Q9Y5I7 (CLD16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Claudin-16

Alternative name(s):
Paracellin-1
Short name=PCLN-1

Gene names

Name:	CLDN16
Synonyms:	PCLN1

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	305 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. Involved in paracellular magnesium reabsorption. Required for a selective paracellular conductance. May form, alone or in partnership with other constituents, an intercellular pore permitting paracellular passage of magnesium and calcium ions down their electrochemical gradients. Alternatively, it could be a sensor of magnesium concentration that could alter paracellular permeability mediated by other factors.
Subcellular location	Cell junction › tight junction. Cell membrane; Multi-pass membrane protein.
Tissue specificity	Kidney-specific, including the thick ascending limb of Henle (TAL).
Involvement in disease	Hypomagnesemia 3 (HOMG3) [MIM:248250]: A progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis. Recurrent urinary tract infections and kidney stones are often observed. In spite of hypercalciuria, patients do not show hypocalcemia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.3 Ref.4
Sequence similarities	Belongs to the claudin family.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Tight junction
Disease	Disease mutation Primary hypomagnesemia
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium-independent cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB cellular metal ion homeostasis Traceable author statement Ref.1. Source: ProtInc excretion Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell tight junction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	identical protein binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc 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 – 305	305	Claudin-16		PRO_0000144774
Regions
	Topological domain	1 – 73	73	Cytoplasmic Potential
	Transmembrane	74 – 94	21	Helical; Potential
	Topological domain	95 – 150	56	Extracellular Potential
	Transmembrane	151 – 171	21	Helical; Potential
	Topological domain	172 – 185	14	Cytoplasmic Potential
	Transmembrane	186 – 206	21	Helical; Potential
	Topological domain	207 – 239	33	Extracellular Potential
	Transmembrane	240 – 260	21	Helical; Potential
	Topological domain	261 – 305	45	Cytoplasmic Potential
Natural variations
	Natural variant	71	1	M → R in HOMG3. Ref.1		VAR_008173
	Natural variant	141	1	H → D in HOMG3. Ref.3 Ref.4		VAR_017228
	Natural variant	145	1	L → P in HOMG3. Ref.3 Ref.4		VAR_017229
	Natural variant	149	1	R → L in HOMG3. Ref.4		VAR_017230
	Natural variant	151	1	L → F in HOMG3. Ref.3 Ref.4		VAR_017231
	Natural variant	151	1	L → P in HOMG3. Ref.3		VAR_017232
	Natural variant	151	1	L → W in HOMG3. Ref.3 Ref.4		VAR_017233
	Natural variant	167	1	L → P in HOMG3. Ref.1		VAR_008174
	Natural variant	191	1	G → R in HOMG3. Ref.1		VAR_008175
	Natural variant	198	1	G → A in HOMG3. Ref.4		VAR_017234
	Natural variant	198	1	G → D in HOMG3. Ref.1 Ref.3		VAR_008176
	Natural variant	209	1	A → T in HOMG3. Ref.4		VAR_017235
	Natural variant	216	1	R → T in HOMG3. Ref.4		VAR_017236
	Natural variant	232	1	F → C in HOMG3. Ref.1		VAR_008177
	Natural variant	233	1	G → D in HOMG3. Ref.1		VAR_008178
	Natural variant	235	1	S → F in HOMG3. Ref.1		VAR_008179
	Natural variant	235	1	S → P in HOMG3. Ref.4		VAR_017237
	Natural variant	239	1	G → R in HOMG3. Ref.1 Ref.3 Ref.4		VAR_008172

