Q99543 (DNJC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DnaJ homolog subfamily C member 2

Alternative name(s):
M-phase phosphoprotein 11
Zuotin-related factor 1

Gene names

Name:	DNAJC2
Synonyms:	MPHOSPH11, MPP11, ZRF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	621 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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'. Ref.8 Ref.9 Ref.15
Subunit structure	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. Ref.8
Subcellular location	Nucleus. Cytoplasm › cytosol Ref.8 Ref.15.
Tissue specificity	Widely expressed. Ref.5
Induction	Expression is repressed by CEBPA. Strongly overexpressed in leukemic cells. Ref.6 Ref.7 Ref.11
Domain	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. Ref.15
Post-translational modification	Phosphorylated in M (mitotic) phase. Ref.1
Miscellaneous	Constitutes a myeloid leukemia-associated antigen and might be a target for leukemia T-cell therapy.
Sequence similarities	Contains 1 J domain. Contains 2 SANT domains.
Sequence caution	The sequence AAI39752.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAA66913.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Molecular function	Activator Chaperone Chromatin regulator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	'de novo' cotranslational protein folding Traceable author statement Ref.8. Source: UniProtKB DNA replication Inferred from electronic annotation. Source: Compara G2 phase of mitotic cell cycle Inferred from electronic annotation. Source: Compara chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.15. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Inferred from direct assay Ref.8Ref.15. Source: UniProtKB nuclear membrane Inferred from direct assay. Source: HPA
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro chromatin binding Inferred from direct assay Ref.15. Source: UniProtKB histone binding Inferred from direct assay Ref.15. Source: UniProtKB ubiquitin binding Inferred from direct assay Ref.15. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q99543-1)

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.

Isoform 2 (identifier: Q99543-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.3
	Chain	2 – 621	620	DnaJ homolog subfamily C member 2		PRO_0000071123
Regions
	Domain	88 – 161	74	J
	Domain	449 – 511	63	SANT 1
	Domain	549 – 604	56	SANT 2
	Region	23 – 31	9	Epitope (recognized by CD8(+) cytotoxic T-lymphocytes)
	Region	160 – 250	91	ZRF1-UBD
Amino acid modifications
	Modified residue	47	1	Phosphoserine Ref.10 Ref.13 Ref.16 Ref.18
	Modified residue	49	1	Phosphoserine Ref.10 Ref.13 Ref.16 Ref.18
	Modified residue	60	1	Phosphoserine Ref.10
	Modified residue	63	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	362 – 414	53	Missing in isoform 2.		VSP_023562
Experimental info
	Mutagenesis	512 – 513	2	HQ → AA: Loss of function. Ref.9
	Sequence conflict	252	1	R → G in CAA66913. Ref.1
	Sequence conflict	472	1	G → R in CAA66913. Ref.1
	Sequence conflict	578	1	E → K in AAI39752. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 4. Checksum: E4DAEE7A73D0F64C	FASTA	621	71,996
	10 20 30 40 50 60 MLLLPSAADG RGTAITHALT SASTLCQVEP VGRWFEAFVK RRNRNASASF QELEDKKELS 70 80 90 100 110 120 EESEDEELQL EEFPMLKTLD PKDWKNQDHY AVLGLGHVRY KATQRQIKAA HKAMVLKHHP 130 140 150 160 170 180 DKRKAAGEPI KEGDNDYFTC ITKAYEMLSD PVKRRAFNSV DPTFDNSVPS KSEAKDNFFE 190 200 210 220 230 240 VFTPVFERNS RWSNKKNVPK LGDMNSSFED VDIFYSFWYN FDSWREFSYL DEEEKEKAEC 250 260 270 280 290 300 RDERRWIEKQ NRATRAQRKK EEMNRIRTLV DNAYSCDPRI KKFKEEEKAK KEAEKKAKAE 310 320 330 340 350 360 AKRKEQEAKE KQRQAELEAA RLAKEKEEEE VRQQALLAKK EKDIQKKAIK KERQKLRNSC 370 380 390 400 410 420 KTWNHFSDNE AERVKMMEEV EKLCDRLELA SLQCLNETLT SCTKEVGKAA LEKQIEEINE 430 440 450 460 470 480 QIRKEKEEAE ARMRQASKNT EKSTGGGGNG SKNWSEDDLQ LLIKAVNLFP AGTNSRWEVI 490 500 510 520 530 540 ANYMNIHSSS GVKRTAKDVI GKAKSLQKLD PHQKDDINKK AFDKFKKEHG VVPQADNATP 550 560 570 580 590 600 SERFEGPYTD FTPWTTEEQK LLEQALKTYP VNTPERWEKI AEAVPGRTKK DCMKRYKELV 610 620 EMVKAKKAAQ EQVLNASRAK K
	Isoform 2 [UniParc]. Checksum: 390BA8AC8C0DFCAD	FASTA	568	65,913
	10 20 30 40 50 60 MLLLPSAADG RGTAITHALT SASTLCQVEP VGRWFEAFVK RRNRNASASF QELEDKKELS 70 80 90 100 110 120 EESEDEELQL EEFPMLKTLD PKDWKNQDHY AVLGLGHVRY KATQRQIKAA HKAMVLKHHP 130 140 150 160 170 180 DKRKAAGEPI KEGDNDYFTC ITKAYEMLSD PVKRRAFNSV DPTFDNSVPS KSEAKDNFFE 190 200 210 220 230 240 VFTPVFERNS RWSNKKNVPK LGDMNSSFED VDIFYSFWYN FDSWREFSYL DEEEKEKAEC 250 260 270 280 290 300 RDERRWIEKQ NRATRAQRKK EEMNRIRTLV DNAYSCDPRI KKFKEEEKAK KEAEKKAKAE 310 320 330 340 350 360 AKRKEQEAKE KQRQAELEAA RLAKEKEEEE VRQQALLAKK EKDIQKKAIK KERQKLRNSC 370 380 390 400 410 420 KIEEINEQIR KEKEEAEARM RQASKNTEKS TGGGGNGSKN WSEDDLQLLI KAVNLFPAGT 430 440 450 460 470 480 NSRWEVIANY MNIHSSSGVK RTAKDVIGKA KSLQKLDPHQ KDDINKKAFD KFKKEHGVVP 490 500 510 520 530 540 QADNATPSER FEGPYTDFTP WTTEEQKLLE QALKTYPVNT PERWEKIAEA VPGRTKKDCM 550 560 KRYKELVEMV KAKKAAQEQV LNASRAKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of novel M phase phosphoproteins by expression cloning." Matsumoto-Taniura N., Pirollet F., Monroe R., Gerace L., Westendorf J.M. Mol. Biol. Cell 7:1455-1469(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PHOSPHORYLATION. Tissue: Blood.
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Bienvenut W.V., Glen H., Frame M.C. Submitted (MAR-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11, CLEAVAGE OF INITIATOR METHIONINE, MASS SPECTROMETRY. Tissue: Osteosarcoma.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 7-621 (ISOFORM 1). Tissue: Cervix.
[5]	"A putative oncogenic role for MPP11 in head and neck squamous cell cancer." Resto V.A., Caballero O.L., Buta M.R., Westra W.H., Wu L., Westendorf J.M., Jen J., Hieter P., Sidransky D. Cancer Res. 60:5529-5535(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Characterization of several leukemia-associated antigens inducing humoral immune responses in acute and chronic myeloid leukemia." Greiner J., Ringhoffer M., Taniguchi M., Hauser T., Schmitt A., Dohner H., Schmitt M. Int. J. Cancer 106:224-231(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION IN LEUKEMIA.
[7]	"mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies." Greiner J., Ringhoffer M., Taniguchi M., Li L., Schmitt A., Shiku H., Dohner H., Schmitt M. Int. J. Cancer 108:704-711(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION IN LEUKEMIA.
[8]	"The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex." Otto H., Conz C., Maier P., Wolfle T., Suzuki C.K., Jeno P., Rucknagel P., Stahl J., Rospert S. Proc. Natl. Acad. Sci. U.S.A. 102:10064-10069(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE RAC COMPLEX, INTERACTION WITH HSPA14.
[9]	"Human Mpp11 J protein: ribosome-tethered molecular chaperones are ubiquitous." Hundley H.A., Walter W., Bairstow S., Craig E.A. Science 308:1032-1034(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF 512-HIS-GLN-513.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47; SER-49; SER-60 AND SER-63, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"C/EBPalphap30 plays transcriptional regulatory roles distinct from C/EBPalphap42." Wang C., Chen X., Wang Y., Gong J., Hu G. Cell Res. 17:374-383(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-49, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Identification of a novel peptide derived from the M-phase phosphoprotein 11 (MPP11) leukemic antigen recognized by human CD8+ cytotoxic T lymphocytes." Al Qudaihi G., Lehe C., Dickinson A., Eltayeb K., Rasheed W., Chaudhri N., Aljurf M., Dermime S. Hematol. Oncol. Stem Cell Ther. 3:24-33(2010) [PubMed] [Europe PMC] [Abstract] Cited for: EPITOPE REGION.
[15]	"Transcriptional activation of polycomb-repressed genes by ZRF1." Richly H., Rocha-Viegas L., Ribeiro J.D., Demajo S., Gundem G., Lopez-Bigas N., Nakagawa T., Rospert S., Ito T., Di Croce L. Nature 468:1124-1128(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS CHROMATIN REGULATOR, SUBCELLULAR LOCATION, UBIQUITIN-BINDING, DOMAIN ZRF1-UBD.
[16]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-49, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47 AND SER-49, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00455199.
IPI00830108.

