TBC14_HUMAN
ID TBC14_HUMAN Reviewed; 693 AA.
AC Q9P2M4; B9A6L5; D3DVT4; E9PAZ6; Q8IW15; Q8NDK3;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=TBC1 domain family member 14;
GN Name=TBC1D14; Synonyms=KIAA1322;
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 [MRNA], AND VARIANT VAL-41.
RC TISSUE=Brain;
RX PubMed=19077034; DOI=10.1111/j.1365-2443.2008.01251.x;
RA Ishibashi K., Kanno E., Itoh T., Fukuda M.;
RT "Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC)
RT protein that possesses Rab3A-GAP activity.";
RL Genes Cells 14:41-52(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-41.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 313-693.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP FUNCTION, INTERACTION WITH RAB11A; RAB11 AND ULK1, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF ARG-472 AND GLN-508.
RX PubMed=22613832; DOI=10.1083/jcb.201111079;
RA Longatti A., Lamb C.A., Razi M., Yoshimura S., Barr F.A., Tooze S.A.;
RT "TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive
RT recycling endosomes.";
RL J. Cell Biol. 197:659-675(2012).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91, 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295, 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).
RN [10]
RP FUNCTION, INTERACTION WITH TRAPPC8, AND SUBCELLULAR LOCATION.
RX PubMed=26711178; DOI=10.15252/embj.201592695;
RA Lamb C.A., Nuehlen S., Judith D., Frith D., Snijders A.P., Behrends C.,
RA Tooze S.A.;
RT "TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic.";
RL EMBO J. 35:281-301(2016).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 372-672.
RX PubMed=18186464; DOI=10.1002/prot.21885;
RA Tempel W., Tong Y., Dimov S., Bochkarev A., Park H.;
RT "First crystallographic models of human TBC domains in the context of a
RT family-wide structural analysis.";
RL Proteins 71:497-502(2008).
CC -!- FUNCTION: Plays a role in the regulation of starvation-induced
CC autophagosome formation (PubMed:22613832). Together with the TRAPPIII
CC complex, regulates a constitutive trafficking step from peripheral
CC recycling endosomes to the early Golgi, maintaining the cycling pool of
CC ATG9 required for initiation of autophagy.
CC {ECO:0000269|PubMed:22613832, ECO:0000269|PubMed:26711178}.
CC -!- SUBUNIT: Interacts with ULK1 (PubMed:22613832). May interact with
CC RAB11A and RAB11B, but does not exhibit any GTPase-activating activity
CC toward these proteins (PubMed:22613832). Interacts with TRAPPC8
CC (PubMed:26711178). {ECO:0000269|PubMed:22613832,
CC ECO:0000269|PubMed:26711178}.
CC -!- INTERACTION:
CC Q9P2M4; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-2797718, EBI-398874;
CC Q9P2M4; Q15907: RAB11B; NbExp=2; IntAct=EBI-2797718, EBI-722234;
CC Q9P2M4; O75385: ULK1; NbExp=4; IntAct=EBI-2797718, EBI-908831;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, cis-Golgi network
CC {ECO:0000269|PubMed:22613832, ECO:0000269|PubMed:26711178}. Golgi
CC apparatus, trans-Golgi network {ECO:0000269|PubMed:22613832}.
CC Note=After amino acid starvation, Golgi apparatus-associated protein
CC levels increase compared with fed conditions. May be cycling between
CC the Golgi apparatus and an endosomal pool, redistributing to the Golgi
CC apparatus upon starvation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9P2M4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P2M4-2; Sequence=VSP_041460, VSP_041461;
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH41167.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA92560.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB449900; BAH16643.1; -; mRNA.
DR EMBL; AB037743; BAA92560.1; ALT_INIT; mRNA.
DR EMBL; AC092463; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097382; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC106045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471131; EAW82375.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82376.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82377.1; -; Genomic_DNA.
DR EMBL; BC041167; AAH41167.1; ALT_INIT; mRNA.
DR EMBL; AL833868; CAD38726.1; -; mRNA.
DR CCDS; CCDS3394.2; -. [Q9P2M4-1]
DR CCDS; CCDS47006.1; -. [Q9P2M4-2]
DR RefSeq; NP_001106832.1; NM_001113361.1. [Q9P2M4-1]
DR RefSeq; NP_001106834.1; NM_001113363.1. [Q9P2M4-2]
DR RefSeq; NP_001273734.1; NM_001286805.1.
DR RefSeq; NP_001317567.1; NM_001330638.1.
DR RefSeq; NP_065824.2; NM_020773.2. [Q9P2M4-1]
DR RefSeq; XP_006713958.1; XM_006713895.2. [Q9P2M4-1]
DR PDB; 2QQ8; X-ray; 2.00 A; A=372-687.
DR PDBsum; 2QQ8; -.
DR AlphaFoldDB; Q9P2M4; -.
DR SMR; Q9P2M4; -.
DR BioGRID; 121592; 38.
DR IntAct; Q9P2M4; 37.
DR MINT; Q9P2M4; -.
DR STRING; 9606.ENSP00000386921; -.
DR iPTMnet; Q9P2M4; -.
DR PhosphoSitePlus; Q9P2M4; -.
DR BioMuta; TBC1D14; -.
DR DMDM; 172044690; -.
DR EPD; Q9P2M4; -.
DR jPOST; Q9P2M4; -.
DR MassIVE; Q9P2M4; -.
DR MaxQB; Q9P2M4; -.
DR PaxDb; Q9P2M4; -.
DR PeptideAtlas; Q9P2M4; -.
DR PRIDE; Q9P2M4; -.
DR ProteomicsDB; 83847; -. [Q9P2M4-1]
DR ProteomicsDB; 83848; -. [Q9P2M4-2]
DR Antibodypedia; 43347; 104 antibodies from 16 providers.
DR DNASU; 57533; -.
DR Ensembl; ENST00000409757.9; ENSP00000386921.4; ENSG00000132405.19. [Q9P2M4-1]
DR Ensembl; ENST00000448507.5; ENSP00000404041.1; ENSG00000132405.19. [Q9P2M4-1]
DR Ensembl; ENST00000451522.6; ENSP00000388886.2; ENSG00000132405.19. [Q9P2M4-2]
DR GeneID; 57533; -.
DR KEGG; hsa:57533; -.
DR MANE-Select; ENST00000409757.9; ENSP00000386921.4; NM_020773.3; NP_065824.2.
DR UCSC; uc003gjs.5; human. [Q9P2M4-1]
DR CTD; 57533; -.
DR DisGeNET; 57533; -.
DR GeneCards; TBC1D14; -.
DR HGNC; HGNC:29246; TBC1D14.
DR HPA; ENSG00000132405; Low tissue specificity.
DR MIM; 614855; gene.
DR neXtProt; NX_Q9P2M4; -.
DR OpenTargets; ENSG00000132405; -.
DR PharmGKB; PA128394697; -.
DR VEuPathDB; HostDB:ENSG00000132405; -.
DR eggNOG; KOG2223; Eukaryota.
DR GeneTree; ENSGT00940000157250; -.
DR HOGENOM; CLU_015133_1_1_1; -.
DR InParanoid; Q9P2M4; -.
DR OMA; MANTAHD; -.
DR OrthoDB; 798837at2759; -.
DR PhylomeDB; Q9P2M4; -.
DR TreeFam; TF313318; -.
DR PathwayCommons; Q9P2M4; -.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR SignaLink; Q9P2M4; -.
DR BioGRID-ORCS; 57533; 14 hits in 1079 CRISPR screens.
DR ChiTaRS; TBC1D14; human.
DR EvolutionaryTrace; Q9P2M4; -.
DR GenomeRNAi; 57533; -.
DR Pharos; Q9P2M4; Tbio.
DR PRO; PR:Q9P2M4; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9P2M4; protein.
DR Bgee; ENSG00000132405; Expressed in secondary oocyte and 185 other tissues.
DR ExpressionAtlas; Q9P2M4; baseline and differential.
DR Genevisible; Q9P2M4; HS.
DR GO; GO:0005776; C:autophagosome; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:BHF-UCL.
DR GO; GO:0071955; P:recycling endosome to Golgi transport; IMP:UniProtKB.
DR GO; GO:2000785; P:regulation of autophagosome assembly; IMP:BHF-UCL.
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 3D-structure; Alternative splicing; Autophagy; Golgi apparatus;
KW GTPase activation; Phosphoprotein; Reference proteome.
FT CHAIN 1..693
FT /note="TBC1 domain family member 14"
FT /id="PRO_0000208040"
FT DOMAIN 401..611
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 108..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..291
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..280
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041460"
FT VAR_SEQ 281
FT /note="K -> M (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041461"
FT VARIANT 41
FT /note="L -> V (in dbSNP:rs34860182)"
FT /evidence="ECO:0000269|PubMed:10718198,
FT ECO:0000269|PubMed:19077034"
FT /id="VAR_067442"
FT VARIANT 446
FT /note="E -> Q (in dbSNP:rs11731231)"
FT /id="VAR_059856"
FT MUTAGEN 472
FT /note="R->A: Loss of inhibition of autophagosome formation;
FT when associated with A-508."
FT /evidence="ECO:0000269|PubMed:22613832"
FT MUTAGEN 508
FT /note="Q->A: Loss of inhibition of autophagosome formation;
FT when associated with A-472."
FT /evidence="ECO:0000269|PubMed:22613832"
FT HELIX 373..379
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 392..399
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 404..415
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 423..436
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 462..471
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 475..477
FT /evidence="ECO:0007829|PDB:2QQ8"
FT STRAND 479..481
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 487..500
FT /evidence="ECO:0007829|PDB:2QQ8"
FT TURN 502..504
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 510..520
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 523..534
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 537..543
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 548..564
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 566..574
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 579..581
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 583..588
FT /evidence="ECO:0007829|PDB:2QQ8"
FT TURN 589..594
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 597..610
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 612..625
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 627..631
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 635..643
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 651..660
FT /evidence="ECO:0007829|PDB:2QQ8"
FT HELIX 670..678
FT /evidence="ECO:0007829|PDB:2QQ8"
SQ SEQUENCE 693 AA; 78137 MW; 6E1332D236DE45BD CRC64;
MTDGKLSTST NGVAFMGILD GRPGNPLQNL QHVNLKAPRL LSAPEYGPKL KLRALEDRHS
LQSVDSGIPT LEIGNPEPVP CSAVHVRRKQ SDSDLIPERA FQSACALPSC APPAPSSTER
EQSVRKSSTF PRTGYDSVKL YSPTSKALTR SDDVSVCSVS SLGTELSTTL SVSNEDILDL
VVTSSSSAIV TLENDDDPQF TNVTLSSIKE TRGLHQQDCV HEAEEGSKLK ILGPFSNFFA
RNLLARKQSA RLDKHNDLGW KLFGKAPLRE NAQKDSKRIQ KEYEDKAGRP SKPPSPKQNV
RKNLDFEPLS TTALILEDRP ANLPAKPAEE AQKHRQQYEE MVVQAKKREL KEAQRRKKQL
EERCRVEESI GNAVLTWNNE ILPNWETMWC SRKVRDLWWQ GIPPSVRGKV WSLAIGNELN
ITHELFDICL ARAKERWRSL STGGSEVENE DAGFSAADRE ASLELIKLDI SRTFPNLCIF
QQGGPYHDML HSILGAYTCY RPDVGYVQGM SFIAAVLILN LDTADAFIAF SNLLNKPCQM
AFFRVDHGLM LTYFAAFEVF FEENLPKLFA HFKKNNLTPD IYLIDWIFTL YSKSLPLDLA
CRIWDVFCRD GEEFLFRTAL GILKLFEDIL TKMDFIHMAQ FLTRLPEDLP AEELFASIAT
IQMQSRNKKW AQVLTALQKD SREMEKGSPS LRH
