UniProt functional annotation for P03950



	UniProt functional annotation for P03950

UniProt code: P03950.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo. {ECO:0000269|PubMed:12051708, ECO:0000269|PubMed:1400510, ECO:0000269|PubMed:19354288, ECO:0000269|PubMed:21855800}.

Subunit: Homodimer (PubMed:25372031). Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur. {ECO:0000269|PubMed:10413501, ECO:0000269|PubMed:11468363, ECO:0000269|PubMed:19354288, ECO:0000269|PubMed:25372031, ECO:0000269|PubMed:9311977}.

Subcellular location: Cytoplasmic vesicle, secretory vesicle lumen {ECO:0000250|UniProtKB:Q3TMQ6}. Secreted {ECO:0000250|UniProtKB:P10152}. Nucleus {ECO:0000269|PubMed:12051708, ECO:0000269|PubMed:25372031}. Nucleus, nucleolus {ECO:0000269|PubMed:7945327}. Note=Rapidly endocytosed by target cells and translocated to the nucleus where it accumulates in the nucleolus and binds to DNA (PubMed:12051708). {ECO:0000269|PubMed:12051708}.

Tissue specificity: Expressed predominantly in the liver. Also detected in endothelial cells and spinal cord neurons. {ECO:0000269|PubMed:17886298, ECO:0000269|PubMed:2440105}.

Developmental stage: Low level expression in the developing fetus, increased in the neonate, and maximal in the adult.

Disease: Amyotrophic lateral sclerosis 9 (ALS9) [MIM:611895]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:15557516, ECO:0000269|PubMed:16501576, ECO:0000269|PubMed:17703939, ECO:0000269|PubMed:17886298, ECO:0000269|PubMed:17900154, ECO:0000269|PubMed:18087731, ECO:0000269|PubMed:22292843, ECO:0000269|PubMed:25372031}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity: Belongs to the pancreatic ribonuclease family. {ECO:0000305}.

Sequence caution: Sequence=AAH20704.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo. {ECO:0000269\|PubMed:12051708, ECO:0000269\|PubMed:1400510, ECO:0000269\|PubMed:19354288, ECO:0000269\|PubMed:21855800}.


Subunit:		Homodimer (PubMed:25372031). Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur. {ECO:0000269\|PubMed:10413501, ECO:0000269\|PubMed:11468363, ECO:0000269\|PubMed:19354288, ECO:0000269\|PubMed:25372031, ECO:0000269\|PubMed:9311977}.
Subcellular location:		Cytoplasmic vesicle, secretory vesicle lumen {ECO:0000250\|UniProtKB:Q3TMQ6}. Secreted {ECO:0000250\|UniProtKB:P10152}. Nucleus {ECO:0000269\|PubMed:12051708, ECO:0000269\|PubMed:25372031}. Nucleus, nucleolus {ECO:0000269\|PubMed:7945327}. Note=Rapidly endocytosed by target cells and translocated to the nucleus where it accumulates in the nucleolus and binds to DNA (PubMed:12051708). {ECO:0000269\|PubMed:12051708}.
Tissue specificity:		Expressed predominantly in the liver. Also detected in endothelial cells and spinal cord neurons. {ECO:0000269\|PubMed:17886298, ECO:0000269\|PubMed:2440105}.
Developmental stage:		Low level expression in the developing fetus, increased in the neonate, and maximal in the adult.
Disease:		Amyotrophic lateral sclerosis 9 (ALS9) [MIM:611895]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269\|PubMed:15557516, ECO:0000269\|PubMed:16501576, ECO:0000269\|PubMed:17703939, ECO:0000269\|PubMed:17886298, ECO:0000269\|PubMed:17900154, ECO:0000269\|PubMed:18087731, ECO:0000269\|PubMed:22292843, ECO:0000269\|PubMed:25372031}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Similarity:		Belongs to the pancreatic ribonuclease family. {ECO:0000305}.
Sequence caution:		Sequence=AAH20704.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};