ID   HS12A_HUMAN             Reviewed;         675 AA.
AC   O43301;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2003, sequence version 2.
DT   28-JAN-2026, entry version 167.
DE   RecName: Full=Heat shock 70 kDa protein 12A;
DE   AltName: Full=Heat shock protein family A member 12A;
GN   Name=HSPA12A; Synonyms=KIAA0417;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA   Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA   Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT   new cDNA clones from brain which code for large proteins in vitro.";
RL   DNA Res. 4:307-313(1997).
RN   [2]
RP   IDENTIFICATION, AND TISSUE SPECIFICITY.
RX   PubMed=12552099; DOI=10.1073/pnas.252764399;
RA   Han Z., Truong Q.A., Park S., Breslow J.L.;
RT   "Two Hsp70 family members expressed in atherosclerotic lesions.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:1256-1261(2003).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH SORL1.
RX   PubMed=30679749; DOI=10.1038/s41598-018-37336-6;
RA   Madsen P., Isaksen T.J., Siupka P., Toth A.E., Nyegaard M., Gustafsen C.,
RA   Nielsen M.S.;
RT   "HSPA12A targets the cytoplasmic domain and affects the trafficking of the
RT   Amyloid Precursor Protein receptor SorLA.";
RL   Sci. Rep. 9:611-611(2019).
CC   -!- FUNCTION: Adapter protein for SORL1, but not SORT1. Delays SORL1
CC       internalization and affects SORL1 subcellular localization.
CC       {ECO:0000269|PubMed:30679749}.
CC   -!- SUBUNIT: Interacts with SORL1 (via cytosolic C-terminus); this
CC       interaction affects SORL1 internalization and subcellular localization.
CC       {ECO:0000269|PubMed:30679749}.
CC   -!- INTERACTION:
CC       O43301; Q96MM6: HSPA12B; NbExp=6; IntAct=EBI-296980, EBI-10291310;
CC       O43301; Q92673: SORL1; NbExp=5; IntAct=EBI-296980, EBI-1171329;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8K0U4}. Nucleus
CC       {ECO:0000250|UniProtKB:Q8K0U4}.
CC   -!- TISSUE SPECIFICITY: Widely expressed with highest levels in brain,
CC       kidney and muscle. {ECO:0000269|PubMed:12552099}.
CC   -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA24847.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AB007877; BAA24847.1; ALT_INIT; mRNA.
DR   CCDS; CCDS41569.1; -.
DR   PIR; T00055; T00055.
DR   RefSeq; NP_079291.2; NM_025015.2.
DR   AlphaFoldDB; O43301; -.
DR   SMR; O43301; -.
DR   BioGRID; 129226; 122.
DR   FunCoup; O43301; 582.
DR   IntAct; O43301; 80.
DR   MINT; O43301; -.
DR   STRING; 9606.ENSP00000489674; -.
DR   GlyCosmos; O43301; 2 sites, 1 glycan.
DR   GlyGen; O43301; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; O43301; -.
DR   PhosphoSitePlus; O43301; -.
DR   SwissPalm; O43301; -.
DR   BioMuta; HSPA12A; -.
DR   jPOST; O43301; -.
DR   MassIVE; O43301; -.
DR   PaxDb; 9606-ENSP00000358211; -.
DR   PeptideAtlas; O43301; -.
DR   ProteomicsDB; 48876; -.
DR   Pumba; O43301; -.
DR   Antibodypedia; 2201; 107 antibodies from 24 providers.
DR   DNASU; 259217; -.
DR   Ensembl; ENST00000369209.8; ENSP00000358211.3; ENSG00000165868.16.
DR   GeneID; 259217; -.
DR   KEGG; hsa:259217; -.
DR   MANE-Select; ENST00000369209.8; ENSP00000358211.3; NM_025015.3; NP_079291.2.
DR   UCSC; uc001lct.3; human.
DR   AGR; HGNC:19022; -.
DR   ClinPGx; PA38779; -.
DR   CTD; 259217; -.
DR   DisGeNET; 259217; -.
DR   GeneCards; HSPA12A; -.
DR   HGNC; HGNC:19022; HSPA12A.
DR   HPA; ENSG00000165868; Tissue enhanced (brain).
DR   MIM; 610701; gene.
DR   OpenTargets; ENSG00000165868; -.
DR   VEuPathDB; HostDB:ENSG00000165868; -.
DR   eggNOG; KOG0101; Eukaryota.
DR   GeneTree; ENSGT00940000154551; -.
DR   HOGENOM; CLU_009958_5_3_1; -.
DR   InParanoid; O43301; -.
DR   OMA; MGRCTSR; -.
DR   OrthoDB; 2963168at2759; -.
DR   PAN-GO; O43301; 0 GO annotations based on evolutionary models.
DR   PhylomeDB; O43301; -.
DR   PathwayCommons; O43301; -.
DR   Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR   SignaLink; O43301; -.
DR   Agora; ENSG00000165868; -.
DR   BioGRID-ORCS; 259217; 6 hits in 1141 CRISPR screens.
DR   CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities.
DR   ChiTaRS; HSPA12A; human.
DR   GenomeRNAi; 259217; -.
DR   Pharos; O43301; Tbio.
DR   PRO; PR:O43301; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; O43301; protein.
DR   Bgee; ENSG00000165868; Expressed in lateral nuclear group of thalamus and 178 other cell types or tissues.
DR   ExpressionAtlas; O43301; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0051170; P:import into nucleus; IEA:Ensembl.
DR   GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR   GO; GO:0001889; P:liver development; IEA:Ensembl.
DR   GO; GO:0042116; P:macrophage activation; IEA:Ensembl.
DR   CDD; cd11735; ASKHA_NBD_HSP70_HSPA12A; 1.
DR   FunFam; 3.30.420.40:FF:000061; Heat shock protein family A (Hsp70) member 12A; 1.
DR   FunFam; 3.90.640.10:FF:000011; Heat shock protein family A (Hsp70) member 12A; 1.
DR   Gene3D; 3.30.420.40; -; 2.
DR   Gene3D; 3.90.640.10; Actin, Chain A, domain 4; 1.
DR   InterPro; IPR043129; ATPase_NBD.
DR   InterPro; IPR026685; HSPA12A_NBD.
DR   PANTHER; PTHR14187; ALPHA KINASE/ELONGATION FACTOR 2 KINASE; 1.
DR   PANTHER; PTHR14187:SF46; HEAT SHOCK 70 KDA PROTEIN 12A; 1.
DR   SUPFAM; SSF53067; Actin-like ATPase domain; 2.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Cytoplasm; Nucleotide-binding; Nucleus;
KW   Proteomics identification; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CHAIN           2..675
FT                   /note="Heat shock 70 kDa protein 12A"
FT                   /id="PRO_0000078292"
FT   REGION          1..45
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..13
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        16..25
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        34..45
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
SQ   SEQUENCE   675 AA;  74978 MW;  5DF35D68F9D76437 CRC64;
     MADKEAGGSD GPRETAPTSA YSSPARSLGD TGITPLSPSH IVNDTDSNVS EQQSFLVVVA
     VDFGTTSSGY AYSFTKEPEC IHVMRRWEGG DPGVSNQKTP TTILLTPERK FHSFGYAARD
     FYHDLDPNEA KQWLYLEKFK MKLHTTGDLT MDTDLTAANG KKVKALEIFA YALQYFKEQA
     LKELSDQAGS EFENSDVRWV ITVPAIWKQP AKQFMRQAAY QAGLASPENS EQLIIALEPE
     AASIYCRKLR LHQMIELSSK AAVNGYSGSD TVGAGFTQAK EHIRRNRQSR TFLVENVIGE
     IWSELEEGDK YVVVDSGGGT VDLTVHQIRL PEGHLKELYK ATGGPYGSLG VDYEFEKLLY
     KIFGEDFIEQ FKIKRPAAWV DLMIAFESRK RAAAPDRTNP LNITLPFSFI DYYKKFRGHS
     VEHALRKSNV DFVKWSSQGM LRMSPDAMNA LFKPTIDSII EHLRDLFQKP EVSTVKFLFL
     VGGFAEAPLL QQAVQAAFGD QCRIIIPQDV GLTILKGAVL FGLDPAVIKV RRSPLTYGVG
     VLNRYVEGKH PPEKLLVKDG TRWCTDVFDK FISADQSVAL GELVKRSYTP AKPSQLVIVI
     NIYSSEHDNV SFITDPGVKK CGTLRLDLTG TSGTAVPARR EIQTLMQFGD TEIKATAIDI
     ATSKSVKVGI DFLNY
//