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P47869

- GBRA2_HUMAN

UniProt

P47869 - GBRA2_HUMAN

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Protein

Gamma-aminobutyric acid receptor subunit alpha-2

Gene
GABRA2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

GO - Molecular functioni

  1. benzodiazepine receptor activity Source: UniProtKB
  2. chloride channel activity Source: UniProtKB-KW
  3. extracellular ligand-gated ion channel activity Source: InterPro
  4. GABA-A receptor activity Source: InterPro

GO - Biological processi

  1. gamma-aminobutyric acid signaling pathway Source: UniProtKB
  2. ion transmembrane transport Source: Reactome
  3. neurotransmitter transport Source: UniProtKB
  4. regulation of neurotransmitter levels Source: UniProtKB
  5. synaptic transmission Source: Reactome
  6. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

Chloride

Enzyme and pathway databases

ReactomeiREACT_24987. GABA A receptor activation.
REACT_25387. Ligand-gated ion channel transport.

Protein family/group databases

TCDBi1.A.9.5.2. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-aminobutyric acid receptor subunit alpha-2
Alternative name(s):
GABA(A) receptor subunit alpha-2
Gene namesi
Name:GABRA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:4076. GABRA2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini29 – 251223Extracellular InferredAdd
BLAST
Transmembranei252 – 27322Helical; InferredAdd
BLAST
Transmembranei279 – 30022Helical; InferredAdd
BLAST
Transmembranei313 – 33422Helical; InferredAdd
BLAST
Topological domaini335 – 41985Cytoplasmic InferredAdd
BLAST
Transmembranei420 – 44122Helical; InferredAdd
BLAST

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cell junction Source: UniProtKB-KW
  3. chloride channel complex Source: UniProtKB-KW
  4. integral component of synaptic vesicle membrane Source: UniProtKB
  5. plasma membrane Source: Reactome
  6. postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Organism-specific databases

MIMi103780. phenotype.
PharmGKBiPA28490.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828 Reviewed predictionAdd
BLAST
Chaini29 – 451423Gamma-aminobutyric acid receptor subunit alpha-2PRO_0000000433Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi38 – 381N-linked (GlcNAc...) Reviewed prediction
Glycosylationi138 – 1381N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi166 ↔ 180 By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP47869.
PRIDEiP47869.

PTM databases

PhosphoSiteiP47869.

Expressioni

Gene expression databases

ArrayExpressiP47869.
BgeeiP47869.
CleanExiHS_GABRA2.
GenevestigatoriP47869.

Organism-specific databases

HPAiHPA014261.

Interactioni

Subunit structurei

Binds UBQLN1 By similarity. Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.

Protein-protein interaction databases

BioGridi108829. 2 interactions.
IntActiP47869. 1 interaction.
STRINGi9606.ENSP00000348897.

Structurei

3D structure databases

ProteinModelPortaliP47869.
SMRiP47869. Positions 43-359.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG238757.
HOGENOMiHOG000231337.
HOVERGENiHBG051707.
InParanoidiP47869.
KOiK05175.
OrthoDBiEOG7JX342.
PhylomeDBiP47869.
TreeFamiTF315453.

Family and domain databases

Gene3Di2.70.170.10. 1 hit.
InterProiIPR006028. GABAA/Glycine_rcpt.
IPR001390. GABAAa_rcpt.
IPR005432. GABBAa2_rcpt.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view]
PRINTSiPR01079. GABAARALPHA.
PR01615. GABAARALPHA2.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P47869-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MKTKLNIYNM QFLLFVFLVW DPARLVLANI QEDEAKNNIT IFTRILDRLL    50
DGYDNRLRPG LGDSITEVFT NIYVTSFGPV SDTDMEYTID VFFRQKWKDE 100
RLKFKGPMNI LRLNNLMASK IWTPDTFFHN GKKSVAHNMT MPNKLLRIQD 150
DGTLLYTMRL TVQAECPMHL EDFPMDAHSC PLKFGSYAYT TSEVTYIWTY 200
NASDSVQVAP DGSRLNQYDL LGQSIGKETI KSSTGEYTVM TAHFHLKRKI 250
GYFVIQTYLP CIMTVILSQV SFWLNRESVP ARTVFGVTTV LTMTTLSISA 300
RNSLPKVAYA TAMDWFIAVC YAFVFSALIE FATVNYFTKR GWAWDGKSVV 350
NDKKKEKASV MIQNNAYAVA VANYAPNLSK DPVLSTISKS ATTPEPNKKP 400
ENKPAEAKKT FNSVSKIDRM SRIVFPVLFG TFNLVYWATY LNREPVLGVS 450
P 451
Length:451
Mass (Da):51,326
Last modified:February 20, 2007 - v2
Checksum:i43F9F708B5A00FFD
GO
Isoform 2 (identifier: P47869-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: MKTKLNIYNM...SFGPVSDTDM → MRLKITLPSLREFLTDFWMVTIIGLDQDWE
     353-353: K → KSPSIKAEGITLTYNSVKAILQGAKLIWSKYIAFSWPSLFQEKTLEYLEKWMDCLTFKQSS

Note: No experimental confirmation available.

Show »
Length:456
Mass (Da):52,064
Checksum:i040306CCB7836206
GO

Sequence cautioni

The sequence BAD92532.1 differs from that shown. Reason: Erroneous initiation.

Polymorphismi

Genetic variations in GABRA2 determine the genetic susceptibility to alcoholism [MIMi:103780].

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8585MKTKL…SDTDM → MRLKITLPSLREFLTDFWMV TIIGLDQDWE in isoform 2. VSP_054277Add
BLAST
Alternative sequencei353 – 3531K → KSPSIKAEGITLTYNSVKAI LQGAKLIWSKYIAFSWPSLF QEKTLEYLEKWMDCLTFKQS S in isoform 2. VSP_054278

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti10 – 112MQ → IE in AAB27278. 1 Publication
Sequence conflicti343 – 3431A → T in AAB27278. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S62907 mRNA. Translation: AAB27278.1.
AK125179 mRNA. Translation: BAG54159.1.
AK289662 mRNA. Translation: BAF82351.1.
AK293466 mRNA. Translation: BAH11514.1.
AB209295 mRNA. Translation: BAD92532.1. Different initiation.
AC084352 Genomic DNA. No translation available.
AC093745 Genomic DNA. No translation available.
AC095060 Genomic DNA. No translation available.
AC104072 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW93022.1.
CCDSiCCDS3471.1. [P47869-1]
CCDS68692.1. [P47869-2]
PIRiI57947.
RefSeqiNP_000798.2. NM_000807.2. [P47869-1]
NP_001107647.1. NM_001114175.1. [P47869-1]
NP_001273756.1. NM_001286827.1. [P47869-2]
XP_006714065.1. XM_006714002.1. [P47869-1]
UniGeneiHs.116250.

Genome annotation databases

EnsembliENST00000356504; ENSP00000348897; ENSG00000151834.
ENST00000381620; ENSP00000371033; ENSG00000151834.
ENST00000510861; ENSP00000421828; ENSG00000151834.
ENST00000514090; ENSP00000421300; ENSG00000151834.
ENST00000540012; ENSP00000444409; ENSG00000151834.
GeneIDi2555.
KEGGihsa:2555.
UCSCiuc003gxc.3. human. [P47869-1]

Polymorphism databases

DMDMi126302547.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S62907 mRNA. Translation: AAB27278.1 .
AK125179 mRNA. Translation: BAG54159.1 .
AK289662 mRNA. Translation: BAF82351.1 .
AK293466 mRNA. Translation: BAH11514.1 .
AB209295 mRNA. Translation: BAD92532.1 . Different initiation.
AC084352 Genomic DNA. No translation available.
AC093745 Genomic DNA. No translation available.
AC095060 Genomic DNA. No translation available.
AC104072 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW93022.1 .
CCDSi CCDS3471.1. [P47869-1 ]
CCDS68692.1. [P47869-2 ]
PIRi I57947.
RefSeqi NP_000798.2. NM_000807.2. [P47869-1 ]
NP_001107647.1. NM_001114175.1. [P47869-1 ]
NP_001273756.1. NM_001286827.1. [P47869-2 ]
XP_006714065.1. XM_006714002.1. [P47869-1 ]
UniGenei Hs.116250.

3D structure databases

ProteinModelPortali P47869.
SMRi P47869. Positions 43-359.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108829. 2 interactions.
IntActi P47869. 1 interaction.
STRINGi 9606.ENSP00000348897.

Chemistry

BindingDBi P47869.
ChEMBLi CHEMBL2094130.
DrugBanki DB00404. Alprazolam.
DB01558. Bromazepam.
DB00829. Diazepam.
DB00189. Ethchlorvynol.
DB01567. Fludiazepam.
DB01544. Flunitrazepam.
DB00690. Flurazepam.
DB00186. Lorazepam.
DB00371. Meprobamate.
DB00683. Midazolam.
GuidetoPHARMACOLOGYi 405.

Protein family/group databases

TCDBi 1.A.9.5.2. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

PTM databases

PhosphoSitei P47869.

Polymorphism databases

DMDMi 126302547.

Proteomic databases

PaxDbi P47869.
PRIDEi P47869.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000356504 ; ENSP00000348897 ; ENSG00000151834 .
ENST00000381620 ; ENSP00000371033 ; ENSG00000151834 .
ENST00000510861 ; ENSP00000421828 ; ENSG00000151834 .
ENST00000514090 ; ENSP00000421300 ; ENSG00000151834 .
ENST00000540012 ; ENSP00000444409 ; ENSG00000151834 .
GeneIDi 2555.
KEGGi hsa:2555.
UCSCi uc003gxc.3. human. [P47869-1 ]

Organism-specific databases

CTDi 2555.
GeneCardsi GC04M046167.
HGNCi HGNC:4076. GABRA2.
HPAi HPA014261.
MIMi 103780. phenotype.
137140. gene.
neXtProti NX_P47869.
PharmGKBi PA28490.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG238757.
HOGENOMi HOG000231337.
HOVERGENi HBG051707.
InParanoidi P47869.
KOi K05175.
OrthoDBi EOG7JX342.
PhylomeDBi P47869.
TreeFami TF315453.

Enzyme and pathway databases

Reactomei REACT_24987. GABA A receptor activation.
REACT_25387. Ligand-gated ion channel transport.

Miscellaneous databases

ChiTaRSi GABRA2. human.
GeneWikii GABRA2.
GenomeRNAii 2555.
NextBioi 10091.
PROi P47869.
SOURCEi Search...

Gene expression databases

ArrayExpressi P47869.
Bgeei P47869.
CleanExi HS_GABRA2.
Genevestigatori P47869.

Family and domain databases

Gene3Di 2.70.170.10. 1 hit.
InterProi IPR006028. GABAA/Glycine_rcpt.
IPR001390. GABAAa_rcpt.
IPR005432. GABBAa2_rcpt.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
[Graphical view ]
PANTHERi PTHR18945. PTHR18945. 1 hit.
Pfami PF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 2 hits.
[Graphical view ]
PRINTSi PR01079. GABAARALPHA.
PR01615. GABAARALPHA2.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
SUPFAMi SSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsi TIGR00860. LIC. 1 hit.
PROSITEi PS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors."
    Hadingham K.L., Wingrove P., le Bourdelles B., Palmer K.J., Ragan C.I., Whiting P.J.
    Mol. Pharmacol. 43:970-975(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Amygdala, Brain and Cerebellum.
  4. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
    Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations."
    Edenberg H.J., Dick D.M., Xuei X., Tian H., Almasy L., Bauer L.O., Crowe R.R., Goate A., Hesselbrock V., Jones K., Kwon J., Li T.-K., Nurnberger J.I. Jr., O'Connor S.J., Reich T., Rice J., Schuckit M.A., Porjesz B., Foroud T., Begleiter H.
    Am. J. Hum. Genet. 74:705-714(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM.

Entry informationi

Entry nameiGBRA2_HUMAN
AccessioniPrimary (citable) accession number: P47869
Secondary accession number(s): A8K0U7, B7Z1H8, Q59G14
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 20, 2007
Last modified: September 3, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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