TM108_HUMAN
ID TM108_HUMAN Reviewed; 575 AA.
AC Q6UXF1; D3DNC9; Q9BQH1; Q9BW81; Q9C0H3;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Transmembrane protein 108 {ECO:0000312|HGNC:HGNC:28451};
DE AltName: Full=Retrolinkin {ECO:0000305};
GN Name=TMEM108 {ECO:0000312|HGNC:HGNC:28451}; Synonyms=KIAA1690, RTLN;
GN ORFNames=UNQ1875/PRO4318;
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), AND VARIANT LEU-84.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 7-575 (ISOFORM 2), AND VARIANT
RP LEU-84.
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 113-575 (ISOFORM 1).
RC TISSUE=Amygdala;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
CC -!- FUNCTION: Transmembrane protein required for proper cognitive
CC functions. Involved in the development of dentate gyrus (DG) neuron
CC circuitry, is necessary for AMPA receptors surface expression and
CC proper excitatory postsynaptic currents of DG granule neurons.
CC Regulates the organization and stability of the microtubule network of
CC sensory neurons to allow axonal transport. Through the interaction with
CC DST, mediates the docking of the dynein/dynactin motor complex to
CC vesicle cargos for retrograde axonal transport. In hippocampal neurons,
CC required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2
CC and recruits the WAVE1 complex to facilitate actin-dependent BDNF:NTRK2
CC early endocytic trafficking and mediate signaling from early endosomes.
CC {ECO:0000250|UniProtKB:Q8BHE4}.
CC -!- SUBUNIT: Interacts with DST (isoform 1). Interacts with SH3GL2.
CC Interacts (via N-terminus) with CYFIP1 and CYFIP2; the interactions
CC associate TMEM108 with the WAVE1 complex.
CC {ECO:0000250|UniProtKB:Q8BHE4}.
CC -!- INTERACTION:
CC Q6UXF1; Q13643: FHL3; NbExp=3; IntAct=EBI-7100456, EBI-741101;
CC Q6UXF1; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-7100456, EBI-3918971;
CC Q6UXF1; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-7100456, EBI-744081;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q8BHE4}; Multi-
CC pass membrane protein {ECO:0000255}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q8BHE4}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q8BHE4}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q8BHE4}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q8BHE4}. Early endosome
CC {ECO:0000250|UniProtKB:Q8BHE4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6UXF1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UXF1-2; Sequence=VSP_019494, VSP_019495;
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q8BHE4}.
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DR EMBL; AY358381; AAQ88747.1; -; mRNA.
DR EMBL; CH471052; EAW79182.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79183.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79184.1; -; Genomic_DNA.
DR EMBL; BC000568; AAH00568.1; -; mRNA.
DR EMBL; AB051477; BAB21781.1; -; mRNA.
DR EMBL; AL136578; CAB66513.3; -; mRNA.
DR CCDS; CCDS33858.1; -. [Q6UXF1-1]
DR RefSeq; NP_001129941.1; NM_001136469.2. [Q6UXF1-1]
DR RefSeq; NP_001269794.1; NM_001282865.1.
DR RefSeq; NP_076432.1; NM_023943.3. [Q6UXF1-1]
DR RefSeq; XP_011511399.1; XM_011513097.2.
DR AlphaFoldDB; Q6UXF1; -.
DR BioGRID; 122447; 68.
DR IntAct; Q6UXF1; 26.
DR MINT; Q6UXF1; -.
DR STRING; 9606.ENSP00000324651; -.
DR iPTMnet; Q6UXF1; -.
DR PhosphoSitePlus; Q6UXF1; -.
DR BioMuta; TMEM108; -.
DR DMDM; 109895211; -.
DR MassIVE; Q6UXF1; -.
DR PaxDb; Q6UXF1; -.
DR PeptideAtlas; Q6UXF1; -.
DR PRIDE; Q6UXF1; -.
DR ProteomicsDB; 67601; -. [Q6UXF1-1]
DR ProteomicsDB; 67602; -. [Q6UXF1-2]
DR Antibodypedia; 17731; 88 antibodies from 19 providers.
DR DNASU; 66000; -.
DR Ensembl; ENST00000321871.11; ENSP00000324651.6; ENSG00000144868.14. [Q6UXF1-1]
DR Ensembl; ENST00000393130.7; ENSP00000376838.3; ENSG00000144868.14. [Q6UXF1-1]
DR GeneID; 66000; -.
DR KEGG; hsa:66000; -.
DR MANE-Select; ENST00000321871.11; ENSP00000324651.6; NM_023943.4; NP_076432.1.
DR UCSC; uc003eph.5; human. [Q6UXF1-1]
DR CTD; 66000; -.
DR DisGeNET; 66000; -.
DR GeneCards; TMEM108; -.
DR HGNC; HGNC:28451; TMEM108.
