O95832 (CLD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Claudin-1

Alternative name(s):
Senescence-associated epithelial membrane protein

Gene names

Name:	CLDN1
Synonyms:	CLD1, SEMP1
ORF Names:	UNQ481/PRO944

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	211 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity By similarity. Acts as a co-receptor for HCV entry into hepatic cells.
Subunit structure	Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN3, but not CLDN2, homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with MPDZ and INADL By similarity. May interact with HCV E1 and E2 proteins. Ref.11
Subcellular location	Cell junction › tight junction By similarity. Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Strongly expressed in liver and kidney. Expressed in heart, brain, spleen, lung and testis. Ref.8
Involvement in disease	Ichthyosis-sclerosing cholangitis neonatal syndrome (NISCH) [MIM:607626]: A rare autosomal recessive complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, mild diffuse ichthyosis, sclerosing cholangitis and leukocyte vacuolization. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10
Sequence similarities	Belongs to the claudin family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell junction Cell membrane Membrane Tight junction
Disease	Ichthyosis
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium-independent cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB cell-cell junction organization Inferred from mutant phenotype PubMed 20164257. Source: MGI virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.8. Source: ProtInc lateral plasma membrane Inferred from electronic annotation. Source: Compara tight junction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	identical protein binding Inferred from sequence or structural similarity. 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 – 211	211	Claudin-1		PRO_0000144729
Regions
	Topological domain	1 – 7	7	Cytoplasmic Potential
	Transmembrane	8 – 28	21	Helical; Potential
	Topological domain	29 – 81	53	Extracellular Potential
	Transmembrane	82 – 102	21	Helical; Potential
	Topological domain	103 – 115	13	Cytoplasmic Potential
	Transmembrane	116 – 136	21	Helical; Potential
	Topological domain	137 – 163	27	Extracellular Potential
	Transmembrane	164 – 184	21	Helical; Potential
	Topological domain	185 – 211	27	Cytoplasmic Potential
	Region	210 – 211	2	Interactions with TJP1, TJP2, TJP3 and INADL By similarity
Amino acid modifications
	Modified residue	205	1	Phosphoserine By similarity
	Modified residue	206	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	32	1	I → M: 90% loss of HCV infection susceptibility in cell culture. Ref.11
	Mutagenesis	48	1	E → K: No effect on HCV infection susceptibility in cell culture. Ref.11
	Sequence conflict	62	1	I → V in AAD22962. Ref.2
	Sequence conflict	135	1	V → A in AAD22962. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O95832 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 07269000E6C214F0	FASTA	211	22,744
	10 20 30 40 50 60 MANAGLQLLG FILAFLGWIG AIVSTALPQW RIYSYAGDNI VTAQAMYEGL WMSCVSQSTG 70 80 90 100 110 120 QIQCKVFDSL LNLSSTLQAT RALMVVGILL GVIAIFVATV GMKCMKCLED DEVQKMRMAV 130 140 150 160 170 180 IGGAIFLLAG LAILVATAWY GNRIVQEFYD PMTPVNARYE FGQALFTGWA AASLCLLGGA 190 200 210 LLCCSCPRKT TSYPTPRPYP KPAPSSGKDY V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily." Swisshelm K.L., Machl A., Planitzer S., Robertson R., Kubbies M., Hosier S. Gene 226:285-295(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human claudin-1 isolated from Caco-2 mRNA." Mitic L.M., Anderson J.M. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Assignment of claudin-1 (CLDN1) to human chromosome 3q28-->q29 with somatic cell hybrids." Halford S., Spencer P., Greenwood J., Winton H., Hunt D.M., Adamson P. Cytogenet. Cell Genet. 88:217-217(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Genomic organization of claudin-1 and its assessment in hereditary and sporadic breast cancer." Kraemer F., White K., Kubbies M., Swisshelm K.L., Weber B.H.F. Hum. Genet. 107:249-256(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"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]. Tissue: Urinary bladder.
[8]	"Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin." Furuse M., Fujita K., Hiiragi T., Fujimoto K., Tsukita S. J. Cell Biol. 141:1539-1550(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, TISSUE SPECIFICITY.
[9]	"Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease." Hadj-Rabia S., Baala L., Vabres P., Hamel-Teillac D., Jacquemin E., Fabre M., Lyonnet S., De Prost Y., Munnich A., Hadchouel M., Smahi A. Gastroenterology 127:1386-1390(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN NISCH.
[10]	"Confirmation of the origin of NISCH syndrome." Feldmeyer L., Huber M., Fellmann F., Beckmann J.S., Frenk E., Hohl D. Hum. Mutat. 27:408-410(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN NISCH.
[11]	"Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry." Evans M.J., von Hahn T., Tscherne D.M., Syder A.J., Panis M., Wolk B., Hatziioannou T., McKeating J.A., Bieniasz P.D., Rice C.M. Nature 446:801-805(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCV E1 AND E2 PROTEINS, MUTAGENESIS OF ILE-32 AND GLU-48.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF101051 mRNA. Translation: AAD16433.1. AF115546 mRNA. Translation: AAD22962.1. AF134160 mRNA. Translation: AAF61393.1. AF260406 , AF260403, AF260404, AF260405 Genomic DNA. Translation: AAK20945.1. AY358652 mRNA. Translation: AAQ89015.1. CR457138 mRNA. Translation: CAG33419.1. BC012471 mRNA. Translation: AAH12471.1.
IPI	IPI00000691.
RefSeq	NP_066924.1. NM_021101.4.
UniGene	Hs.439060.
3D structure databases
ProteinModelPortal	O95832.
ModBase	Search...
Protein-protein interaction databases
IntAct	O95832. 2 interactions.
MINT	MINT-5002336.
STRING	9606.ENSP00000295522.
PTM databases
PhosphoSite	O95832.
Proteomic databases
PaxDb	O95832.
PRIDE	O95832.
Protocols and materials databases
DNASU	9076.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295522; ENSP00000295522; ENSG00000163347.
GeneID	9076.
KEGG	hsa:9076.
UCSC	uc003fsh.3. human.
Organism-specific databases
CTD	9076.
GeneCards	GC03M190023.
HGNC	HGNC:2032. CLDN1.
HPA	CAB002602.
MIM	603718. gene. 607626. phenotype.
neXtProt	NX_O95832.
Orphanet	59303. Ichthyosis - hypotrichosis - sclerosing cholangitis.
PharmGKB	PA26557.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG47316.
HOGENOM	HOG000220937.
HOVERGEN	HBG000643.
InParanoid	O95832.
KO	K06087.
OMA	IYEGLWM.
OrthoDB	EOG4G7C0B.
PhylomeDB	O95832.
Enzyme and pathway databases
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	O95832.
Bgee	O95832.
CleanEx	HS_CLDN1.
Genevestigator	O95832.
GermOnline	ENSG00000163347. Homo sapiens.
Family and domain databases
InterPro	IPR006187. Claudin. IPR003548. Claudin1. IPR017974. Claudin_CS. IPR004031. PMP22/EMP/MP20/Claudin. [Graphical view]
PANTHER	PTHR12002. PTHR12002. 1 hit. PTHR12002:SF29. PTHR12002:SF29. 1 hit.
Pfam	PF00822. PMP22_Claudin. 1 hit. [Graphical view]
PRINTS	PR01077. CLAUDIN. PR01377. CLAUDIN1.
PROSITE	PS01346. CLAUDIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CLDN1. human.
GenomeRNAi	9076.
NextBio	34009.
SOURCE	Search...

Entry information

Entry name

CLD1_HUMAN

Accession

Primary (citable) accession number: O95832

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 116 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.