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Q9Y2T1

- AXIN2_HUMAN

UniProt

Q9Y2T1 - AXIN2_HUMAN

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Protein
Axin-2
Gene
AXIN2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Inhibitor of the Wnt signaling pathway. Down-regulates beta-catenin. Probably facilitate the phosphorylation of beta-catenin and APC by GSK3B By similarity.

GO - Molecular functioni

  1. GTPase activator activity Source: RefGenome
  2. armadillo repeat domain binding Source: RefGenome
  3. beta-catenin binding Source: BHF-UCL
  4. enzyme binding Source: UniProtKB
  5. protein binding Source: IntAct
  6. protein kinase binding Source: RefGenome
  7. signal transducer activity Source: InterPro
  8. ubiquitin protein ligase binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. Wnt signaling pathway involved in somitogenesis Source: RefGenome
  2. bone mineralization Source: Ensembl
  3. cell proliferation Source: Ensembl
  4. cellular protein localization Source: BHF-UCL
  5. cellular response to organic cyclic compound Source: RefGenome
  6. chondrocyte differentiation involved in endochondral bone morphogenesis Source: Ensembl
  7. dorsal/ventral axis specification Source: RefGenome
  8. intramembranous ossification Source: RefGenome
  9. mRNA stabilization Source: BHF-UCL
  10. maintenance of DNA repeat elements Source: BHF-UCL
  11. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  12. negative regulation of catenin import into nucleus Source: BHF-UCL
  13. negative regulation of cell proliferation Source: BHF-UCL
  14. negative regulation of osteoblast differentiation Source: RefGenome
  15. odontogenesis Source: BHF-UCL
  16. positive regulation of GTPase activity Source: GOC
  17. positive regulation of cell death Source: BHF-UCL
  18. positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  19. positive regulation of protein phosphorylation Source: BHF-UCL
  20. regulation of centromeric sister chromatid cohesion Source: BHF-UCL
  21. regulation of chondrocyte development Source: Ensembl
  22. regulation of mismatch repair Source: BHF-UCL
  23. termination of G-protein coupled receptor signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_200766. degradation of AXIN.
REACT_200777. TCF dependent signaling in response to WNT.
REACT_200799. binding of TCF/LEF:CTNNB1 to target gene promoters.
SignaLinkiQ9Y2T1.

Names & Taxonomyi

Protein namesi
Recommended name:
Axin-2
Alternative name(s):
Axin-like protein
Short name:
Axil
Axis inhibition protein 2
Conductin
Gene namesi
Name:AXIN2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:904. AXIN2.

Subcellular locationi

GO - Cellular componenti

  1. beta-catenin destruction complex Source: BHF-UCL
  2. cell cortex Source: RefGenome
  3. centrosome Source: BHF-UCL
  4. cytoplasm Source: UniProtKB
  5. cytoplasmic membrane-bounded vesicle Source: RefGenome
  6. cytoplasmic microtubule Source: RefGenome
  7. nucleus Source: UniProtKB
  8. plasma membrane Source: RefGenome
  9. postsynaptic density Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: The gene represented in this entry is involved in disease pathogenesis.
Oligodontia-colorectal cancer syndrome (ODCRCS) [MIM:608615]: Affected individuals manifest severe tooth agenesis and colorectal cancer or precancerous lesions of variable types.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication

Organism-specific databases

MIMi114500. phenotype.
608615. phenotype.
Orphaneti2227. Hypodontia.
99798. Oligodontia.
300576. Oligodontia - cancer predisposition syndrome.
PharmGKBiPA25196.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 843843Axin-2
PRO_0000220895Add
BLAST

Post-translational modificationi

Probably phosphorylated by GSK3B and dephosphorylated by PP2A By similarity.
ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway.
Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription.3 Publications

Keywords - PTMi

ADP-ribosylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9Y2T1.
PaxDbiQ9Y2T1.
PRIDEiQ9Y2T1.

PTM databases

PhosphoSiteiQ9Y2T1.

Expressioni

Tissue specificityi

Expressed in brain and lymphoblast.

Gene expression databases

ArrayExpressiQ9Y2T1.
BgeeiQ9Y2T1.
CleanExiHS_AXIN2.
GenevestigatoriQ9Y2T1.

Organism-specific databases

HPAiCAB012283.
CAB017783.
HPA042344.

Interactioni

Subunit structurei

Interacts with glycogen synthase kinase-3 beta (GSK3B) and beta-catenin. The interaction between axin and beta-catenin occurs via the armadillo repeats contained in beta-catenin By similarity. Interacts with SMAD7 and RNF111. Interacts with ANKRD6.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AMER3Q8N9442EBI-4400025,EBI-8869590
PPP2CBP627144EBI-4400025,EBI-1044367

Protein-protein interaction databases

BioGridi113910. 10 interactions.
DIPiDIP-59293N.
IntActiQ9Y2T1. 10 interactions.
MINTiMINT-3085018.
STRINGi9606.ENSP00000302625.

Structurei

3D structure databases

ProteinModelPortaliQ9Y2T1.
SMRiQ9Y2T1. Positions 74-199, 764-843.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini81 – 200120RGS
Add
BLAST
Domaini761 – 84383DIX
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni327 – 41387Interaction with GSK3B By similarity
Add
BLAST
Regioni413 – 47664Interaction with beta-catenin By similarity
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi21 – 3010Tankyrase-binding motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi469 – 4746Poly-His

Domaini

The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2 By similarity.

Sequence similaritiesi

Contains 1 DIX domain.
Contains 1 RGS domain.

Phylogenomic databases

eggNOGiNOG238205.
HOVERGENiHBG004324.
InParanoidiQ9Y2T1.
KOiK04385.
OrthoDBiEOG79PJQ0.
PhylomeDBiQ9Y2T1.
TreeFamiTF315454.

Family and domain databases

Gene3Di1.10.196.10. 2 hits.
InterProiIPR014936. Axin_b-cat-bd.
IPR001158. DIX.
IPR024066. Regulat_G_prot_signal_dom1.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF08833. Axin_b-cat_bind. 1 hit.
PF00778. DIX. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR01301. RGSPROTEIN.
SMARTiSM00021. DAX. 1 hit.
SM00315. RGS. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS50841. DIX. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y2T1-1 [UniParc]FASTAAdd to Basket

« Hide

MSSAMLVTCL PDPSSSFRED APRPPVPGEE GETPPCQPGV GKGQVTKPMS    50
VSSNTRRNED GLGEPEGRAS PDSPLTRWTK SLHSLLGDQD GAYLFRTFLE 100
REKCVDTLDF WFACNGFRQM NLKDTKTLRV AKAIYKRYIE NNSIVSKQLK 150
PATKTYIRDG IKKQQIDSIM FDQAQTEIQS VMEENAYQMF LTSDIYLEYV 200
RSGGENTAYM SNGGLGSLKV VCGYLPTLNE EEEWTCADFK CKLSPTVVGL 250
SSKTLRATAS VRSTETVDSG YRSFKRSDPV NPYHIGSGYV FAPATSANDS 300
EISSDALTDD SMSMTDSSVD GIPPYRVGSK KQLQREMHRS VKANGQVSLP 350
HFPRTHRLPK EMTPVEPATF AAELISRLEK LKLELESRHS LEERLQQIRE 400
DEEREGSELT LNSREGAPTQ HPLSLLPSGS YEEDPQTILD DHLSRVLKTP 450
GCQSPGVGRY SPRSRSPDHH HHHHSQYHSL LPPGGKLPPA AASPGACPLL 500
GGKGFVTKQT TKHVHHHYIH HHAVPKTKEE IEAEATQRVH CFCPGGSEYY 550
CYSKCKSHSK APETMPSEQF GGSRGSTLPK RNGKGTEPGL ALPAREGGAP 600
GGAGALQLPR EEGDRSQDVW QWMLESERQS KPKPHSAQST KKAYPLESAR 650
SSPGERASRH HLWGGNSGHP RTTPRAHLFT QDPAMPPLTP PNTLAQLEEA 700
CRRLAEVSKP PKQRCCVASQ QRDRNHSATV QTGATPFSNP SLAPEDHKEP 750
KKLAGVHALQ ASELVVTYFF CGEEIPYRRM LKAQSLTLGH FKEQLSKKGN 800
YRYYFKKASD EFACGAVFEE IWEDETVLPM YEGRILGKVE RID 843
Length:843
Mass (Da):93,558
Last modified:November 1, 1999 - v1
Checksum:iF7B62BED6AB4664D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501S → P in polymorphism associated with increased risk of lung cancer. 1 Publication
Corresponds to variant rs2240308 [ dbSNP | Ensembl ].
VAR_054860

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti37 – 6226QPGVG…NEDGL → HHGGQGPGHQTHVCLFQHQA ERRWV in AAF22799. 1 Publication
Add
BLAST
Sequence conflicti346 – 3461Q → R in AAF22799. 1 Publication
Sequence conflicti572 – 63665Missing in AAF22799. 1 Publication
Add
BLAST
Sequence conflicti687 – 6871P → S in AAF22799. 1 Publication
Sequence conflicti696 – 6961Q → H in AAF22799. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF078165 mRNA. Translation: AAD20976.1.
AF205888 mRNA. Translation: AAF22799.1.
AC115994 Genomic DNA. No translation available.
BC101533 mRNA. Translation: AAI01534.1.
AB052751 mRNA. Translation: BAB19762.1.
CCDSiCCDS11662.1.
RefSeqiNP_004646.3. NM_004655.3.
UniGeneiHs.156527.

Genome annotation databases

EnsembliENST00000307078; ENSP00000302625; ENSG00000168646.
GeneIDi8313.
KEGGihsa:8313.
UCSCiuc002jfi.3. human.

Polymorphism databases

DMDMi12643949.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF078165 mRNA. Translation: AAD20976.1 .
AF205888 mRNA. Translation: AAF22799.1 .
AC115994 Genomic DNA. No translation available.
BC101533 mRNA. Translation: AAI01534.1 .
AB052751 mRNA. Translation: BAB19762.1 .
CCDSi CCDS11662.1.
RefSeqi NP_004646.3. NM_004655.3.
UniGenei Hs.156527.

3D structure databases

ProteinModelPortali Q9Y2T1.
SMRi Q9Y2T1. Positions 74-199, 764-843.
ModBasei Search...

Protein-protein interaction databases

BioGridi 113910. 10 interactions.
DIPi DIP-59293N.
IntActi Q9Y2T1. 10 interactions.
MINTi MINT-3085018.
STRINGi 9606.ENSP00000302625.

Chemistry

ChEMBLi CHEMBL1255167.

PTM databases

PhosphoSitei Q9Y2T1.

Polymorphism databases

DMDMi 12643949.

Proteomic databases

MaxQBi Q9Y2T1.
PaxDbi Q9Y2T1.
PRIDEi Q9Y2T1.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000307078 ; ENSP00000302625 ; ENSG00000168646 .
GeneIDi 8313.
KEGGi hsa:8313.
UCSCi uc002jfi.3. human.

Organism-specific databases

CTDi 8313.
GeneCardsi GC17M063524.
HGNCi HGNC:904. AXIN2.
HPAi CAB012283.
CAB017783.
HPA042344.
MIMi 114500. phenotype.
604025. gene.
608615. phenotype.
neXtProti NX_Q9Y2T1.
Orphaneti 2227. Hypodontia.
99798. Oligodontia.
300576. Oligodontia - cancer predisposition syndrome.
PharmGKBi PA25196.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG238205.
HOVERGENi HBG004324.
InParanoidi Q9Y2T1.
KOi K04385.
OrthoDBi EOG79PJQ0.
PhylomeDBi Q9Y2T1.
TreeFami TF315454.

Enzyme and pathway databases

Reactomei REACT_200766. degradation of AXIN.
REACT_200777. TCF dependent signaling in response to WNT.
REACT_200799. binding of TCF/LEF:CTNNB1 to target gene promoters.
SignaLinki Q9Y2T1.

Miscellaneous databases

ChiTaRSi AXIN2. human.
GeneWikii AXIN2.
GenomeRNAii 8313.
NextBioi 31133.
PROi Q9Y2T1.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9Y2T1.
Bgeei Q9Y2T1.
CleanExi HS_AXIN2.
Genevestigatori Q9Y2T1.

Family and domain databases

Gene3Di 1.10.196.10. 2 hits.
InterProi IPR014936. Axin_b-cat-bd.
IPR001158. DIX.
IPR024066. Regulat_G_prot_signal_dom1.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view ]
Pfami PF08833. Axin_b-cat_bind. 1 hit.
PF00778. DIX. 1 hit.
PF00615. RGS. 1 hit.
[Graphical view ]
PRINTSi PR01301. RGSPROTEIN.
SMARTi SM00021. DAX. 1 hit.
SM00315. RGS. 1 hit.
[Graphical view ]
SUPFAMi SSF48097. SSF48097. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEi PS50841. DIX. 1 hit.
PS50132. RGS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24."
    Mai M., Qian C., Yokomizo A., Smith D.I., Liu W.
    Genomics 55:341-344(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Properties of mouse Axin2 and human AXIN2: chromosomal location, expression pattern, interaction with Axin and effects on embryonic axis formation."
    Zhang T., Fagotto F., Hsu W., Zeng L., Gilbert D., Copeland N.G., Jenkins N.A., Warburton D., Costantini F.
    Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain and Lymphoblast.
  3. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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: Brain.
  5. "Identification of 3' UTR of Axin2."
    Takahashi M., Furukawa Y.
    Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 697-843.
  6. "Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling."
    Liu W., Dong X., Mai M., Seelan R.S., Taniguchi K., Krishnadath K.K., Halling K.C., Cunningham J.M., Qian C., Christensen E., Roches P.C., Smith D.I., Thibodeau S.N.
    Nat. Genet. 26:146-147(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN COLORECTAL CANCER.
  7. "Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer."
    Lammi L., Arte S., Somer M., Jarvinen H., Lahermo P., Thesleff I., Pirinen S., Nieminen P.
    Am. J. Hum. Genet. 74:1043-1050(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN ODCRCS.
  8. "Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia."
    Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S., Chan S.C., Chen Y.-G., Han J., Lin S.-C.
    EMBO J. 25:1646-1658(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SMAD7 AND RNF111.
  9. Cited for: ADP-RIBOSYLATION, UBIQUITINATION, INTERACTION WITH TNKS AND TNKS2.
  10. "The Ubiquitin specific protease USP34 regulates Axin stability and Wnt/beta-catenin signaling."
    Lui T.T., Lacroix C., Ahmed S.M., Goldenberg S.J., Leach C.A., Daulat A.M., Angers S.
    Mol. Cell. Biol. 31:2053-2065(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP34.
  11. "RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling."
    Zhang Y., Liu S., Mickanin C., Feng Y., Charlat O., Michaud G.A., Schirle M., Shi X., Hild M., Bauer A., Myer V.E., Finan P.M., Porter J.A., Huang S.M., Cong F.
    Nat. Cell Biol. 13:623-629(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ADP-RIBOSYLATION, UBIQUITINATION, INTERACTION WITH RNF146; TNKS AND TNKS2.
  12. "Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population."
    Kanzaki H., Ouchida M., Hanafusa H., Yano M., Suzuki H., Aoe M., Imai K., Shimizu N., Nakachi K., Shimizu K.
    Int. J. Mol. Med. 18:279-284(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PRO-50.

Entry informationi

Entry nameiAXIN2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2T1
Secondary accession number(s): Q3MJ88, Q9H3M6, Q9UH84
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: September 3, 2014
This is version 139 of the entry and version 1 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 17
    Human chromosome 17: 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

External Data

Dasty 3

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