Q6ZMI0 · PPR21_HUMAN
- ProteinProtein phosphatase 1 regulatory subunit 21
- GenePPP1R21
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids780 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary) (PubMed:37267905, PubMed:37267906).
The FERRY complex directly interacts with mRNAs and RAB5A, and functions as a RAB5A effector involved in the localization and the distribution of specific mRNAs most likely by mediating their endosomal transport. The complex recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction (PubMed:37267905).
In the complex, PPP1R21 serves as a binding hub connecting all five complex subunits and mediating the binding to mRNA and early endosomes via RAB5A (PubMed:37267906).
Putative regulator of protein phosphatase 1 (PP1) activity (PubMed:19389623).
May play a role in the endosomal sorting process or in endosome maturation pathway (Probable) (PubMed:30520571).
The FERRY complex directly interacts with mRNAs and RAB5A, and functions as a RAB5A effector involved in the localization and the distribution of specific mRNAs most likely by mediating their endosomal transport. The complex recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction (PubMed:37267905).
In the complex, PPP1R21 serves as a binding hub connecting all five complex subunits and mediating the binding to mRNA and early endosomes via RAB5A (PubMed:37267906).
Putative regulator of protein phosphatase 1 (PP1) activity (PubMed:19389623).
May play a role in the endosomal sorting process or in endosome maturation pathway (Probable) (PubMed:30520571).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | early endosome | |
Cellular Component | membrane | |
Molecular Function | RNA binding |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein phosphatase 1 regulatory subunit 21
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6ZMI0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (NEDHFBA)
- Note
- DescriptionAn autosomal recessive disorder characterized by global developmental delay, severely impaired intellectual development, hypotonia, coarse facial features, and muscle weakness, often resulting in the inability to walk or sit. Additional features include feeding difficulties, respiratory distress, scoliosis, poor visual function, and rotary nystagmus. Brain imaging shows variable abnormalities, including enlarged ventricles, decreased white matter volume, white matter changes, thin corpus callosum, and cerebellar hypoplasia.
- See alsoMIM:619383
Natural variants in NEDHFBA
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085954 | 65-780 | missing | in NEDHFBA | |
VAR_082035 | 143-780 | missing | in NEDHFBA | |
VAR_082036 | 697-780 | missing | in NEDHFBA; abolishes interaction with RAB5A. Does not affect FERRY complex assembly. Does not affect FERRY complex binding to mRNA | |
VAR_084655 | 728-780 | missing | in NEDHFBA; uncertain significance; decreases interaction with RAB5A. Affects FERRY complex assembly. Does not affect FERRY complex binding to mRNA |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_085954 | 65-780 | in NEDHFBA | |||
Sequence: Missing | ||||||
Natural variant | VAR_082035 | 143-780 | in NEDHFBA | |||
Sequence: Missing | ||||||
Natural variant | VAR_082036 | 697-780 | in NEDHFBA; abolishes interaction with RAB5A. Does not affect FERRY complex assembly. Does not affect FERRY complex binding to mRNA | |||
Sequence: Missing | ||||||
Natural variant | VAR_084655 | 728-780 | in NEDHFBA; uncertain significance; decreases interaction with RAB5A. Affects FERRY complex assembly. Does not affect FERRY complex binding to mRNA | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,069 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000286098 | 1-780 | UniProt | Protein phosphatase 1 regulatory subunit 21 | |||
Sequence: MASAELQGKYQKLAQEYSKLRAQNQVLKKGVVDEQANSAALKEQLKMKDQSLRKLQQEMDSLTFRNLQLAKRVELLQDELALSEPRGKKNKKSGESSSQLSQEQKSVFDEDLQKKIEENERLHIQFFEADEQHKHVEAELRSRLATLETEAAQHQAVVDGLTRKYMETIEKLQNDKAKLEVKSQTLEKEAKECRLRTEECQLQLKTLHEDLSGRLEESLSIINEKVPFNDTKYSQYNALNVPLHNRRHQLKMRDIAGQALAFVQDLVTALLNFHTYTEQRIQIFPVDSAIDTISPLNQKFSQYLHENASYVRPLEEGMLHLFESITEDTVTVLETTVKLKTFSEHLTSYICFLRKILPYQLKSLEEECESSLCTSALRARNLELSQDMKKMTAVFEKLQTYIALLALPSTEPDGLLRTNYSSVLTNVGAALHGFHDVMKDISKHYSQKAAIEHELPTATQKLITTNDCILSSVVALTNGAGKIASFFSNNLDYFIASLSYGPKAASGFISPLSAECMLQYKKKAAAYMKSLRKPLLESVPYEEALANRRILLSSTESREGLAQQVQQSLEKISKLEQEKEHWMLEAQLAKIKLEKENQRIADKLKNTGSAQLVGLAQENAAVSNTAGQDEATAKAVLEPIQSTSLIGTLTRTSDSEVPDVESREDLIKNHYMARIVELTSQLQLADSKSVHFYAECRALSKRLALAEKSKEALTEEMKLASQNISRLQDELTTTKRSYEDQLSMMSDHLCSMNETLSKQREEIDTLKMSSKGNSKKNKSR | |||||||
Modified residue (large scale data) | 93 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 652 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 652 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 653 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the FERRY complex, composed of five subunits: TBCK, PPP1R21, FERRY3, CRYZL1 and GATAD1, with a ratio of 1:2:1:2:4 respectively (PubMed:37267905, PubMed:37267906).
PPP1R21 serves as a binding hub connecting all five complex subunits to mediate the binding to specific mitochondrial mRNAs (PubMed:37267906).
Interacts with the GTP-bound form of RAB5A (via its C-terminal region); linking the mRNP complex onto trafficking endosomes for active mRNA transport (PubMed:37267905, PubMed:37267906).
Interacts with PPP1CA (PubMed:19389623).
PPP1R21 serves as a binding hub connecting all five complex subunits to mediate the binding to specific mitochondrial mRNAs (PubMed:37267906).
Interacts with the GTP-bound form of RAB5A (via its C-terminal region); linking the mRNP complex onto trafficking endosomes for active mRNA transport (PubMed:37267905, PubMed:37267906).
Interacts with PPP1CA (PubMed:19389623).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for coiled coil, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Coiled coil | 1-207 | |||||
Sequence: MASAELQGKYQKLAQEYSKLRAQNQVLKKGVVDEQANSAALKEQLKMKDQSLRKLQQEMDSLTFRNLQLAKRVELLQDELALSEPRGKKNKKSGESSSQLSQEQKSVFDEDLQKKIEENERLHIQFFEADEQHKHVEAELRSRLATLETEAAQHQAVVDGLTRKYMETIEKLQNDKAKLEVKSQTLEKEAKECRLRTEECQLQLKTL | ||||||
Region | 84-104 | Disordered | ||||
Sequence: EPRGKKNKKSGESSSQLSQEQ | ||||||
Coiled coil | 556-607 | |||||
Sequence: ESREGLAQQVQQSLEKISKLEQEKEHWMLEAQLAKIKLEKENQRIADKLKNT | ||||||
Coiled coil | 693-742 | |||||
Sequence: YAECRALSKRLALAEKSKEALTEEMKLASQNISRLQDELTTTKRSYEDQL | ||||||
Region | 760-780 | Disordered | ||||
Sequence: REEIDTLKMSSKGNSKKNKSR |
Domain
Coiled-coil domains of PPP1R21 are essential for RNA binding.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
Q6ZMI0-1
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.
- Name1
- Length780
- Mass (Da)88,314
- Last updated2004-07-05 v1
- Checksum8D265213DC80841A
Q6ZMI0-2
- Name2
- Differences from canonical
- 646-656: Missing
Q6ZMI0-5
- Name5
Q6ZMI0-3
- Name3
Q6ZMI0-4
- Name4
- Differences from canonical
- 363-779: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 235 | in Ref. 1; BAD18739 | ||||
Sequence: Q → R | ||||||
Alternative sequence | VSP_024984 | 363-779 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 476 | in Ref. 1; BAD18739 | ||||
Sequence: L → S | ||||||
Alternative sequence | VSP_043216 | 534-564 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_024985 | 566-574 | in isoform 3 | |||
Sequence: QQSLEKISK → WHWENYGNC | ||||||
Alternative sequence | VSP_024986 | 575-780 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_024987 | 646-656 | in isoform 2 and isoform 5 | |||
Sequence: Missing | ||||||
Sequence conflict | 670 | in Ref. 1; BAD18739 | ||||
Sequence: H → R |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK172753 EMBL· GenBank· DDBJ | BAD18739.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AK172762 EMBL· GenBank· DDBJ | BAD18745.1 EMBL· GenBank· DDBJ | mRNA | ||
AY134855 EMBL· GenBank· DDBJ | AAN08625.1 EMBL· GenBank· DDBJ | mRNA | ||
AC093635 EMBL· GenBank· DDBJ | AAX93161.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00200.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC011978 EMBL· GenBank· DDBJ | AAH11978.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC040721 EMBL· GenBank· DDBJ | AAH40721.1 EMBL· GenBank· DDBJ | mRNA | ||
BC111059 EMBL· GenBank· DDBJ | AAI11060.1 EMBL· GenBank· DDBJ | mRNA | ||
BC117279 EMBL· GenBank· DDBJ | AAI17280.1 EMBL· GenBank· DDBJ | mRNA | ||
BC143463 EMBL· GenBank· DDBJ | AAI43464.1 EMBL· GenBank· DDBJ | mRNA | ||
BC143466 EMBL· GenBank· DDBJ | AAI43467.1 EMBL· GenBank· DDBJ | mRNA |