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UniProtKB - O95995 (DRC4_HUMAN)

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Protein

Dynein regulatory complex subunit 4

Gene

GAS8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 faciltating 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

View the complete GO annotation on QuickGO ...

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 Source: Ensembl
  • flagellated sperm motility Source: UniProtKB
  • negative regulation of cell 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
View the complete GO annotation on QuickGO ...

Enzyme and pathway databases

ReactomeiR-HSA-5635838 Activation of SMO

Names & Taxonomyi

Protein namesi
Recommended name:
Dynein regulatory complex subunit 41 Publication
Alternative 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000141013.14
HGNCiHGNC:4166 GAS8
MIMi605178 gene
neXtProtiNX_O95995

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Cytoskeleton, Flagellum, Golgi apparatus, Microtubule

Pathology & 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.
See also OMIM:616726
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080336183 – 478Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST296
Natural variantiVAR_080337334 – 478Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST145
Natural variantiVAR_080338391A → 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 dyskinesia

Organism-specific databases

DisGeNETi2622
MalaCardsiGAS8
MIMi616726 phenotype
OpenTargetsiENSG00000141013
PharmGKBiPA28579

Polymorphism and mutation databases

BioMutaiGAS8

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002203771 – 478Dynein regulatory complex subunit 4Add BLAST478

Proteomic databases

EPDiO95995
MaxQBiO95995
PaxDbiO95995
PeptideAtlasiO95995
PRIDEiO95995
ProteomicsDBi51170

PTM databases

iPTMnetiO95995
PhosphoSitePlusiO95995

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

BgeeiENSG00000141013
CleanExiHS_GAS8
ExpressionAtlasiO95995 baseline and differential
GenevisibleiO95995 HS

Organism-specific databases

HPAiHPA041311
HPA048238

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 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GRIPAP1Q4V3284EBI-1052570,EBI-717919

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108892, 6 interactors
CORUMiO95995
IntActiO95995, 110 interactors
STRINGi9606.ENSP00000268699

Structurei

3D structure databases

ProteinModelPortaliO95995
SMRiO95995
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 114Regulates microtubule-bindingBy similarityAdd BLAST114
Regioni115 – 258Microtubule-bindingBy similarityAdd BLAST144
Regioni357 – 478Interaction with SMO1 PublicationAdd BLAST122

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili242 – 427Sequence analysisAdd BLAST186

Sequence similaritiesi

Belongs to the DRC4 family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IE2T Eukaryota
ENOG410XPBD LUCA
GeneTreeiENSGT00390000009477
HOGENOMiHOG000038763
HOVERGENiHBG039458
InParanoidiO95995
KOiK19942
OMAiAREEMSE
OrthoDBiEOG091G0851
PhylomeDBiO95995
TreeFamiTF323819

Family and domain databases

InterProiView protein in InterPro
IPR039308 GAS8
IPR025593 GAS8_dom
PANTHERiPTHR31543 PTHR31543, 1 hit
PfamiView protein in Pfam
PF13851 GAS, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95995-1) [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

        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
Length:478
Mass (Da):56,356
Last modified:May 1, 1999 - v1
Checksum:i2EDBC7981868EB12
GO
Isoform 2 (identifier: O95995-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Show »
Length:453
Mass (Da):53,809
Checksum:i2EAE549BCB61A155
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33E → G in BAH12677 (PubMed:14702039).Curated1
Sequence conflicti87A → V in BAH12677 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080336183 – 478Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST296
Natural variantiVAR_016006199E → K1 PublicationCorresponds to variant dbSNP:rs868044EnsemblClinVar.1
Natural variantiVAR_049230259R → Q. Corresponds to variant dbSNP:rs17178299Ensembl.1
Natural variantiVAR_080337334 – 478Missing in CILD33; loss of localization to cilia; abnormal cilia with axonemal disorganization. 1 PublicationAdd BLAST145
Natural variantiVAR_080338391A → 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 keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0548051 – 25Missing in isoform 2. 1 PublicationAdd BLAST25

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
CCDSiCCDS10992.1 [O95995-1]
CCDS67101.1 [O95995-2]
RefSeqiNP_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 [O95995-2]
UniGeneiHs.431792

Genome annotation databases

EnsembliENST00000268699; ENSP00000268699; ENSG00000141013 [O95995-1]
ENST00000536122; ENSP00000440977; ENSG00000141013 [O95995-2]
GeneIDi2622
KEGGihsa:2622
UCSCiuc002fqi.1 human [O95995-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDRC4_HUMAN
AccessioniPrimary (citable) accession number: O95995
Secondary accession number(s): B2RCT1
, B7Z4U1, G3V1L5, Q2M234
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2003
Last sequence update: May 1, 1999
Last modified: July 18, 2018
This is version 134 of the entry and version 1 of the sequence. See 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 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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