P33076 (C2TA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
MHC class II transactivator
Short name=CIITA

Gene names

Name:	CIITA
Synonyms:	MHC2TA

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	1130 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. No DNA binding of in vitro translated CIITA was detected. May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both. Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter. Ref.5 Ref.6
Subunit structure	Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-2). Ref.5 Ref.6 Ref.7
Subcellular location	Nucleus. Nucleus › PML body. Note: Recruited to PML body by PML. Ref.7
Involvement in disease	Bare lymphocyte syndrome 2 (BLS2) [MIM:209920]: A severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon-gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.8 Ref.9 Ref.11
Sequence similarities	Contains 4 LRR (leucine-rich) repeats. Contains 1 NACHT domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation SCID
Domain	Leucine-rich repeat Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of collagen biosynthetic process Inferred by curator PubMed 19041327. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 19041327. Source: BHF-UCL positive regulation of MHC class I biosynthetic process Inferred from direct assay PubMed 20639463. Source: BHF-UCL positive regulation of MHC class II biosynthetic process Inferred by curator PubMed 9171108. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20639463. Source: BHF-UCL response to antibiotic Inferred from direct assay PubMed 107465. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PML body Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein complex binding Inferred from direct assay Ref.5. Source: UniProtKB transcription coactivator activity Traceable author statement Ref.2. Source: ProtInc transcription regulatory region DNA binding Inferred from direct assay PubMed 19041327. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SIRT1	Q96EB6	4	EBI-1538819,EBI-1802965
ZXDA	P98168	4	EBI-1538819,EBI-1538980
ZXDC	Q2QGD7	6	EBI-1538819,EBI-1538838

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1130	1130	MHC class II transactivator		PRO_0000089241
Regions
	Domain	414 – 724	311	NACHT
	Repeat	985 – 1008	24	LRR 1
	Repeat	1016 – 1037	22	LRR 2
	Repeat	1045 – 1066	22	LRR 3
	Repeat	1073 – 1093	21	LRR 4
	Nucleotide binding	420 – 427	8	ATP Potential
	Compositional bias	52 – 137	86	Asp/Glu-rich (acidic)
Natural variations
	Natural variant	45	1	L → V. Corresponds to variant rs2229317 [ dbSNP | Ensembl ].		VAR_029270
	Natural variant	120	1	K → IE in BLS2.		VAR_005127
	Natural variant	174	1	R → G. Ref.1 Ref.2 Corresponds to variant rs8046121 [ dbSNP | Ensembl ].		VAR_047907
	Natural variant	469	1	L → P in BLS2; mild immunodeficiency; has residual MHC class II trans activation activity. Ref.9		VAR_015551
	Natural variant	500	1	G → A. Ref.1 Ref.2 Corresponds to variant rs4774 [ dbSNP | Ensembl ].		VAR_005128
	Natural variant	658	1	A → G. Corresponds to variant rs2229319 [ dbSNP | Ensembl ].		VAR_015552
	Natural variant	781	1	S → L. Corresponds to variant rs13330686 [ dbSNP | Ensembl ].		VAR_060104
	Natural variant	782	1	V → A. Corresponds to variant rs13336804 [ dbSNP | Ensembl ].		VAR_057711
	Natural variant	900	1	Q → R. Ref.1 Ref.2 Corresponds to variant rs7197779 [ dbSNP | Ensembl ].		VAR_047908
	Natural variant	940 – 963	24	Missing in BLS2.		VAR_005129
	Natural variant	962	1	F → S in BLS2. Ref.8		VAR_015553
	Natural variant	964 – 991	28	Missing in BLS2.		VAR_015554
	Natural variant	1027	1	Missing in BLS2. Ref.11		VAR_015555

Sequences

	Sequence		Length	Mass (Da)
	P33076 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 7A61CAA4F3FFECE0	FASTA	1,130	123,514
	10 20 30 40 50 60 MRCLAPRPAG SYLSEPQGSS QCATMELGPL EGGYLELLNS DADPLCLYHF YDQMDLAGEE 70 80 90 100 110 120 EIELYSEPDT DTINCDQFSR LLCDMEGDEE TREAYANIAE LDQYVFQDSQ LEGLSKDIFK 130 140 150 160 170 180 HIGPDEVIGE SMEMPAEVGQ KSQKRPFPEE LPADLKHWKP AEPPTVVTGS LLVRPVSDCS 190 200 210 220 230 240 TLPCLPLPAL FNQEPASGQM RLEKTDQIPM PFSSSSLSCL NLPEGPIQFV PTISTLPHGL 250 260 270 280 290 300 WQISEAGTGV SSIFIYHGEV PQASQVPPPS GFTVHGLPTS PDRPGSTSPF APSATDLPSM 310 320 330 340 350 360 PEPALTSRAN MTEHKTSPTQ CPAAGEVSNK LPKWPEPVEQ FYRSLQDTYG AEPAGPDGIL 370 380 390 400 410 420 VEVDLVQARL ERSSSKSLER ELATPDWAER QLAQGGLAEV LLAAKEHRRP RETRVIAVLG 430 440 450 460 470 480 KAGQGKSYWA GAVSRAWACG RLPQYDFVFS VPCHCLNRPG DAYGLQDLLF SLGPQPLVAA 490 500 510 520 530 540 DEVFSHILKR PDRVLLILDG FEELEAQDGF LHSTCGPAPA EPCSLRGLLA GLFQKKLLRG 550 560 570 580 590 600 CTLLLTARPR GRLVQSLSKA DALFELSGFS MEQAQAYVMR YFESSGMTEH QDRALTLLRD 610 620 630 640 650 660 RPLLLSHSHS PTLCRAVCQL SEALLELGED AKLPSTLTGL YVGLLGRAAL DSPPGALAEL 670 680 690 700 710 720 AKLAWELGRR HQSTLQEDQF PSADVRTWAM AKGLVQHPPR AAESELAFPS FLLQCFLGAL 730 740 750 760 770 780 WLALSGEIKD KELPQYLALT PRKKRPYDNW LEGVPRFLAG LIFQPPARCL GALLGPSAAA 790 800 810 820 830 840 SVDRKQKVLA RYLKRLQPGT LRARQLLELL HCAHEAEEAG IWQHVVQELP GRLSFLGTRL 850 860 870 880 890 900 TPPDAHVLGK ALEAAGQDFS LDLRSTGICP SGLGSLVGLS CVTRFRAALS DTVALWESLQ 910 920 930 940 950 960 QHGETKLLQA AEEKFTIEPF KAKSLKDVED LGKLVQTQRT RSSSEDTAGE LPAVRDLKKL 970 980 990 1000 1010 1020 EFALGPVSGP QAFPKLVRIL TAFSSLQHLD LDALSENKIG DEGVSQLSAT FPQLKSLETL 1030 1040 1050 1060 1070 1080 NLSQNNITDL GAYKLAEALP SLAASLLRLS LYNNCICDVG AESLARVLPD MVSLRVMDVQ 1090 1100 1110 1120 1130 YNKFTAAGAQ QLAASLRRCP HVETLAMWTP TIPFSVQEHL QQQDSRISLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)." Steimle V., Otten L.A., Zufferey M., Mach B. Cell 75:135-146(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS BLS2 LYS-120 DEL ILE-GLU INS AND 940-THR--ALA-963 DEL, VARIANTS GLY-174; ALA-500 AND ARG-900.
[2]	"Activation of class II MHC genes requires both the X box region and the class II transactivator (CIITA)." Riley J.L., Westerheide S.D., Price J.A., Brown J.A., Boss J.M. Immunity 2:533-543(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLY-174; ALA-500 AND ARG-900.
[3]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription." Al-Kandari W., Koneni R., Navalgund V., Aleksandrova A., Jambunathan S., Fontes J.D. J. Mol. Biol. 369:1175-1187(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZXDA AND ZXDC.
[6]	"ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription." Al-Kandari W., Jambunathan S., Navalgund V., Koneni R., Freer M., Parimi N., Mudhasani R., Fontes J.D. Mol. Immunol. 44:311-321(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZXDC.
[7]	"PML promotes MHC class II gene expression by stabilizing the class II transactivator." Ulbricht T., Alzrigat M., Horch A., Reuter N., von Mikecz A., Steimle V., Schmitt E., Kraemer O.H., Stamminger T., Hemmerich P. J. Cell Biol. 199:49-63(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PML.
[8]	"Absence of MHC class II gene expression in a patient with a single amino acid substitution in the class II transactivator protein CIITA." Quan V., Towey M., Sacks S., Kelly A.P. Immunogenetics 49:957-963(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BLS2 GROUP A SER-962.
[9]	"Mutation in the class II trans-activator leading to a mild immunodeficiency." Wiszniewski W., Fondaneche M.-C., Le Deist F., Kanariou M., Selz F., Brousse N., Steimle V., Barbieri G., Alcaide-Loridan C., Charron D., Fischer A., Lisowska-Grospierre B. J. Immunol. 167:1787-1794(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BLS2 GROUP A PRO-469.
[10]	Erratum Wiszniewski W., Fondaneche M.-C., Le Deist F., Kanariou M., Selz F., Brousse N., Steimle V., Barbieri G., Alcaide-Loridan C., Charron D., Fischer A., Lisowska-Grospierre B. J. Immunol. 169:607-607(2002)
[11]	"Three novel mutations of the CIITA gene in MHC class II-deficient patients with a severe immunodeficiency." Dziembowska M., Fondaneche M.-C., Vedrenne J., Barbieri G., Wiszniewski W., Picard C., Cant A.J., Steimle V., Charron D., Alcaide-Loridan C., Fischer A., Lisowska-Grospierre B. Immunogenetics 53:821-829(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BLS2 GROUP A 964-LEU--ASP-991 DEL AND ILE-1027 DEL.
+	Additional computationally mapped references.

Web resources

CIITAbase

CIITA mutation db

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	X74301 mRNA. Translation: CAA52354.1. U18259 mRNA. Translation: AAA88861.1. AC133065 Genomic DNA. No translation available. CH471112 Genomic DNA. Translation: EAW85169.1. CH471112 Genomic DNA. Translation: EAW85172.1.
IPI	IPI00186224.
PIR	A48843.
RefSeq	NP_000237.2. NM_000246.3.
UniGene	Hs.701991.
3D structure databases
ProteinModelPortal	P33076.
SMR	P33076. Positions 951-1098.
ModBase	Search...
Protein-protein interaction databases
IntAct	P33076. 3 interactions.
STRING	9606.ENSP00000316328.
PTM databases
PhosphoSite	P33076.
Polymorphism databases
DMDM	218511957.
Proteomic databases
PaxDb	P33076.
PRIDE	P33076.
Protocols and materials databases
DNASU	4261.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324288; ENSP00000316328; ENSG00000179583.
GeneID	4261.
KEGG	hsa:4261.
UCSC	uc002dag.2. human.
Organism-specific databases
CTD	4261.
GeneCards	GC16P010879.
HGNC	HGNC:7067. CIITA.
HPA	CAB016084.
MIM	209920. phenotype. 600005. gene.
neXtProt	NX_P33076.
Orphanet	572. Immunodeficiency by defective expression of HLA class 2.
PharmGKB	PA30795.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG269671.
HOGENOM	HOG000107439.
HOVERGEN	HBG000174.
KO	K08060.
OMA	PQAFPKL.
OrthoDB	EOG48PMJD.
PhylomeDB	P33076.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P33076.
Bgee	P33076.
CleanEx	HS_CIITA.
Genevestigator	P33076.
GermOnline	ENSG00000179583. Homo sapiens.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. IPR025875. Leu-rich_rpt_4. IPR008095. MHC_II_transact. IPR007111. NACHT_NTPase. [Graphical view]
Pfam	PF12799. LRR_4. 1 hit. [Graphical view]
PRINTS	PR01719. MHCIIACTVATR.
PROSITE	PS51450. LRR. 4 hits. PS50837. NACHT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4261.
NextBio	16805.
SOURCE	Search...

Entry information

Entry name

C2TA_HUMAN

Accession

Primary (citable) accession number: P33076
Secondary accession number(s): D3DUG0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	January 11, 2011
Last modified:	May 1, 2013
This is version 136 of the entry and version 3 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.