Q16625 (OCLN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Occludin

Gene names

Name:

OCLN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	522 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions. Ref.11
Subunit structure	Interacts with TJP1/ZO1 and with VAPA. Ref.9
Subcellular location	Membrane; Multi-pass membrane protein. Cell junction › tight junction Ref.9 Ref.10 Ref.11.
Tissue specificity	Localized at tight junctions of both epithelial and endothelial cells. Highly expressed in kidney. Not detected in testis.
Domain	The C-terminal is cytoplasmic and is important for interaction with ZO-1. Sufficient for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction By similarity. The first extracellular loop participates in an adhesive interaction. Ref.2
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Dephosphorylated by PTPRJ. The tyrosine phosphorylation on Tyr-398 and Tyr-402 reduces its ability to interact with TJP1. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Involvement in disease	Defects in OCLN are the cause of band-like calcification with simplified gyration and polymicrogyria (BLCPMG) [MIM:251290]; also known as pseudo-TORCH syndrome. BLCPMG is a neurologic disorder with characteristic clinical and neuroradiologic features that mimic intrauterine TORCH infection in the absence of evidence of infection. Affected individuals have congenital microcephaly, intracranial calcifications, and severe developmental delay. Ref.12
Sequence similarities	Belongs to the ELL/occludin family. Contains 1 MARVEL domain.

Ontologies

Keywords
Cellular component	Cell junction Membrane Tight junction
Disease	Disease mutation
Domain	Coiled coil Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular component disassembly involved in apoptosis Traceable author statement. Source: Reactome protein complex assembly Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW tight junction Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction Ref.10. Source: UniProtKB structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 522

522

Occludin

PRO_0000146739

Regions

Topological domain

1 – 66

66

Cytoplasmic Potential

Transmembrane

67 – 89

23

Helical; Potential

Topological domain

90 – 135

46

Extracellular Ref.2

Transmembrane

136 – 160

25

Helical; Potential

Topological domain

161 – 170

10

Cytoplasmic Potential

Transmembrane

171 – 195

25

Helical; Potential

Topological domain

196 – 243

48

Extracellular Potential

Transmembrane

244 – 265

22

Helical; Potential

Topological domain

266 – 522

257

Cytoplasmic Potential

Domain

60 – 269

210

MARVEL

Coiled coil

426 – 489

64

Potential

Compositional bias

92 – 131

40

Gly/Tyr-rich

Amino acid modifications

Modified residue

305

1

Phosphothreonine Ref.7

Modified residue

398

1

Phosphotyrosine Ref.9

Modified residue

402

1

Phosphotyrosine Ref.9

Modified residue

403

1

Phosphothreonine; by PKC/PRKCH Ref.11

Modified residue

404

1

Phosphothreonine; by PKC/PRKCH Ref.11

Modified residue

408

1

Phosphoserine Ref.8

Natural variations

Natural variant

219

1

F → S in BLCPMG. Ref.12

VAR_064910

Experimental info

Mutagenesis

398

1

Y → A: Loss of phosphorylation and loss of regulation of TJP1 binding; when associated with A-402. Ref.9

Mutagenesis

398

1

Y → D: Loss of phosphorylation, almost complete loss of binding to TJP1, loss of regulation of TJP1 binding and loss of localization to plasma membrane and sites of cell-cell contact; when associated with D-402. Ref.9

Mutagenesis

398

1

Y → F: Loss of phosphorylation, decrease in binding to TJP1 and significant loss of regulation of TJP1 binding; when associated with F-402. Ref.9

Mutagenesis

402

1

Y → A: Loss of phosphorylation and loss of regulation of TJP1 binding; when associated with A-398. Ref.9

Mutagenesis

402

1

Y → D: Loss of phosphorylation, almost complete loss of binding to TJP1, loss of regulation of TJP1 binding and loss of localization to plasma membrane and sites of cell-cell contact; when associated with D-398. Ref.9

Mutagenesis

402

1

Y → F: Loss of phosphorylation, decrease in binding to TJP1 and significant loss of regulation of TJP1 binding; when associated with F-398. Ref.9

Mutagenesis

404

1

T → A: Loss of localization to the tight junctions. Ref.11

Sequence conflict

233

1

L → S in AAH29886. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

522

Helix Strand Turn

Details...

