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Protein

Transcriptional repressor NF-X1

Gene

NFX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri358 – 409RING-type; atypicalPROSITE-ProRule annotationAdd BLAST52
Zinc fingeri453 – 471NF-X1-type 1Add BLAST19
Zinc fingeri506 – 525NF-X1-type 2Add BLAST20
Zinc fingeri567 – 586NF-X1-type 3Add BLAST20
Zinc fingeri632 – 655NF-X1-type 4Add BLAST24
Zinc fingeri694 – 713NF-X1-type 5Add BLAST20
Zinc fingeri721 – 740NF-X1-type 6Add BLAST20
Zinc fingeri832 – 854NF-X1-type 7Add BLAST23
Zinc fingeri863 – 884NF-X1-type 8Add BLAST22

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • RNA binding Source: UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • inflammatory response Source: ProtInc
  • negative regulation of MHC class II biosynthetic process Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • transcription from RNA polymerase II promoter Source: ProtInc
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding, Ligase, Repressor
Biological processHost-virus interaction, Transcription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

SIGNORiQ12986.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcriptional repressor NF-X1 (EC:6.3.2.-)
Alternative name(s):
Nuclear transcription factor, X box-binding protein 1
Gene namesi
Name:NFX1
Synonyms:NFX2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000086102.18.
HGNCiHGNC:7803. NFX1.

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20F → A: Reduces PABPC1 and PABC4 binding. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000086102.
PharmGKBiPA31608.

Polymorphism and mutation databases

BioMutaiNFX1.
DMDMi189047116.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559791 – 1120Transcriptional repressor NF-X1Add BLAST1120

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50PhosphoserineCombined sources1
Modified residuei82PhosphoserineBy similarity1
Modified residuei95PhosphoserineCombined sources1
Modified residuei129PhosphoserineBy similarity1
Modified residuei150PhosphoserineCombined sources1
Modified residuei326PhosphoserineCombined sources1

Post-translational modificationi

Isoform 3 is polyubiquitinated in the presence of HPV16 E6 protein; which leads to proteasomal degradation. Isoform 1 is not polyubiquitinated.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ12986.
MaxQBiQ12986.
PaxDbiQ12986.
PeptideAtlasiQ12986.
PRIDEiQ12986.

PTM databases

iPTMnetiQ12986.
PhosphoSitePlusiQ12986.

Expressioni

Inductioni

By IFNG/IFN-gamma.

Gene expression databases

BgeeiENSG00000086102.
CleanExiHS_NFX1.
GenevisibleiQ12986. HS.

Organism-specific databases

HPAiHPA056310.
HPA061382.
HPA073519.

Interactioni

Subunit structurei

Isoform 1 and isoform 3 interact with human papillomavirus (HPV) type-16 E6 oncoprotein. Isoform 1 interacts with PABPC1 and PABPC4.2 Publications

Protein-protein interaction databases

BioGridi110865. 44 interactors.
ELMiQ12986.
IntActiQ12986. 4 interactors.
STRINGi9606.ENSP00000368856.

Structurei

3D structure databases

ProteinModelPortaliQ12986.
SMRiQ12986.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini994 – 1062R3HPROSITE-ProRule annotationAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni9 – 26Interaction with PABPC1 and PABC41 PublicationAdd BLAST18

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1084 – 1089Poly-Pro6

Domaini

The RING-type zinc finger domain interacts with an ubiquitin-conjugating enzyme (E2) and facilitates ubiquitination.

Sequence similaritiesi

Belongs to the NFX1 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri358 – 409RING-type; atypicalPROSITE-ProRule annotationAdd BLAST52
Zinc fingeri453 – 471NF-X1-type 1Add BLAST19
Zinc fingeri506 – 525NF-X1-type 2Add BLAST20
Zinc fingeri567 – 586NF-X1-type 3Add BLAST20
Zinc fingeri632 – 655NF-X1-type 4Add BLAST24
Zinc fingeri694 – 713NF-X1-type 5Add BLAST20
Zinc fingeri721 – 740NF-X1-type 6Add BLAST20
Zinc fingeri832 – 854NF-X1-type 7Add BLAST23
Zinc fingeri863 – 884NF-X1-type 8Add BLAST22

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1952. Eukaryota.
ENOG410XR02. LUCA.
GeneTreeiENSGT00400000022083.
HOGENOMiHOG000006942.
HOVERGENiHBG003827.
InParanoidiQ12986.
KOiK12236.
OMAiHPCNILC.
OrthoDBiEOG091G057V.
PhylomeDBiQ12986.
TreeFamiTF105889.

