Q75V66 (ANO5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Anoctamin-5

Alternative name(s):
Gnathodiaphyseal dysplasia 1 protein
Transmembrane protein 16E

Gene names

Name:	ANO5
Synonyms:	GDD1, TMEM16E

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

General annotation (Comments)

Function	Does not exhibit calcium-activated chloride channel (CaCC) activity.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell membrane. Note: Co-localized with CALR/calreticulin. Shows an intracellular localization according to Ref.6. Ref.1 Ref.3 Ref.6 Ref.8
Tissue specificity	Highly expressed in brain, heart, kidney, lung, and skeletal muscle. Weakly expressed in bone marrow, fetal liver, placenta, spleen, thymus, osteoblasts and periodontal ligament cells. Ref.1 Ref.2
Involvement in disease	Gnathodiaphyseal dysplasia (GDD) [MIM:166260]: Rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. Patients experience frequent bone fractures caused by trivial accidents in childhood; however the fractures heal normally without bone deformity. The jaw lesions replace the tooth-bearing segments of the maxilla and mandible with fibrous connective tissues, including various amounts of cementum-like calcified mass, sometimes causing facial deformities. Patients also have a propensity for jaw infection and often suffer from purulent osteomyelitis-like symptoms, such as swelling of and pus discharge from the gums, mobility of the teeth, insufficient healing after tooth extraction and exposure of the lesions into the oral cavity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Limb-girdle muscular dystrophy 2L (LGMD2L) [MIM:611307]: An autosomal recessive degenerative myopathy characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Miyoshi muscular dystrophy 3 (MMD3) [MIM:613319]: A late-onset muscular dystrophy characterized by distal muscle weakness of the lower limbs, calf muscle discomfort and weakness, quadriceps atrophy. Muscle weakness and atrophy may be asymmetric. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10
Miscellaneous	The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.
Sequence similarities	Belongs to the anoctamin family.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Limb-girdle muscular dystrophy Osteogenesis imperfecta
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intracellular Inferred from direct assay Ref.6. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 913	913	Anoctamin-5		PRO_0000191755
Regions
	Topological domain	1 – 299	299	Cytoplasmic Potential
	Transmembrane	300 – 320	21	Helical; Potential
	Topological domain	321 – 380	60	Extracellular Potential
	Transmembrane	381 – 401	21	Helical; Potential
	Topological domain	402 – 462	61	Cytoplasmic Potential
	Transmembrane	463 – 483	21	Helical; Potential
	Topological domain	484 – 511	28	Extracellular Potential
	Transmembrane	512 – 532	21	Helical; Potential
	Topological domain	533 – 557	25	Cytoplasmic Potential
	Transmembrane	558 – 578	21	Helical; Potential
	Topological domain	579 – 679	101	Extracellular Potential
	Transmembrane	680 – 700	21	Helical; Potential
	Topological domain	701 – 732	32	Cytoplasmic Potential
	Transmembrane	733 – 753	21	Helical; Potential
	Topological domain	754 – 834	81	Extracellular Potential
	Transmembrane	835 – 855	21	Helical; Potential
	Topological domain	856 – 913	58	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	335	1	N-linked (GlcNAc...) Potential
	Glycosylation	366	1	N-linked (GlcNAc...) Potential
	Glycosylation	380	1	N-linked (GlcNAc...) Potential
	Glycosylation	768	1	N-linked (GlcNAc...) Potential
	Glycosylation	778	1	N-linked (GlcNAc...) Potential
	Glycosylation	791	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	58	1	R → W Found in a patient with hyper-CK-emia and a neurasthenic syndrome; unknown pathological significance. Ref.10		VAR_068247
	Natural variant	231	1	G → V in LGMD2L. Ref.9		VAR_063582
	Natural variant	322	1	L → F. Corresponds to variant rs7481951 [ dbSNP | Ensembl ].		VAR_052339
	Natural variant	356	1	C → G in GDD; decreases cell adhesion and changes cell morphology to a round shape. Ref.1		VAR_023524
	Natural variant	356	1	C → R in GDD; decreases cell adhesion and changes cell morphology to a round shape. Ref.1		VAR_023525
	Natural variant	655	1	W → C in MMD3; unknown pathological significance. Ref.10		VAR_068248
	Natural variant	758	1	R → C in MMD3. Ref.9		VAR_063583
	Natural variant	882	1	N → K. Corresponds to variant rs34969327 [ dbSNP | Ensembl ].		VAR_052340

Sequences

	Sequence		Length	Mass (Da)
	Q75V66 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 98BC40318678C073	FASTA	913	107,188
	10 20 30 40 50 60 MGDPDLLEVL AEEGEKVNKH IDYSFQMSEQ SLSSRETSFL INEETMPAKR FNLFLRRRLM 70 80 90 100 110 120 FQKNQQSKDS IFFRDGIRQI DFVLSYVDDV KKDAELKAER RKEFETNLRK TGLELEIEDK 130 140 150 160 170 180 RDSEDGRTYF VKIHAPWEVL VTYAEVLGIK MPIKESDIPR PKHTPISYVL GPVRLPLSVK 190 200 210 220 230 240 YPHPEYFTAQ FSRHRQELFL IEDQATFFPS SSRNRIVYYI LSRCPFGIED GKKRFGIERL 250 260 270 280 290 300 LNSNTYSSAY PLHDGQYWKP SEPPNPTNER YTLHQNWARF SYFYKEQPLD LIKNYYGEKI 310 320 330 340 350 360 GIYFVFLGFY TEMLFFAAVV GLACFIYGLL SMEHNTSSTE ICDPEIGGQM IMCPLCDQVC 370 380 390 400 410 420 DYWRLNSTCL ASKFSHLFDN ESTVFFAIFM GIWVTLFLEF WKQRQARLEY EWDLVDFEEE 430 440 450 460 470 480 QQQLQLRPEF EAMCKHRKLN AVTKEMEPYM PLYTRIPWYF LSGATVTLWM SLVVTSMVAV 490 500 510 520 530 540 IVYRLSVFAT FASFMESDAS LKQVKSFLTP QITTSLTGSC LNFIVILILN FFYEKISAWI 550 560 570 580 590 600 TKMEIPRTYQ EYESSLTLKM FLFQFVNFYS SCFYVAFFKG KFVGYPGKYT YLFNEWRSEE 610 620 630 640 650 660 CDPGGCLIEL TTQLTIIMTG KQIFGNIKEA IYPLALNWWR RRKARTNSEK LYSRWEQDHD 670 680 690 700 710 720 LESFGPLGLF YEYLETVTQF GFVTLFVASF PLAPLLALIN NIVEIRVDAW KLTTQYRRTV 730 740 750 760 770 780 ASKAHSIGVW QDILYGMAVL SVATNAFIVA FTSDIIPRLV YYYAYSTNAT QPMTGYVNNS 790 800 810 820 830 840 LSVFLIADFP NHTAPSEKRD FITCRYRDYR YPPDDENKYF HNMQFWHVLA AKMTFIIVME 850 860 870 880 890 900 HVVFLVKFLL AWMIPDVPKD VVERIKREKL MTIKILHDFE LNKLKENLGI NSNEFAKHVM 910 IEENKAQLAK STL

References

[1]	"The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD)." Tsutsumi S., Kamata N., Vokes T.J., Maruoka Y., Nakakuki K., Enomoto S., Omura K., Amagasa T., Nagayama M., Saito-Ohara F., Inazawa J., Moritani M., Yamaoka T., Inoue H., Itakura M. Am. J. Hum. Genet. 74:1255-1261(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANTS GDD GLY-356 AND ARG-356, CHARACTERIZATION OF VARIANTS GDD GLY-356 AND ARG-356. Tissue: Skeletal muscle.
[2]	"Identification and characterization of TMEM16E and TMEM16F genes in silico." Katoh M., Katoh M. Int. J. Oncol. 24:1345-1349(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[3]	"Expression and function of epithelial anoctamins." Schreiber R., Uliyakina I., Kongsuphol P., Warth R., Mirza M., Martins J.R., Kunzelmann K. J. Biol. Chem. 285:7838-7845(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY, SUBCELLULAR LOCATION.
[4]	"Physiological roles and diseases of Tmem16/Anoctamin proteins: are they all chloride channels?" Duran C., Hartzell H.C. Acta Pharmacol. Sin. 32:685-692(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[5]	"Anoctamins." Kunzelmann K., Tian Y., Martins J.R., Faria D., Kongsuphol P., Ousingsawat J., Thevenod F., Roussa E., Rock J., Schreiber R. Pflugers Arch. 462:195-208(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[6]	"ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins." Duran C., Qu Z., Osunkoya A.O., Cui Y., Hartzell H.C. Am. J. Physiol. 302:C482-C493(2012) [PubMed] [Europe PMC] [Abstract] Cited for: ABSENCE OF CALCIUM-ACTIVATED CHLORIDE CHANNEL ACTIVITY, SUBCELLULAR LOCATION.
[7]	"The anoctamin (TMEM16) gene family: calcium-activated chloride channels come of age." Winpenny J.P., Gray M.A. Exp. Physiol. 97:175-176(2012) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[8]	"Anoctamins are a family of Ca2+ activated Cl- channels." Tian Y., Schreiber R., Kunzelmann K. J. Cell Sci. 125:4991-4998(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies." Bolduc V., Marlow G., Boycott K.M., Saleki K., Inoue H., Kroon J., Itakura M., Robitaille Y., Parent L., Baas F., Mizuta K., Kamata N., Richard I., Linssen W.H., Mahjneh I., de Visser M., Bashir R., Brais B. Am. J. Hum. Genet. 86:213-221(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LGMD2L VAL-231, VARIANT MMD3 CYS-758.
[10]	"Novel ANO5 mutations causing hyper-CK-emia, limb girdle muscular weakness and Miyoshi type of muscular dystrophy." Schessl J., Kress W., Schoser B. Muscle Nerve 45:740-742(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-58, VARIANT MMD3 CYS-655.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB125267 mRNA. Translation: BAD17859.1.
IPI	IPI00412694.
RefSeq	NP_001136121.1. NM_001142649.1. NP_998764.1. NM_213599.2.
UniGene	Hs.154329.
3D structure databases
ProteinModelPortal	Q75V66.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000315371.
PTM databases
PhosphoSite	Q75V66.
Polymorphism databases
DMDM	74749827.
Proteomic databases
PaxDb	Q75V66.
PRIDE	Q75V66.
Protocols and materials databases
DNASU	203859.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324559; ENSP00000315371; ENSG00000171714.
GeneID	203859.
KEGG	hsa:203859.
UCSC	uc001mqi.2. human.
Organism-specific databases
CTD	203859.
GeneCards	GC11P022172.
HGNC	HGNC:27337. ANO5.
MIM	166260. phenotype. 608662. gene. 611307. phenotype. 613319. phenotype.
neXtProt	NX_Q75V66.
Orphanet	206549. Autosomal recessive limb-girdle muscular dystrophy type 2L. 53697. Gnathodiaphyseal dysplasia. 45448. Miyoshi myopathy.
PharmGKB	PA164715641.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG320103.
HOGENOM	HOG000006509.
HOVERGEN	HBG069519.
InParanoid	Q75V66.
OMA	FTTCRYR.
OrthoDB	EOG4M397V.
PhylomeDB	Q75V66.
Gene expression databases
Bgee	Q75V66.
CleanEx	HS_ANO5.
Genevestigator	Q75V66.
GermOnline	ENSG00000171714. Homo sapiens.
Family and domain databases
InterPro	IPR007632. Anoctamin. [Graphical view]
PANTHER	PTHR12308. PTHR12308. 1 hit.
Pfam	PF04547. Anoctamin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	203859.
NextBio	90462.
SOURCE	Search...

Entry information

Entry name

ANO5_HUMAN

Accession

Primary (citable) accession number: Q75V66

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 81 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.