Reviewed, UniProtKB/Swiss-Prot O95832 (CLD1_HUMAN)

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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	211 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
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	Defects in CLDN1 are the cause of ichthyosis-sclerosing cholangitis neonatal syndrome (NISCH) [MIM:607626]; also called ichthyosis with leukocyte vacuoles alopecia and sclerosing cholangitis (ILVASC). NISCH is a rare autosomal recessive complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, vulgar type ichthyosis, and sclerosing cholangitis. 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
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	calcium-independent cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Ref.8 Traceable author statement. Source: ProtInc tight junction Ref.1 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	Potential
	Topological domain	29 – 81	53	Extracellular Potential
	Transmembrane	82 – 102	21	Potential
	Topological domain	103 – 115	13	Cytoplasmic Potential
	Transmembrane	116 – 136	21	Potential
	Topological domain	137 – 163	27	Extracellular Potential
	Transmembrane	164 – 184	21	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)
	O95832-1 [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: 9931503] [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: 10828592] [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: 11071387] [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: 12975309] [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: 15489334] [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: 9647647] [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: 15521008] [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: 16619213] [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: 17325668] [Abstract] Cited for: INTERACTION WITH HCV E1 AND E2 PROTEINS, MUTAGENESIS OF ILE-32 AND GLU-48.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.439060
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O95832. 1 interaction.
PTM databases
PhosphoSite	O95832.
Proteomic databases
PRIDE	O95832.
Genome annotation databases
Ensembl	ENSG00000163347. Homo sapiens. [Contig view]
GeneID	9076.
KEGG	hsa:9076.
Organism-specific databases
GeneCards	GC03M191506.
H-InvDB	HIX0003947.
HGNC	HGNC:2032. CLDN1.
HPA	CAB002602.
MIM	603718. gene. 607626. phenotype.
Orphanet	59303. Neonatal ichthyosis - sclerosing cholangitis.
PharmGKB	PA26557.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95832.
HOVERGEN	O95832.
OMA	O95832. IYEGLWM.
Gene expression databases
ArrayExpress	O95832.
Bgee	O95832.
CleanEx	HS_CLDN1.
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. Claudin. 1 hit. PTHR12002:SF29. Claudin1. 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 Resources
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:	June 16, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)