TBC25_HUMAN
ID TBC25_HUMAN Reviewed; 688 AA.
AC Q3MII6; Q08AN9; Q3MII4; Q8TAR9;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=TBC1 domain family member 25;
GN Name=TBC1D25; Synonyms=OATL1;
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 GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP SER-277.
RC TISSUE=Brain, and Pancreas;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAP1LC3B; GABARAP AND
RP GABARAPL2, AND MUTAGENESIS OF 134-GLU-ASP-135 AND TRP-136.
RX PubMed=21383079; DOI=10.1083/jcb.201008107;
RA Itoh T., Kanno E., Uemura T., Waguri S., Fukuda M.;
RT "OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal
RT maturation.";
RL J. Cell Biol. 192:839-853(2011).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Acts as a GTPase-activating protein specific for RAB33B.
CC Involved in the regulation of autophagosome maturation, the process in
CC which autophagosomes fuse with endosomes and lysosomes.
CC {ECO:0000269|PubMed:21383079}.
CC -!- SUBUNIT: Interacts (via N-terminus) with MAP1LC3B, GABARAP and
CC GABARAPL2. {ECO:0000269|PubMed:21383079}.
CC -!- INTERACTION:
CC Q3MII6; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-11899977, EBI-10175124;
CC Q3MII6; Q9H0R8: GABARAPL1; NbExp=4; IntAct=EBI-11899977, EBI-746969;
CC Q3MII6; P60520: GABARAPL2; NbExp=4; IntAct=EBI-11899977, EBI-720116;
CC Q3MII6; Q9NZI2-2: KCNIP1; NbExp=3; IntAct=EBI-11899977, EBI-22452746;
CC Q3MII6; Q659C4-6: LARP1B; NbExp=3; IntAct=EBI-11899977, EBI-12036449;
CC Q3MII6; Q8TCE9: LGALS14; NbExp=3; IntAct=EBI-11899977, EBI-10274069;
CC Q3MII6; Q8IXW0: LMNTD2; NbExp=3; IntAct=EBI-11899977, EBI-12028858;
CC Q3MII6; Q9BXW4: MAP1LC3C; NbExp=3; IntAct=EBI-11899977, EBI-2603996;
CC Q3MII6; P61019: RAB2A; NbExp=3; IntAct=EBI-11899977, EBI-752037;
CC Q3MII6; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-11899977, EBI-6257312;
CC Q3MII6; Q8N7C3: TRIML2; NbExp=3; IntAct=EBI-11899977, EBI-11059915;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21383079}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:21383079}.
CC Note=It is dispersed in the cytoplasm under nutrient-rich conditions.
CC Localizes at autophagosomes under cell starving conditions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3MII6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3MII6-2; Sequence=VSP_025703, VSP_025704;
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DR EMBL; AC115618; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF196969; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026050; AAH26050.1; -; mRNA.
DR EMBL; BC101817; AAI01818.1; -; mRNA.
DR EMBL; BC101819; AAI01820.1; -; mRNA.
DR EMBL; BC125088; AAI25089.1; -; mRNA.
DR EMBL; BC125089; AAI25090.2; -; mRNA.
DR CCDS; CCDS35242.1; -. [Q3MII6-1]
DR RefSeq; NP_001335191.1; NM_001348262.1.
DR RefSeq; NP_002527.1; NM_002536.3. [Q3MII6-1]
DR AlphaFoldDB; Q3MII6; -.
DR SMR; Q3MII6; -.
DR BioGRID; 110997; 59.
DR IntAct; Q3MII6; 17.
DR STRING; 9606.ENSP00000365962; -.
DR GlyGen; Q3MII6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q3MII6; -.
DR PhosphoSitePlus; Q3MII6; -.
DR BioMuta; TBC1D25; -.
DR DMDM; 296452922; -.
DR EPD; Q3MII6; -.
DR jPOST; Q3MII6; -.
DR MassIVE; Q3MII6; -.
DR MaxQB; Q3MII6; -.
DR PaxDb; Q3MII6; -.
DR PeptideAtlas; Q3MII6; -.
DR PRIDE; Q3MII6; -.
DR ProteomicsDB; 61786; -. [Q3MII6-1]
DR ProteomicsDB; 61787; -. [Q3MII6-2]
DR Antibodypedia; 54837; 45 antibodies from 16 providers.
DR DNASU; 4943; -.
DR Ensembl; ENST00000376771.9; ENSP00000365962.4; ENSG00000068354.16. [Q3MII6-1]
DR Ensembl; ENST00000481090.6; ENSP00000476787.1; ENSG00000068354.16. [Q3MII6-2]
DR GeneID; 4943; -.
DR KEGG; hsa:4943; -.
DR MANE-Select; ENST00000376771.9; ENSP00000365962.4; NM_002536.4; NP_002527.1.
DR UCSC; uc004dka.2; human. [Q3MII6-1]
DR CTD; 4943; -.
DR DisGeNET; 4943; -.
DR GeneCards; TBC1D25; -.
DR HGNC; HGNC:8092; TBC1D25.
DR HPA; ENSG00000068354; Low tissue specificity.
DR MIM; 311240; gene.
DR neXtProt; NX_Q3MII6; -.
DR OpenTargets; ENSG00000068354; -.
DR PharmGKB; PA162405201; -.
DR VEuPathDB; HostDB:ENSG00000068354; -.
DR eggNOG; KOG2197; Eukaryota.
DR GeneTree; ENSGT00940000159173; -.
DR HOGENOM; CLU_004382_1_0_1; -.
DR InParanoid; Q3MII6; -.
DR OMA; YYTARNE; -.
DR OrthoDB; 1495285at2759; -.
DR PhylomeDB; Q3MII6; -.
DR TreeFam; TF323518; -.
DR PathwayCommons; Q3MII6; -.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR SignaLink; Q3MII6; -.
DR SIGNOR; Q3MII6; -.
DR BioGRID-ORCS; 4943; 10 hits in 708 CRISPR screens.
DR ChiTaRS; TBC1D25; human.
DR GenomeRNAi; 4943; -.
DR Pharos; Q3MII6; Tbio.
DR PRO; PR:Q3MII6; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q3MII6; protein.
DR Bgee; ENSG00000068354; Expressed in ileal mucosa and 128 other tissues.
DR ExpressionAtlas; Q3MII6; baseline and differential.
DR Genevisible; Q3MII6; HS.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:1901096; P:regulation of autophagosome maturation; IMP:UniProtKB.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autophagy; Cytoplasm; Cytoplasmic vesicle;
KW GTPase activation; Phosphoprotein; Reference proteome.
FT CHAIN 1..688
FT /note="TBC1 domain family member 25"
FT /id="PRO_0000288508"
FT DOMAIN 228..434
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 544..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 544..575
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A1A5B6"
FT MOD_RES 160
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A1A5B6"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT VAR_SEQ 79..100
FT /note="KKNFGISYLGRDRLGQEVYLSL -> PIARRLGHNQPQRCHWLRRVAG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025703"
FT VAR_SEQ 101..688
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025704"
FT VARIANT 277
FT /note="N -> S (in dbSNP:rs2293948)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_057345"
FT MUTAGEN 134..135
FT /note="ED->AA: Severely affects interaction with GABARAP.
FT Does not localize at autophagosomes."
FT /evidence="ECO:0000269|PubMed:21383079"
FT MUTAGEN 136
FT /note="W->A: Abolishes interaction with GABARAP. Does not
FT localize at autophagosomes."
FT /evidence="ECO:0000269|PubMed:21383079"
FT CONFLICT 455
FT /note="A -> T (in Ref. 2; AAI01818/AAI01820/AAI25089)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 688 AA; 76327 MW; 5B070FE11D78D0A4 CRC64;
MATASGASDL SGSGAPPPGV GAQAAAAAEE EEREVVRVRV KKCESFLPPE FRSFAVDPQI
TSLDVLQHIL IRAFDLSGKK NFGISYLGRD RLGQEVYLSL LSDWDLSTAF ATASKPYLQL
RVDIRPSEDS PLLEDWDIIS PKDVIGSDVL LAEKRSSLTT AALPFTQSIL TQVGRTLSKV
QQVLSWSYGE DVKPFKPPLS DAEFHTYLNH EGQLSRPEEL RLRIYHGGVE PSLRKVVWRY
LLNVYPDGLT GRERMDYMKR KSREYEQLKS EWAQRANPED LEFIRSTVLK DVLRTDRAHP
YYAGPEDGPH LRALHDLLTT YAVTHPQVSY CQGMSDLASP ILAVMDHEGH AFVCFCGIMK
RLAANFHPDG RAMATKFAHL KLLLRHADPD FYQYLQEAGA DDLFFCYRWL LLELKREFAF
DDALRMLEVT WSSLPPDPPE HEVELVGPPS QVADAGFGGH RGWPVRQRHM LRPAGGGGST
FEDAVDHLAT ASQGPGGGGR LLRQASLDGL QQLRDNMGSR RDPLVQLPHP AALISSKSLS
EPLLNSPDPL LSSFSHPDSP SSSSPPSTQE ASPTGDMAVG SPLMQEVGSP KDPGKSLPPV
PPMGLPPPQE FGRGNPFMLF LCLAILLEHR DHIMRNGLDY NELAMHFDRL VRKHHLGRVL
RRARALFADY LQSEVWDSEE GAEATAAS