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5I7 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 2A85A19A39727329	FASTA	305	33,836
	10 20 30 40 50 60 MTSRTPLLVT ACLYYSYCNS RHLQQGVRKS KRPVFSHCQV PETQKTDTRH LSGARAGVCP 70 80 90 100 110 120 CCHPDGLLAT MRDLLQYIAC FFAFFSAGFL IVATWTDCWM VNADDSLEVS TKCRGLWWEC 130 140 150 160 170 180 VTNAFDGIRT CDEYDSILAE HPLKLVVTRA LMITADILAG FGFLTLLLGL DCVKFLPDEP 190 200 210 220 230 240 YIKVRICFVA GATLLIAGTP GIIGSVWYAV DVYVERSTLV LHNIFLGIQY KFGWSCWLGM 250 260 270 280 290 300 AGSLGCFLAG AVLTCCLYLF KDVGPERNYP YSLRKAYSAA GVSMAKSYSA PRTETAKMYA VDTRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption." Simon D.B., Lu Y., Choate K.A., Velazquez H., Al-Sabban E., Praga M., Casari G., Bettinelli A., Colussi G., Rodriguez-Soriano J., McCredie D., Milford D., Sanjad S., Lifton R.P. Science 285:103-106(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HOMG3 ARG-71; PRO-167; ARG-191; ASP-198; CYS-232; ASP-233; PHE-235 AND ARG-239.
[2]	"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].
[3]	"Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene." Weber S., Hoffmann K., Jeck N., Saar K., Boeswald M., Kuwertz-Broeking E., Meij I.I., Knoers N.V., Cochat P., Sulakova T., Bonzel K.E., Soergel M., Manz F., Schaerer K., Seyberth H.W., Reis A., Konrad M. Eur. J. Hum. Genet. 8:414-422(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HOMG3 ASP-141; PRO-145; PHE-151; PRO-151; TRP-151; ASP-198 AND ARG-239.
[4]	"Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with hypercalciuria and nephrocalcinosis." Weber S., Schneider L., Peters M., Misselwitz J., Roennefarth G., Boeswald M., Bonzel K.E., Seeman T., Sulakova T., Kuwertz-Broeking E., Gregoric A., Palcoux J.-B., Tasic V., Manz F., Schaerer K., Seyberth H.W., Konrad M. J. Am. Soc. Nephrol. 12:1872-1881(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HOMG3 ASP-141; PRO-145; LEU-149; PHE-151; TRP-151; ALA-198; THR-209; THR-216; PRO-235 AND ARG-239.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF152101 mRNA. Translation: AAD43096.1. BC069662 mRNA. Translation: AAH69662.1. BC069682 mRNA. Translation: AAH69682.1. BC069759 mRNA. Translation: AAH69759.1. BC069777 mRNA. Translation: AAH69777.1.
IPI	IPI00001521.
RefSeq	NP_006571.1. NM_006580.3.
UniGene	Hs.251391.
3D structure databases
ProteinModelPortal	Q9Y5I7.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48951N.
MINT	MINT-8387823.
STRING	9606.ENSP00000264734.
Protein family/group databases
TCDB	1.H.1.1.1. claudin tight junction (Claudin) family.
PTM databases
PhosphoSite	Q9Y5I7.
Polymorphism databases
DMDM	6685318.
Proteomic databases
PaxDb	Q9Y5I7.
PRIDE	Q9Y5I7.
Protocols and materials databases
DNASU	10686.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264734; ENSP00000264734; ENSG00000113946.
GeneID	10686.
KEGG	hsa:10686.
UCSC	uc003fsi.3. human.
Organism-specific databases
CTD	10686.
GeneCards	GC03P190040.
HGNC	HGNC:2037. CLDN16.
HPA	HPA018040.
MIM	248250. phenotype. 603959. gene.
neXtProt	NX_Q9Y5I7.
Orphanet	31043. Familial hypomagnesemia - hypercalciuria - nephrocalcinosis.
PharmGKB	PA26563.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG38970.
HOGENOM	HOG000111787.
HOVERGEN	HBG050987.
InParanoid	Q9Y5I7.
KO	K06087.
OMA	LLQYVAC.
OrthoDB	EOG4DZ1VQ.
PhylomeDB	Q9Y5I7.
Enzyme and pathway databases
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	Q9Y5I7.
Bgee	Q9Y5I7.
CleanEx	HS_CLDN16.
Genevestigator	Q9Y5I7.
GermOnline	ENSG00000113946. Homo sapiens.
Family and domain databases
InterPro	IPR006187. Claudin. IPR003927. Claudin16. IPR017974. Claudin_CS. IPR004031. PMP22/EMP/MP20/Claudin. [Graphical view]
PANTHER	PTHR12002. PTHR12002. 1 hit. PTHR12002:SF56. PTHR12002:SF56. 1 hit.
Pfam	PF00822. PMP22_Claudin. 1 hit. [Graphical view]
PRINTS	PR01077. CLAUDIN. PR01447. CLAUDIN16.
PROSITE	PS01346. CLAUDIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10686.
NextBio	40621.
SOURCE	Search...

Entry information

Entry name

CLD16_HUMAN

Accession

Primary (citable) accession number: Q9Y5I7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1999
Last modified:	May 29, 2013
This is version 114 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.