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Q14938 (NFIX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear factor 1 X-type

Short name=NF1-X
Short name=Nuclear factor 1/X
Alternative name(s):
CCAAT-box-binding transcription factor
Short name=CTF
Nuclear factor I/X
Short name=NF-I/X
Short name=NFI-X
TGGCA-binding protein
Gene names
Name:NFIX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length502 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.

Subunit structure

Binds DNA as a homodimer.

Subcellular location

Nucleus.

Tissue specificity

Widely expressed. Ref.10

Developmental stage

Prominent expression is observed in the central and peripheral nervous system in the embryo at Carnagie stage 17 (CS17; gestational day 42); at this stage it is also observed in the mandibular arch, cartilage primordium of the humerus, scapula, and vertebrae; in the limb expression is detected in the perichondrium. Expressed in the cerebral cortex, hippocampus, and faintly in the thalamus in fetal brain at 22 weeks of gestation,. Ref.10

Involvement in disease

Sotos syndrome 2 (SOTOS2) [MIM:614753]: A form of Sotos syndrome, a childhood overgrowth syndrome characterized by prenatal and postnatal overgrowth, developmental delay, mental retardation, advanced bone age, and abnormal craniofacial morphology. SOTOS2 patients have macrocephaly, long narrow face, high forehead, slender habitus, scoliosis, and unusual behavior characterized especially by anxiety.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11

Marshall-Smith syndrome (MRSHSS) [MIM:602535]: A distinct malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia. Additional skeletal findings include long and thin tubular bones, broad middle phalanges with relatively narrow distal phalanges, and scoliosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the CTF/NF-I family.

Contains 1 CTF/NF-I DNA-binding domain.

Ontologies

Keywords
   Biological processDNA replication
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from electronic annotation. Source: UniProtKB-KW

astrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

cerebellar Purkinje cell layer development

Inferred from electronic annotation. Source: Ensembl

cerebellar granule cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19706729. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19706729. Source: UniProtKB

transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.8PubMed 8340106. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14938-1)

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: Q14938-2)

The sequence of this isoform differs from the canonical sequence as follows:
     318-359: Missing.
Isoform 3 (identifier: Q14938-3)

The sequence of this isoform differs from the canonical sequence as follows:
     419-441: PNGSGQGKVPGSFLLPPPPPVAR → HSQRQAPPLPTGLSASDPGTATF
     442-502: Missing.
Isoform 4 (identifier: Q14938-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MYSPYCLTQ → M
Isoform 5 (identifier: Q14938-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MYSPYCLT → MLPACRL
     419-441: PNGSGQGKVPGSFLLPPPPPVAR → HSQRQAPPLPTGLSASDPGTATF
     442-502: Missing.
Isoform 6 (identifier: Q14938-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MYSPYCLTQ → M
     419-441: PNGSGQGKVPGSFLLPPPPPVAR → HSQRQAPPLPTGLSASDPGTATF
     442-502: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 502502Nuclear factor 1 X-type
PRO_0000100203

Regions

DNA binding1 – 194194CTF/NF-I

Amino acid modifications

Modified residue2801Phosphoserine Ref.9
Modified residue2881Phosphoserine By similarity
Modified residue3011Phosphoserine By similarity
Modified residue3411Phosphoserine By similarity

Natural variations

Alternative sequence1 – 99MYSPYCLTQ → M in isoform 4 and isoform 6.
VSP_003558
Alternative sequence1 – 88MYSPYCLT → MLPACRL in isoform 5.
VSP_003559
Alternative sequence318 – 35942Missing in isoform 2.
VSP_003560
Alternative sequence419 – 44123PNGSG…PPVAR → HSQRQAPPLPTGLSASDPGT ATF in isoform 3, isoform 5 and isoform 6.
VSP_003561
Alternative sequence442 – 50261Missing in isoform 3, isoform 5 and isoform 6.
VSP_003562
Natural variant601L → P in SOTOS2. Ref.11
VAR_068720
Natural variant1211R → P in SOTOS2. Ref.11
VAR_068721

Experimental info

Sequence conflict911F → Y in AAA53422. Ref.1
Sequence conflict3991S → P in BAG59737. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 2.
Checksum: 55B40A7DC505EA21

FASTA50255,098
        10         20         30         40         50         60 
MYSPYCLTQD EFHPFIEALL PHVRAFSYTW FNLQARKRKY FKKHEKRMSK DEERAVKDEL 

        70         80         90        100        110        120 
LGEKPEIKQK WASRLLAKLR KDIRPEFRED FVLTITGKKP PCCVLSNPDQ KGKIRRIDCL 

       130        140        150        160        170        180 
RQADKVWRLD LVMVILFKGI PLESTDGERL YKSPQCSNPG LCVQPHHIGV TIKELDLYLA 

       190        200        210        220        230        240 
YFVHTPESGQ SDSSNQQGDA DIKPLPNGHL SFQDCFVTSG VWNVTELVRV SQTPVATASG 

       250        260        270        280        290        300 
PNFSLADLES PSYYNINQVT LGRRSITSPP STSTTKRPKS IDDSEMESPV DDVFYPGTGR 

       310        320        330        340        350        360 
SPAAGSSQSS GWPNDVDAGP ASLKKSGKLD FCSALSSQGS SPRMAFTHHP LPVLAGVRPG 

       370        380        390        400        410        420 
SPRATASALH FPSTSIIQQS SPYFTHPTIR YHHHHGQDSL KEFVQFVCSD GSGQATGQPN 

       430        440        450        460        470        480 
GSGQGKVPGS FLLPPPPPVA RPVPLPMPDS KSTSTAPDGA ALTPPSPSFA TTGASSANRF 

       490        500 
VSIGPRDGNF LNIPQQSQSW FL 

« Hide

Isoform 2 [UniParc].

Checksum: 057954AC4937AFBE
Show »

FASTA46050,811
Isoform 3 [UniParc].

Checksum: 38CB7326FDC82859
Show »

FASTA44148,867
Isoform 4 [UniParc].

Checksum: 8924298844FFA791
Show »

FASTA49454,142
Isoform 5 [UniParc].

Checksum: 1B415FEA50613C96
Show »

FASTA44048,693
Isoform 6 [UniParc].

Checksum: 7E70888E782E68B5
Show »

FASTA43347,911

References

« Hide 'large scale' references
[1]"Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner."
Apt D., Liu Y., Bernard H.U.
Nucleic Acids Res. 22:3825-3833(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Foreskin.
[2]"Expression of multiple classes of the nuclear factor-1 family in the developing human brain: differential expression of two classes of NF-1 genes."
Sumner C., Shinohara T., Durham L., Traub R., Major E.O., Amemiya K.
J. Neurovirol. 2:87-100(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5).
Tissue: Brain.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
Tissue: Brain.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[5]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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. expand/collapse author list , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 5).
Tissue: Brain.
[8]"Chromosomal localization of the four genes (NFIA, B, C, and X) for the human transcription factor nuclear factor I by FISH."
Qian F., Kruse U., Lichter P., Sippel A.E.
Genomics 28:66-73(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-228.
[9]"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-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome."
Malan V., Rajan D., Thomas S., Shaw A.C., Louis Dit Picard H., Layet V., Till M., van Haeringen A., Mortier G., Nampoothiri S., Puseljic S., Legeai-Mallet L., Carter N.P., Vekemans M., Munnich A., Hennekam R.C., Colleaux L., Cormier-Daire V.
Am. J. Hum. Genet. 87:189-198(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SOTOS2 AND MRSHSS, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[11]"Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features."
Yoneda Y., Saitsu H., Touyama M., Makita Y., Miyamoto A., Hamada K., Kurotaki N., Tomita H., Nishiyama K., Tsurusaki Y., Doi H., Miyake N., Ogata K., Naritomi K., Matsumoto N.
J. Hum. Genet. 57:207-211(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SOTOS2 PRO-60 AND PRO-121.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L31881 mRNA. Translation: AAA53422.1.
U18759 mRNA. Translation: AAB52369.1.
U18761 mRNA. Translation: AAB52371.1.
AK297261 mRNA. Translation: BAG59737.1.
BT019732 mRNA. Translation: AAV38537.1.
AC004660 Genomic DNA. Translation: AAC15752.1.
AC007787 Genomic DNA. Translation: AAD38240.1.
AC007787 Genomic DNA. Translation: AAD38241.1.
CH471106 Genomic DNA. Translation: EAW84340.1.
BC117113 mRNA. Translation: AAI17114.1.
BC117115 mRNA. Translation: AAI17116.1.
U07811 mRNA. Translation: AAA93126.1.
CCDSCCDS45996.1. [Q14938-3]
PIRS50112.
RefSeqNP_001257973.1. NM_001271044.2.
NP_002492.2. NM_002501.3. [Q14938-3]
XP_005259975.1. XM_005259918.2. [Q14938-1]
UniGeneHs.257970.

3D structure databases

ProteinModelPortalQ14938.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110856. 8 interactions.
IntActQ14938. 1 interaction.
MINTMINT-4533016.
STRING9606.ENSP00000353219.

PTM databases

PhosphoSiteQ14938.

Polymorphism databases

DMDM14195678.

Proteomic databases

MaxQBQ14938.
PaxDbQ14938.
PRIDEQ14938.

Protocols and materials databases

DNASU4784.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000397661; ENSP00000380781; ENSG00000008441. [Q14938-3]
ENST00000585575; ENSP00000468794; ENSG00000008441. [Q14938-4]
ENST00000587260; ENSP00000467785; ENSG00000008441. [Q14938-5]
ENST00000587760; ENSP00000466389; ENSG00000008441.
ENST00000592199; ENSP00000467512; ENSG00000008441. [Q14938-1]
GeneID4784.
KEGGhsa:4784.
UCSCuc002mwd.3. human. [Q14938-3]
uc002mwe.4. human. [Q14938-5]

Organism-specific databases

CTD4784.
GeneCardsGC19P013106.
HGNCHGNC:7788. NFIX.
HPAHPA007533.
MIM164005. gene.
602535. phenotype.
614753. phenotype.
neXtProtNX_Q14938.
Orphanet561. Marshall-Smith syndrome.
821. Sotos syndrome.
PharmGKBPA31594.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG252172.
HOVERGENHBG006561.
InParanoidQ14938.
KOK09171.
OMAGQHSQRQ.
OrthoDBEOG7WDN2K.
PhylomeDBQ14938.
TreeFamTF313889.

Gene expression databases

ArrayExpressQ14938.
BgeeQ14938.
CleanExHS_NFIX.
GenevestigatorQ14938.

Family and domain databases

InterProIPR000647. CTF/NFI.
IPR020604. CTF/NFI_DNA-bd-dom.
IPR019739. CTF/NFI_DNA-bd_CS.
IPR019548. CTF/NFI_DNA-bd_N.
IPR003619. MAD_homology1_Dwarfin-type.
[Graphical view]
PANTHERPTHR11492. PTHR11492. 1 hit.
PfamPF00859. CTF_NFI. 1 hit.
PF03165. MH1. 1 hit.
PF10524. NfI_DNAbd_pre-N. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
[Graphical view]
PROSITEPS00349. CTF_NFI_1. 1 hit.
PS51080. CTF_NFI_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNFIX. human.
GeneWikiNFIX.
GenomeRNAi4784.
NextBio18450.
PROQ14938.
SOURCESearch...

Entry information

Entry nameNFIX_HUMAN
AccessionPrimary (citable) accession number: Q14938
Secondary accession number(s): B4DM25 expand/collapse secondary AC list , O60413, Q0VG09, Q12859, Q13050, Q13052, Q5U094, Q9UPH1, Q9Y6R8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM