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Protein

DnaJ homolog subfamily C member 2

Gene

DNAJC2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: 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, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation. Specifically binds DNA sequence 5'-GTCAAGC-3'.3 Publications

Miscellaneous

Constitutes a myeloid leukemia-associated antigen and might be a target for leukemia T-cell therapy.

GO - Molecular functioni

  • ATPase activator activity Source: Reactome
  • chromatin binding Source: UniProtKB
  • DNA binding Source: InterPro
  • histone binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • ubiquitin modification-dependent histone binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator, Chaperone, Chromatin regulator
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-3371453 Regulation of HSF1-mediated heat shock response

Names & Taxonomyi

Protein namesi
Recommended name:
DnaJ homolog subfamily C member 2
Alternative name(s):
M-phase phosphoprotein 11
Zuotin-related factor 1
Cleaved into the following chain:
Gene namesi
Name:DNAJC2
Synonyms:MPHOSPH11, MPP11, ZRF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000105821.14
HGNCiHGNC:13192 DNAJC2
MIMi605502 gene
neXtProtiNX_Q99543

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi512 – 513HQ → AA: Loss of function. 1 Publication2

Organism-specific databases

DisGeNETi27000
OpenTargetsiENSG00000105821
PharmGKBiPA162383835

Polymorphism and mutation databases

BioMutaiDNAJC2
DMDMi296439472

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004257521 – 621DnaJ homolog subfamily C member 2Add BLAST621
Initiator methionineiRemoved; alternate1 Publication
ChainiPRO_00000711232 – 621DnaJ homolog subfamily C member 2, N-terminally processedAdd BLAST620

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei47PhosphoserineCombined sources1
Modified residuei49PhosphoserineCombined sources1
Modified residuei60PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated in M (mitotic) phase.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ99543
MaxQBiQ99543
PaxDbiQ99543
PeptideAtlasiQ99543
PRIDEiQ99543

PTM databases

iPTMnetiQ99543
PhosphoSitePlusiQ99543

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

Expression is repressed by CEBPA. Strongly overexpressed in leukemic cells.3 Publications

Gene expression databases

BgeeiENSG00000105821
CleanExiHS_DNAJC2
ExpressionAtlasiQ99543 baseline and differential
GenevisibleiQ99543 HS

Organism-specific databases

HPAiHPA020454

Interactioni

Subunit structurei

Interacts (via ZRF1-UBD region) with ID1 (By similarity). Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
HIST1H2AMP0C0S82EBI-11017224,EBI-1390628

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • ubiquitin modification-dependent histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi117946, 21 interactors
DIPiDIP-60462N
IntActiQ99543, 5 interactors
STRINGi9606.ENSP00000368565

Structurei

Secondary structure

1621
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi556 – 568Combined sources13
Helixi576 – 583Combined sources8
Helixi589 – 618Combined sources30

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M2ENMR-A551-621[»]
ProteinModelPortaliQ99543
SMRiQ99543
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini88 – 161JPROSITE-ProRule annotationAdd BLAST74
Domaini449 – 511SANT 1PROSITE-ProRule annotationAdd BLAST63
Domaini549 – 604SANT 2PROSITE-ProRule annotationAdd BLAST56

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni23 – 31Epitope (recognized by CD8(+) cytotoxic T-lymphocytes)9
Regioni160 – 250ZRF1-UBDAdd BLAST91

Domaini

The ZRF1-UBD region specifically recognizes and binds H2AK119ub. The ZRF1-UBD region is also involved in protein-protein interactions with other proteins, suggesting that it may be masked by some regulator, thereby preventing its association with H2AK119ub.1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0724 Eukaryota
COG5269 LUCA
GeneTreeiENSGT00530000063419
HOGENOMiHOG000006900
HOVERGENiHBG008782
InParanoidiQ99543
KOiK09522
OMAiTTPDRWD
OrthoDBiEOG091G04S8
PhylomeDBiQ99543
TreeFamiTF105834

