TRAM2_HUMAN
ID TRAM2_HUMAN Reviewed; 370 AA.
AC Q15035; A8K6T6;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Translocating chain-associated membrane protein 2;
GN Name=TRAM2; Synonyms=KIAA0057;
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].
RC TISSUE=Bone marrow;
RX PubMed=7584044; DOI=10.1093/dnares/1.5.223;
RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N.,
RA Kawarabayasi Y., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. II. The
RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 1:223-229(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP FUNCTION, AND INTERACTION WITH SERCA2B AND COL1A1.
RX PubMed=14749390; DOI=10.1128/mcb.24.4.1758-1768.2004;
RA Stefanovic B., Stefanovic L., Schnabl B., Bataller R., Brenner D.A.;
RT "TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and
RT is necessary for collagen type I synthesis.";
RL Mol. Cell. Biol. 24:1758-1768(2004).
RN [7]
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 [8]
RP FUNCTION.
RX PubMed=27499293; DOI=10.1016/j.molcel.2016.06.032;
RA Chen Q., Denard B., Lee C.E., Han S., Ye J.S., Ye J.;
RT "Inverting the topology of a transmembrane protein by regulating the
RT translocation of the first transmembrane helix.";
RL Mol. Cell 63:567-578(2016).
CC -!- FUNCTION: Necessary for collagen type I synthesis. May couple the
CC activity of the ER Ca(2+) pump SERCA2B with the activity of the
CC translocon. This coupling may increase the local Ca(2+) concentration
CC at the site of collagen synthesis, and a high Ca(2+) concentration may
CC be necessary for the function of molecular chaperones involved in
CC collagen folding. Required for proper insertion of the first
CC transmembrane helix N-terminus of TM4SF20 into the ER lumen, may act as
CC a ceramide sensor for regulated alternative translocation (RAT)
CC (PubMed:27499293). {ECO:0000269|PubMed:14749390,
CC ECO:0000269|PubMed:27499293}.
CC -!- SUBUNIT: Interacts with SERCA2B and COL1A1.
CC {ECO:0000269|PubMed:14749390}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the TRAM family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA06540.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D31762; BAA06540.2; ALT_INIT; mRNA.
DR EMBL; AK291751; BAF84440.1; -; mRNA.
DR EMBL; AL049611; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04373.1; -; Genomic_DNA.
DR EMBL; BC028121; AAH28121.1; -; mRNA.
DR CCDS; CCDS34477.1; -.
DR RefSeq; NP_036420.1; NM_012288.3.
DR AlphaFoldDB; Q15035; -.
DR BioGRID; 115049; 8.
DR IntAct; Q15035; 1.
DR STRING; 9606.ENSP00000182527; -.
DR TCDB; 9.B.311.2.4; the 6-7 tms tram-lag (tram-lag) family.
DR GlyGen; Q15035; 1 site.
DR iPTMnet; Q15035; -.
DR PhosphoSitePlus; Q15035; -.
DR SwissPalm; Q15035; -.
DR BioMuta; TRAM2; -.
DR DMDM; 18202502; -.
DR EPD; Q15035; -.
DR jPOST; Q15035; -.
DR MassIVE; Q15035; -.
DR MaxQB; Q15035; -.
DR PaxDb; Q15035; -.
DR PeptideAtlas; Q15035; -.
DR PRIDE; Q15035; -.
DR ProteomicsDB; 60384; -.
DR Antibodypedia; 30914; 174 antibodies from 27 providers.
DR DNASU; 9697; -.
DR Ensembl; ENST00000182527.4; ENSP00000182527.3; ENSG00000065308.5.
DR GeneID; 9697; -.
DR KEGG; hsa:9697; -.
DR MANE-Select; ENST00000182527.4; ENSP00000182527.3; NM_012288.4; NP_036420.1.
DR UCSC; uc003paq.4; human.
DR CTD; 9697; -.
DR DisGeNET; 9697; -.
DR GeneCards; TRAM2; -.
DR HGNC; HGNC:16855; TRAM2.
DR HPA; ENSG00000065308; Low tissue specificity.
DR MIM; 608485; gene.
DR neXtProt; NX_Q15035; -.
DR OpenTargets; ENSG00000065308; -.
DR PharmGKB; PA128394555; -.
DR VEuPathDB; HostDB:ENSG00000065308; -.
DR eggNOG; KOG1608; Eukaryota.
DR GeneTree; ENSGT00510000046470; -.
DR HOGENOM; CLU_062830_0_0_1; -.
DR InParanoid; Q15035; -.
DR OMA; CRLCMLL; -.
DR OrthoDB; 831082at2759; -.
DR PhylomeDB; Q15035; -.
DR TreeFam; TF314319; -.
DR PathwayCommons; Q15035; -.
DR SignaLink; Q15035; -.
DR BioGRID-ORCS; 9697; 22 hits in 1071 CRISPR screens.
DR ChiTaRS; TRAM2; human.
DR GeneWiki; TRAM2; -.
DR GenomeRNAi; 9697; -.
DR Pharos; Q15035; Tbio.
DR PRO; PR:Q15035; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q15035; protein.
DR Bgee; ENSG00000065308; Expressed in oocyte and 169 other tissues.
DR ExpressionAtlas; Q15035; baseline and differential.
DR Genevisible; Q15035; HS.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0032964; P:collagen biosynthetic process; IMP:UniProtKB.
DR GO; GO:0045048; P:protein insertion into ER membrane; IDA:UniProtKB.
DR GO; GO:0006616; P:SRP-dependent cotranslational protein targeting to membrane, translocation; IEA:InterPro.
DR InterPro; IPR006634; TLC-dom.
DR InterPro; IPR013599; TRAM1.
DR InterPro; IPR016447; Translocation_assoc_membrane.
DR PANTHER; PTHR12371; PTHR12371; 1.
DR Pfam; PF08390; TRAM1; 1.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR PIRSF; PIRSF005449; Translocation_assoc_membrane; 1.
DR SMART; SM00724; TLC; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Membrane; Protein transport; Reference proteome;
KW Translocation; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..370
FT /note="Translocating chain-associated membrane protein 2"
FT /id="PRO_0000185532"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..75
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..119
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 120..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..159
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 192..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..214
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..250
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..287
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..370
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 112..321
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT REGION 348..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 370 AA; 43328 MW; 9B5183F1A3D45366 CRC64;
MAFRRRTKSY PLFSQEFVIH NHADIGFCLV LCVLIGLMFE VTAKTAFLFI LPQYNISVPT
ADSETVHYHY GPKDLVTILF YIFITIILHA VVQEYILDKI SKRLHLSKVK HSKFNESGQL
VVFHFTSVIW CFYVVVTEGY LTNPRSLWED YPHVHLPFQV KFFYLCQLAY WLHALPELYF
QKVRKEEIPR QLQYICLYLV HIAGAYLLNL SRLGLILLLL QYSTEFLFHT ARLFYFADEN
NEKLFSAWAA VFGVTRLFIL TLAVLAIGFG LARMENQAFD PEKGNFNTLF CRLCVLLLVC
AAQAWLMWRF IHSQLRHWRE YWNEQSAKRR VPATPRLPAR LIKRESGYHE NGVVKAENGT
SPRTKKLKSP
