Q8N4S9 (MALD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
MARVEL domain-containing protein 2

Alternative name(s):
Tricellulin

Gene names

Name:	MARVELD2
Synonyms:	TRIC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	558 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Plays a role in the formation of the epithelial barriers. The separation of the endolymphatic and perilymphatic spaces of the organ of Corti from one another by epithelial barriers is required for normal hearing. Ref.2
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › tight junction By similarity. Note: Found at tricellular contacts By similarity.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Deafness, autosomal recessive, 49 (DFNB49) [MIM:610153]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2
Sequence similarities	Contains 1 MARVEL domain.

Ontologies

Keywords
Biological process	Hearing
Cellular component	Cell junction Cell membrane Membrane Tight junction
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Non-syndromic deafness
Domain	Coiled coil Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell junction organization Inferred from mutant phenotype PubMed 20164257. Source: MGI sensory perception of sound Inferred from mutant phenotype Ref.2. Source: MGI
Cellular_component	Schmidt-Lanterman incisure Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW paranodal junction Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell tight junction Inferred from direct assay PubMed 20164257. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N4S9-1)

Also known as: A; TRIC;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8N4S9-2)

Also known as: TRICbeta;

The sequence of this isoform differs from the canonical sequence as follows:
     431-457: GHIPKPIVMPDYVAKYPVIQTDDERER → RPANFFVFLVEMGFHRVSQDDLDLLTS
     458-558: Missing.

Isoform 3 (identifier: Q8N4S9-3)

Also known as: A1;

The sequence of this isoform differs from the canonical sequence as follows:
     383-394: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 558	558	MARVEL domain-containing protein 2		PRO_0000271526
Regions
	Topological domain	1 – 194	194	Cytoplasmic Potential
	Transmembrane	195 – 215	21	Helical; Potential
	Topological domain	216 – 223	8	Extracellular Potential
	Transmembrane	224 – 244	21	Helical; Potential
	Topological domain	245 – 254	10	Cytoplasmic Potential
	Transmembrane	255 – 275	21	Helical; Potential
	Topological domain	276 – 291	16	Extracellular Potential
	Transmembrane	292 – 312	21	Helical; Potential
	Topological domain	313 – 319	7	Cytoplasmic Potential
	Transmembrane	320 – 337	18	Helical; Potential
	Topological domain	338 – 341	4	Extracellular Potential
	Transmembrane	342 – 362	21	Helical; Potential
	Topological domain	363 – 558	196	Cytoplasmic Potential
	Domain	188 – 367	180	MARVEL
	Coiled coil	466 – 490	25	Potential
	Coiled coil	524 – 548	25	Potential
	Compositional bias	45 – 52	8	Poly-Pro
	Compositional bias	514 – 517	4	Poly-Lys
Natural variations
	Alternative sequence	383 – 394	12	Missing in isoform 3.		VSP_035760
	Alternative sequence	431 – 457	27	GHIPK…DERER → RPANFFVFLVEMGFHRVSQD DLDLLTS in isoform 2.		VSP_022320
	Alternative sequence	458 – 558	101	Missing in isoform 2.		VSP_022321
	Natural variant	33	1	T → I. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs1185246 [ dbSNP | Ensembl ].		VAR_047436
Experimental info
	Sequence conflict	356	1	L → P in BAF85651. Ref.3
	Sequence conflict	435	1	K → R in BAF85651. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) (TRIC) [UniParc]. Last modified January 11, 2011. Version 2. Checksum: 04F3FCB2CFDB162B	FASTA	558	64,168
	10 20 30 40 50 60 MSNDGRSRNR DRRYDEVPSD LPYQDTTIRT HPTLHDSERA VSADPLPPPP LPLQPPFGPD 70 80 90 100 110 120 FYSSDTEEPA IAPDLKPVRR FVPDSWKNFF RGKKKDPEWD KPVSDIRYIS DGVECSPPAS 130 140 150 160 170 180 PARPNHRSPL NSCKDPYGGS EGTFSSRKEA DAVFPRDPYG SLDRHTQTVR TYSEKVEEYN 190 200 210 220 230 240 LRYSYMKSWA GLLRILGVVE LLLGAGVFAC VTAYIHKDSE WYNLFGYSQP YGMGGVGGLG 250 260 270 280 290 300 SMYGGYYYTG PKTPFVLVVA GLAWITTIII LVLGMSMYYR TILLDSNWWP LTEFGINVAL 310 320 330 340 350 360 FILYMAAAIV YVNDTNRGGL CYYPLFNTPV NAVFCRVEGG QIAAMIFLFV TMIVYLISAL 370 380 390 400 410 420 VCLKLWRHEA ARRHREYMEQ QEINEPSLSS KRKMCEMATS GDRQRDSEVN FKELRTAKMK 430 440 450 460 470 480 PELLSGHIPP GHIPKPIVMP DYVAKYPVIQ TDDERERYKA VFQDQFSEYK ELSAEVQAVL 490 500 510 520 530 540 RKFDELDAVM SRLPHHSESR QEHERISRIH EEFKKKKNDP TFLEKKERCD YLKNKLSHIK 550 QRIQEYDKVM NWDVQGYS
	Isoform 2 (TRICbeta) [UniParc]. Checksum: AC283BB19827AFFE	FASTA	457	51,839
	10 20 30 40 50 60 MSNDGRSRNR DRRYDEVPSD LPYQDTTIRT HPTLHDSERA VSADPLPPPP LPLQPPFGPD 70 80 90 100 110 120 FYSSDTEEPA IAPDLKPVRR FVPDSWKNFF RGKKKDPEWD KPVSDIRYIS DGVECSPPAS 130 140 150 160 170 180 PARPNHRSPL NSCKDPYGGS EGTFSSRKEA DAVFPRDPYG SLDRHTQTVR TYSEKVEEYN 190 200 210 220 230 240 LRYSYMKSWA GLLRILGVVE LLLGAGVFAC VTAYIHKDSE WYNLFGYSQP YGMGGVGGLG 250 260 270 280 290 300 SMYGGYYYTG PKTPFVLVVA GLAWITTIII LVLGMSMYYR TILLDSNWWP LTEFGINVAL 310 320 330 340 350 360 FILYMAAAIV YVNDTNRGGL CYYPLFNTPV NAVFCRVEGG QIAAMIFLFV TMIVYLISAL 370 380 390 400 410 420 VCLKLWRHEA ARRHREYMEQ QEINEPSLSS KRKMCEMATS GDRQRDSEVN FKELRTAKMK 430 440 450 PELLSGHIPP RPANFFVFLV EMGFHRVSQD DLDLLTS
	Isoform 3 (A1) [UniParc]. Checksum: F0BE767148439FCA	FASTA	546	62,796
	10 20 30 40 50 60 MSNDGRSRNR DRRYDEVPSD LPYQDTTIRT HPTLHDSERA VSADPLPPPP LPLQPPFGPD 70 80 90 100 110 120 FYSSDTEEPA IAPDLKPVRR FVPDSWKNFF RGKKKDPEWD KPVSDIRYIS DGVECSPPAS 130 140 150 160 170 180 PARPNHRSPL NSCKDPYGGS EGTFSSRKEA DAVFPRDPYG SLDRHTQTVR TYSEKVEEYN 190 200 210 220 230 240 LRYSYMKSWA GLLRILGVVE LLLGAGVFAC VTAYIHKDSE WYNLFGYSQP YGMGGVGGLG 250 260 270 280 290 300 SMYGGYYYTG PKTPFVLVVA GLAWITTIII LVLGMSMYYR TILLDSNWWP LTEFGINVAL 310 320 330 340 350 360 FILYMAAAIV YVNDTNRGGL CYYPLFNTPV NAVFCRVEGG QIAAMIFLFV TMIVYLISAL 370 380 390 400 410 420 VCLKLWRHEA ARRHREYMEQ QECEMATSGD RQRDSEVNFK ELRTAKMKPE LLSGHIPPGH 430 440 450 460 470 480 IPKPIVMPDY VAKYPVIQTD DERERYKAVF QDQFSEYKEL SAEVQAVLRK FDELDAVMSR 490 500 510 520 530 540 LPHHSESRQE HERISRIHEE FKKKKNDPTF LEKKERCDYL KNKLSHIKQR IQEYDKVMNW DVQGYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells." Ikenouchi J., Furuse M., Furuse K., Sasaki H., Tsukita S., Tsukita S. J. Cell Biol. 171:939-945(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-33.
[2]	"Tricellulin is a tight-junction protein necessary for hearing." Riazuddin S., Ahmed Z.M., Fanning A.S., Lagziel A., Kitajiri S., Ramzan K., Khan S.N., Chattaraj P., Friedman P.L., Anderson J.M., Belyantseva I.A., Forge A., Riazuddin S., Friedman T.B. Am. J. Hum. Genet. 79:1040-1051(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), INVOLVEMENT IN DFNB49, FUNCTION, VARIANT ILE-33. Tissue: Lung.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-33. Tissue: Brain and Trachea.
[4]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-33.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-33. Tissue: Lung.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB219936 mRNA. Translation: BAE54513.1. AB219937 mRNA. Translation: BAE54514.1. DQ682656 mRNA. Translation: ABG89104.1. DQ682657 mRNA. Translation: ABG89105.1. AK055094 mRNA. Translation: BAB70853.1. AK292962 mRNA. Translation: BAF85651.1. AC145146 Genomic DNA. No translation available. CH471137 Genomic DNA. Translation: EAW51277.1. BC033689 mRNA. Translation: AAH33689.1.
IPI	IPI00296784. IPI00914894. IPI00940741.
RefSeq	NP_001033692.2. NM_001038603.2. NP_001231663.1. NM_001244734.1.
UniGene	Hs.657687.
3D structure databases
ProteinModelPortal	Q8N4S9.
SMR	Q8N4S9. Positions 441-548.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000323264.
PTM databases
PhosphoSite	Q8N4S9.
Polymorphism databases
DMDM	74728895.
Proteomic databases
PaxDb	Q8N4S9.
PRIDE	Q8N4S9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000325631; ENSP00000323264; ENSG00000152939. ENST00000454295; ENSP00000396244; ENSG00000152939. ENST00000573599; ENSP00000460291; ENSG00000263043. ENST00000576933; ENSP00000461265; ENSG00000263043.
GeneID	153562.
KEGG	hsa:153562.
UCSC	uc003jwq.3. human. uc010ixf.3. human.
Organism-specific databases
CTD	153562.
GeneCards	GC05P068746.
H-InvDB	HIX0004923.
HGNC	HGNC:26401. MARVELD2.
HPA	HPA018119.
MIM	610153. phenotype. 610572. gene.
neXtProt	NX_Q8N4S9.
Orphanet	90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKB	PA134954584.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG264085.
HOGENOM	HOG000155323.
HOVERGEN	HBG079727.
InParanoid	Q8N4S9.
OMA	DSWKNFF.
OrthoDB	EOG44F697.
PhylomeDB	Q8N4S9.
Gene expression databases
ArrayExpress	Q8N4S9.
Bgee	Q8N4S9.
CleanEx	HS_MARVELD2.
Genevestigator	Q8N4S9.
Family and domain databases
InterPro	IPR008253. Marvel. IPR021128. MARVEL-like_dom. IPR010844. Occludin_RNApol2_elong_fac_ELL. [Graphical view]
Pfam	PF01284. MARVEL. 1 hit. PF07303. Occludin_ELL. 1 hit. [Graphical view]
PROSITE	PS51225. MARVEL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MARVELD2. human.
GenomeRNAi	153562.
NextBio	87132.
SOURCE	Search...

Entry information

Entry name

MALD2_HUMAN

Accession

Primary (citable) accession number: Q8N4S9
Secondary accession number(s): A1BQX0 , A1BQX1, A8KA97, Q96NM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.