Reviewed, UniProtKB/Swiss-Prot P33076 (C2TA_HUMAN)

Names and origin

Protein names

Recommended name:
    MHC class II transactivator
      Short name=CIITA

Gene names

Name:	CIITA
Synonyms:	MHC2TA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1130 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.4 Ref.5
Subunit structure	Interacts with ZXDA and ZXDC. Ref.4 Ref.5
Subcellular location	Nucleus.
Involvement in disease	Defects in CIITA are a cause of bare lymphocyte syndrome type 2 (BLS2) [MIM:209920]; also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency. BLS2 is 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. Ref.1 Ref.6 Ref.7 Ref.9
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
Gene Ontology (GO)
Biological process	immune response Ref.1 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to antibiotic Inferred from direct assay. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II transcription factor activity Ref.1 Traceable author statement. Source: ProtInc transcription coactivator activity Ref.2 Traceable author statement. Source: ProtInc ubiquitin binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ZXDC	Q2QGD7	3	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
	Repeat	98 – 121	24	LRR 1
	Repeat	214 – 238	25	LRR 2
	Domain	414 – 724	311	NACHT
	Repeat	1014 – 1037	24	LRR 3
	Repeat	1071 – 1094	24	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: dbSNP rs2229317.		VAR_029270
	Natural variant	120	1	K → IE in BLS2. Ref.1		VAR_005127
	Natural variant	174	1	G → R: dbSNP rs8046121. Ref.1 Ref.2 Ref.3		VAR_047907
	Natural variant	469	1	L → P in BLS2; mild immunodeficiency; has residual MHC class II trans activation activity. Ref.7		VAR_015551
	Natural variant	500	1	G → A: dbSNP rs4774. Ref.1 Ref.2		VAR_005128
	Natural variant	658	1	A → G: dbSNP rs2229319.		VAR_015552
	Natural variant	782	1	V → A: dbSNP rs13336804.		VAR_057711
	Natural variant	900	1	R → Q: dbSNP rs7197779. Ref.1 Ref.2 Ref.3		VAR_047908
	Natural variant	940 – 963	24	Missing in BLS2. Ref.1		VAR_005129
	Natural variant	962	1	F → S in BLS2. Ref.6		VAR_015553
	Natural variant	964 – 991	28	Missing in BLS2.		VAR_015554
	Natural variant	1027	1	Missing in BLS2. Ref.9		VAR_015555

Sequences

	Sequence		Length	Mass (Da)
	P33076-1 [UniParc]. Last modified December 16, 2008. Version 2. Checksum: E2F64E18038338CA	FASTA	1,130	123,443
	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 LLVGPVSDCS 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 DTVALWESLR 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: 8402893] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS BLS2 LYS-120 DEL ILE-GLU INS AND 940-THR--ALA-963 DEL, VARIANTS ARG-174; ALA-500 AND GLN-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: 7749984] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-174; ALA-500 AND GLN-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: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS ARG-174 AND GLN-900.
[4]	"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: 17493635] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZXDA AND ZXDC.
[5]	"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: 16600381] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZXDC.
[6]	"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: 10501838] [Abstract] Cited for: VARIANT BLS2 GROUP A SER-962.
[7]	"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: 11466404] [Abstract] Cited for: VARIANT BLS2 GROUP A PRO-469.
[8]	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)
[9]	"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: 11862382] [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
EMBLGenBankDDBJ	X74301 mRNA. Translation: CAA52354.1. U18259 mRNA. Translation: AAA88861.1. AC133065 Genomic DNA. No translation available.
IPI	IPI00186224.
PIR	A48843.
RefSeq	NP_000237.2.
UniGene	Hs.701991
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P33076. 2 interactions.
PTM databases
PhosphoSite	P33076.
Proteomic databases
PRIDE	P33076.
Genome annotation databases
Ensembl	ENSG00000179583. Homo sapiens. [Contig view]
GeneID	4261.
KEGG	hsa:4261.
Organism-specific databases
GeneCards	GC16P010879.
H-InvDB	HIX0038559.
HGNC	HGNC:7067. CIITA.
HPA	CAB016084.
MIM	209920. phenotype. 600005. gene.
Orphanet	572. Immunodeficiency by defective expression of HLA class 2.
PharmGKB	PA30795.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P33076.
Gene expression databases
ArrayExpress	P33076.
Bgee	P33076.
CleanEx	HS_CIITA.
GermOnline	ENSG00000179583. Homo sapiens.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. IPR008095. MHC_II_transact. IPR007111. NACHT_NTPase. [Graphical view]
Pfam	PF00560. LRR_1. 1 hit. PF05729. NACHT. 1 hit. [Graphical view]
PRINTS	PR01719. MHCIIACTVATR.
PROSITE	PS50837. NACHT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	16805.
SOURCE	Search...

Entry information

Entry name

C2TA_HUMAN

Accession

Primary (citable) accession number: P33076

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	December 16, 2008
Last modified:	June 16, 2009
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)