TM129_HUMAN
ID TM129_HUMAN Reviewed; 362 AA.
AC A0AVI4; A6NH49; A6NI98; D3DVP8;
DT 12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=E3 ubiquitin-protein ligase TM129;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase TM129 {ECO:0000305};
GN Name=TMEM129;
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=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 [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] (ISOFORMS 1 AND 2).
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 FUNCTION, CATALYTIC ACTIVITY, TOPOLOGY, AND SUBCELLULAR LOCATION.
RX PubMed=24807418; DOI=10.1038/ncomms4832;
RA van de Weijer M.L., Bassik M.C., Luteijn R.D., Voorburg C.M., Lohuis M.A.,
RA Kremmer E., Hoeben R.C., Leproust E.M., Chen S., Hoelen H., Ressing M.E.,
RA Patena W., Weissman J.S., McManus M.T., Wiertz E.J., Lebbink R.J.;
RT "A high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved
RT in ER-associated protein degradation.";
RL Nat. Commun. 5:3832-3832(2014).
CC -!- FUNCTION: E3 ubiquitin-protein ligase involved in ER-associated protein
CC degradation, preferentially associates with the E2 enzyme UBE2J2.
CC Exploited by viral US11 proteins to mediate HLA class I proteins
CC degradation. {ECO:0000269|PubMed:24807418}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Integral component of ER-resident dislocation complexes.
CC -!- INTERACTION:
CC A0AVI4-2; P04792: HSPB1; NbExp=3; IntAct=EBI-25871541, EBI-352682;
CC A0AVI4-2; P02766: TTR; NbExp=3; IntAct=EBI-25871541, EBI-711909;
CC A0AVI4-2; O76024: WFS1; NbExp=3; IntAct=EBI-25871541, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:24807418}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:24807418}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A0AVI4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0AVI4-2; Sequence=VSP_036641, VSP_036642;
CC -!- DOMAIN: The RING-type zinc finger domain is responsible for E3
CC ubiquitin ligase activity.
CC -!- SIMILARITY: Belongs to the TMEM129 family. {ECO:0000305}.
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DR EMBL; AC016773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471131; EAW82569.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82570.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82571.1; -; Genomic_DNA.
DR EMBL; BC009331; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC126370; AAI26371.1; -; mRNA.
DR CCDS; CCDS3351.1; -. [A0AVI4-2]
DR CCDS; CCDS46998.1; -. [A0AVI4-1]
DR RefSeq; NP_001120738.1; NM_001127266.1. [A0AVI4-1]
DR RefSeq; NP_612394.1; NM_138385.3. [A0AVI4-2]
DR AlphaFoldDB; A0AVI4; -.
DR BioGRID; 124932; 46.
DR IntAct; A0AVI4; 6.
DR MINT; A0AVI4; -.
DR STRING; 9606.ENSP00000372394; -.
DR iPTMnet; A0AVI4; -.
DR PhosphoSitePlus; A0AVI4; -.
DR BioMuta; TMEM129; -.
DR EPD; A0AVI4; -.
DR jPOST; A0AVI4; -.
DR MassIVE; A0AVI4; -.
DR MaxQB; A0AVI4; -.
DR PaxDb; A0AVI4; -.
DR PeptideAtlas; A0AVI4; -.
DR PRIDE; A0AVI4; -.
DR ProteomicsDB; 22; -. [A0AVI4-1]
DR ProteomicsDB; 23; -. [A0AVI4-2]
DR Antibodypedia; 64956; 4 antibodies from 3 providers.
DR DNASU; 92305; -.
DR Ensembl; ENST00000303277.6; ENSP00000305243.2; ENSG00000168936.11. [A0AVI4-2]
DR Ensembl; ENST00000382936.8; ENSP00000372394.3; ENSG00000168936.11. [A0AVI4-1]
DR Ensembl; ENST00000536901.1; ENSP00000441812.1; ENSG00000168936.11. [A0AVI4-1]
DR GeneID; 92305; -.
DR KEGG; hsa:92305; -.
DR MANE-Select; ENST00000382936.8; ENSP00000372394.3; NM_001127266.2; NP_001120738.1.
DR UCSC; uc003gdm.4; human. [A0AVI4-1]
DR CTD; 92305; -.
DR DisGeNET; 92305; -.
DR GeneCards; TMEM129; -.
DR HGNC; HGNC:25137; TMEM129.
DR HPA; ENSG00000168936; Low tissue specificity.
DR MIM; 615975; gene.
DR neXtProt; NX_A0AVI4; -.
DR OpenTargets; ENSG00000168936; -.
DR PharmGKB; PA143485649; -.
DR VEuPathDB; HostDB:ENSG00000168936; -.
DR eggNOG; KOG3899; Eukaryota.
DR GeneTree; ENSGT00390000013284; -.
DR HOGENOM; CLU_048119_0_0_1; -.
DR InParanoid; A0AVI4; -.
DR OMA; AEYGELC; -.
DR OrthoDB; 647242at2759; -.
DR PhylomeDB; A0AVI4; -.
DR TreeFam; TF314487; -.
DR PathwayCommons; A0AVI4; -.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; A0AVI4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 92305; 8 hits in 1112 CRISPR screens.
DR GenomeRNAi; 92305; -.
DR Pharos; A0AVI4; Tbio.
DR PRO; PR:A0AVI4; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; A0AVI4; protein.
DR Bgee; ENSG00000168936; Expressed in tendon of biceps brachii and 177 other tissues.
DR ExpressionAtlas; A0AVI4; baseline and differential.
DR Genevisible; A0AVI4; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:ParkinsonsUK-UCL.
DR InterPro; IPR018801; TM129.
DR PANTHER; PTHR31322; PTHR31322; 1.
DR Pfam; PF10272; Tmpp129; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Membrane; Metal-binding;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Unfolded protein response; Zinc; Zinc-finger.
FT CHAIN 1..362
FT /note="E3 ubiquitin-protein ligase TM129"
FT /id="PRO_0000291041"
FT TOPO_DOM 1..6
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..94
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 285..350
FT /note="RING-type; degenerate"
FT VAR_SEQ 228..232
FT /note="LNSTE -> SWRPA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036641"
FT VAR_SEQ 233..362
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036642"
FT VARIANT 83
FT /note="L -> I (in dbSNP:rs798752)"
FT /id="VAR_032803"
SQ SEQUENCE 362 AA; 40464 MW; 861C9876B492DC56 CRC64;
MDSPEVTFTL AYLVFAVCFV FTPNEFHAAG LTVQNLLSGW LGSEDAAFVP FHLRRTAATL
LCHSLLPLGY YVGMCLAASE KRLHALSQAP EAWRLFLLLA VTLPSIACIL IYYWSRDRWA
CHPLARTLAL YALPQSGWQA VASSVNTEFR RIDKFATGAP GARVIVTDTW VMKVTTYRVH
VAQQQDVHLT VTESRQHELS PDSNLPVQLL TIRVASTNPA VQAFDIWLNS TEYGELCEKL
RAPIRRAAHV VIHQSLGDLF LETFASLVEV NPAYSVPSSQ ELEACIGCMQ TRASVKLVKT
CQEAATGECQ QCYCRPMWCL TCMGKWFASR QDPLRPDTWL ASRVPCPTCR ARFCILDVCT
VR
