# HSPA14 (HSP70L1 / HSP70-like protein 1) — research notes

UniProt: Q0VDF9 (HSP7E_HUMAN), 509 aa. Gene synonyms HSP60, HSP70L1.

## Core identity
HSP70-family protein and the Hsp70/DnaK-type subunit of the mammalian
ribosome-associated complex (RAC), a heterodimer with the Hsp40/DnaJ-type
co-chaperone DNAJC2 (MPP11). RAC acts at the ribosomal exit tunnel to assist
co-translational folding of nascent polypeptides.

- [file:human/HSPA14/HSPA14-uniprot.txt "FUNCTION: 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, binds to the nascent polypeptide chain, while DNAJC2 stimulates its ATPase activity."]
- [file:human/HSPA14/HSPA14-uniprot.txt "SUBUNIT: Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2."]
- [file:human/HSPA14/HSPA14-uniprot.txt "SUBCELLULAR LOCATION: Cytoplasm, cytosol"]

## RAC paper (PMID:16002468, Otto et al. 2005 PNAS)
Identified the mammalian RAC as MPP11(DNAJC2)/Hsp70L1.
- [PMID:16002468 "Purification of MPP11 revealed that it forms a stable complex with Hsp70L1, a distantly related homolog of Ssz1p."]
- [PMID:16002468 "On the sequence level neither peptide binding domain nor ATPase domains of Hsp70L1 are particularly similar to Ssz1p"]
- Important nuance: like its yeast counterpart Ssz1p, Hsp70L1 is an ATYPICAL Hsp70. In yeast RAC, Ssz1p/zuotin (RAC) act to stimulate the ATPase of the ribosome-bound Hsp70 Ssb1/2p; RAC itself is the co-chaperone module. So HSPA14's own ATP-hydrolysis "chaperone" role is not a canonical autonomous foldase.
- [PMID:16002468 "only the complex of zuotin and Ssz1p (RAC) is able to stimulate the ATPase of the yeast ribosome-bound Hsp70 Ssb1/2p"]
- HeLa immunofluorescence + rat liver fractionation: cytosolic, ribosome-associated.
- [PMID:16002468 "Hsp70L1 comigrated with polysomes and ribosomes and was released by high-salt treatment"]

## GO annotation review notes (goa.tsv)
- IBA nucleus / plasma membrane: family-level PANTHER transfers from canonical Hsp70s; no experimental support for HSPA14 in nucleus or PM. UniProt SUBCELLULAR LOCATION = cytoplasm/cytosol only. -> MARK_AS_OVER_ANNOTATED.
- IBA ATP hydrolysis activity / IEA ATP hydrolysis: HSP70 fold present; HSPA14 has nucleotide-binding domain. ATPase is stimulated by DNAJC2 in the RAC. Keep ATP binding (KW) and ATP hydrolysis as supported by fold + UniProt FUNCTION (DNAJC2 stimulates its ATPase activity). Core enzymatic-ish MF.
- IBA heat shock protein binding GO:0031072: as RAC subunit it binds DNAJC2 (an Hsp40); reasonable. ACCEPT non-core? It binds its J-protein partner. Keep as supporting.
- IBA / IEA protein folding chaperone (GO:0044183 / GO:0140662): HSPA14 functions in co-translational folding as part of RAC. GO:0044183 protein folding chaperone is a reasonable core-ish MF. But it is a co-chaperone module (with DNAJC2), assisting nascent-chain folding — keep as core MF (chaperone) with caveat.
- protein refolding GO:0042026 IBA: canonical Hsp70 refolding transferred from family; HSPA14 is specialized for co-translational (de novo) folding, not stress refolding. MARK_AS_OVER_ANNOTATED / KEEP_AS_NON_CORE.
- ribosome (GO:0005840) colocalizes_with IBA + IDA (PMID:16002468): directly shown. ACCEPT.
- cytosol GO:0005829 IBA/IEA/IDA (PMID:21231916, PMID:16002468): ACCEPT (IDA core localization).
- membrane GO:0016020 HDA (PMID:19946888): high-throughput membrane-proteome detection; HSPA14 is cytosolic/ribosome-associated; peripheral. KEEP_AS_NON_CORE.
- protein folding GO:0006457 NAS (ComplexPortal, PMID:16002468): RAC role. KEEP_AS_NON_CORE (downstream process of chaperone module).
- protein folding chaperone complex GO:0101031 part_of IPI (PMID:16002468): the RAC complex. ACCEPT (this is exactly RAC).
- 'de novo' cotranslational protein folding GO:0051083 TAS (PMID:16002468): the precise BP for RAC. ACCEPT as core process.
- protein binding IPI: partners DNAJC2 (Q99543) — informative (RAC partner) -> capture as Hsp70/chaperone binding; NFAM1 (Q8NET5) — HT interactome, not chaperone-related. Keep DNAJC2 ones meaningful, NFAM1 over-annotated.

Partner ID map: Q99543=DNAJC2(MPP11); Q8NET5=NFAM1.

## Immunoadjuvant / DC activation
Hsp70L1 was reported to activate dendritic cells and act as a Th1 adjuvant
(PubMed:14592822, 15930317, 18851947). This is an applied/immunology property,
not a core GO molecular function; not in GOA. Noted, not annotated.

## Core function synthesis
1. Hsp70/DnaK-type chaperone subunit of RAC — ATP-dependent, co-translational
   folding of nascent chains (GO:0044183 protein folding chaperone; process
   GO:0051083 de novo cotranslational protein folding; complex GO:0101031).
2. ATP binding / ATP hydrolysis (HSP70 NBD), stimulated by DNAJC2.