Human Gene HSPA8 (ENST00000453788.6) from GENCODE V44
Description: Homo sapiens heat shock protein family A (Hsp70) member 8 (HSPA8), transcript variant 2, mRNA. (from RefSeq NM_153201) RefSeq Summary (NM_153201): This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]. Gencode Transcript: ENST00000453788.6 Gencode Gene: ENSG00000109971.14 Transcript (Including UTRs) Position: hg38 chr11:123,057,489-123,062,335 Size: 4,847 Total Exon Count: 8 Strand: - Coding Region Position: hg38 chr11:123,057,734-123,061,324 Size: 3,591 Coding Exon Count: 7
ID:HSP7C_HUMAN DESCRIPTION: RecName: Full=Heat shock cognate 71 kDa protein; AltName: Full=Heat shock 70 kDa protein 8; FUNCTION: Acts 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. SUBUNIT: Identified in a mRNP granule complex, at least composed of ACTB, ACTN4, DHX9, ERG, HNRNPA1, HNRNPA2B1, HNRNPAB, HNRNPD, HNRNPL, HNRNPR, HNRNPU, HSPA1, HSPA8, IGF2BP1, ILF2, ILF3, NCBP1, NCL, PABPC1, PABPC4, PABPN1, RPLP0, RPS3, RPS3A, RPS4X, RPS8, RPS9, SYNCRIP, TROVE2, YBX1 and untranslated mRNAs. Interacts with PACRG. Interacts with HSPH1/HSP105. Interacts with IRAK1BP1 and BAG1. Interacts with DNAJC7. 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. INTERACTION: P60709:ACTB; NbExp=2; IntAct=EBI-351896, EBI-353944; P49407:ARRB1; NbExp=4; IntAct=EBI-351896, EBI-743313; P32121:ARRB2; NbExp=4; IntAct=EBI-351896, EBI-714559; Q9UNE7:STUB1; NbExp=3; IntAct=EBI-351896, EBI-357085; SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Nucleus, nucleolus. 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. TISSUE SPECIFICITY: Ubiquitous. INDUCTION: Constitutively synthesized. DOMAIN: The N-terminal 1-386 residues constitute the ATPase domain, while residues 387-646 form the peptide-binding domain. PTM: Acetylated. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: ISGylated. SIMILARITY: Belongs to the heat shock protein 70 family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P11142
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000398 mRNA splicing, via spliceosome GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006397 mRNA processing GO:0006457 protein folding GO:0006986 response to unfolded protein GO:0008380 RNA splicing GO:0009267 cellular response to starvation GO:0016032 viral process GO:0019221 cytokine-mediated signaling pathway GO:0031647 regulation of protein stability GO:0042026 protein refolding GO:0043254 regulation of protein complex assembly GO:0043312 neutrophil degranulation GO:0043488 regulation of mRNA stability GO:0044788 modulation by host of viral process GO:0044829 positive regulation by host of viral genome replication GO:0045892 negative regulation of transcription, DNA-templated GO:0046034 ATP metabolic process GO:0048026 positive regulation of mRNA splicing, via spliceosome GO:0051085 chaperone mediated protein folding requiring cofactor GO:0051726 regulation of cell cycle GO:0061024 membrane organization GO:0061635 regulation of protein complex stability GO:0061684 chaperone-mediated autophagy GO:0061738 late endosomal microautophagy GO:0061740 protein targeting to lysosome involved in chaperone-mediated autophagy GO:0061741 chaperone-mediated protein transport involved in chaperone-mediated autophagy GO:0072318 clathrin coat disassembly GO:1900034 regulation of cellular response to heat GO:1902904 negative regulation of supramolecular fiber organization GO:1904589 regulation of protein import GO:1904764 chaperone-mediated autophagy translocation complex disassembly
JD304292 - Sequence 285316 from Patent EP1572962. AF217511 - Homo sapiens uncharacterized bone marrow protein BM034 mRNA, complete cds. BC007276 - Homo sapiens heat shock 70kDa protein 8, mRNA (cDNA clone IMAGE:3162067), partial cds. AB073886 - Homo sapiens primary neuroblastoma cDNA, clone:Nbla02874, full insert sequence. BC016660 - Homo sapiens heat shock 70kDa protein 8, mRNA (cDNA clone MGC:9495 IMAGE:3923981), complete cds. EU668349 - Homo sapiens epididymis luminal protein 33 (HEL-33) mRNA, complete cds. AK222628 - Homo sapiens mRNA for heat shock 70kDa protein 8 isoform 2 variant, clone: CBL04813. AK096100 - Homo sapiens cDNA FLJ38781 fis, clone LIVER2000216, highly similar to HEAT SHOCK COGNATE 71 KDA PROTEIN. FJ224294 - Homo sapiens epididymis secretory sperm binding protein Li 72p (HEL-S-72p) mRNA, complete cds. GQ891398 - Homo sapiens clone HEL-S-92 epididymis secretory sperm binding protein mRNA, complete cds. JD304291 - Sequence 285315 from Patent EP1572962. AK129885 - Homo sapiens cDNA FLJ26375 fis, clone HRT06292, highly similar to Heat shock cognate 71 kDa protein. AK000571 - Homo sapiens cDNA FLJ20564 fis, clone KAT12033. BC008907 - Homo sapiens heat shock 70kDa protein 8, mRNA (cDNA clone IMAGE:3836086), partial cds. BC015699 - Homo sapiens, clone IMAGE:3906958, mRNA, partial cds. BC016179 - Homo sapiens heat shock 70kDa protein 8, mRNA (cDNA clone MGC:17984 IMAGE:3920744), complete cds. BC112920 - Homo sapiens heat shock 70kDa protein 8, mRNA (cDNA clone IMAGE:7484542), **** WARNING: chimeric clone ****. BC042163 - Homo sapiens heat shock 70kDa protein 8, mRNA (cDNA clone IMAGE:4862437), **** WARNING: chimeric clone ****. BC019816 - Homo sapiens heat shock 70kDa protein 8, mRNA (cDNA clone MGC:29929 IMAGE:2899894), complete cds. AK292067 - Homo sapiens cDNA FLJ77848 complete cds. AF352832 - Homo sapiens constitutive heat shock protein 70 (HSC70) mRNA, complete cds. JD288827 - Sequence 269851 from Patent EP1572962. AK303935 - Homo sapiens cDNA FLJ55485 complete cds, highly similar to Heat shock cognate 71 kDa protein. AK222785 - Homo sapiens mRNA for heat shock 70kDa protein 8 isoform 1 variant, clone: HEP02822. AB034951 - Homo sapiens HSC54 mRNA for heat shock cognate protein 54, complete cds. KJ905785 - Synthetic construct Homo sapiens clone ccsbBroadEn_15455 HSPA8 gene, encodes complete protein. GQ891324 - Homo sapiens clone HEL-S-55b epididymis secretory sperm binding protein mRNA, complete cds. KJ901499 - Synthetic construct Homo sapiens clone ccsbBroadEn_10893 HSPA8 gene, encodes complete protein. KJ897016 - Synthetic construct Homo sapiens clone ccsbBroadEn_06410 HSPA8 gene, encodes complete protein. DQ891145 - Synthetic construct clone IMAGE:100003775; FLH169720.01X; RZPDo839F0596D heat shock 70kDa protein 8 (HSPA8) gene, encodes complete protein. DQ894325 - Synthetic construct Homo sapiens clone IMAGE:100008785; FLH169716.01L; RZPDo839F0595D heat shock 70kDa protein 8 (HSPA8) gene, encodes complete protein. AB527307 - Synthetic construct DNA, clone: pF1KB5306, Homo sapiens HSPA8 gene for heat shock 70kDa protein 8, without stop codon, in Flexi system. JD143036 - Sequence 124060 from Patent EP1572962. JD492279 - Sequence 473303 from Patent EP1572962. JD546621 - Sequence 527645 from Patent EP1572962. AK310467 - Homo sapiens cDNA, FLJ17509. AK300404 - Homo sapiens cDNA FLJ59163 complete cds, highly similar to Heat shock cognate 71 kDa protein. DL490036 - Novel nucleic acids. JD328913 - Sequence 309937 from Patent EP1572962. DQ595374 - Homo sapiens piRNA piR-61486, complete sequence. JD020302 - Sequence 1326 from Patent EP1572962. JD027769 - Sequence 8793 from Patent EP1572962. DQ591926 - Homo sapiens piRNA piR-59038, complete sequence. JD369809 - Sequence 350833 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03040 - Spliceosome hsa04010 - MAPK signaling pathway hsa04144 - Endocytosis hsa04612 - Antigen processing and presentation
Reactome (by CSHL, EBI, and GO)
Protein P11142 (Reactome details) participates in the following event(s):
R-HSA-445087 CHL1 interacts with HSP7C R-HSA-450551 AUF1 binds translation and heat shock proteins R-HSA-888589 Release of GABA at the synapse R-HSA-8932221 METTL21A transfers 3xCH3 from 3xAdoMet to HSPA8 R-HSA-421836 trans-Golgi Network Derived Vesicle Uncoating R-HSA-432688 trans-Golgi Network Derived Lysosomal Vesicle Uncoating R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle R-HSA-917744 GABA loaded synaptic vesicle Docking and Priming R-HSA-72124 Formation of the Spliceosomal A Complex R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins R-HSA-6798748 Exocytosis of secretory granule lumen proteins R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating R-HSA-5252079 HSP110s exchange ATP for ADP on HSP70s:ADP R-HSA-5251959 HSP40s activate intrinsic ATPase activity of HSP70s in the cytosol R-HSA-5251942 Hikeshi binds HSP70s:ATP R-HSA-3371503 STIP1(HOP) binds HSP90 and HSP70:HSP40:nascent protein R-HSA-3371422 ATP hydrolysis by HSP70 R-HSA-3371590 HSP70 binds to HSP40:nascent protein R-HSA-5618098 p23 (PTGES3) binds HSP90:ATP:FKBP5:nascent protein R-HSA-5618110 p23 (PTGES3) binds HSP90:ATP:FKBP4:nascent protein R-HSA-5251955 HSP40s activate intrinsic ATPase activity of HSP70s in the nucleoplasm R-HSA-72143 Lariat Formation and 5'-Splice Site Cleavage R-HSA-72139 Formation of the active Spliceosomal C (B*) complex R-HSA-72127 Formation of the Spliceosomal B Complex R-HSA-72130 Formation of an intermediate Spliceosomal C (Bact) complex R-HSA-156661 Formation of Exon Junction Complex R-HSA-5082384 HSP70:DNAJB1 binds HSF1 R-HSA-5252041 NPC transports Hikeshi:HSP70s:ATP from cytosol to nucleoplasm R-HSA-5618085 FKBP4 binds HSP90:ATP:STIP1:HSP70:nascent protein R-HSA-5618105 FKBP5 binds HSP90:ATP:STIP1:HSP70:nascent protein R-HSA-5618107 ATP binding to HSP90 triggers conformation change R-HSA-5082369 Acetylated HSF1 dissociates from DNA R-HSA-3371518 SIRT1 binds to HSF1 R-HSA-3371554 HSF1 acetylation at Lys80 R-HSA-3371467 SIRT1 deacetylates HSF1 R-HSA-447041 CHL1 interactions R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA R-HSA-888590 GABA synthesis, release, reuptake and degradation R-HSA-8876725 Protein methylation R-HSA-432722 Golgi Associated Vesicle Biogenesis R-HSA-432720 Lysosome Vesicle Biogenesis R-HSA-8856828 Clathrin-mediated endocytosis R-HSA-6785807 Interleukin-4 and 13 signaling R-HSA-373760 L1CAM interactions R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-112310 Neurotransmitter release cycle R-HSA-72163 mRNA Splicing - Major Pathway R-HSA-3371571 HSF1-dependent transactivation R-HSA-597592 Post-translational protein modification R-HSA-6798695 Neutrophil degranulation R-HSA-421837 Clathrin derived vesicle budding R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-199991 Membrane Trafficking R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) R-HSA-449147 Signaling by Interleukins R-HSA-422475 Axon guidance R-HSA-8953854 Metabolism of RNA R-HSA-112315 Transmission across Chemical Synapses R-HSA-72172 mRNA Splicing R-HSA-3371568 Attenuation phase R-HSA-3371556 Cellular response to heat stress R-HSA-392499 Metabolism of proteins R-HSA-168249 Innate Immune System R-HSA-199992 trans-Golgi Network Vesicle Budding R-HSA-5653656 Vesicle-mediated transport R-HSA-2262752 Cellular responses to stress R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-1266738 Developmental Biology R-HSA-112316 Neuronal System R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA R-HSA-168256 Immune System R-HSA-8953897 Cellular responses to external stimuli