Reviewed,
UniProtKB/Swiss-Prot P55196 (AFAD_HUMAN)
Last modified
June 16, 2009.
Version 99.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Afadin Alternative name(s): Protein AF-6 | ||||
| Gene names |
| ||||
| 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 | 1816 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. |
| Subunit structure | Homodimer. Interacts with F-actin, nectin and PVRL3/nectin-3. Essential for the association of nectin and E-cadherin. Isoform 2/s-afadin does not interact with F-actin. Interacts with ZO-1 and occludin, but probably in an indirect manner. Interacts with RIT1 and RIT2 By similarity. Interacts with NRXN1 and BCR. |
| Subcellular location | Cell junction › adherens junction. Note: Not found at cell-matrix AJs. |
| Domain | The PDZ/DHR domain interacts with the C-terminus of nectin and the Pro-rich N-terminus domain interacts with F-actin. |
| Involvement in disease | A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein. |
| Sequence similarities | Contains 1 dilute domain. Contains 1 FHA domain. Contains 1 PDZ (DHR) domain. Contains 2 Ras-associating domains. |
| Sequence caution | The sequence CAB82312.1 differs from that shown. Reason: Frameshift at positions 1492, 1495 and 1684. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Cell adhesion |
| Cellular component | Cell junction |
| Coding sequence diversity | Alternative splicing Chromosomal rearrangement |
| Disease | Proto-oncogene |
| Domain | Coiled coil Repeat |
| PTM | Phosphoprotein |
| Technical term | 3D-structure |
| Gene Ontology (GO) | |
| Biological process | cell adhesion Traceable author statement. Source: ProtInc cell-cell signaling Ref.1Traceable author statement. Source: ProtInc signal transduction Ref.1Traceable author statement. Source: ProtInc |
| Cellular component | adherens junction Inferred from electronic annotation. Source: UniProtKB-SubCell cell-cell junctionTraceable author statement. Source: ProtInc |
| Molecular function | protein C-terminus binding Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 2 (identifier: P55196-1) Also known as: l-afadin; 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 1 (identifier: P55196-2) Also known as: s-afadin; The sequence of this isoform differs from the canonical sequence as follows: 1031-1031: D → DV 1588-1611: LQDEERRRQQQLEEMRKREAEDRA → VKGGVLWLCPSVVPILASACFPWG 1612-1816: Missing. | ||||||
| Isoform 3 (identifier: P55196-3) The sequence of this isoform differs from the canonical sequence as follows: 1666-1743: LCRPPLPRDY...SSTRKSHGDL → PNSYPGSTGA...TELENELNTK 1744-1816: Missing. | ||||||
| Isoform 4 (identifier: P55196-4) The sequence of this isoform differs from the canonical sequence as follows: 137-137: P → PK 391-391: P → PGRRNHFAYYNYHTYE 1031-1031: D → DV 1730-1816: QDKYSSTRKS...KRVTNQLSLS → PNSYPGSTGA...TELENELNTK | ||||||
| Isoform 5 (identifier: P55196-5) The sequence of this isoform differs from the canonical sequence as follows: 391-391: P → PGRRNHFAYYNYHTYE 1031-1031: D → DV 1587-1587: R → RTAMPAISVLDL 1730-1816: QDKYSSTRKS...KRVTNQLSLS → PNSYPGSTGA...TELENELNTK |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1816 | 1816 | Afadin | PRO_0000215918 | |||||||||||||||||||||
Regions | |||||||||||||||||||||||||
| Domain | 39 – 133 | 95 | Ras-associating 1 | ||||||||||||||||||||||
| Domain | 245 – 347 | 103 | Ras-associating 2 | ||||||||||||||||||||||
| Domain | 425 – 491 | 67 | FHA | ||||||||||||||||||||||
| Domain | 652 – 892 | 241 | Dilute | ||||||||||||||||||||||
| Domain | 991 – 1076 | 86 | PDZ | ||||||||||||||||||||||
| Coiled coil | 145 – 184 | 40 | Potential | ||||||||||||||||||||||
| Coiled coil | 1391 – 1431 | 41 | Potential | ||||||||||||||||||||||
| Coiled coil | 1506 – 1650 | 145 | Potential | ||||||||||||||||||||||
| Compositional bias | 162 – 174 | 13 | Glu/Lys-rich | ||||||||||||||||||||||
| Compositional bias | 1329 – 1375 | 47 | Pro-rich | ||||||||||||||||||||||
| Compositional bias | 1561 – 1571 | 11 | Asp/Glu-rich (acidic) | ||||||||||||||||||||||
| Compositional bias | 1661 – 1691 | 31 | Pro-rich | ||||||||||||||||||||||
Sites | |||||||||||||||||||||||||
| Site | 26 | 1 | Breakpoint for translocation to form MLL-MLLT4 | ||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||
| Modified residue | 94 | 1 | Phosphotyrosine Ref.11 | ||||||||||||||||||||||
| Modified residue | 215 | 1 | Phosphoserine Ref.14 | ||||||||||||||||||||||
