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Protein

Forkhead box protein E1

Gene

FOXE1

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

Functioni

Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. Involved in proper palate formation, most probably through the expression of MSX1 and TGFB3 genes which are direct targets of this transcription factor. Also implicated in thyroid gland morphogenesis. May indirectly play a role in cell growth and migration through the regulation of WNT5A expression.8 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi53 – 14795Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • anatomical structure morphogenesis Source: UniProtKB
  • cell migration Source: UniProtKB
  • cranial skeletal system development Source: UniProtKB
  • embryonic organ morphogenesis Source: UniProtKB
  • hair follicle morphogenesis Source: UniProtKB
  • hard palate development Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • palate development Source: UniProtKB
  • pharynx development Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • soft palate development Source: UniProtKB
  • thymus development Source: UniProtKB
  • thyroid gland development Source: UniProtKB
  • thyroid hormone generation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein E1
Alternative name(s):
Forkhead box protein E2
Forkhead-related protein FKHL15
HFKH4
HNF-3/fork head-like protein 5
Short name:
HFKL5
Thyroid transcription factor 2
Short name:
TTF-2
Gene namesi
Name:FOXE1
Synonyms:FKHL15, FOXE2, TITF2, TTF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:3806. FOXE1.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Bamforth-Lazarus syndrome (BLS)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by thyroid agenesis, cleft palate and choanal atresia.
See also OMIM:241850
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571S → N in BLS; without choanal atresia; no effect on protein abundance; no effect on localization to the nucleus; decreased sequence-specific DNA binding; decreased transcriptional activity. 2 Publications
Corresponds to variant rs28937575 [ dbSNP | Ensembl ].
VAR_016882
Natural varianti65 – 651A → V in BLS; loss of sequence-specific DNA binding; loss of transcriptional activity. 3 Publications
VAR_008857
Natural varianti73 – 731R → S in BLS; no effect on protein abundance; no effect on sequence-specific DNA binding; enhances transcriptional activity toward TG and TPO genes. 1 Publication
VAR_075978
Thyroid cancer, non-medullary, 4 (NMTC4)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
See also OMIM:616534
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti248 – 2481A → G in NMTC4; increased cell growth; increased cell migration; associated with increased expression of the WNT5A gene. 1 Publication
VAR_075981

Keywords - Diseasei

Congenital hypothyroidism, Disease mutation

Organism-specific databases

MalaCardsiFOXE1.
MIMi241850. phenotype.
616534. phenotype.
Orphaneti95713. Athyreosis.
1226. Bamforth-Lazarus syndrome.
146. Papillary or follicular thyroid carcinoma.
95720. Thyroid hypoplasia.
PharmGKBiPA28223.

Polymorphism and mutation databases

BioMutaiFOXE1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 373373Forkhead box protein E1PRO_0000091826Add
BLAST

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO00358.
PRIDEiO00358.

PTM databases

iPTMnetiO00358.
PhosphoSiteiO00358.

Expressioni

Tissue specificityi

Detected in adult brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, heart, colon, small intestine testis and thymus. Expression was strongest in heart and pancreas.

Gene expression databases

BgeeiO00358.
CleanExiHS_FOXE1.
HS_TTF2.
GenevisibleiO00358. HS.

Interactioni

Protein-protein interaction databases

BioGridi108593. 77 interactions.
IntActiO00358. 74 interactions.
STRINGi9606.ENSP00000364265.

Structurei

3D structure databases

ProteinModelPortaliO00358.
SMRiO00358. Positions 53-148.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi164 – 309146Ala-richAdd
BLAST
Compositional biasi164 – 17714Poly-AlaAdd
BLAST
Compositional biasi180 – 24162Pro-richAdd
BLAST

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231286.
HOVERGENiHBG051642.
InParanoidiO00358.
KOiK09398.
OMAiMTAESGP.
OrthoDBiEOG7C8GHD.
PhylomeDBiO00358.
TreeFamiTF316127.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O00358-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAESGPPPP QPEVLATVKE ERGETAAGAG VPGEATGRGA GGRRRKRPLQ
60 70 80 90 100
RGKPPYSYIA LIAMAIAHAP ERRLTLGGIY KFITERFPFY RDNPKKWQNS
110 120 130 140 150
IRHNLTLNDC FLKIPREAGR PGKGNYWALD PNAEDMFESG SFLRRRKRFK
160 170 180 190 200
RSDLSTYPAY MHDAAAAAAA AAAAAAAAAI FPGAVPAARP PYPGAVYAGY
210 220 230 240 250
APPSLAAPPP VYYPAASPGP CRVFGLVPER PLSPELGPAP SGPGGSCAFA
260 270 280 290 300
SAGAPATTTG YQPAGCTGAR PANPSAYAAA YAGPDGAYPQ GAGSAIFAAA
310 320 330 340 350
GRLAGPASPP AGGSSGGVET TVDFYGRTSP GQFGALGACY NPGGQLGGAS
360 370
AGAYHARHAA AYPGGIDRFV SAM
Length:373
Mass (Da):38,076
Last modified:September 23, 2008 - v3
Checksum:iD201EAF05572FCF0
GO

