UniProtKB - O95995 (DRC4_HUMAN)
Protein
Dynein regulatory complex subunit 4
Gene
GAS8
Organism
Homo sapiens (Human)
Status
Functioni
Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays an important role in the assembly of the N-DRC linker (By similarity). Plays dual roles at both the primary (or non-motile) cilia to regulate hedgehog signaling and in motile cilia to coordinate cilia movement. Required for proper motile cilia functioning (PubMed:26387594, PubMed:27120127, PubMed:27472056). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity in a GRK2-dependent manner (By similarity).By similarity3 Publications
GO - Molecular functioni
- microtubule binding Source: UniProtKB
- Rab GTPase binding Source: GO_Central
GO - Biological processi
- axoneme assembly Source: UniProtKB
- brain development Source: Ensembl
- cellular protein localization Source: GO_Central
- cilium movement involved in cell motility Source: GO_Central
- determination of left/right symmetry Source: Ensembl
- epithelial cilium movement involved in extracellular fluid movement Source: Ensembl
- flagellated sperm motility Source: UniProtKB
- negative regulation of cell population proliferation Source: ProtInc
- positive regulation of protein localization to cilium Source: UniProtKB
- positive regulation of smoothened signaling pathway Source: UniProtKB
- regulation of microtubule binding Source: UniProtKB
Enzyme and pathway databases
PathwayCommonsi | O95995 |
Reactomei | R-HSA-5635838, Activation of SMO |
Names & Taxonomyi
Protein namesi | Recommended name: Dynein regulatory complex subunit 41 PublicationAlternative name(s): Growth arrest-specific protein 11 Short name: GAS-11 Growth arrest-specific protein 8 Short name: GAS-8 |
Gene namesi | Name:GAS8 Synonyms:DRC41 Publication, GAS11 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000141013.14 |
HGNCi | HGNC:4166, GAS8 |
MIMi | 605178, gene |
neXtProti | NX_O95995 |
Subcellular locationi
Cytoskeleton
- cytoskeleton 1 Publication
- cilium axoneme 2 Publications
- cilium basal body By similarity
- flagellum axoneme By similarity
Golgi apparatus
- Golgi apparatus 1 Publication
Other locations
Note: Associates with microtubules (PubMed:10969087). Localized to the cytoplasm of round spermatids, the tails of elongating spermatids, and mature spermatid tail bundles protruding into the lumen, and in the flagellum of epididymal spermatozoa (By similarity).By similarity1 Publication
Cytoskeleton
- axoneme Source: UniProtKB
- ciliary basal body Source: UniProtKB
- microtubule Source: UniProtKB
Extracellular region or secreted
- extracellular region Source: GOC
Golgi apparatus
- Golgi apparatus Source: GO_Central
Other locations
- cilium Source: UniProtKB
- motile cilium Source: UniProtKB
- sperm flagellum Source: Ensembl
Keywords - Cellular componenti
Cell projection, Cilium, Cytoplasm, Cytoskeleton, Flagellum, Golgi apparatus, MicrotubulePathology & Biotechi
Involvement in diseasei
Ciliary dyskinesia, primary, 33 (CILD33)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD33 inheritance is autosomal recessive.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080336 | 183 – 478 | Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST | 296 | |
Natural variantiVAR_080337 | 334 – 478 | Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST | 145 | |
Natural variantiVAR_080338 | 391 | A → V in CILD33; the same mutation in the mouse sequence shows a moderate decrease in cilia motility. 1 PublicationCorresponds to variant dbSNP:rs147993982Ensembl. | 1 |
Keywords - Diseasei
Ciliopathy, Primary ciliary dyskinesiaOrganism-specific databases
DisGeNETi | 2622 |
MalaCardsi | GAS8 |
MIMi | 616726, phenotype |
OpenTargetsi | ENSG00000141013 |
Orphaneti | 244, Primary ciliary dyskinesia |
PharmGKBi | PA28579 |
Miscellaneous databases
Pharosi | O95995, Tbio |
Polymorphism and mutation databases
BioMutai | GAS8 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220377 | 1 – 478 | Dynein regulatory complex subunit 4Add BLAST | 478 |
Proteomic databases
MassIVEi | O95995 |
MaxQBi | O95995 |
PaxDbi | O95995 |
PeptideAtlasi | O95995 |
PRIDEi | O95995 |
ProteomicsDBi | 32370 51170 [O95995-1] |
PTM databases
iPTMneti | O95995 |
PhosphoSitePlusi | O95995 |
Expressioni
Tissue specificityi
Expressed in respiratory epithelial cells (at protein level) (PubMed:26387594). Expressed in the heart, skeletal muscle, pancreas, liver, brain, trachea and lung. Weakly or not expressed in placenta and kidney (PubMed:9790751).3 Publications
Gene expression databases
Bgeei | ENSG00000141013, Expressed in testis and 216 other tissues |
ExpressionAtlasi | O95995, baseline and differential |
Genevisiblei | O95995, HS |
Organism-specific databases
HPAi | ENSG00000141013, Low tissue specificity |
Interactioni
Subunit structurei
Component of the nexin-dynein regulatory complex (N-DRC).
