CIITA

Protein identityUniProt · HPA

UniProt accession

P33076

Gene

CIITA

Ensembl

ENSG00000179583

Chromosome

16

Canonical length

1130 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a protein with an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein is located in the nucleus and acts as a positive regulator of class II major histocompatibility complex gene transcription, and is referred to as the """"""""""""""""""""""""""""""""master control factor"""""""""""""""""""""""""""""""" for the expression of these genes. The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus it does not bind DNA but rather uses an intrinsic acetyltransferase (AT) activity to act in a coactivator-like fashion. Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly myocardial infarction. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

Canonical amino-acid sequenceUniProt

1130 residues, UniProt reviewed canonical sequence.

>P33076|CIITA
     1  MRCLAPRPAG SYLSEPQGSS QCATMELGPL EGGYLELLNS DADPLCLYHF YDQMDLAGEE
    61  EIELYSEPDT DTINCDQFSR LLCDMEGDEE TREAYANIAE LDQYVFQDSQ LEGLSKDIFK
   121  HIGPDEVIGE SMEMPAEVGQ KSQKRPFPEE LPADLKHWKP AEPPTVVTGS LLVGPVSDCS
   181  TLPCLPLPAL FNQEPASGQM RLEKTDQIPM PFSSSSLSCL NLPEGPIQFV PTISTLPHGL
   241  WQISEAGTGV SSIFIYHGEV PQASQVPPPS GFTVHGLPTS PDRPGSTSPF APSATDLPSM
   301  PEPALTSRAN MTEHKTSPTQ CPAAGEVSNK LPKWPEPVEQ FYRSLQDTYG AEPAGPDGIL
   361  VEVDLVQARL ERSSSKSLER ELATPDWAER QLAQGGLAEV LLAAKEHRRP RETRVIAVLG
   421  KAGQGKSYWA GAVSRAWACG RLPQYDFVFS VPCHCLNRPG DAYGLQDLLF SLGPQPLVAA
   481  DEVFSHILKR PDRVLLILDG FEELEAQDGF LHSTCGPAPA EPCSLRGLLA GLFQKKLLRG
   541  CTLLLTARPR GRLVQSLSKA DALFELSGFS MEQAQAYVMR YFESSGMTEH QDRALTLLRD
   601  RPLLLSHSHS PTLCRAVCQL SEALLELGED AKLPSTLTGL YVGLLGRAAL DSPPGALAEL
   661  AKLAWELGRR HQSTLQEDQF PSADVRTWAM AKGLVQHPPR AAESELAFPS FLLQCFLGAL
   721  WLALSGEIKD KELPQYLALT PRKKRPYDNW LEGVPRFLAG LIFQPPARCL GALLGPSAAA
   781  SVDRKQKVLA RYLKRLQPGT LRARQLLELL HCAHEAEEAG IWQHVVQELP GRLSFLGTRL
   841  TPPDAHVLGK ALEAAGQDFS LDLRSTGICP SGLGSLVGLS CVTRFRAALS DTVALWESLQ
   901  QHGETKLLQA AEEKFTIEPF KAKSLKDVED LGKLVQTQRT RSSSEDTAGE LPAVRDLKKL
   961  EFALGPVSGP QAFPKLVRIL TAFSSLQHLD LDALSENKIG DEGVSQLSAT FPQLKSLETL
  1021  NLSQNNITDL GAYKLAEALP SLAASLLRLS LYNNCICDVG AESLARVLPD MVSLRVMDVQ
  1081  YNKFTAAGAQ QLAASLRRCP HVETLAMWTP TIPFSVQEHL QQQDSRISLR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CIITA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

50 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CIITA.

Disease | AllUniProt

Conditions CIITA is implicated in, by any mechanism.

• MHC class II deficiency 1 (MHC2D1) MIM:209920

Disease | GeneticClinVar

105 pathogenic / likely-pathogenic of 1,892 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• MHC class II deficiency
• MHC class II deficiency 1
• Rheumatoid arthritis
• Acute myeloid leukemia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.58

gnomAD pLI

0

gnomAD missense Z

-0.93

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• host-mediated suppression of symbiont invasion
• immune response
• negative regulation of collagen biosynthetic process
• negative regulation of transcription by RNA polymerase II
• positive regulation of MHC class I biosynthetic process
• positive regulation of MHC class II biosynthetic process
• positive regulation of transcription by RNA polymerase II
• response to antibiotic
• response to type II interferon
• type II interferon-mediated signaling pathway

Molecular functions

• acyltransferase activity
• ATP binding
• DNA-binding transcription factor binding
• GTP binding
• histone deacetylase binding
• protein serine kinase activity
• protein serine/threonine kinase activity
• protein-containing complex binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• transcription coactivator activity
• transcription corepressor activity

Cellular components

• cytosol
• nucleoplasm
• PML body

Protein domainsUniProt · Pfam · InterPro

• Leucine-rich repeat
• NACHT nucleoside triphosphatase
• P-loop containing nucleoside triphosphate hydrolase
• Leucine-rich repeat domain superfamily
• NACHT domain
• Leucine Rich repeat
• MHC class II transactivator

KeywordsUniProt

• Activator
• Acyltransferase
• ATP-binding
• GTP-binding
• Kinase
• Leucine-rich repeat
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Repeat
• SCID
• Transcription
• Transcription regulation
• Transferase

InteractionsUniProt · HPA

Protein binding partners of CIITA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PML
• TAF7
• ZXDA
• ZXDC
• FBXO11
• ZXDB