Sequence cautioni

The sequence CAA64246.1 differs from that shown.Several conflicts.Curated

Polymorphismi

An alanine stretch that varies from 12 to 19 residues is present. This polymorphisms can be used as a marker to study the role of FOXE1 in other cases of thyroid dysgenesis, especially in familial cases.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571S → N in BLS; without choanal atresia; no effect on protein abundance; no effect on localization to the nucleus; decreased sequence-specific DNA binding; decreased transcriptional activity. 2 Publications
Corresponds to variant rs28937575 [ dbSNP | Ensembl ].
VAR_016882
Natural varianti65 – 651A → V in BLS; loss of sequence-specific DNA binding; loss of transcriptional activity. 3 Publications
VAR_008857
Natural varianti73 – 731R → S in BLS; no effect on protein abundance; no effect on sequence-specific DNA binding; enhances transcriptional activity toward TG and TPO genes. 1 Publication
VAR_075978
Natural varianti102 – 1021R → C in congenital hypothyroidism; with absence of thyroid agenesis; loss of sequence-specific DNA binding; loss of transcriptional activity. 2 Publications
VAR_027508
Natural varianti132 – 1321N → D in congenital hypothyroidism; slightly decreased sequence-specific DNA binding to the TPO promoter; 0.5 fold decreased transcriptional activity. 1 Publication
VAR_075979
Natural varianti137 – 1371F → S in congenital hypothyroidism; loss of sequence-specific DNA binding; loss of transcriptional activity. 2 Publications
VAR_075980
Natural varianti179 – 1791A → AAA.
VAR_037643
Natural varianti248 – 2481A → G in NMTC4; increased cell growth; increased cell migration; associated with increased expression of the WNT5A gene. 1 Publication
VAR_075981

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94553 mRNA. Translation: CAA64246.1. Sequence problems.
U89995 mRNA. Translation: AAC51294.1.
Y13386 Genomic DNA. Translation: CAA73816.1.
AL499604 Genomic DNA. Translation: CAI12803.1.
CH471105 Genomic DNA. Translation: EAW58856.1.
CCDSiCCDS35078.1.
RefSeqiNP_004464.2. NM_004473.3.
UniGeneiHs.159234.

Genome annotation databases

EnsembliENST00000375123; ENSP00000364265; ENSG00000178919.
GeneIDi2304.
KEGGihsa:2304.
UCSCiuc004axu.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X94553 mRNA. Translation: CAA64246.1. Sequence problems.
U89995 mRNA. Translation: AAC51294.1.
Y13386 Genomic DNA. Translation: CAA73816.1.
AL499604 Genomic DNA. Translation: CAI12803.1.
CH471105 Genomic DNA. Translation: EAW58856.1.
CCDSiCCDS35078.1.
RefSeqiNP_004464.2. NM_004473.3.
UniGeneiHs.159234.

3D structure databases

ProteinModelPortaliO00358.
SMRiO00358. Positions 53-148.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108593. 77 interactions.
IntActiO00358. 74 interactions.
STRINGi9606.ENSP00000364265.

PTM databases

iPTMnetiO00358.
PhosphoSiteiO00358.

Polymorphism and mutation databases

BioMutaiFOXE1.

Proteomic databases

PaxDbiO00358.
PRIDEiO00358.

Protocols and materials databases

DNASUi2304.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375123; ENSP00000364265; ENSG00000178919.
GeneIDi2304.
KEGGihsa:2304.
UCSCiuc004axu.4. human.

Organism-specific databases

CTDi2304.
GeneCardsiFOXE1.
H-InvDBHIX0034929.
HGNCiHGNC:3806. FOXE1.
MalaCardsiFOXE1.
MIMi241850. phenotype.
602617. gene.
616534. phenotype.
neXtProtiNX_O00358.
Orphaneti95713. Athyreosis.
1226. Bamforth-Lazarus syndrome.
146. Papillary or follicular thyroid carcinoma.
95720. Thyroid hypoplasia.
PharmGKBiPA28223.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231286.
HOVERGENiHBG051642.
InParanoidiO00358.
KOiK09398.
OMAiMTAESGP.
OrthoDBiEOG7C8GHD.
PhylomeDBiO00358.
TreeFamiTF316127.

Miscellaneous databases

GeneWikiiFOXE1.
GenomeRNAii2304.
PROiO00358.
SOURCEiSearch...

Gene expression databases

BgeeiO00358.
CleanExiHS_FOXE1.
HS_TTF2.
GenevisibleiO00358. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The novel human HNF-3/fork head-like 5 gene: chromosomal localization and expression pattern."
    Wiese S., Emmerich D., Schroeder B., Murphy D.B., Grzeschik K.H., Van Kessel A.G., Thies U.
    DNA Cell Biol. 16:165-171(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Fetal brain.
  2. "FKHL15, a new human member of the forkhead gene family located on chromosome 9q22."
    Chadwick B.P., Obermayr F., Frischauf A.-M.
    Genomics 41:390-396(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], POLYMORPHISM OF POLY-ALA REGION.
    Tissue: Keratinocyte.
  3. "Cloning, chromosomal localization and identification of polymorphisms in the human thyroid transcription factor 2 gene (TITF2)."
    Macchia P.E., Mattei M.-G., Lapi P., Fenzi G., Di Lauro R.
    Biochimie 81:433-440(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM.
  4. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia."
    Clifton-Bligh R.J., Wentworth J.M., Heinz P., Crisp M.S., John R., Lazarus J.H., Ludgate M., Chatterjee V.K.
    Nat. Genet. 19:399-401(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INVOLVEMENT IN BLS, VARIANT BLS VAL-65, CHARACTERIZATION OF VARIANT BLS VAL-65.
  7. "MSX1 and TGF-beta3 are novel target genes functionally regulated by FOXE1."
    Venza I., Visalli M., Parrillo L., De Felice M., Teti D., Venza M.
    Hum. Mol. Genet. 20:1016-1025(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS BLS ASN-57 AND VAL-65, CHARACTERIZATION OF VARIANTS CONGENITAL HYPOTHYROIDISM CYS-102 AND SER-137.
  8. "Identification of a novel germline FOXE1 variant in patients with familial non-medullary thyroid carcinoma (FNMTC)."
    Pereira J.S., da Silva J.G., Tomaz R.A., Pinto A.E., Bugalho M.J., Leite V., Cavaco B.M.
    Endocrine 49:204-214(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INVOLVEMENT IN NMTC4, VARIANT NMTC4 GLY-248, CHARACTERIZATION OF VARIANT NMTC4 GLY-248.
  9. "A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate."
    Castanet M., Park S.M., Smith A., Bost M., Leger J., Lyonnet S., Pelet A., Czernichow P., Chatterjee K., Polak M.
    Hum. Mol. Genet. 11:2051-2059(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT BLS ASN-57, CHARACTERIZATION OF VARIANT BLS ASN-57 AND VAL-65, FUNCTION.
  10. "A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis."
    Baris I., Arisoy A.E., Smith A., Agostini M., Mitchell C.S., Park S.M., Halefoglu A.M., Zengin E., Chatterjee V.K., Battaloglu E.
    J. Clin. Endocrinol. Metab. 91:4183-4187(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CONGENITAL HYPOTHYROIDISM CYS-102, CHARACTERIZATION OF VARIANT CONGENITAL HYPOTHYROIDISM CYS-102, FUNCTION.
  11. "Characterization of mutations in the FOXE1 gene in a cohort of unrelated Malaysian patients with congenital hypothyroidism and thyroid dysgenesis."
    Kang I.N., Musa M., Harun F., Junit S.M.
    Biochem. Genet. 48:141-151(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CONGENITAL HYPOTHYROIDISM ASP-132, CHARACTERIZATION OF VARIANT CONGENITAL HYPOTHYROIDISM ASP-132, FUNCTION.
  12. "Maternal isodisomy for chromosome 9 causing homozygosity for a novel FOXE1 mutation in syndromic congenital hypothyroidism."
    Castanet M., Mallya U., Agostini M., Schoenmakers E., Mitchell C., Demuth S., Raymond F.L., Schwabe J., Gurnell M., Chatterjee V.K.
    J. Clin. Endocrinol. Metab. 95:4031-4036(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CONGENITAL HYPOTHYROIDISM SER-137, CHARACTERIZATION OF VARIANT CONGENITAL HYPOTHYROIDISM SER-137, FUNCTION.
  13. "A novel FOXE1 mutation (R73S) in Bamforth-Lazarus syndrome causing increased thyroidal gene expression."
    Carre A., Hamza R.T., Kariyawasam D., Guillot L., Teissier R., Tron E., Castanet M., Dupuy C., El Kholy M., Polak M.
    Thyroid 24:649-654(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT BLS SER-73, CHARACTERIZATION OF VARIANT BLS SER-73, FUNCTION.

Entry informationi

Entry nameiFOXE1_HUMAN
AccessioniPrimary (citable) accession number: O00358
Secondary accession number(s): O75765, Q5T109, Q99526
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 23, 2008
Last modified: July 6, 2016
This is version 153 of the entry and version 3 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.