Interacts with microtubules (By similarity).
Interacts with SMO (PubMed:21659505).
Interacts (via coiled-coil domains) with RAB3B (in GTP-bound form) (By similarity).
By similarity1 PublicationBinary interactionsi
O95995
GO - Molecular functioni
- microtubule binding Source: UniProtKB
- Rab GTPase binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 108892, 118 interactors |
CORUMi | O95995 |
IntActi | O95995, 110 interactors |
STRINGi | 9606.ENSP00000268699 |
Miscellaneous databases
RNActi | O95995, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 114 | Regulates microtubule-bindingBy similarityAdd BLAST | 114 | |
Regioni | 115 – 258 | Microtubule-bindingBy similarityAdd BLAST | 144 | |
Regioni | 357 – 478 | Interaction with SMO1 PublicationAdd BLAST | 122 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 242 – 427 | Sequence analysisAdd BLAST | 186 |
Sequence similaritiesi
Belongs to the DRC4 family.Curated
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | ENOG502QQDA, Eukaryota |
GeneTreei | ENSGT00390000009477 |
HOGENOMi | CLU_045343_0_0_1 |
InParanoidi | O95995 |
OMAi | MRNYFQL |
OrthoDBi | 1257437at2759 |
PhylomeDBi | O95995 |
TreeFami | TF323819 |
Family and domain databases
InterProi | View protein in InterPro IPR039308, GAS8 IPR025593, GAS8_dom |
PANTHERi | PTHR31543, PTHR31543, 1 hit |
Pfami | View protein in Pfam PF13851, GAS, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: O95995-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAPKKKGKKG KAKGTPIVDG LAPEDMSKEQ VEEHVSRIRE ELDREREERN
60 70 80 90 100
YFQLERDKIH TFWEITRRQL EEKKAELRNK DREMEEAEER HQVEIKVYKQ
110 120 130 140 150
KVKHLLYEHQ NNLTEMKAEG TVVMKLAQKE HRIQESVLRK DMRALKVELK
160 170 180 190 200
EQELASEVVV KNLRLKHTEE ITRMRNDFER QVREIEAKYD KKMKMLRDEL
210 220 230 240 250
DLRRKTELHE VEERKNGQIH TLMQRHEEAF TDIKNYYNDI TLNNLALINS
260 270 280 290 300
LKEQMEDMRK KEDHLEREMA EVSGQNKRLA DPLQKAREEM SEMQKQLANY
310 320 330 340 350
ERDKQILLCT KARLKVREKE LKDLQWEHEV LEQRFTKVQQ ERDELYRKFT
360 370 380 390 400
AAIQEVQQKT GFKNLVLERK LQALSAAVEK KEVQFNEVLA ASNLDPAALT
410 420 430 440 450
LVSRKLEDVL ESKNSTIKDL QYELAQVCKA HNDLLRTYEA KLLAFGIPLD
460 470
NVGFKPLETA VIGQTLGQGP AGLVGTPT
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WZT7 | A0A087WZT7_HUMAN | Dynein regulatory complex subunit 4 | GAS8 | 395 | Annotation score: | ||
H3BP65 | H3BP65_HUMAN | Dynein regulatory complex subunit 4 | GAS8 | 95 | Annotation score: | ||
H3BUA7 | H3BUA7_HUMAN | Dynein regulatory complex subunit 4 | GAS8 | 60 | Annotation score: | ||
H3BME0 | H3BME0_HUMAN | Dynein regulatory complex subunit 4 | GAS8 | 35 | Annotation score: | ||
H3BQT7 | H3BQT7_HUMAN | Dynein regulatory complex subunit 4 | GAS8 | 111 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 33 | E → G in BAH12677 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 87 | A → V in BAH12677 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080336 | 183 – 478 | Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST | 296 | |
Natural variantiVAR_016006 | 199 | E → K1 PublicationCorresponds to variant dbSNP:rs868044EnsemblClinVar. | 1 | |
Natural variantiVAR_049230 | 259 | R → Q. Corresponds to variant dbSNP:rs17178299EnsemblClinVar. | 1 | |
Natural variantiVAR_080337 | 334 – 478 | Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST | 145 | |
Natural variantiVAR_080338 | 391 | A → V in CILD33; the same mutation in the mouse sequence shows a moderate decrease in cilia motility. 1 PublicationCorresponds to variant dbSNP:rs147993982Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054805 | 1 – 25 | Missing in isoform 2. 1 PublicationAdd BLAST | 25 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF050079 mRNA Translation: AAC69519.1 AF050078 , AF050068, AF050069, AF050070, AF050071, AF050072, AF050073, AF050074, AF050075, AF050076, AF050077 Genomic DNA Translation: AAC69518.1 AK315261 mRNA Translation: BAG37678.1 AK297857 mRNA Translation: BAH12677.1 AC133919 Genomic DNA No translation available. CH471184 Genomic DNA Translation: EAW66661.1 CH471184 Genomic DNA Translation: EAW66659.1 BC104785 mRNA Translation: AAI04786.1 BC112121 mRNA Translation: AAI12122.1 |
