Heat shock cognate 71 kDa protein (EC 3.6.4.10) (Heat shock 70 kDa protein 8) (Lipopolysaccharide-associated protein 1) (LAP-1) (LPS-associated protein 1)
1_MSKGP 6_ AVGID 11_ LGTTY 16_ SCVGV 21_ FQHGK 26_ VEIIA 31_ NDQGN 36_ RTTPS 41_ YVAFT 46_ DTERL 51_ IGDAA 56_ KNQVA 61_ MNPTN 66_ TVFDA 71_ KRLIG 76_ RRFDD 81_ AVVQS 86_ DMKHW 91_ PFMVV 96_ NDAGR 101_ PKVQV 106_ EYKGE 111_ TKSFY 116_ PEEVS 121_ SMVLT 126_ KMKEI 131_ AEAYL 136_ GKTVT 141_ NAVVT 146_ VPAYF 151_ NDSQR 156_ QATKD 161_ AGTIA 166_ GLNVL 171_ RIINE 176_ PTAAA 181_ IAYGL 186_ DKKVG 191_ AERNV 196_ LIFDL 201_ GGGTF 206_ DVSIL 211_ TIEDG 216_ IFEVK 221_ STAGD 226_ THLGG 231_ EDFDN 236_ RMVNH 241_ FIAEF 246_ KRKHK 251_ KDISE 256_ NKRAV 261_ RRLRT 266_ ACERA 271_ KRTLS 276_ SSTQA 281_ SIEID 286_ SLYEG 291_ IDFYT 296_ SITRA 301_ RFEEL 306_ NADLF 311_ RGTLD 316_ PVEKA 321_ LRDAK 326_ LDKSQ 331_ IHDIV 336_ LVGGS 341_ TRIPK 346_ IQKLL 351_ QDFFN 356_ GKELN 361_ KSINP 366_ DEAVA 371_ YGAAV 376_ QAAIL 381_ SGDKS 386_ ENVQD 391_ LLLLD 396_ VTPLS 401_ LGIET 406_ AGGVM 411_ TVLIK 416_ RNTTI 421_ PTKQT 426_ QTFTT 431_ YSDNQ 436_ PGVLI 441_ QVYEG 446_ ERAMT 451_ KDNNL 456_ LGKFE 461_ LTGIP 466_ PAPRG 471_ VPQIE 476_ VTFDI 481_ DANGI 486_ LNVSA 491_ VDKST 496_ GKENK 501_ ITITN 506_ DKGRL 511_ SKEDI 516_ ERMVQ 521_ EAEKY 526_ KAEDE 531_ KQRDK 536_ VSSKN 541_ SLESY 546_ AFNMK 551_ ATVED 556_ EKLQG 561_ KINDE 566_ DKQKI 571_ LDKCN 576_ EIINW 581_ LDKNQ 586_ TAEKE 591_ EFEHQ 596_ QKELE 601_ KVCNP 606_ IITKL 611_ YQSAG 616_ GMPGG 621_ MPGGF 626_ PGGGA 631_ PPSGG 636_ ASSGP 641_TIEEV
1: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661, PubMed:2799391, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24121476, PubMed:24318877, PubMed:26865365, PubMed:27474739). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. 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) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:11559757, PubMed:2799391, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:11559757, PubMed:2799391, PubMed:36586411). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane (PubMed:15894275). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity)