TPC6B_HUMAN
ID TPC6B_HUMAN Reviewed; 158 AA.
AC Q86SZ2; B3KPS2; Q5JPD6; Q86U35; Q86X35;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Trafficking protein particle complex subunit 6B {ECO:0000303|PubMed:28626029};
DE Short=TRAPP complex subunit 6B;
GN Name=TRAPPC6B {ECO:0000303|PubMed:28397838, ECO:0000303|PubMed:28626029,
GN ECO:0000312|HGNC:HGNC:23066};
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 1).
RC TISSUE=Cervix carcinoma, and Fetal liver;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph node;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [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 2).
RC TISSUE=Uterus;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP INVOLVEMENT IN NEDMEBA, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=28626029; DOI=10.1136/jmedgenet-2017-104627;
RA Marin-Valencia I., Novarino G., Johansen A., Rosti B., Issa M.Y.,
RA Musaev D., Bhat G., Scott E., Silhavy J.L., Stanley V., Rosti R.O.,
RA Gleeson J.W., Imam F.B., Zaki M.S., Gleeson J.G.;
RT "A homozygous founder mutation in TRAPPC6B associates with a
RT neurodevelopmental disorder characterised by microcephaly, epilepsy and
RT autistic features.";
RL J. Med. Genet. 55:48-54(2018).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), IDENTIFICATION BY MASS SPECTROMETRY,
RP SUBUNIT, INTERACTION WITH TRAPPC3, AND FUNCTION.
RX PubMed=16025134; DOI=10.1038/sj.embor.7400463;
RA Kuemmel D., Mueller J.J., Roske Y., Misselwitz R., Buessow K.,
RA Heinemann U.;
RT "The structure of the TRAPP subunit TPC6 suggests a model for a TRAPP
RT subcomplex.";
RL EMBO Rep. 6:787-793(2005).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH TRAPPC3, SUBUNIT,
RP INTERACTION WITH TRAPPC3 AND TRAPPC1, MUTAGENESIS OF 31-ARG-CYS-32, AND
RP FUNCTION.
RX PubMed=16828797; DOI=10.1016/j.jmb.2006.06.012;
RA Kummel D., Muller J.J., Roske Y., Henke N., Heinemann U.;
RT "Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs form trimeric
RT complexes with Bet3 and Mum2.";
RL J. Mol. Biol. 361:22-32(2006).
RN [10]
RP INVOLVEMENT IN NEDMEBA, AND VARIANT NEDMEBA 42-ARG--LEU-158 DEL.
RX PubMed=28397838; DOI=10.1038/mp.2017.60;
RA Harripaul R., Vasli N., Mikhailov A., Rafiq M.A., Mittal K.,
RA Windpassinger C., Sheikh T.I., Noor A., Mahmood H., Downey S., Johnson M.,
RA Vleuten K., Bell L., Ilyas M., Khan F.S., Khan V., Moradi M., Ayaz M.,
RA Naeem F., Heidari A., Ahmed I., Ghadami S., Agha Z., Zeinali S., Qamar R.,
RA Mozhdehipanah H., John P., Mir A., Ansar M., French L., Ayub M.,
RA Vincent J.B.;
RT "Mapping autosomal recessive intellectual disability: combined microarray
RT and exome sequencing identifies 26 novel candidate genes in 192
RT consanguineous families.";
RL Mol. Psychiatry 23:973-984(2018).
CC -!- FUNCTION: Component of a transport protein particle (TRAPP) complex
CC that may function in specific stages of inter-organelle traffic
CC (PubMed:16025134, PubMed:16828797). Specifically involved in the early
CC development of neural circuitry, likely by controlling the frequency
CC and amplitude of intracellular calcium transients implicated in the
CC regulation of neuron differentiation and survival (Probable).
CC {ECO:0000269|PubMed:16025134, ECO:0000269|PubMed:16828797,
CC ECO:0000305|PubMed:28626029}.
CC -!- SUBUNIT: Homodimer (PubMed:16025134, PubMed:16828797). Part of a TRAPP
CC complex. Heterodimer with TRAPPC3 (PubMed:16025134, PubMed:16828797).
CC The heterodimer TRAPPC6B-TRAPPC3 interacts with TRAPPC1 likely
CC providing a core for TRAPP complex formation (PubMed:16828797).
CC {ECO:0000269|PubMed:16025134, ECO:0000269|PubMed:16828797}.
CC -!- INTERACTION:
CC Q86SZ2; O43617: TRAPPC3; NbExp=3; IntAct=EBI-6160531, EBI-743566;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, cis-Golgi network {ECO:0000250}.
CC Endoplasmic reticulum {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86SZ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86SZ2-2; Sequence=VSP_009659;
CC -!- TISSUE SPECIFICITY: Both isoforms are expressed ubiquitously (at
CC transcript level), isoform 1 being the most predominant
CC (PubMed:28626029). Expressed in the fetal brain and different regions
CC of the adult brain and spinal cord (PubMed:28626029).
CC {ECO:0000269|PubMed:28626029}.
CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, epilepsy, and
CC brain atrophy (NEDMEBA) [MIM:617862]: An autosomal recessive
CC neurodevelopmental disorder characterized by microcephaly, global
CC developmental delay, hypotonia, intellectual disability, autistic
CC features such as poor social interaction, language impairment and
CC repetitive automatism behaviors, and generalized tonic-clonic seizures.
CC Brain imaging shows cortical atrophy, thin corpus callosum, and
CC cerebellar and brainstem atrophy. {ECO:0000269|PubMed:28397838,
CC ECO:0000269|PubMed:28626029}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TRAPP small subunits family. BET3 subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: May not be essential for endoplasmic reticulum-to-Golgi
CC transport. {ECO:0000269|PubMed:28626029}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD62341.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BX161510; CAD61947.1; -; mRNA.
DR EMBL; BX248013; CAD62341.1; ALT_INIT; mRNA.
DR EMBL; AL833179; CAI46185.1; -; mRNA.
DR EMBL; AK056690; BAG51784.1; -; mRNA.
DR EMBL; CH471078; EAW65823.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65824.1; -; Genomic_DNA.
DR EMBL; BC047328; AAH47328.1; -; mRNA.
DR CCDS; CCDS41947.1; -. [Q86SZ2-1]
DR CCDS; CCDS9670.1; -. [Q86SZ2-2]
DR RefSeq; NP_001073005.1; NM_001079537.1. [Q86SZ2-1]
DR RefSeq; NP_803235.1; NM_177452.3. [Q86SZ2-2]
DR PDB; 2BJN; X-ray; 1.70 A; A/B=1-158.
DR PDB; 2CFH; X-ray; 2.30 A; C/D=1-158.
DR PDB; 3KXC; X-ray; 2.00 A; C=1-158.
DR PDBsum; 2BJN; -.
DR PDBsum; 2CFH; -.
DR PDBsum; 3KXC; -.
DR AlphaFoldDB; Q86SZ2; -.
DR SMR; Q86SZ2; -.
DR BioGRID; 125777; 41.
DR ComplexPortal; CPX-4749; TRAPP II complex, TRAPPC2 variant.
DR ComplexPortal; CPX-6902; TRAPP II complex, TRAPPC2B variant.
DR CORUM; Q86SZ2; -.
DR DIP; DIP-47626N; -.
DR IntAct; Q86SZ2; 15.
DR MINT; Q86SZ2; -.
DR STRING; 9606.ENSP00000330289; -.
DR DrugBank; DB08342; S-palmitoyl-L-cysteine.
DR iPTMnet; Q86SZ2; -.
DR PhosphoSitePlus; Q86SZ2; -.
DR BioMuta; TRAPPC6B; -.
DR DMDM; 45477299; -.
DR EPD; Q86SZ2; -.
DR jPOST; Q86SZ2; -.
DR MassIVE; Q86SZ2; -.
DR MaxQB; Q86SZ2; -.
DR PaxDb; Q86SZ2; -.
DR PeptideAtlas; Q86SZ2; -.
DR PRIDE; Q86SZ2; -.
DR ProteomicsDB; 69650; -. [Q86SZ2-1]
DR ProteomicsDB; 69651; -. [Q86SZ2-2]
DR Antibodypedia; 23365; 70 antibodies from 18 providers.
DR DNASU; 122553; -.
DR Ensembl; ENST00000330149.10; ENSP00000330289.5; ENSG00000182400.15. [Q86SZ2-1]
DR Ensembl; ENST00000347691.9; ENSP00000335171.6; ENSG00000182400.15. [Q86SZ2-2]
DR GeneID; 122553; -.
DR KEGG; hsa:122553; -.
DR MANE-Select; ENST00000330149.10; ENSP00000330289.5; NM_001079537.2; NP_001073005.1.
DR UCSC; uc001wut.2; human. [Q86SZ2-1]
DR CTD; 122553; -.
DR DisGeNET; 122553; -.
DR GeneCards; TRAPPC6B; -.
