UniProt functional annotation for Q99543



	UniProt functional annotation for Q99543

UniProt code: Q99543.

Organism: Homo sapiens (Human).

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

Function: Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation. {ECO:0000269|PubMed:15802566, ECO:0000269|PubMed:16002468, ECO:0000269|PubMed:21179169}.

Subunit: Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2 (PubMed:16002468). Interacts (via ZRF1-UBD region) with ID1 (By similarity). {ECO:0000250|UniProtKB:P54103, ECO:0000269|PubMed:16002468}.

Subcellular location: Nucleus {ECO:0000269|PubMed:21179169}. Cytoplasm, cytosol {ECO:0000269|PubMed:16002468, ECO:0000269|PubMed:21179169}.

Tissue specificity: Widely expressed. {ECO:0000269|PubMed:11034098}.

Induction: Expression is repressed by CEBPA. Strongly overexpressed in leukemic cells. {ECO:0000269|PubMed:12800198, ECO:0000269|PubMed:14696097, ECO:0000269|PubMed:17242690}.

Domain: The ZRF1-UBD region specifically recognizes and binds H2AK119ub. The ZRF1-UBD region is also involved in protein-protein interactions with other proteins, suggesting that it may be masked by some regulator, thereby preventing its association with H2AK119ub. {ECO:0000269|PubMed:21179169}.

Ptm: Phosphorylated in M (mitotic) phase. {ECO:0000269|PubMed:8885239}.

Miscellaneous: Constitutes a myeloid leukemia-associated antigen and might be a target for leukemia T-cell therapy.

Sequence caution: Sequence=AAI39752.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA66913.1; Type=Erroneous initiation; Note=Extended 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:		Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation. {ECO:0000269\|PubMed:15802566, ECO:0000269\|PubMed:16002468, ECO:0000269\|PubMed:21179169}.


Subunit:		Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2 (PubMed:16002468). Interacts (via ZRF1-UBD region) with ID1 (By similarity). {ECO:0000250\|UniProtKB:P54103, ECO:0000269\|PubMed:16002468}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:21179169}. Cytoplasm, cytosol {ECO:0000269\|PubMed:16002468, ECO:0000269\|PubMed:21179169}.
Tissue specificity:		Widely expressed. {ECO:0000269\|PubMed:11034098}.
Induction:		Expression is repressed by CEBPA. Strongly overexpressed in leukemic cells. {ECO:0000269\|PubMed:12800198, ECO:0000269\|PubMed:14696097, ECO:0000269\|PubMed:17242690}.
Domain:		The ZRF1-UBD region specifically recognizes and binds H2AK119ub. The ZRF1-UBD region is also involved in protein-protein interactions with other proteins, suggesting that it may be masked by some regulator, thereby preventing its association with H2AK119ub. {ECO:0000269\|PubMed:21179169}.
Ptm:		Phosphorylated in M (mitotic) phase. {ECO:0000269\|PubMed:8885239}.
Miscellaneous:		Constitutes a myeloid leukemia-associated antigen and might be a target for leukemia T-cell therapy.
Sequence caution:		Sequence=AAI39752.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA66913.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};