DR HPA; ENSG00000144868; Tissue enhanced (retina, skeletal muscle).
DR MIM; 617361; gene.
DR neXtProt; NX_Q6UXF1; -.
DR OpenTargets; ENSG00000144868; -.
DR PharmGKB; PA142670759; -.
DR VEuPathDB; HostDB:ENSG00000144868; -.
DR eggNOG; ENOG502RXTY; Eukaryota.
DR GeneTree; ENSGT00390000000626; -.
DR HOGENOM; CLU_040547_1_0_1; -.
DR InParanoid; Q6UXF1; -.
DR OMA; KPMGATS; -.
DR OrthoDB; 1160560at2759; -.
DR PhylomeDB; Q6UXF1; -.
DR TreeFam; TF336337; -.
DR PathwayCommons; Q6UXF1; -.
DR SignaLink; Q6UXF1; -.
DR BioGRID-ORCS; 66000; 14 hits in 1068 CRISPR screens.
DR ChiTaRS; TMEM108; human.
DR GenomeRNAi; 66000; -.
DR Pharos; Q6UXF1; Tbio.
DR PRO; PR:Q6UXF1; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q6UXF1; protein.
DR Bgee; ENSG00000144868; Expressed in cortical plate and 143 other tissues.
DR ExpressionAtlas; Q6UXF1; baseline and differential.
DR Genevisible; Q6UXF1; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0036477; C:somatodendritic compartment; ISS:UniProtKB.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; ISS:UniProtKB.
DR GO; GO:0097484; P:dendrite extension; ISS:UniProtKB.
DR GO; GO:0021542; P:dentate gyrus development; ISS:UniProtKB.
DR GO; GO:0098815; P:modulation of excitatory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0051388; P:positive regulation of neurotrophin TRK receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0097106; P:postsynaptic density organization; ISS:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:UniProtKB.
DR GO; GO:0008090; P:retrograde axonal transport; ISS:UniProtKB.
DR InterPro; IPR031508; TMEM108.
DR PANTHER; PTHR28673; PTHR28673; 1.
DR Pfam; PF15759; TMEM108; 1.
DR PROSITE; PS00430; TONB_DEPENDENT_REC_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Endosome; Glycoprotein; Membrane;
KW Reference proteome; Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..575
FT /note="Transmembrane protein 108"
FT /id="PRO_0000243913"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 469..489
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 31..169
FT /note="Interaction with SH3GL2"
FT /evidence="ECO:0000250|UniProtKB:Q8BHE4"
FT REGION 65..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..407
FT /note="Interaction with DST (isoform 1)"
FT /evidence="ECO:0000250|UniProtKB:Q8BHE4"
FT REGION 490..575
FT /note="Interaction with CYFIP2"
FT /evidence="ECO:0000250|UniProtKB:Q8BHE4"
FT COMPBIAS 96..122
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..270
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..398
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 485..487
FT /note="VLL -> DPI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214970"
FT /id="VSP_019494"
FT VAR_SEQ 488..575
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11214970"
FT /id="VSP_019495"
FT VARIANT 84
FT /note="P -> L (in dbSNP:rs34111099)"
FT /evidence="ECO:0000269|PubMed:11214970,
FT ECO:0000269|PubMed:12975309"
FT /id="VAR_051427"
FT CONFLICT 108
FT /note="H -> Y (in Ref. 1; AAQ88747)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 575 AA; 59948 MW; ED25B263837BBF33 CRC64;
MKRSLQALYC QLLSFLLILA LTEALAFAIQ EPSPRESLQV LPSGTPPGTM VTAPHSSTRH
TSVVMLTPNP DGPPSQAAAP MATPTPRAEG HPPTHTISTI AATVTAPHSE SSLSTGPAPA
AMATTSSKPE GRPRGQAAPT ILLTKPPGAT SRPTTAPPRT TTRRPPRPPG SSRKGAGNSS
RPVPPAPGGH SRSKEGQRGR NPSSTPLGQK RPLGKIFQIY KGNFTGSVEP EPSTLTPRTP
LWGYSSSPQP QTVAATTVPS NTSWAPTTTS LGPAKDKPGL RRAAQGGGST FTSQGGTPDA
TAASGAPVSP QAAPVPSQRP HHGDPQDGPS HSDSWLTVTP GTSRPLSTSS GVFTAATGPT
PAAFDTSVSA PSQGIPQGAS TTPQAPTHPS RVSESTISGA KEETVATLTM TDRVPSPLST
VVSTATGNFL NRLVPAGTWK PGTAGNISHV AEGDKPQHRA TICLSKMDIA WVILAISVPI
SSCSVLLTVC CMKRKKKTAN PENNLSYWNN TITMDYFNRH AVELPREIQS LETSEDQLSE
PRSPANGDYR DTGMVLVNPF CQETLFVGND QVSEI
