MALD2_MOUSE
ID MALD2_MOUSE Reviewed; 555 AA.
AC Q3UZP0; Q80UJ4; Q99LE8;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=MARVEL domain-containing protein 2 {ECO:0000305};
DE AltName: Full=Tricellulin {ECO:0000303|PubMed:21245199, ECO:0000303|PubMed:23239027, ECO:0000303|PubMed:25217574};
GN Name=Marveld2 {ECO:0000312|MGI:MGI:2446166}; Synonyms=Mrvldc2, Tric;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TOPOLOGY, FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=16365161; DOI=10.1083/jcb.200510043;
RA Ikenouchi J., Furuse M., Furuse K., Sasaki H., Tsukita S., Tsukita S.;
RT "Tricellulin constitutes a novel barrier at tricellular contacts of
RT epithelial cells.";
RL J. Cell Biol. 171:939-945(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Cochlea;
RX PubMed=17186462; DOI=10.1086/510022;
RA Riazuddin S., Ahmed Z.M., Fanning A.S., Lagziel A., Kitajiri S., Ramzan K.,
RA Khan S.N., Chattaraj P., Friedman P.L., Anderson J.M., Belyantseva I.A.,
RA Forge A., Riazuddin S., Friedman T.B.;
RT "Tricellulin is a tight-junction protein necessary for hearing.";
RL Am. J. Hum. Genet. 79:1040-1051(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 120-555.
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary gland;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117 AND SER-121, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH LSR.
RX PubMed=21245199; DOI=10.1242/jcs.072058;
RA Masuda S., Oda Y., Sasaki H., Ikenouchi J., Higashi T., Akashi M.,
RA Nishi E., Furuse M.;
RT "LSR defines cell corners for tricellular tight junction formation in
RT epithelial cells.";
RL J. Cell Sci. 124:548-555(2011).
RN [7]
RP TISSUE SPECIFICITY, INTERACTION WITH LSR; ILDR1 AND ILDR2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23239027; DOI=10.1242/jcs.116442;
RA Higashi T., Tokuda S., Kitajiri S., Masuda S., Nakamura H., Oda Y.,
RA Furuse M.;
RT "Analysis of the 'angulin' proteins LSR, ILDR1 and ILDR2--tricellulin
RT recruitment, epithelial barrier function and implication in deafness
RT pathogenesis.";
RL J. Cell Sci. 126:966-977(2013).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=24889144; DOI=10.1111/gtc.12158;
RA Nakatsu D., Kano F., Taguchi Y., Sugawara T., Nishizono T., Nishikawa K.,
RA Oda Y., Furuse M., Murata M.;
RT "JNK1/2-dependent phosphorylation of angulin-1/LSR is required for the
RT exclusive localization of angulin-1/LSR and tricellulin at tricellular
RT contacts in EpH4 epithelial sheet.";
RL Genes Cells 19:565-581(2014).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=25217574; DOI=10.1093/hmg/ddu474;
RA Morozko E.L., Nishio A., Ingham N.J., Chandra R., Fitzgerald T.,
RA Martelletti E., Borck G., Wilson E., Riordan G.P., Wangemann P., Forge A.,
RA Steel K.P., Liddle R.A., Friedman T.B., Belyantseva I.A.;
RT "ILDR1 null mice, a model of human deafness DFNB42, show structural
RT aberrations of tricellular tight junctions and degeneration of auditory
RT hair cells.";
RL Hum. Mol. Genet. 24:609-624(2015).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=26677943; DOI=10.1038/srep18402;
RA Kamitani T., Sakaguchi H., Tamura A., Miyashita T., Yamazaki Y.,
RA Tokumasu R., Inamoto R., Matsubara A., Mori N., Hisa Y., Tsukita S.;
RT "Deletion of Tricellulin Causes Progressive Hearing Loss Associated with
RT Degeneration of Cochlear Hair Cells.";
RL Sci. Rep. 5:18402-18402(2015).
CC -!- FUNCTION: Plays a role in the formation of tricellular tight junctions
CC and of epithelial barriers (PubMed:16365161, PubMed:21245199). Required
CC for normal hearing via its role in the separation of the endolymphatic
CC and perilymphatic spaces of the organ of Corti in the inner ear, and
CC for normal survival of hair cells in the organ of Corti
CC (PubMed:26677943). {ECO:0000269|PubMed:16365161,
CC ECO:0000269|PubMed:21245199, ECO:0000269|PubMed:26677943}.
CC -!- SUBUNIT: Interacts with TJP1. Interacts with the ubiquitin ligase ITCH.
CC Interacts (via C-terminal cytoplasmic domain) with LSR (via the
CC cytoplasmic domain), ILDR1 and ILDR2; the interaction is required to
CC recruit MARVELD2 to tricellular contacts (PubMed:21245199,
CC PubMed:23239027). {ECO:0000250|UniProtKB:Q8N4S9,
CC ECO:0000269|PubMed:21245199, ECO:0000269|PubMed:23239027}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16365161,
CC ECO:0000269|PubMed:17186462, ECO:0000269|PubMed:26677943}; Multi-pass
CC membrane protein {ECO:0000305}. Cell junction, tight junction
CC {ECO:0000269|PubMed:16365161, ECO:0000269|PubMed:17186462,
CC ECO:0000269|PubMed:21245199, ECO:0000269|PubMed:23239027,
CC ECO:0000269|PubMed:24889144, ECO:0000269|PubMed:25217574,
CC ECO:0000269|PubMed:26677943}. Note=Found at tricellular contacts.
CC {ECO:0000269|PubMed:16365161, ECO:0000269|PubMed:17186462,
CC ECO:0000269|PubMed:21245199, ECO:0000269|PubMed:23239027,
CC ECO:0000269|PubMed:24889144, ECO:0000269|PubMed:25217574,
CC ECO:0000269|PubMed:26677943}.
CC -!- TISSUE SPECIFICITY: Detected in small intestine, stomach and kidney, in
CC epithelial cells (PubMed:16365161). Detected in pancreas, retina and
CC lung, and in stria vascularis, utricle and the organ of Conti in the
CC inner ear (at protein level) (PubMed:26677943, PubMed:17186462).
CC Predominantly detected in small intestine, lung and kidney, with lower
CC levels in liver, testis and brain (PubMed:16365161). In colon,
CC expressed in the entire crypts (PubMed:23239027).
CC {ECO:0000269|PubMed:16365161, ECO:0000269|PubMed:17186462,
CC ECO:0000269|PubMed:23239027, ECO:0000269|PubMed:26677943}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:16365161}.
CC -!- PTM: Ubiquitinated by ITCH; but this ubiquitination does not lead to
CC proteasomal degradation. {ECO:0000250|UniProtKB:Q8N4S9}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth. Mutant mice have
CC normal gait and equilibrium and are fertile. They display severe and
CC rapidly progressing hearing loss already 14 days after birth, and
CC completely lack response to a 90 dB sound 21 days after birth.
CC Endocochlear potential and paracellular permeability in the stria
CC vascularis are not affected. The arrangement of inner and outer hair
CC cells in the organ of Corti appears normal at 12 days after birth, but
CC outer hair cells and inner hair cells have disappeared by 21 days after
CC birth. Hair cells survive on cochlear explants (in vitro), suggesting
CC that hair cell degeneration is due to K(+) leakage from the endolymph
CC to the perilymph. {ECO:0000269|PubMed:26677943}.
CC -!- SIMILARITY: Belongs to the ELL/occludin family. {ECO:0000255|PROSITE-
CC ProRule:PRU01324}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH49919.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB219935; BAE54512.1; -; mRNA.
DR EMBL; DQ143929; ABA18656.1; -; mRNA.
DR EMBL; AK133741; BAE21816.1; -; mRNA.
DR EMBL; BC003296; AAH03296.1; -; mRNA.
DR EMBL; BC049919; AAH49919.1; ALT_INIT; mRNA.
DR CCDS; CCDS26732.1; -.
DR RefSeq; NP_001033691.1; NM_001038602.4.
DR RefSeq; XP_006517668.1; XM_006517605.1.
DR AlphaFoldDB; Q3UZP0; -.
DR SMR; Q3UZP0; -.
DR BioGRID; 230044; 1.
DR STRING; 10090.ENSMUSP00000022137; -.
DR iPTMnet; Q3UZP0; -.
DR PhosphoSitePlus; Q3UZP0; -.
DR MaxQB; Q3UZP0; -.
DR PaxDb; Q3UZP0; -.
DR PRIDE; Q3UZP0; -.
DR ProteomicsDB; 287301; -.
DR Antibodypedia; 23961; 178 antibodies from 25 providers.
DR DNASU; 218518; -.
DR Ensembl; ENSMUST00000022137; ENSMUSP00000022137; ENSMUSG00000021636.
DR Ensembl; ENSMUST00000168772; ENSMUSP00000126438; ENSMUSG00000021636.