RefSeq

NP_001123359.1. NM_001129887.1.
NP_055192.1. NM_014377.1.

UniGene

Hs.558476.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2M2E	NMR	-	A	551-621	[»]

ProteinModelPortal

Q99543.

SMR

Q99543. Positions 553-600.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000368565.

PTM databases

PhosphoSite

Q99543.

Polymorphism databases

DMDM

296439472.

Proteomic databases

PaxDb

Q99543.

PRIDE

Q99543.

Protocols and materials databases

DNASU

27000.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000249270; ENSP00000249270; ENSG00000105821.
ENST00000379263; ENSP00000368565; ENSG00000105821.

GeneID

27000.

KEGG

hsa:27000.

UCSC

uc003vbo.3. human.
uc010lix.3. human.

Organism-specific databases

CTD

27000.

GeneCards

GC07M102952.

HGNC

HGNC:13192. DNAJC2.

HPA

HPA020454.

MIM

605502. gene.

neXtProt

NX_Q99543.

PharmGKB

PA162383835.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5269.

HOGENOM

HOG000006900.

HOVERGEN

HBG008782.

InParanoid

Q99543.

KO

K09522.

OMA

RWFEAFI.

Gene expression databases

ArrayExpress

Q99543.

Bgee

Q99543.

CleanEx

HS_DNAJC2.

Genevestigator

Q99543.

GermOnline

ENSG00000105821. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.
1.10.287.110. 1 hit.

InterPro

IPR001623. DnaJ_domain.
IPR018253. DnaJ_domain_CS.
IPR009057. Homeodomain-like.
IPR001005. SANT/Myb.
IPR017884. SANT_dom.
[Graphical view]

Pfam

PF00226. DnaJ. 1 hit.
PF00249. Myb_DNA-binding. 2 hits.
[Graphical view]

SMART

SM00271. DnaJ. 1 hit.
SM00717. SANT. 2 hits.
[Graphical view]

SUPFAM

SSF46565. DnaJ_N. 1 hit.
SSF46689. Homeodomain_like. 2 hits.

PROSITE

PS00636. DNAJ_1. 1 hit.
PS50076. DNAJ_2. 1 hit.
PS51293. SANT. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

27000.

NextBio

49486.

SOURCE

Search...

Entry information

Entry name

DNJC2_HUMAN

Accession

Primary (citable) accession number: Q99543
Secondary accession number(s): A4VCI0, Q9BVX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 118 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.