CCDSi | CCDS10992.1 [O95995-1] CCDS67101.1 [O95995-2] |
RefSeqi | NP_001273134.1, NM_001286205.1 NP_001273137.1, NM_001286208.1 NP_001273138.1, NM_001286209.1 [O95995-2] NP_001472.1, NM_001481.2 [O95995-1] XP_005256361.1, XM_005256304.4 |
Genome annotation databases
Ensembli | ENST00000268699; ENSP00000268699; ENSG00000141013 [O95995-1] ENST00000536122; ENSP00000440977; ENSG00000141013 [O95995-2] |
GeneIDi | 2622 |
KEGGi | hsa:2622 |
UCSCi | uc002fqi.1, human [O95995-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF050079 mRNA Translation: AAC69519.1 AF050078 , AF050068, AF050069, AF050070, AF050071, AF050072, AF050073, AF050074, AF050075, AF050076, AF050077 Genomic DNA Translation: AAC69518.1 AK315261 mRNA Translation: BAG37678.1 AK297857 mRNA Translation: BAH12677.1 AC133919 Genomic DNA No translation available. CH471184 Genomic DNA Translation: EAW66661.1 CH471184 Genomic DNA Translation: EAW66659.1 BC104785 mRNA Translation: AAI04786.1 BC112121 mRNA Translation: AAI12122.1 |
CCDSi | CCDS10992.1 [O95995-1] CCDS67101.1 [O95995-2] |
RefSeqi | NP_001273134.1, NM_001286205.1 NP_001273137.1, NM_001286208.1 NP_001273138.1, NM_001286209.1 [O95995-2] NP_001472.1, NM_001481.2 [O95995-1] XP_005256361.1, XM_005256304.4 |
3D structure databases
SMRi | O95995 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108892, 118 interactors |
CORUMi | O95995 |
IntActi | O95995, 110 interactors |
STRINGi | 9606.ENSP00000268699 |
PTM databases
iPTMneti | O95995 |
PhosphoSitePlusi | O95995 |
Polymorphism and mutation databases
BioMutai | GAS8 |
Proteomic databases
MassIVEi | O95995 |
MaxQBi | O95995 |
PaxDbi | O95995 |
PeptideAtlasi | O95995 |
PRIDEi | O95995 |
ProteomicsDBi | 32370 51170 [O95995-1] |
Protocols and materials databases
Antibodypediai | 30991, 158 antibodies |
Genome annotation databases
Ensembli | ENST00000268699; ENSP00000268699; ENSG00000141013 [O95995-1] ENST00000536122; ENSP00000440977; ENSG00000141013 [O95995-2] |
GeneIDi | 2622 |
KEGGi | hsa:2622 |
UCSCi | uc002fqi.1, human [O95995-1] |
Organism-specific databases
CTDi | 2622 |
DisGeNETi | 2622 |
EuPathDBi | HostDB:ENSG00000141013.14 |
GeneCardsi | GAS8 |
HGNCi | HGNC:4166, GAS8 |
HPAi | ENSG00000141013, Low tissue specificity |
MalaCardsi | GAS8 |
MIMi | 605178, gene 616726, phenotype |
neXtProti | NX_O95995 |
OpenTargetsi | ENSG00000141013 |
Orphaneti | 244, Primary ciliary dyskinesia |
PharmGKBi | PA28579 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQDA, Eukaryota |
GeneTreei | ENSGT00390000009477 |
HOGENOMi | CLU_045343_0_0_1 |
InParanoidi | O95995 |
OMAi | MRNYFQL |
OrthoDBi | 1257437at2759 |
PhylomeDBi | O95995 |
TreeFami | TF323819 |
Enzyme and pathway databases
PathwayCommonsi | O95995 |
Reactomei | R-HSA-5635838, Activation of SMO |
Miscellaneous databases
BioGRID-ORCSi | 2622, 11 hits in 844 CRISPR screens |
ChiTaRSi | GAS8, human |
GenomeRNAii | 2622 |
Pharosi | O95995, Tbio |
PROi | PR:O95995 |
RNActi | O95995, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000141013, Expressed in testis and 216 other tissues |
ExpressionAtlasi | O95995, baseline and differential |
Genevisiblei | O95995, HS |
Family and domain databases
InterProi | View protein in InterPro IPR039308, GAS8 IPR025593, GAS8_dom |
PANTHERi | PTHR31543, PTHR31543, 1 hit |
Pfami | View protein in Pfam PF13851, GAS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DRC4_HUMAN | |
Accessioni | O95995Primary (citable) accession number: O95995 Secondary accession number(s): B2RCT1 Q2M234 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2003 |
Last sequence update: | May 1, 1999 | |
Last modified: | December 2, 2020 | |
This is version 151 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations