ID MALD2_HUMAN Reviewed; 558 AA. AC Q8N4S9; A1BQX0; A1BQX1; A8KA97; Q96NM9; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 2. DT 24-JAN-2024, entry version 169. DE RecName: Full=MARVEL domain-containing protein 2 {ECO:0000305}; DE AltName: Full=Tricellulin {ECO:0000303|PubMed:16365161}; GN Name=MARVELD2 {ECO:0000312|HGNC:HGNC:26401}; Synonyms=TRIC; 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 [MRNA] (ISOFORMS 1 AND 2), AND VARIANT ILE-33. 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] (ISOFORMS 1 AND 3), INVOLVEMENT IN DFNB49, RP FUNCTION, INTERACTION WITH TJP1, AND VARIANT ILE-33. RC TISSUE=Lung; 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] (ISOFORMS 1 AND 2), AND VARIANT RP ILE-33. RC TISSUE=Brain, and Trachea; 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], AND VARIANT ILE-33. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-33. RC TISSUE=Lung; 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116 AND SER-120, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116 AND SER-120, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161; THR-166 AND SER-387, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP UBIQUITINATION, AND INTERACTION WITH ITCH. RX PubMed=28436082; DOI=10.1111/nyas.13349; RA Jennek S., Mittag S., Reiche J., Westphal J.K., Seelk S., Doerfel M.J., RA Pfirrmann T., Friedrich K., Schuetz A., Heinemann U., Huber O.; RT "Tricellulin is a target of the ubiquitin ligase Itch."; RL Ann. N. Y. Acad. Sci. 1397:157-168(2017). RN [12] {ECO:0007744|PDB:5N7H, ECO:0007744|PDB:5N7I, ECO:0007744|PDB:5N7K} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 439-551, SUBCELLULAR LOCATION, RP INTERACTION WITH TJP1, AND COILED COIL. RX PubMed=28661558; DOI=10.1111/nyas.13408; RA Schuetz A., Radusheva V., Krug S.M., Heinemann U.; RT "Crystal structure of the tricellulin C-terminal coiled-coil domain reveals RT a unique mode of dimerization."; RL Ann. N. Y. Acad. Sci. 1405:147-159(2017). CC -!- FUNCTION: Plays a role in the formation of tricellular tight junctions CC and of epithelial barriers (By similarity). Required for normal hearing CC via its role in the separation of the endolymphatic and perilymphatic CC spaces of the organ of Corti in the inner ear, and for normal survival CC of hair cells in the organ of Corti (PubMed:17186462). CC {ECO:0000250|UniProtKB:Q3UZP0, ECO:0000269|PubMed:17186462}. CC -!- SUBUNIT: Interacts with TJP1 (PubMed:17186462). Interacts with the CC ubiquitin ligase ITCH (PubMed:28436082). Interacts (via C-terminal CC cytoplasmic domain) with LSR (via the cytoplasmic domain), ILDR1 and CC ILDR2; the interaction is required to recruit MARVELD2 to tricellular CC contacts (By similarity). {ECO:0000250|UniProtKB:Q3UZP0, CC ECO:0000269|PubMed:17186462, ECO:0000269|PubMed:28436082}. CC -!- INTERACTION: CC Q8N4S9; Q969F0: FATE1; NbExp=3; IntAct=EBI-6875061, EBI-743099; CC Q8N4S9; P00747: PLG; NbExp=2; IntAct=EBI-6875061, EBI-999394; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28661558}; CC Multi-pass membrane protein {ECO:0000305}. Cell junction, tight CC junction {ECO:0000269|PubMed:28661558}. Note=Located at tricellular CC contacts. {ECO:0000269|PubMed:28661558}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=A, TRIC; CC IsoId=Q8N4S9-1; Sequence=Displayed; CC Name=2; Synonyms=TRICbeta; CC IsoId=Q8N4S9-2; Sequence=VSP_022320, VSP_022321; CC Name=3; Synonyms=A1; CC IsoId=Q8N4S9-3; Sequence=VSP_035760; CC -!- PTM: Ubiquitinated by ITCH; but this ubiquitination does not lead to CC proteasomal degradation. {ECO:0000269|PubMed:28436082}. CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q3UZP0}. CC -!- DISEASE: Deafness, autosomal recessive, 49 (DFNB49) [MIM:610153]: A CC form of non-syndromic sensorineural hearing loss. Sensorineural CC deafness results from damage to the neural receptors of the inner ear, CC the nerve pathways to the brain, or the area of the brain that receives CC sound information. {ECO:0000269|PubMed:17186462}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ELL/occludin family. {ECO:0000255|PROSITE- CC ProRule:PRU01324}. 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; AB219936; BAE54513.1; -; mRNA. DR EMBL; AB219937; BAE54514.1; -; mRNA. DR EMBL; DQ682656; ABG89104.1; -; mRNA. DR EMBL; DQ682657; ABG89105.1; -; mRNA. DR EMBL; AK055094; BAB70853.1; -; mRNA. DR EMBL; AK292962; BAF85651.1; -; mRNA. DR EMBL; AC145146; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471137; EAW51277.1; -; Genomic_DNA. DR EMBL; BC033689; AAH33689.1; -; mRNA. DR CCDS; CCDS34175.1; -. [Q8N4S9-1] DR CCDS; CCDS58956.1; -. [Q8N4S9-3] DR RefSeq; NP_001033692.2; NM_001038603.2. [Q8N4S9-1] DR RefSeq; NP_001231663.1; NM_001244734.1. [Q8N4S9-3] DR RefSeq; XP_005248502.1; XM_005248445.4. [Q8N4S9-1] DR RefSeq; XP_005248503.1; XM_005248446.4. [Q8N4S9-1] DR RefSeq; XP_005248504.1; XM_005248447.4. [Q8N4S9-3] DR PDB; 5N7H; X-ray; 2.20 A; A=439-551. DR PDB; 5N7I; X-ray; 2.88 A; A/B=439-551. DR PDB; 5N7K; X-ray; 2.81 A; A/B/C/D=439-551. DR PDBsum; 5N7H; -. DR PDBsum; 5N7I; -. DR PDBsum; 5N7K; -. DR AlphaFoldDB; Q8N4S9; -. DR SMR; Q8N4S9; -. DR BioGRID; 127502; 63. DR IntAct; Q8N4S9; 27. DR MINT; Q8N4S9; -. DR STRING; 9606.ENSP00000323264; -. DR TCDB; 9.B.41.2.1; the occludin (occludin) family. DR iPTMnet; Q8N4S9; -. DR PhosphoSitePlus; Q8N4S9; -. DR SwissPalm; Q8N4S9; -. DR BioMuta; MARVELD2; -. DR DMDM; 317373387; -. DR EPD; Q8N4S9; -. DR jPOST; Q8N4S9; -. DR MassIVE; Q8N4S9; -. DR MaxQB; Q8N4S9; -. DR PaxDb; 9606-ENSP00000323264; -. DR PeptideAtlas; Q8N4S9; -. DR ProteomicsDB; 71965; -. [Q8N4S9-1] DR ProteomicsDB; 71966; -. [Q8N4S9-2] DR ProteomicsDB; 71967; -. [Q8N4S9-3] DR Pumba; Q8N4S9; -. DR Antibodypedia; 23961; 204 antibodies from 25 providers. DR DNASU; 153562; -. DR Ensembl; ENST00000325631.10; ENSP00000323264.5; ENSG00000152939.17. [Q8N4S9-1] DR Ensembl; ENST00000454295.6; ENSP00000396244.2; ENSG00000152939.17. [Q8N4S9-3] DR Ensembl; ENST00000614617.4; ENSP00000480044.1; ENSG00000274671.4. DR Ensembl; ENST00000622835.4; ENSP00000480068.1; ENSG00000274671.4. DR Ensembl; ENST00000645446.1; ENSP00000494616.1; ENSG00000152939.17. [Q8N4S9-1] DR Ensembl; ENST00000647531.1; ENSP00000493858.1; ENSG00000152939.17. [Q8N4S9-3] DR GeneID; 153562; -. DR KEGG; hsa:153562; -. DR MANE-Select; ENST00000325631.10; ENSP00000323264.5; NM_001038603.3; NP_001033692.2. DR UCSC; uc003jwq.4; human. [Q8N4S9-1] DR AGR; HGNC:26401; -. DR CTD; 153562; -. DR DisGeNET; 153562; -. DR GeneCards; MARVELD2; -. DR GeneReviews; MARVELD2; -. DR HGNC; HGNC:26401; MARVELD2. DR HPA; ENSG00000152939; Tissue enhanced (thyroid). DR MalaCards; MARVELD2; -. DR MIM; 610153; phenotype. DR MIM; 610572; gene. DR neXtProt; NX_Q8N4S9; -. DR OpenTargets; ENSG00000152939; -. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR PharmGKB; PA134954584; -. DR VEuPathDB; HostDB:ENSG00000152939; -. DR eggNOG; KOG4796; Eukaryota. DR GeneTree; ENSGT00940000155771; -. DR HOGENOM; CLU_039176_1_0_1; -. DR InParanoid; Q8N4S9; -. DR OMA; LLDSTWW; -. DR OrthoDB; 2910197at2759; -. DR PhylomeDB; Q8N4S9; -. DR TreeFam; TF326161; -. DR PathwayCommons; Q8N4S9; -. DR SignaLink; Q8N4S9; -. DR BioGRID-ORCS; 153562; 9 hits in 1133 CRISPR screens. DR ChiTaRS; MARVELD2; human. DR GeneWiki; MARVELD2; -. DR GenomeRNAi; 153562; -. DR Pharos; Q8N4S9; Tbio. DR PRO; PR:Q8N4S9; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q8N4S9; Protein. DR Bgee; ENSG00000152939; Expressed in islet of Langerhans and 105 other cell types or tissues. DR ExpressionAtlas; Q8N4S9; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0033010; C:paranodal junction; IEA:Ensembl. DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IEA:Ensembl. DR GO; GO:0070160; C:tight junction; IDA:UniProtKB. DR GO; GO:0061689; C:tricellular tight junction; IDA:UniProtKB. DR GO; GO:0070830; P:bicellular tight junction assembly; IMP:UniProtKB. DR GO; GO:0045216; P:cell-cell junction organization; IMP:MGI. DR GO; GO:0061028; P:establishment of endothelial barrier; IMP:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI. DR Gene3D; 6.10.140.340; -; 1. DR InterPro; IPR031176; ELL/occludin. DR InterPro; IPR008253; Marvel. DR InterPro; IPR010844; Occludin_ELL. DR PANTHER; PTHR23288:SF3; MARVEL DOMAIN-CONTAINING PROTEIN 2; 1. DR PANTHER; PTHR23288; OCCLUDIN AND RNA POLYMERASE II ELONGATION FACTOR ELL; 1. DR Pfam; PF01284; MARVEL; 1. DR Pfam; PF07303; Occludin_ELL; 1. DR SUPFAM; SSF144292; occludin/ELL-like; 1. DR PROSITE; PS51225; MARVEL; 1. DR PROSITE; PS51980; OCEL; 1. DR Genevisible; Q8N4S9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell junction; Cell membrane; KW Coiled coil; Deafness; Hearing; Membrane; Non-syndromic deafness; KW Phosphoprotein; Reference proteome; Tight junction; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT CHAIN 1..558 FT /note="MARVEL domain-containing protein 2" FT /id="PRO_0000271526" FT TOPO_DOM 1..194 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 195..215 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 216..223 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 224..244 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 245..254 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 255..275 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 276..291 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 292..312 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 313..319 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 320..337 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 338..341 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 342..362 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 363..558 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 188..367 FT /note="MARVEL" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00581" FT DOMAIN 440..551 FT /note="OCEL" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01324" FT REGION 1..58 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 115..145 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 439..548 FT /evidence="ECO:0000269|PubMed:28661558" FT COMPBIAS 1..19 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 43..57 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 116 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648" FT MOD_RES 120 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648" FT MOD_RES 161 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 166 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 387 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 383..394 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17186462" FT /id="VSP_035760" FT VAR_SEQ 431..457 FT /note="GHIPKPIVMPDYVAKYPVIQTDDERER -> RPANFFVFLVEMGFHRVSQDD FT LDLLTS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:16365161" FT /id="VSP_022320" FT VAR_SEQ 458..558 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:16365161" FT /id="VSP_022321" FT VARIANT 33 FT /note="T -> I (in dbSNP:rs1185246)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15372022, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:16365161, ECO:0000269|PubMed:17186462" FT /id="VAR_047436" FT CONFLICT 356 FT /note="L -> P (in Ref. 3; BAF85651)" FT /evidence="ECO:0000305" FT CONFLICT 435 FT /note="K -> R (in Ref. 3; BAF85651)" FT /evidence="ECO:0000305" FT HELIX 442..445 FT /evidence="ECO:0007829|PDB:5N7H" FT HELIX 452..487 FT /evidence="ECO:0007829|PDB:5N7H" FT HELIX 489..492 FT /evidence="ECO:0007829|PDB:5N7K" FT HELIX 493..495 FT /evidence="ECO:0007829|PDB:5N7K" FT HELIX 500..517 FT /evidence="ECO:0007829|PDB:5N7H" FT HELIX 520..549 FT /evidence="ECO:0007829|PDB:5N7H" SQ SEQUENCE 558 AA; 64168 MW; 04F3FCB2CFDB162B CRC64; MSNDGRSRNR DRRYDEVPSD LPYQDTTIRT HPTLHDSERA VSADPLPPPP LPLQPPFGPD FYSSDTEEPA IAPDLKPVRR FVPDSWKNFF RGKKKDPEWD KPVSDIRYIS DGVECSPPAS PARPNHRSPL NSCKDPYGGS EGTFSSRKEA DAVFPRDPYG SLDRHTQTVR TYSEKVEEYN LRYSYMKSWA GLLRILGVVE LLLGAGVFAC VTAYIHKDSE WYNLFGYSQP YGMGGVGGLG SMYGGYYYTG PKTPFVLVVA GLAWITTIII LVLGMSMYYR TILLDSNWWP LTEFGINVAL FILYMAAAIV YVNDTNRGGL CYYPLFNTPV NAVFCRVEGG QIAAMIFLFV TMIVYLISAL VCLKLWRHEA ARRHREYMEQ QEINEPSLSS KRKMCEMATS GDRQRDSEVN FKELRTAKMK PELLSGHIPP GHIPKPIVMP DYVAKYPVIQ TDDERERYKA VFQDQFSEYK ELSAEVQAVL RKFDELDAVM SRLPHHSESR QEHERISRIH EEFKKKKNDP TFLEKKERCD YLKNKLSHIK QRIQEYDKVM NWDVQGYS //