Family and domain databases

CDDicd02643. R3H_NF-X1. 1 hit.
Gene3Di3.30.1370.50. 1 hit.
InterProiView protein in InterPro
IPR034078. NFX1_fam.
IPR001374. R3H_dom.
IPR036867. R3H_dom_sf.
IPR034076. R3H_NF-X1.
IPR019786. Zinc_finger_PHD-type_CS.
IPR000967. Znf_NFX1.
IPR019787. Znf_PHD-finger.
IPR001841. Znf_RING.
PANTHERiPTHR12360. PTHR12360. 1 hit.
PfamiView protein in Pfam
PF01424. R3H. 1 hit.
PF01422. zf-NF-X1. 8 hits.
SMARTiView protein in SMART
SM00393. R3H. 1 hit.
SM00184. RING. 1 hit.
SM00438. ZnF_NFX. 9 hits.
SUPFAMiSSF82708. SSF82708. 1 hit.
PROSITEiView protein in PROSITE
PS51061. R3H. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q12986-1) [UniParc]FASTAAdd to basket
Also known as: NFX-123

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
MAEAPPVSGT FKFNTDAAEF IPQEKKNSGL NCGTQRRLDS NRIGRRNYSS
60 70 80 90 100
PPPCHLSRQV PYDEISAVHQ HSYHPSGSKP KSQQTSFQSS PCNKSPKSHG
110 120 130 140 150
LQNQPWQKLR NEKHHIRVKK AQSLAEQTSD TAGLESSTRS ESGTDLREHS
160 170 180 190 200
PSESEKEVVG ADPRGAKPKK ATQFVYSYGR GPKVKGKLKC EWSNRTTPKP
210 220 230 240 250
EDAGPESTKP VGVFHPDSSE ASSRKGVLDG YGARRNEQRR YPQKRPPWEV
260 270 280 290 300
EGARPRPGRN PPKQEGHRHT NAGHRNNMGP IPKDDLNERP AKSTCDSENL
310 320 330 340 350
AVINKSSRRV DQEKCTVRRQ DPQVVSPFSR GKQNHVLKNV ETHTGSLIEQ
360 370 380 390 400
LTTEKYECMV CCELVRVTAP VWSCQSCYHV FHLNCIKKWA RSPASQADGQ
410 420 430 440 450
SGWRCPACQN VSAHVPNTYT CFCGKVKNPE WSRNEIPHSC GEVCRKKQPG
460 470 480 490 500
QDCPHSCNLL CHPGPCPPCP AFMTKTCECG RTRHTVRCGQ AVSVHCSNPC
510 520 530 540 550
ENILNCGQHQ CAELCHGGQC QPCQIILNQV CYCGSTSRDV LCGTDVGKSD
560 570 580 590 600
GFGDFSCLKI CGKDLKCGNH TCSQVCHPQP CQQCPRLPQL VRCCPCGQTP
610 620 630 640 650
LSQLLELGSS SRKTCMDPVP SCGKVCGKPL PCGSLDFIHT CEKLCHEGDC
660 670 680 690 700
GPCSRTSVIS CRCSFRTKEL PCTSLKSEDA TFMCDKRCNK KRLCGRHKCN
710 720 730 740 750
EICCVDKEHK CPLICGRKLR CGLHRCEEPC HRGNCQTCWQ ASFDELTCHC
760 770 780 790 800
GASVIYPPVP CGTRPPECTQ TCARVHECDH PVYHSCHSEE KCPPCTFLTQ
810 820 830 840 850
KWCMGKHEFR SNIPCHLVDI SCGLPCSATL PCGMHKCQRL CHKGECLVDE
860 870 880 890 900
PCKQPCTTPR ADCGHPCMAP CHTSSPCPVT ACKAKVELQC ECGRRKEMVI
910 920 930 940 950
CSEASSTYQR IAAISMASKI TDMQLGGSVE ISKLITKKEV HQARLECDEE
960 970 980 990 1000
CSALERKKRL AEAFHISEDS DPFNIRSSGS KFSDSLKEDA RKDLKFVSDV
1010 1020 1030 1040 1050
EKEMETLVEA VNKGKNSKKS HSFPPMNRDH RRIIHDLAQV YGLESVSYDS
1060 1070 1080 1090 1100
EPKRNVVVTA IRGKSVCPPT TLTGVLEREM QARPPPPIPH HRHQSDKNPG
1110 1120
SSNLQKITKE PIIDYFDVQD
Length:1,120
Mass (Da):124,395
Last modified:May 20, 2008 - v2
Checksum:iF2203BE1DB6437E6
GO
Isoform 2 (identifier: Q12986-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1014-1024: GKNSKKSHSFP → VEVETSHWTFL
     1025-1120: Missing.

