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Protein

Homeobox protein homothorax

Gene

hth

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

All isoforms are required for patterning of the embryonic cuticle. Acts with exd to delimit the eye field and prevent inappropriate eye development. Isoforms that carry the homeodomain are required for proper localization of chordotonal organs within the peripheral nervous system and antennal identity; required to activate antennal-specific genes, such as sal and to repress the leg-like expression of dac. Necessary for the nuclear localization of the essential HOX cofactor, extradenticle (exd). Both necessary and sufficient for inner photoreceptors to adopt the polarization-sensitive 'dorsal rim area' (DRA) of the eye fate instead of the color-sensitive default state. This occurs by increasing rhabdomere size and uncoupling R7-R8 communication to allow both cells to express the same opsin rather than different ones as required for color vision.5 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi365 – 42763Homeobox; TALE-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • enhancer binding Source: FlyBase
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: FlyBase
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: FlyBase

GO - Biological processi

  • brain development Source: FlyBase
  • compound eye development Source: FlyBase
  • compound eye photoreceptor fate commitment Source: FlyBase
  • eye development Source: UniProtKB
  • haltere morphogenesis Source: FlyBase
  • head morphogenesis Source: FlyBase
  • imaginal disc-derived leg morphogenesis Source: FlyBase
  • imaginal disc-derived wing morphogenesis Source: FlyBase
  • leg disc proximal/distal pattern formation Source: FlyBase
  • peripheral nervous system development Source: UniProtKB
  • positive regulation of decapentaplegic signaling pathway Source: FlyBase
  • positive regulation of transcription from RNA polymerase II promoter Source: FlyBase
  • protein import into nucleus, translocation Source: UniProtKB
  • protein localization to nucleus Source: FlyBase
  • proximal/distal pattern formation Source: FlyBase
  • regulation of cell fate specification Source: FlyBase
  • regulation of neuron differentiation Source: FlyBase
  • regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • salivary gland boundary specification Source: FlyBase
  • segmentation Source: FlyBase
  • somatic muscle development Source: FlyBase
  • specification of organ identity Source: FlyBase
  • specification of segmental identity, antennal segment Source: FlyBase
  • specification of segmental identity, head Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

SignaLinkiO46339.

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein homothorax
Alternative name(s):
Homeobox protein dorsotonals
Gene namesi
Name:hthImported
Synonyms:dtlImported
ORF Names:CG17117
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 3R

Organism-specific databases

FlyBaseiFBgn0001235. hth.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: FlyBase
  • cytosol Source: FlyBase
  • nucleus Source: FlyBase
  • transcription factor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Severe head defects, including a failure of head involution and transformation of the thoracic and abdominal segments into a more posterior identity.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 487487Homeobox protein homothoraxPRO_0000341484Add
BLAST

Proteomic databases

PaxDbiO46339.
PRIDEiO46339.

Expressioni

Tissue specificityi

In the wing disk, the expression is present in the regions corresponding to notum, wing hinge and ventral pleura. In the leg disk, the expression is in the periphery region, corresponding to the proximal segments of the legs. In the antennal disk, the expression is in all but the arista region. In the eye disk, the expression is strong in the anterior region surrounding the eye field, including the regions corresponding to ptilinum, ocellus and head capsules, and weak in the posterior and lateral margins of the eye disk. Expressed specifically in maturating inner photoreceptors of the DRA and maintained through adulthood.3 Publications

Developmental stagei

Isoform C, isoform E and isoform F have very similar expression patterns during embryonic and larval stages, suggesting coexpression in the same tissues.1 Publication

Gene expression databases

BgeeiO46339.
ExpressionAtlasiO46339. differential.
GenevisibleiO46339. DM.

Interactioni

Subunit structurei

Interacts with exd; required for nuclear translocation of exd.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
exdP4042713EBI-137488,EBI-101537

GO - Molecular functioni

  • transcription factor binding Source: FlyBase

Protein-protein interaction databases

BioGridi66419. 20 interactions.
IntActiO46339. 48 interactions.
MINTiMINT-947560.
STRINGi7227.FBpp0081732.

Structurei

3D structure databases

ProteinModelPortaliO46339.
SMRiO46339. Positions 372-427.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TALE/MEIS homeobox family.Sequence analysis
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0773. Eukaryota.
ENOG410XPMQ. LUCA.
GeneTreeiENSGT00550000074260.
InParanoidiO46339.
KOiK16672.
OMAiHTNSMPP.
OrthoDBiEOG76HQ2W.
PhylomeDBiO46339.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
IPR032453. PKNOX/Meis_N.
[Graphical view]
PfamiPF05920. Homeobox_KN. 1 hit.
PF16493. Meis_PKNOX_N. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform C2 Publications (identifier: O46339-1) [UniParc]FASTAAdd to basket

Also known as: hth11 Publication

, HthFL1 Publication

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

        10         20         30         40         50
MAQPRYDDGL HGYGMDSGAA AAAMYDPHAG HRPPGLQGLP SHHSPHMTHA
60 70 80 90 100
AAAAATVGMH GYHSGAGGHG TPSHVSPVGN HLMGAIPEVH KRDKDAIYEH
110 120 130 140 150
PLFPLLALIF EKCELATCTP REPGVQGGDV CSSESFNEDI AMFSKQIRSQ
160 170 180 190 200
KPYYTADPEV DSLMVQAIQV LRFHLLELEK VHELCDNFCH RYISCLKGKM
210 220 230 240 250
PIDLVIDERD TTKPPELGSA NGEGRSNADS TSHTDGASTP DVRPPSSSLS
260 270 280 290 300
YGGAMNDDAR SPGAGSTPGP LSQQPPALDT SDPDGKFLSS LNPSELTYDG
310 320 330 340 350
RWCRREWSSP ADARNADASR RLYSSVFLGS PDNFGTSASG DASNASIGSG
360 370 380 390 400
EGTGEEDDDA SGKKNQKKRG IFPKVATNIL RAWLFQHLTH PYPSEDQKKQ
410 420 430 440 450
LAQDTGLTIL QVNNWFINAR RRIVQPMIDQ SNRAVYTPHP GPSGYGHDAM
460 470 480
GYMMDSQAHM MHRPPGDPGF HQGYPHYPPA EYYGQHL
Length:487
Mass (Da):52,784
Last modified:June 1, 1998 - v1
Checksum:i7EA4D7D1EFB16F8A
GO
Isoform A1 Publication (identifier: O46339-2) [UniParc]FASTAAdd to basket

Also known as: hth21 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     284-398: Missing.

Show »
Length:372
Mass (Da):40,219
Checksum:i02F04B6DE5C19565
GO
Isoform E1 Publication (identifier: O46339-5) [UniParc]FASTAAdd to basket

Also known as: HDless 7'1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     243-266: RPPSSSLSYGGAMNDDARSPGAGS → PSTQDFSPLEETYASYRIKHEADF
     267-487: Missing.

Note: Protein lacks the homeodomain but is still capable of interacting with exd.1 Publication
Show »
Length:266
Mass (Da):28,867
Checksum:iBEDFA03DB6BC2AB2
GO
Isoform F1 Publication (identifier: O46339-6) [UniParc]FASTAAdd to basket

Also known as: HDless 6'1 Publication

, IImported

The sequence of this isoform differs from the canonical sequence as follows:
     243-266: RPPSSSLSYGGAMNDDARSPGAGS → VSTPFAGAHGPILASYNAVVHPCS
     267-487: Missing.

Note: Protein lacks the homeodomain but is still capable of interacting with exd.1 Publication
Show »
Length:266
Mass (Da):28,431
Checksum:i6F7B0554A98FA4A9
GO
Isoform H1 Publication (identifier: O46339-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
     284-398: Missing.

Show »
Length:358
Mass (Da):38,657
Checksum:i47B1C910C9076A19
GO

Sequence cautioni

The sequence AAQ23556.1 differs from that shown. Reason: Frameshift at position 68. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1414Missing in isoform H. 2 PublicationsVSP_052821Add
BLAST
Alternative sequencei243 – 26624RPPSS…PGAGS → PSTQDFSPLEETYASYRIKH EADF in isoform E. 2 PublicationsVSP_052822Add
BLAST
Alternative sequencei243 – 26624RPPSS…PGAGS → VSTPFAGAHGPILASYNAVV HPCS in isoform F. 2 PublicationsVSP_052823Add
BLAST
Alternative sequencei267 – 487221Missing in isoform E and isoform F. 2 PublicationsVSP_052824Add
BLAST
Alternative sequencei284 – 398115Missing in isoform A and isoform H. 4 PublicationsVSP_052826Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026788 mRNA. Translation: AAC47759.1.
AF032865 mRNA. Translation: AAB97169.1.
AF035825 mRNA. Translation: AAB88514.1.
AF036584 mRNA. Translation: AAB88863.1.
AE014297 Genomic DNA. Translation: AAF54533.2.
AE014297 Genomic DNA. Translation: AAN13474.1.
AE014297 Genomic DNA. Translation: AAN13475.2.
AE014297 Genomic DNA. Translation: AAX52943.2.
AE014297 Genomic DNA. Translation: AAZ52527.1.
BT010238 mRNA. Translation: AAQ23556.1. Frameshift.
BT024210 mRNA. Translation: ABC86272.1.
BT029117 mRNA. Translation: ABJ17050.1.
RefSeqiNP_001014613.2. NM_001014613.3. [O46339-5]
NP_001027170.1. NM_001031999.2. [O46339-6]
NP_476576.1. NM_057228.5. [O46339-1]
NP_476577.3. NM_057229.5. [O46339-6]
NP_476578.3. NM_057230.6.
UniGeneiDm.2272.

Genome annotation databases

EnsemblMetazoaiFBtr0082255; FBpp0081732; FBgn0001235. [O46339-1]
GeneIDi41273.
KEGGidme:Dmel_CG17117.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026788 mRNA. Translation: AAC47759.1.
AF032865 mRNA. Translation: AAB97169.1.
AF035825 mRNA. Translation: AAB88514.1.
AF036584 mRNA. Translation: AAB88863.1.
AE014297 Genomic DNA. Translation: AAF54533.2.
AE014297 Genomic DNA. Translation: AAN13474.1.
AE014297 Genomic DNA. Translation: AAN13475.2.
AE014297 Genomic DNA. Translation: AAX52943.2.
AE014297 Genomic DNA. Translation: AAZ52527.1.
BT010238 mRNA. Translation: AAQ23556.1. Frameshift.
BT024210 mRNA. Translation: ABC86272.1.
BT029117 mRNA. Translation: ABJ17050.1.
RefSeqiNP_001014613.2. NM_001014613.3. [O46339-5]
NP_001027170.1. NM_001031999.2. [O46339-6]
NP_476576.1. NM_057228.5. [O46339-1]
NP_476577.3. NM_057229.5. [O46339-6]
NP_476578.3. NM_057230.6.
UniGeneiDm.2272.

3D structure databases

ProteinModelPortaliO46339.
SMRiO46339. Positions 372-427.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi66419. 20 interactions.
IntActiO46339. 48 interactions.
MINTiMINT-947560.
STRINGi7227.FBpp0081732.

Proteomic databases

PaxDbiO46339.
PRIDEiO46339.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0082255; FBpp0081732; FBgn0001235. [O46339-1]
GeneIDi41273.
KEGGidme:Dmel_CG17117.

Organism-specific databases

CTDi41273.
FlyBaseiFBgn0001235. hth.

Phylogenomic databases

eggNOGiKOG0773. Eukaryota.
ENOG410XPMQ. LUCA.
GeneTreeiENSGT00550000074260.
InParanoidiO46339.
KOiK16672.
OMAiHTNSMPP.
OrthoDBiEOG76HQ2W.
PhylomeDBiO46339.

Enzyme and pathway databases

SignaLinkiO46339.

Miscellaneous databases

ChiTaRSihth. fly.
GenomeRNAii41273.
PROiO46339.

Gene expression databases

BgeeiO46339.
ExpressionAtlasiO46339. differential.
GenevisibleiO46339. DM.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR001356. Homeobox_dom.
IPR008422. Homeobox_KN_domain.
IPR009057. Homeodomain-like.
IPR032453. PKNOX/Meis_N.
[Graphical view]
PfamiPF05920. Homeobox_KN. 1 hit.
PF16493. Meis_PKNOX_N. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein."
    Rieckhof G.E., Casares F., Ryoo H.D., Abu-Shaar M., Mann R.S.
    Cell 91:171-183(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM H), FUNCTION, INTERACTION WITH EXD, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
    Tissue: AntennaImported.
  2. "Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS."
    Kurant E., Pai C.-Y., Sharf R., Halachmi N., Sun Y.H., Salzberg A.
    Development 125:1037-1048(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), FUNCTION, INTERACTION WITH EXD, SUBCELLULAR LOCATION.
  3. "The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila."
    Pai C.-Y., Kuo T.-S., Jaw T.J., Kurant E., Chen C.-T., Bessarab D.A., Salzberg A., Sun Y.H.
    Genes Dev. 12:435-446(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C), FUNCTION, INTERACTION WITH EXD, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  4. "The genome sequence of Drosophila melanogaster."
    Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D.
    , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
    Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: BerkeleyImported.
  5. Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
    Strain: Berkeley.
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS E AND F).
    Strain: BerkeleyImported.
    Tissue: Embryo.
  7. "Homothorax switches function of Drosophila photoreceptors from color to polarized light sensors."
    Wernet M.F., Labhart T., Baumann F., Mazzoni E.O., Pichaud F., Desplan C.
    Cell 115:267-279(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  8. "Distinct functions of homeodomain-containing and homeodomain-less isoforms encoded by homothorax."
    Noro B., Culi J., McKay D.J., Zhang W., Mann R.S.
    Genes Dev. 20:1636-1650(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH EXD, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiHTH_DROME
AccessioniPrimary (citable) accession number: O46339
Secondary accession number(s): O17427
, Q058V1, Q4AB34, Q59DX7, Q6NR42, Q7KQ21, Q8INL5, Q8INL6, Q9VGY9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: June 1, 1998
Last modified: July 6, 2016
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.