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MGP001517

UniProt Annotations

Entry Information
Gene Nameheat shock 70kDa protein 8
Protein EntryHSP7C_HUMAN
UniProt IDP11142
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P11142-1; Sequence=Displayed; Name=2; Synonyms=HSC54; IsoId=P11142-2; Sequence=VSP_002427;
DomainThe N-terminal 1-386 residues constitute the ATPase domain, while residues 387-646 form the peptide-binding domain. {ECO:0000269|PubMed:9305631}.
FunctionActs as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19- CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase CHIP. {ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:23990462}.
InductionConstitutively synthesized.
InteractionQ99IB8:- (xeno); NbExp=3; IntAct=EBI-351896, EBI-6927928; P60709:ACTB; NbExp=2; IntAct=EBI-351896, EBI-353944; Q9GZX7:AICDA; NbExp=2; IntAct=EBI-351896, EBI-3834328; P49407:ARRB1; NbExp=4; IntAct=EBI-351896, EBI-743313; P32121:ARRB2; NbExp=4; IntAct=EBI-351896, EBI-714559; Q9NQ11:ATP13A2; NbExp=2; IntAct=EBI-351896, EBI-6308763; Q99933:BAG1; NbExp=10; IntAct=EBI-351896, EBI-1030678; O95816:BAG2; NbExp=3; IntAct=EBI-351896, EBI-355275; Q8AZK7:EBNA-LP (xeno); NbExp=3; IntAct=EBI-351896, EBI-1185167; P00533:EGFR; NbExp=5; IntAct=EBI-351896, EBI-297353; O14976:GAK; NbExp=5; IntAct=EBI-351896, EBI-714707; P00338:LDHA; NbExp=4; IntAct=EBI-351896, EBI-372327; Q5S007:LRRK2; NbExp=5; IntAct=EBI-351896, EBI-5323863; P03485:M (xeno); NbExp=4; IntAct=EBI-351896, EBI-2547543; Q9UNE7:STUB1; NbExp=5; IntAct=EBI-351896, EBI-357085;
PtmAcetylated. {ECO:0000269|PubMed:19413330, ECO:0000269|PubMed:19608861, ECO:0000269|Ref.5, ECO:0000269|Ref.6}.
PtmISGylated. {ECO:0000269|PubMed:16139798, ECO:0000269|PubMed:16815975}.
PtmTrimethylation at Lys-561 reduces fibrillar SNCA binding.
SimilarityBelongs to the heat shock protein 70 family. {ECO:0000305}.
Subcellular LocationCytoplasm. Melanosome. Nucleus, nucleolus. Cell membrane. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Translocates rapidly from the cytoplasm to the nuclei, and especially to the nucleoli, upon heat shock.
SubunitIdentified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PACRG. Interacts with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts with DNAJC7 and DNAJB14 (via J domain). Interacts (via C-terminus) with the E3 ligase CHIP forming a 210 kDa complex of one CHIP and two HSPA8 molecules. Interacts with CITED1 (via N-terminus); the interaction suppresses the association of CITED1 to p300/CBP and Smad-mediated transcription transactivation. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts with SV40 VP1. Interacts with TRIM5. Part of a complex composed at least of ASCL2, C11orf30/EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with METTL21A. Following LPS binding, may form a complex with CXCR4, GDF5 and HSP90AA1. Interacts with PARK2. {ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11147964, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:14532270, ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:16815975, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:20053985, ECO:0000269|PubMed:23865999, ECO:0000269|PubMed:23921388, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24270810, ECO:0000269|PubMed:9305631, ECO:0000269|PubMed:9679980}.
Tissue SpecificityUbiquitous. {ECO:0000269|PubMed:11276205}.
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