Q12946 (FOXF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein F1

Alternative name(s):
Forkhead-related activator 1
Short name=FREAC-1
Forkhead-related protein FKHL5
Forkhead-related transcription factor 1

Gene names

Name:	FOXF1
Synonyms:	FKHL5, FREAC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	379 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Probable transcription activator for a number of lung-specific genes. Ref.1
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in lung and placenta. Ref.6
Developmental stage	Expressed in fetal lung. Ref.6
Domain	Activation domains C-terminal of (and distinct from) the forkhead domains are necessary for transcriptional activation.
Involvement in disease	Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) [MIM:265380]: A rare developmental disorder characterized by abnormal development of the capillary vascular system in the lungs. Histological features include failure of formation and ingrowth of alveolar capillaries, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. Affected infants present with respiratory distress and the disease is fatal within the newborn period. Additional features include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs. ACDMPV is a rare cause of persistent pulmonary hypertension of the newborn, an abnormal physiologic state caused by failure of transition of the pulmonary circulation from the high pulmonary vascular resistance of the fetus to the low pulmonary vascular resistance of the newborn. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Contains 1 fork-head DNA-binding domain.
Caution	It is uncertain whether Met-1 or Met-26 is the initiator.
Sequence caution	The sequence AAC50399.1 differs from that shown. Reason: Erroneous initiation. The sequence AAC61576.1 differs from that shown. Reason: Erroneous initiation. The sequence AAH89442.1 differs from that shown. Reason: Erroneous initiation. The sequence BAG36851.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branching involved in open tracheal system development Inferred from mutant phenotype Ref.7. Source: DFLAT cardiac left ventricle morphogenesis Inferred from mutant phenotype Ref.7. Source: DFLAT cell-cell adhesion Inferred from electronic annotation. Source: Ensembl cellular response to cytokine stimulus Inferred from electronic annotation. Source: Ensembl cellular response to organic cyclic compound Inferred from electronic annotation. Source: Ensembl detection of wounding Inferred from electronic annotation. Source: Ensembl determination of left/right symmetry Inferred from electronic annotation. Source: Ensembl ductus arteriosus closure Inferred from mutant phenotype Ref.7. Source: DFLAT embryonic ectodermal digestive tract morphogenesis Inferred from mutant phenotype Ref.7. Source: DFLAT embryonic foregut morphogenesis Inferred from electronic annotation. Source: Ensembl endocardial cushion development Inferred from mutant phenotype Ref.7. Source: DFLAT epithelial cell differentiation involved in mammary gland alveolus development Inferred from electronic annotation. Source: Ensembl epithelial tube branching involved in lung morphogenesis Inferred from electronic annotation. Source: Ensembl establishment of epithelial cell apical/basal polarity Inferred from electronic annotation. Source: Ensembl extracellular matrix organization Inferred from electronic annotation. Source: Ensembl in utero embryonic development Inferred from mutant phenotype Ref.7. Source: DFLAT lateral mesodermal cell differentiation Inferred from electronic annotation. Source: Ensembl lung alveolus development Inferred from electronic annotation. Source: Ensembl lung lobe morphogenesis Inferred from electronic annotation. Source: Ensembl lung vasculature development Inferred from mutant phenotype Ref.7. Source: DFLAT mesenchyme migration Inferred from electronic annotation. Source: Ensembl midgut development Inferred from mutant phenotype Ref.7. Source: DFLAT negative regulation of inflammatory response Inferred from electronic annotation. Source: Ensembl negative regulation of mast cell degranulation Inferred from electronic annotation. Source: Ensembl negative regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome pancreas development Inferred from mutant phenotype Ref.7. Source: DFLAT pattern specification process Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of cell migration Inferred from electronic annotation. Source: Ensembl positive regulation of cell-substrate adhesion Inferred from electronic annotation. Source: Ensembl positive regulation of mesenchymal cell proliferation Inferred from electronic annotation. Source: Ensembl positive regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of smooth muscle cell differentiation Inferred from electronic annotation. Source: Ensembl right lung morphogenesis Inferred from electronic annotation. Source: Ensembl smooth muscle cell differentiation Inferred from electronic annotation. Source: Ensembl smoothened signaling pathway Inferred from electronic annotation. Source: Ensembl somitogenesis Inferred from electronic annotation. Source: Ensembl trachea development Inferred from electronic annotation. Source: Ensembl ureter development Inferred from mutant phenotype Ref.7. Source: DFLAT vasculogenesis Inferred from electronic annotation. Source: Ensembl venous blood vessel development Inferred from mutant phenotype Ref.7. Source: DFLAT
Cellular_component	nucleus Inferred by curator Ref.2. Source: UniProtKB transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	DNA binding, bending Inferred from Biological aspect of Ancestor. Source: RefGenome RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome double-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome sequence-specific DNA binding Inferred from sequence or structural similarity Ref.6. Source: UniProtKB transcription factor binding Inferred from Biological aspect of Ancestor. Source: RefGenome transcription regulatory region DNA binding Inferred from electronic annotation. Source: Ensembl
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 379	379	Forkhead box protein F1		PRO_0000091832
Regions
	DNA binding	47 – 138	92	Fork-head

Sequences

	Sequence		Length	Mass (Da)
	Q12946 [UniParc]. Last modified May 26, 2009. Version 2. Checksum: CA3DE3CEFB94FC3E	FASTA	379	40,122
	10 20 30 40 50 60 MSSAPEKQQP PHGGGGGGGG GGGAAMDPAS SGPSKAKKTN AGIRRPEKPP YSYIALIVMA 70 80 90 100 110 120 IQSSPTKRLT LSEIYQFLQS RFPFFRGSYQ GWKNSVRHNL SLNECFIKLP KGLGRPGKGH 130 140 150 160 170 180 YWTIDPASEF MFEEGSFRRR PRGFRRKCQA LKPMYSMMNG LGFNHLPDTY GFQGSAGGLS 190 200 210 220 230 240 CPPNSLALEG GLGMMNGHLP GNVDGMALPS HSVPHLPSNG GHSYMGGCGG AAAGEYPHHD 250 260 270 280 290 300 SSVPASPLLP TGAGGVMEPH AVYSGSAAAW PPSASAALNS GASYIKQQPL SPCNPAANPL 310 320 330 340 350 360 SGSLSTHSLE QPYLHQNSHN APAELQGIPR YHSQSPSMCD RKEFVFSFNA MASSSMHSAG 370 GGSYYHQQVT YQDIKPCVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Differential activation of lung-specific genes by two forkhead proteins, FREAC-1 and FREAC-2." Hellqvist M., Mahlapuu M., Samuelsson L., Enerbaeck S., Carlsson P. J. Biol. Chem. 271:4482-4490(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROBABLE FUNCTION. Tissue: Lung.
[2]	"FREAC-1 contains a cell-type-specific transcriptional activation domain and is expressed in epithelial-mesenchymal interfaces." Mahlapuu M., Pelto-Huikko M., Aitola M., Enerbaeck S., Carlsson P. Dev. Biol. 202:183-195(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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. , 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]. Tissue: Colon.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Chondrosarcoma.
[6]	"Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending." Pierrou S., Hellqvist M., Samuelsson L., Enerbaeck S., Carlsson P. EMBO J. 13:5002-5012(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Fetus.
[7]	"Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations." Stankiewicz P., Sen P., Bhatt S.S., Storer M., Xia Z., Bejjani B.A., Ou Z., Wiszniewska J., Driscoll D.J., Maisenbacher M.K., Bolivar J., Bauer M., Zackai E.H., McDonald-McGinn D., Nowaczyk M.M., Murray M., Hustead V., Mascotti K. , Schultz R., Hallam L., McRae D., Nicholson A.G., Newbury R., Durham-O'Donnell J., Knight G., Kini U., Shaikh T.H., Martin V., Tyreman M., Simonic I., Willatt L., Paterson J., Mehta S., Rajan D., Fitzgerald T., Gribble S., Prigmore E., Patel A., Shaffer L.G., Carter N.P., Cheung S.W., Langston C., Shaw-Smith C. Am. J. Hum. Genet. 84:780-791(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ACDMPV.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U13219 mRNA. Translation: AAC50399.1. Different initiation. AF085343, AF085342 Genomic DNA. Translation: AAC61576.1. Different initiation. AK314167 mRNA. Translation: BAG36851.1. Frameshift. AC009108 Genomic DNA. No translation available. BC089442 mRNA. Translation: AAH89442.1. Different initiation.
IPI	IPI00871189.
PIR	S51624.
RefSeq	NP_001442.2. NM_001451.2.
UniGene	Hs.155591.
3D structure databases
ProteinModelPortal	Q12946.
SMR	Q12946. Positions 48-137.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000262426.
PTM databases
PhosphoSite	Q12946.
Polymorphism databases
DMDM	238054293.
Proteomic databases
PaxDb	Q12946.
PRIDE	Q12946.
Protocols and materials databases
DNASU	2294.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262426; ENSP00000262426; ENSG00000103241.
GeneID	2294.
KEGG	hsa:2294.
UCSC	uc002fjl.3. human.
Organism-specific databases
CTD	2294.
GeneCards	GC16P086544.
HGNC	HGNC:3809. FOXF1.
HPA	HPA028886.
MIM	265380. phenotype. 601089. gene.
neXtProt	NX_Q12946.
Orphanet	210122. Congenital alveolar capillary dysplasia.
PharmGKB	PA28226.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5025.
HOGENOM	HOG000060124.
HOVERGEN	HBG051644.
InParanoid	Q12946.
KO	K09399.
OMA	MTAEVQQ.
OrthoDB	EOG7D59PX.
Enzyme and pathway databases
SignaLink	Q12946.
Gene expression databases
Bgee	Q12946.
CleanEx	HS_FOXF1.
Genevestigator	Q12946.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
SMART	SM00339. FH. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GeneWiki	FOXF1.
GenomeRNAi	2294.
NextBio	9311.
PRO	Q12946.
SOURCE	Search...

Entry information

Entry name

FOXF1_HUMAN

Accession

Primary (citable) accession number: Q12946
Secondary accession number(s): B2RAF4, Q5FWE5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 26, 2009
Last modified:	November 13, 2013
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.