Reviewed, UniProtKB/Swiss-Prot Q14934 (NFAC4_HUMAN)

Names and origin

Protein names

Recommended name:
    Nuclear factor of activated T-cells, cytoplasmic 4
      Short name=NF-ATc4
      Short name=NFATc4
Alternative name(s):
    T-cell transcription factor NFAT3
      Short name=NF-AT3

Gene names

Name:	NFATC4
Synonyms:	NFAT3

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	902 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 and IL-4 By similarity.
Subunit structure	Member of the multicomponent NFATC transcription complex that consists of at least two components, a pre-existing cytoplasmic component NFATC2 and an inducible nuclear component NFATC1. Other members such as NFATC4, NFATC3 or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the complex. NFATC proteins bind to DNA as monomers.
Subcellular location	Cytoplasm. Nucleus. Note= Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals. The subcellular localization of NFATC play a key role in the gene transcription.
Tissue specificity	Highly expressed in placenta, lung, kidney, testis and ovary. Weakly expressed in spleen and thymus. Not expressed in peripheral blood lymphocytes. Detected in hippocampus.
Domain	Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors By similarity.
Post-translational modification	Phosphorylated by NFATC-kinase; dephosphorylated by calcineurin By similarity.
Sequence similarities	Contains 1 RHD (Rel-like) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	inflammatory response Ref.1 Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	transcription coactivator activity Ref.1 Traceable author statement. Source: ProtInc transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 902

902

Nuclear factor of activated T-cells, cytoplasmic 4

PRO_0000205182

Regions

Repeat

213 – 229

17

SP 1

Repeat

277 – 293

17

SP 2; approximate

Domain

401 – 582

182

RHD

DNA binding

430 – 437

8

Region

114 – 119

6

Calcineurin-binding

Region

213 – 293

81

2 approximate SP repeats

Motif

268 – 270

3

Nuclear localization signal

Motif

672 – 674

3

Nuclear localization signal

Compositional bias

62 – 69

8

Poly-Pro

Compositional bias

297 – 304

8

Poly-Pro

Amino acid modifications

Modified residue

272

1

Phosphoserine

Modified residue

289

1

Phosphoserine

Modified residue

334

1

Phosphoserine

Natural variations

Natural variant

160

1

G → A: dbSNP rs2229309.

VAR_046985

Natural variant

246

1

S → N: dbSNP rs2228231.

VAR_046986

Natural variant

800

1

S → P: dbSNP rs7149586.

VAR_046987

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

902

Helix Strand Turn

Details...

Beta strand

587 – 594

8

Beta strand

602 – 610

9

Beta strand

616 – 620

5

Turn

638 – 640

3

Beta strand

645 – 649

5

Beta strand

662 – 669

8

Beta strand

671 – 673

3

Beta strand

679 – 684

6

Beta strand

687 – 689

3

Sequences

	Sequence		Length	Mass (Da)
	Q14934-1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: AE94C5D1325D24D7	FASTA	902	95,449
	10 20 30 40 50 60 MGAASCEDEE LEFKLVFGEE KEAPPLGAGG LGEELDSEDA PPCCRLALGE PPPYGAAPIG 70 80 90 100 110 120 IPRPPPPRPG MHSPPPRPAP SPGTWESQPA RSVRLGGPGG GAGGAGGGRV LECPSIRITS 130 140 150 160 170 180 ISPTPEPPAA LEDNPDAWGD GSPRDYPPPE GFGGYREAGG QGGGAFFSPS PGSSSLSSWS 190 200 210 220 230 240 FFSDASDEAA LYAACDEVES ELNEAASRFG LGSPLPSPRA SPRPWTPEDP WSLYGPSPGG 250 260 270 280 290 300 RGPEDSWLLL SAPGPTPASP RPASPCGKRR YSSSGTPSSA SPALSRRGSL GEEGSEPPPP 310 320 330 340 350 360 PPLPLARDPG SPGPFDYVGA PPAESIPQKT RRTSSEQAVA LPRSEEPASC NGKLPLGAEE 370 380 390 400 410 420 SVAPPGGSRK EVAGMDYLAV PSPLAWSKAR IGGHSPIFRT SALPPLDWPL PSQYEQLELR 430 440 450 460 470 480 IEVQPRAHHR AHYETEGSRG AVKAAPGGHP VVKLLGYSEK PLTLQMFIGT ADERNLRPHA 490 500 510 520 530 540 FYQVHRITGK MVATASYEAV VSGTKVLEMT LLPENNMAAN IDCAGILKLR NSDIELRKGE 550 560 570 580 590 600 TDIGRKNTRV RLVFRVHVPQ GGGKVVSVQA ASVPIECSQR SAQELPQVEA YSPSACSVRG 610 620 630 640 650 660 GEELVLTGSN FLPDSKVVFI ERGPDGKLQW EEEATVNRLQ SNEVTLTLTV PEYSNKRVSR 670 680 690 700 710 720 PVQVYFYVSN GRRKRSPTQS FRFLPVICKE EPLPDSSLRG FPSASATPFG TDMDFSPPRP 730 740 750 760 770 780 PYPSYPHEDP ACETPYLSEG FGYGMPPLYP QTGPPPSYRP GLRMFPETRG TTGCAQPPAV 790 800 810 820 830 840 SFLPRPFPSD PYGGRGSSFS LGLPFSPPAP FRPPPLPASP PLEGPFPSQS DVHPLPAEGY 850 860 870 880 890 900 NKVGPGYGPG EGAPEQEKSR GGYSSGFRDS VPIQGITLEE VSEIIGRDLS GFPAPPGEEP PA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins." Hoey T., Sun Y.-L., Williamson K., Xu X. Immunity 2:461-472(1995) [PubMed: 7749981] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-160 AND PRO-800. Tissue: T-cell.
[2]	"Alternative splicing and expression of human and mouse NFAT genes." Vihma H., Pruunsild P., Timmusk T. Genomics 0:0-0(2008) [PubMed: 18675896] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[4]	"Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT." Crabtree G.R. Cell 96:611-614(1999) [PubMed: 10089876] [Abstract] Cited for: REVIEW.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272 AND SER-334, MASS SPECTROMETRY.
[7]	"Solution structure of the TIG domain from human nuclear factor of activated T-cells, cytoplasmic 4." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2008) to the PDB data bank Cited for: STRUCTURE BY NMR OF 585-691.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L41066 mRNA. Translation: AAA79175.1.
EU887641 mRNA. Translation: ACG55661.1.
BC053855 mRNA. Translation: AAH53855.1.

UniGene

Hs.77810

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YRP	NMR	-	A	585-691	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q14934.

Genome annotation databases

Ensembl

ENSG00000100968. Homo sapiens. [Contig view]

KEGG

hsa:4776.

Organism-specific databases

HGNC

HGNC:7778. NFATC4.

MIM

602699. gene.

PharmGKB

PA31584.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q14934.

HOVERGEN

Q14934.

Gene expression databases

ArrayExpress

Q14934.

CleanEx

HS_NFATC4.

GermOnline

ENSG00000100968. Homo sapiens.

Family and domain databases

InterPro

IPR013783. Ig-like_fold.
IPR002909. IPT_TIG_rcpt.
IPR000451. NF_Rel_dor.
IPR008366. NFAT.
IPR011539. RHD.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:2.60.40.340. RHD. 1 hit.

PANTHER

PTHR12533. NFAT. 1 hit.

Pfam

PF00554. RHD. 1 hit.
PF01833. TIG. 1 hit.
[Graphical view]

PRINTS

PR01789. NUCFACTORATC.

SMART

SM00429. IPT. 1 hit.
[Graphical view]

PROSITE

PS01204. REL_1. False negative.
PS50254. REL_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

NFAC4_HUMAN

Accession

Primary (citable) accession number: Q14934
Secondary accession number(s): Q7Z598

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 25, 2008
Last modified:	November 25, 2008
This is version 80 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)