Family and domain databases

CDDicd06257 DnaJ, 1 hit
cd00167 SANT, 2 hits
Gene3Di1.10.287.110, 1 hit
InterProiView protein in InterPro
IPR001623 DnaJ_domain
IPR018253 DnaJ_domain_CS
IPR009057 Homeobox-like_sf
IPR036869 J_dom_sf
IPR032003 RAC_head
IPR001005 SANT/Myb
IPR017884 SANT_dom
PfamiView protein in Pfam
PF00226 DnaJ, 1 hit
PF00249 Myb_DNA-binding, 2 hits
PF16717 RAC_head, 1 hit
SMARTiView protein in SMART
SM00271 DnaJ, 1 hit
SM00717 SANT, 2 hits
SUPFAMiSSF46565 SSF46565, 1 hit
SSF46689 SSF46689, 2 hits
PROSITEiView protein in PROSITE
PS00636 DNAJ_1, 1 hit
PS50076 DNAJ_2, 1 hit
PS51293 SANT, 2 hits

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99543-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLLLPSAADG RGTAITHALT SASTLCQVEP VGRWFEAFVK RRNRNASASF
60 70 80 90 100
QELEDKKELS EESEDEELQL EEFPMLKTLD PKDWKNQDHY AVLGLGHVRY
110 120 130 140 150
KATQRQIKAA HKAMVLKHHP DKRKAAGEPI KEGDNDYFTC ITKAYEMLSD
160 170 180 190 200
PVKRRAFNSV DPTFDNSVPS KSEAKDNFFE VFTPVFERNS RWSNKKNVPK
210 220 230 240 250
LGDMNSSFED VDIFYSFWYN FDSWREFSYL DEEEKEKAEC RDERRWIEKQ
260 270 280 290 300
NRATRAQRKK EEMNRIRTLV DNAYSCDPRI KKFKEEEKAK KEAEKKAKAE
310 320 330 340 350
AKRKEQEAKE KQRQAELEAA RLAKEKEEEE VRQQALLAKK EKDIQKKAIK
360 370 380 390 400
KERQKLRNSC KTWNHFSDNE AERVKMMEEV EKLCDRLELA SLQCLNETLT
410 420 430 440 450
SCTKEVGKAA LEKQIEEINE QIRKEKEEAE ARMRQASKNT EKSTGGGGNG
460 470 480 490 500
SKNWSEDDLQ LLIKAVNLFP AGTNSRWEVI ANYMNIHSSS GVKRTAKDVI
510 520 530 540 550
GKAKSLQKLD PHQKDDINKK AFDKFKKEHG VVPQADNATP SERFEGPYTD
560 570 580 590 600
FTPWTTEEQK LLEQALKTYP VNTPERWEKI AEAVPGRTKK DCMKRYKELV
610 620
EMVKAKKAAQ EQVLNASRAK K
Length:621
Mass (Da):71,996
Last modified:May 18, 2010 - v4
Checksum:iE4DAEE7A73D0F64C
GO
Isoform 2 (identifier: Q99543-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     362-414: Missing.

Show »
Length:568
Mass (Da):65,913
Checksum:i390BA8AC8C0DFCAD
GO

Sequence cautioni

The sequence AAI39752 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAA66913 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti252R → G in CAA66913 (PubMed:8885239).Curated1
Sequence conflicti472G → R in CAA66913 (PubMed:8885239).Curated1
Sequence conflicti578E → K in AAI39752 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023562362 – 414Missing in isoform 2. 1 PublicationAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98260 mRNA Translation: CAA66913.1 Different initiation.
AC004668 Genomic DNA No translation available.
BC000859 mRNA Translation: AAH00859.1
BC139751 mRNA Translation: AAI39752.1 Different initiation.
CCDSiCCDS43628.1 [Q99543-1]
CCDS47679.1 [Q99543-2]
RefSeqiNP_001123359.1, NM_001129887.1 [Q99543-2]
NP_055192.1, NM_014377.1 [Q99543-1]
UniGeneiHs.558476

Genome annotation databases

EnsembliENST00000249270; ENSP00000249270; ENSG00000105821 [Q99543-2]
ENST00000379263; ENSP00000368565; ENSG00000105821 [Q99543-1]
GeneIDi27000
KEGGihsa:27000
UCSCiuc003vbo.4 human [Q99543-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiDNJC2_HUMAN
AccessioniPrimary (citable) accession number: Q99543
Secondary accession number(s): A4VCI0, Q9BVX1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 18, 2010
Last modified: May 23, 2018
This is version 168 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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