Turn

417 – 419

3

Helix

426 – 466

41

Helix

472 – 488

17

Helix

491 – 520

30

Sequences

	Sequence		Length	Mass (Da)
	Q16625 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A0CF9574BCF6E974	FASTA	522	59,144
	10 20 30 40 50 60 MSSRPLESPP PYRPDEFKPN HYAPSNDIYG GEMHVRPMLS QPAYSFYPED EILHFYKWTS 70 80 90 100 110 120 PPGVIRILSM LIIVMCIAIF ACVASTLAWD RGYGTSLLGG SVGYPYGGSG FGSYGSGYGY 130 140 150 160 170 180 GYGYGYGYGG YTDPRAAKGF MLAMAAFCFI AALVIFVTSV IRSEMSRTRR YYLSVIIVSA 190 200 210 220 230 240 ILGIMVFIAT IVYIMGVNPT AQSSGSLYGS QIYALCNQFY TPAATGLYVD QYLYHYCVVD 250 260 270 280 290 300 PQEAIAIVLG FMIIVAFALI IFFAVKTRRK MDRYDKSNIL WDKEHIYDEQ PPNVEEWVKN 310 320 330 340 350 360 VSAGTQDVPS PPSDYVERVD SPMAYSSNGK VNDKRFYPES SYKSTPVPEV VQELPLTSPV 370 380 390 400 410 420 DDFRQPRYSS GGNFETPSKR APAKGRAGRS KRTEQDHYET DYTTGGESCD ELEEDWIREY 430 440 450 460 470 480 PPITSDQQRQ LYKRNFDTGL QEYKSLQSEL DEINKELSRL DKELDDYREE SEEYMAAADE 490 500 510 520 YNRLKQVKGS ADYKSKKNHC KQLKSKLSHI KKMVGDYDRQ KT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues." Ando-Akatsuka Y., Saitou M., Hirase T., Kishi M., Sakakibara A., Itoh M., Yonemura S., Furuse M., Tsukita S. J. Cell Biol. 133:43-47(1996) [PubMed: 8601611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Colon carcinoma.
[2]	"Occludin confers adhesiveness when expressed in fibroblasts." Van Itallie C.M., Anderson J.M. J. Cell Sci. 110:1113-1121(1997) [PubMed: 9175707] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DOMAIN, TOPOLOGY. Tissue: Liver.
[3]	"Genomic structure of occludin gene." Fukasawa M., Toyota T., Yoshitsugu K., Yoshikawa T. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed: 19054851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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: 15372022] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Lung.
[7]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-305, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408, MASS SPECTROMETRY. Tissue: Liver.
[9]	"Phosphorylation of Tyr-398 and Tyr-402 in occludin prevents its interaction with ZO-1 and destabilizes its assembly at the tight junctions." Elias B.C., Suzuki T., Seth A., Giorgianni F., Kale G., Shen L., Turner J.R., Naren A., Desiderio D.M., Rao R. J. Biol. Chem. 284:1559-1569(2009) [PubMed: 19017651] [Abstract] Cited for: INTERACTION WITH TJP1, PHOSPHORYLATION AT TYR-398 AND TYR-402, MUTAGENESIS OF TYR-398 AND TYR-402, SUBCELLULAR LOCATION.
[10]	"Density-enhanced phosphatase 1 regulates phosphorylation of tight junction proteins and enhances barrier function of epithelial cells." Sallee J.L., Burridge K. J. Biol. Chem. 284:14997-15006(2009) [PubMed: 19332538] [Abstract] Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRJ, SUBCELLULAR LOCATION.
[11]	"PKC eta regulates occludin phosphorylation and epithelial tight junction integrity." Suzuki T., Elias B.C., Seth A., Shen L., Turner J.R., Giorgianni F., Desiderio D., Guntaka R., Rao R. Proc. Natl. Acad. Sci. U.S.A. 106:61-66(2009) [PubMed: 19114660] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-403 AND THR-404, MUTAGENESIS OF THR-404.
[12]	"Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria." O'Driscoll M.C., Daly S.B., Urquhart J.E., Black G.C., Pilz D.T., Brockmann K., McEntagart M., Abdel-Salam G., Zaki M., Wolf N.I., Ladda R.L., Sell S., D'Arrigo S., Squier W., Dobyns W.B., Livingston J.H., Crow Y.J. Am. J. Hum. Genet. 87:354-364(2010) [PubMed: 20727516] [Abstract] Cited for: VARIANT BLCPMG SER-219.
+	Additional computationally mapped references.

Web resources

Wikipedia

Occludin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U49184 mRNA. Translation: AAC50451.1.
U53823 mRNA. Translation: AAB00195.1.
AF400630 , AF400623, AF400624, AF400625, AF400626, AF400627, AF400628, AF400629 Genomic DNA. Translation: AAL47094.1.
AB451306 mRNA. Translation: BAG70120.1.
AB451437 mRNA. Translation: BAG70251.1.
BC029886 mRNA. Translation: AAH29886.1.

IPI

IPI00003373.

PIR

G02533.

RefSeq

NP_001192183.1. NM_001205254.1.
NP_001192184.1. NM_001205255.1.
NP_002529.1. NM_002538.3.

UniGene

Hs.592605.
Hs.603143.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WPA	X-ray	1.50	A	413-522	[»]
1XAW	X-ray	1.45	A	383-522	[»]
3G7C	X-ray	2.00	A	416-522	[»]

ProteinModelPortal

Q16625.

SMR

Q16625. Positions 416-522.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42791N.

IntAct

Q16625. 1 interaction.

MINT

MINT-5006137.

STRING

Q16625.

PTM databases

PhosphoSite

Q16625.

Polymorphism databases

DMDM

3914196.

Proteomic databases

PRIDE

Q16625.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355237; ENSP00000347379; ENSG00000197822.
ENST00000396442; ENSP00000379719; ENSG00000197822.

GeneID

100506658.

KEGG

hsa:100506658.

UCSC

uc003jwu.1. human.

Organism-specific databases

CTD

100506658.

GeneCards

GC05P068788.

H-InvDB

HIX0200771.

HGNC

HGNC:8104. OCLN.

HPA

CAB013075.
HPA005933.

MIM

251290. phenotype.
602876. gene.

neXtProt

NX_Q16625.

Orphanet

1229. Congenital intrauterine infection-like syndrome.

PharmGKB

PA31893.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17197.

GeneTree

ENSGT00600000084474.

HOGENOM

HBG446890.

HOVERGEN

HBG004523.

InParanoid

Q16625.

OMA

QASGSMY.

OrthoDB

EOG4J9N09.

PhylomeDB

Q16625.

Enzyme and pathway databases

Pathway_Interaction_DB

tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

Q16625.

Bgee

Q16625.

CleanEx

HS_OCLN.

Genevestigator

Q16625.

GermOnline

ENSG00000197822. Homo sapiens.

Family and domain databases

InterPro

IPR008253. Marvel.
IPR021128. MARVEL-like_dom.
IPR002958. Occludin.
IPR010844. Occludin_RNApol2_elong_fac_ELL.
[Graphical view]

KO

K06088.

PANTHER

PTHR23288:SF4. Occludin. 1 hit.

Pfam

PF01284. MARVEL. 1 hit.
PF07303. Occludin_ELL. 1 hit.
[Graphical view]

PIRSF

PIRSF005993. Occludin. 1 hit.

PRINTS

PR01258. OCCLUDIN.

PROSITE

PS51225. MARVEL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

19065.

PMAP-CutDB

Q16625.

SOURCE

Search...

Entry information

Entry name

OCLN_HUMAN

Accession

Primary (citable) accession number: Q16625
Secondary accession number(s): B5BU70, Q8N6K1

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 108 of the entry and version 1 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.