITRAC CIARFWNQLD KADIAVPLVF TKYSEATEHP GAPPQPPPPQ QQAQPALAPP
SARAVAIETQ PAQGELDAVA RATGPAPGPT GEREPAAGPG RSGPGPGLGS GSTSGPADSV
MRQDYRAWKV QRPEPSCRPR SEYQPSDAPF ERETQYQKDF RAWPLPRRGD HPWIPKPVQI
SAASQASAPI LGAPKRRPQS QERWPVQAAA EAREQEAAPG GAGGLAAGKA SGADERDTRR
KAGPAWIVRR AEGLGHEQTP LPAAQAQVQA TGPEAGRGRA AADALNRQIR EEVASAVSSS
YRNEFRAWTD IKPVKPIKAK PQYKPPDDKM VHETSYSAQF KGEASKPTTA DNKVIDRRRI
RSLYSEPFKE PPKVEKPSVQ SSKPKKTSAS HKPTRKAKDK QAVSGQAAKK KSAEGPSTTK
PDDKEQSKEM NNKLAEAKES LAQPVSDSSK TQGPVATEPD KDQGSVVPGL LKGQGPMVQE
PLKKQGSVVP GPPKDLGPMI PLPVKDQDHT VPEPLKNESP VISAPVKDQG PSVPVPPKNQ
SPMVPAKVKD QGSVVPESLK DQGPRIPEPV KNQAPMVPAP VKDEGPMVSA SVKDQGPMVS
APVKDQGPIV PAPVKGEGPI VPAPVKDEGP MVSAPIKDQD PMVPEHPKDE SAMATAPIKN
QGSMVSEPVK NQGLVVSGPV KDQDVVVPEH AKVHDSAVVA PVKNQGPVVP ESVKNQDPIL
PVLVKDQGPT VLQPPKNQGR IVPEPLKNQV PIVPVPLKDQ DPLVPVPAKD QGPAVPEPLK
TQGPRDPQLP TVSPLPRVMI PTAPHTEYIE SSP