Show »
Length:1,024
Mass (Da):113,623
Checksum:i4228E14EEF42E3BC
GO
Isoform 3 (identifier: Q12986-3) [UniParc]FASTAAdd to basket
Also known as: NFX-91

The sequence of this isoform differs from the canonical sequence as follows:
     809-833: FRSNIPCHLVDISCGLPCSATLPCG → QSHYWASTQKKRSHYMKKIPAHACL
     834-1120: Missing.

Show »
Length:833
Mass (Da):92,679
Checksum:iAD2A1E26911EA705
GO

Sequence cautioni

The sequence AAA69517 differs from that shown. Reason: Frameshift at positions 78, 202 and 284.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti179G → A in AAA69517 (Ref. 1) Curated1
Sequence conflicti186G → E in AAA69517 (Ref. 1) Curated1
Sequence conflicti312Q → P in AAA69517 (Ref. 1) Curated1
Sequence conflicti419 – 420YT → FS in AAA69517 (Ref. 1) Curated2
Sequence conflicti560I → T in AAA69517 (Ref. 1) Curated1
Sequence conflicti653C → V in AAA69517 (Ref. 1) Curated1
Sequence conflicti678E → EA in BAF84332 (PubMed:14702039).Curated1
Sequence conflicti714I → N in AAA69517 (Ref. 1) Curated1
Sequence conflicti786C → G in AAA69517 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043380731H → Y. Corresponds to variant dbSNP:rs5017299Ensembl.1
Natural variantiVAR_043381760P → S. Corresponds to variant dbSNP:rs2860036Ensembl.1
Natural variantiVAR_0433821086P → Q. Corresponds to variant dbSNP:rs2274866Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_033682809 – 833FRSNI…TLPCG → QSHYWASTQKKRSHYMKKIP AHACL in isoform 3. CuratedAdd BLAST25
Alternative sequenceiVSP_033683834 – 1120Missing in isoform 3. CuratedAdd BLAST287
Alternative sequenceiVSP_0336841014 – 1024GKNSKKSHSFP → VEVETSHWTFL in isoform 2. 2 PublicationsAdd BLAST11
Alternative sequenceiVSP_0336851025 – 1120Missing in isoform 2. 2 PublicationsAdd BLAST96

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF332009 mRNA. Translation: AAK16545.1.
AK291643 mRNA. Translation: BAF84332.1.
AL356472 Genomic DNA. No translation available.
AL356218 Genomic DNA. No translation available.
CH471071 Genomic DNA. Translation: EAW58510.1.
CH471071 Genomic DNA. Translation: EAW58511.1.
BC012151 mRNA. Translation: AAH12151.1.
U15306 mRNA. Translation: AAA69517.1. Frameshift.
CCDSiCCDS6538.1. [Q12986-1]
CCDS6540.1. [Q12986-3]
PIRiI38869.
RefSeqiNP_002495.2. NM_002504.5. [Q12986-1]
NP_667345.1. NM_147134.3. [Q12986-3]
UniGeneiHs.413074.

Genome annotation databases

EnsembliENST00000318524; ENSP00000317695; ENSG00000086102. [Q12986-3]
ENST00000379540; ENSP00000368856; ENSG00000086102. [Q12986-1]
GeneIDi4799.
KEGGihsa:4799.
UCSCiuc003zso.4. human. [Q12986-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNFX1_HUMAN
AccessioniPrimary (citable) accession number: Q12986
Secondary accession number(s): A8K6H8
, Q5VXW6, Q96EL5, Q9BXI1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 20, 2008
Last modified: November 22, 2017
This is version 172 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families