DR Ensembl; ENSMUST00000225754; ENSMUSP00000153294; ENSMUSG00000021636.
DR GeneID; 218518; -.
DR KEGG; mmu:218518; -.
DR UCSC; uc007rra.2; mouse.
DR CTD; 153562; -.
DR MGI; MGI:2446166; Marveld2.
DR VEuPathDB; HostDB:ENSMUSG00000021636; -.
DR eggNOG; KOG4796; Eukaryota.
DR GeneTree; ENSGT00940000155771; -.
DR HOGENOM; CLU_039176_1_0_1; -.
DR InParanoid; Q3UZP0; -.
DR OMA; YSQPYGV; -.
DR OrthoDB; 335949at2759; -.
DR PhylomeDB; Q3UZP0; -.
DR TreeFam; TF326161; -.
DR BioGRID-ORCS; 218518; 4 hits in 70 CRISPR screens.
DR ChiTaRS; Marveld2; mouse.
DR PRO; PR:Q3UZP0; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q3UZP0; protein.
DR Bgee; ENSMUSG00000021636; Expressed in ear vesicle and 155 other tissues.
DR ExpressionAtlas; Q3UZP0; baseline and differential.
DR Genevisible; Q3UZP0; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005923; C:bicellular tight junction; IDA:MGI.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0033010; C:paranodal junction; IDA:MGI.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IDA:MGI.
DR GO; GO:0070160; C:tight junction; IDA:UniProtKB.
DR GO; GO:0061689; C:tricellular tight junction; IDA:ARUK-UCL.
DR GO; GO:0070830; P:bicellular tight junction assembly; ISO:MGI.
DR GO; GO:0045216; P:cell-cell junction organization; IMP:MGI.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISO:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
DR InterPro; IPR031176; ELL/occludin.
DR InterPro; IPR008253; Marvel.
DR InterPro; IPR031177; MARVELD2.
DR InterPro; IPR010844; Occludin_ELL.
DR PANTHER; PTHR23288; PTHR23288; 1.
DR PANTHER; PTHR23288:SF3; PTHR23288:SF3; 1.
DR Pfam; PF01284; MARVEL; 1.
DR Pfam; PF07303; Occludin_ELL; 1.
DR PROSITE; PS51225; MARVEL; 1.
DR PROSITE; PS51980; OCEL; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Coiled coil; Hearing; Membrane;
KW Phosphoprotein; Reference proteome; Tight junction; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..555
FT /note="MARVEL domain-containing protein 2"
FT /id="PRO_0000271527"
FT TOPO_DOM 1..191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..251
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 310..338
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..555
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 185..364
FT /note="MARVEL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00581"
FT DOMAIN 437..548
FT /note="OCEL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01324"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 521..545
FT /evidence="ECO:0000255"
FT COMPBIAS 1..19
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..58
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N4S9"
FT MOD_RES 163
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8N4S9"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N4S9"
FT CONFLICT 120..131
FT /note="ASPARANHHPYK -> TRPPTRPPTRP (in Ref. 4; AAH03296)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 63662 MW; CF91270F47D4DDD5 CRC64;
MSSSDARSRI RDRGYSEVPR DTSCPDGTIR TFQSLHSSEL AVSADPLPPP PLPLQPPFGP
SFYSSDTEEP AVAPDLKPVR RFVPDSWKNF FRGKKKDPEW DNPVSDIRYI SDGVECSPPA
SPARANHHPY KDPSRGSQGT FNSQHEADAM FAHDPYASLD RRTQTARTYS EKVEEYNLRY
AYMKSWAGLL RILGVVELLL GAGVFACVTA YIHKDNEWYN LFGYTQPYGM GGLGSLGNTY
GGYYYSGPKT PFVLVVAGLA WITTIIILVL GMSMYYRTIL LDSNWWPLTE FGVNVALFIL
YMAAAIVYVN DTNRGGLCYY PLFNTPMNAM FCRVEGGQIA AMIFLFVTMI VYLVSALVCL
KLWRHEAARR HREFLEQQEI NDPSLSSKRK MCEAAISDRQ RDQEVNVKDL RTTTKMTPEL
LSGHIPPGHI PKPIVMPDYV AKYPVIQTDD DRERYKAVFQ DQFSEYKELS AEVQAILRKF
DELDTVMSRL PHHSENRQEH ERISRIHEEF RKKKNDPSFL EKKERCDYLK NKLSHIKQRI
QEYDKVMNWD TQGYP