DR HGNC; HGNC:23066; TRAPPC6B.
DR HPA; ENSG00000182400; Low tissue specificity.
DR MalaCards; TRAPPC6B; -.
DR MIM; 610397; gene.
DR MIM; 617862; phenotype.
DR neXtProt; NX_Q86SZ2; -.
DR OpenTargets; ENSG00000182400; -.
DR PharmGKB; PA134973191; -.
DR VEuPathDB; HostDB:ENSG00000182400; -.
DR eggNOG; KOG3316; Eukaryota.
DR GeneTree; ENSGT00390000012948; -.
DR HOGENOM; CLU_076409_3_1_1; -.
DR InParanoid; Q86SZ2; -.
DR OMA; RTNHHGV; -.
DR OrthoDB; 1566836at2759; -.
DR PhylomeDB; Q86SZ2; -.
DR TreeFam; TF313010; -.
DR PathwayCommons; Q86SZ2; -.
DR Reactome; R-HSA-204005; COPII-mediated vesicle transport.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q86SZ2; -.
DR BioGRID-ORCS; 122553; 6 hits in 1076 CRISPR screens.
DR ChiTaRS; TRAPPC6B; human.
DR EvolutionaryTrace; Q86SZ2; -.
DR GenomeRNAi; 122553; -.
DR Pharos; Q86SZ2; Tbio.
DR PRO; PR:Q86SZ2; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q86SZ2; protein.
DR Bgee; ENSG00000182400; Expressed in calcaneal tendon and 184 other tissues.
DR ExpressionAtlas; Q86SZ2; baseline and differential.
DR Genevisible; Q86SZ2; HS.
DR GO; GO:0005801; C:cis-Golgi network; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IC:ComplexPortal.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0030008; C:TRAPP complex; IBA:GO_Central.
DR GO; GO:1990071; C:TRAPPII protein complex; IC:ComplexPortal.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0006901; P:vesicle coating; IC:ComplexPortal.
DR GO; GO:0099022; P:vesicle tethering; IC:ComplexPortal.
DR CDD; cd14944; TRAPPC6A_Trs33; 1.
DR InterPro; IPR024096; NO_sig/Golgi_transp_ligand-bd.
DR InterPro; IPR007194; TRAPP_component.
DR InterPro; IPR037992; TRAPPC6/Trs33.
DR PANTHER; PTHR12817; PTHR12817; 1.
DR Pfam; PF04051; TRAPP; 1.
DR SUPFAM; SSF111126; SSF111126; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; Endoplasmic reticulum;
KW Epilepsy; Golgi apparatus; Intellectual disability; Neurogenesis;
KW Reference proteome.
FT CHAIN 1..158
FT /note="Trafficking protein particle complex subunit 6B"
FT /id="PRO_0000211587"
FT VAR_SEQ 90..117
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_009659"
FT VARIANT 42..158
FT /note="Missing (in NEDMEBA)"
FT /evidence="ECO:0000269|PubMed:28397838"
FT /id="VAR_080729"
FT MUTAGEN 31..32
FT /note="RC->EL: Impairs interaction with TRAPPC1."
FT /evidence="ECO:0000269|PubMed:16828797"
FT HELIX 1..20
FT /evidence="ECO:0007829|PDB:2BJN"
FT TURN 24..30
FT /evidence="ECO:0007829|PDB:2BJN"
FT HELIX 31..48
FT /evidence="ECO:0007829|PDB:2BJN"
FT HELIX 62..69
FT /evidence="ECO:0007829|PDB:2BJN"
FT HELIX 71..77
FT /evidence="ECO:0007829|PDB:2BJN"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:2BJN"
FT STRAND 91..98
FT /evidence="ECO:0007829|PDB:2BJN"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:2BJN"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:2BJN"
FT HELIX 120..132
FT /evidence="ECO:0007829|PDB:2BJN"
FT STRAND 136..145
FT /evidence="ECO:0007829|PDB:2BJN"
FT STRAND 149..156
FT /evidence="ECO:0007829|PDB:2BJN"
SQ SEQUENCE 158 AA; 17983 MW; 5A8B0474548C304B CRC64;
MADEALFLLL HNEMVSGVYK SAEQGEVENG RCITKLENMG FRVGQGLIER FTKDTARFKD
ELDIMKFICK DFWTTVFKKQ IDNLRTNHQG IYVLQDNKFR LLTQMSAGKQ YLEHASKYLA
FTCGLIRGGL SNLGIKSIVT AEVSSMPACK FQVMIQKL