| Modified residue | 541 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||
| Modified residue | 1090 | 1 | Phosphoserine Ref.14 Ref.9 | ||||||||||||||||||||||
| Modified residue | 1155 | 1 | Phosphoserine Ref.7 | ||||||||||||||||||||||
| Modified residue | 1156 | 1 | Phosphoserine Ref.7 | ||||||||||||||||||||||
| Modified residue | 1165 | 1 | Phosphoserine Ref.14 Ref.8 Ref.12 | ||||||||||||||||||||||
| Modified residue | 1184 | 1 | Phosphoserine Ref.8 | ||||||||||||||||||||||
| Modified residue | 1213 | 1 | Phosphotyrosine By similarity | ||||||||||||||||||||||
| Modified residue | 1215 | 1 | Phosphothreonine Ref.14 | ||||||||||||||||||||||
| Modified residue | 1258 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||
| Modified residue | 1313 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||
| Modified residue | 1317 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||
| Modified residue | 1679 | 1 | Phosphoserine Ref.13 | ||||||||||||||||||||||
| Modified residue | 1681 | 1 | Phosphoserine Ref.10 | ||||||||||||||||||||||
| Modified residue | 1704 | 1 | Phosphoserine Ref.14 | ||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||
| Alternative sequence | 137 | 1 | P → PK in isoform 4. | VSP_019254 | |||||||||||||||||||||
| Alternative sequence | 391 | 1 | P → PGRRNHFAYYNYHTYE in isoform 4 and isoform 5. | VSP_019255 | |||||||||||||||||||||
| Alternative sequence | 1031 | 1 | D → DV in isoform 1, isoform 4 and isoform 5. | VSP_019256 | |||||||||||||||||||||
| Alternative sequence | 1587 | 1 | R → RTAMPAISVLDL in isoform 5. | VSP_019257 | |||||||||||||||||||||
| Alternative sequence | 1588 – 1611 | 24 | LQDEE…AEDRA → VKGGVLWLCPSVVPILASAC FPWG in isoform 1. | VSP_000217 | |||||||||||||||||||||
| Alternative sequence | 1612 – 1816 | 205 | Missing in isoform 1. | VSP_000218 | |||||||||||||||||||||
| Alternative sequence | 1666 – 1743 | 78 | LCRPP…SHGDL → PNSYPGSTGAAVGAHDACRD AKEKRSKSQDADSPGSSGAP ENLTFKERQRLFSQGQDVSN KVKASRKLTELENELNTK in isoform 3. | VSP_000219 | |||||||||||||||||||||
| Alternative sequence | 1730 – 1816 | 87 | QDKYS…QLSLS → PNSYPGSTGAAVGAHDACRD AKEKRSKSQDADSPGSSGAP ENLTFKERQRLFSQGQDVSN KVKASRKLTELENELNTK in isoform 4 and isoform 5. | VSP_019258 | |||||||||||||||||||||
| Alternative sequence | 1744 – 1816 | 73 | Missing in isoform 3. | VSP_000220 | |||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||
| Sequence conflict | 373 | 1 | G → V in AAC50059. Ref.1 | ||||||||||||||||||||||
| Sequence conflict | 1408 | 1 | R → P in AAC50059. Ref.1 | ||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||
| Beta strand | 990 – 997 | 8 | |||||||||||||||||||||||
| Beta strand | 999 – 1001 | 3 | |||||||||||||||||||||||
| Beta strand | 1004 – 1009 | 6 | |||||||||||||||||||||||
| Beta strand | 1018 – 1024 | 7 | |||||||||||||||||||||||
| Helix | 1029 – 1032 | 4 | |||||||||||||||||||||||
| Beta strand | 1037 – 1044 | 8 | |||||||||||||||||||||||
| Helix | 1054 – 1062 | 9 | |||||||||||||||||||||||
| Beta strand | 1066 – 1074 | 9 | |||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation." Prasad R., Gu Y., Alder H., Nakamura T., Canaani O., Saito H., Huebner K., Gale R.P., Nowell P.C., Kuriyama K., Miyazaki Y., Croce C.M., Canaani E. Cancer Res. 53:5624-5628(1993) [PubMed: 8242616] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Complete genomic structure, DNA polymorphisms, and alternative splicing of the human AF-6 gene." Saito S., Matsushima M., Shirahama S., Minaguchi T., Kanamori Y., Minami M., Nakamura Y. DNA Res. 5:115-120(1998) [PubMed: 9679199] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING. Tissue: Fetal brain. |
| [3] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING. |
| [4] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 334-1816 (ISOFORM 4). Tissue: Amygdala. |
| [5] | "Human nectin3/PRR3: a novel member of the PVR/PRR/nectin family that interacts with afadin." Reymond N., Borg J.-P., Lecocq E., Adelaide J., Campadelli-Fiume G., Dubreuil P., Lopez M. Gene 255:347-355(2000) [PubMed: 11024295] [Abstract] Cited for: INTERACTION WITH PVRL3. |
| [6] | "Nectin and afadin: novel organizers of intercellular junctions." Takai Y., Nakanishi H. J. Cell Sci. 116:17-27(2003) [PubMed: 12456712] [Abstract] Cited for: REVIEW ON INTERACTION. |
| [7] | "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1155 AND SER-1156, MASS SPECTROMETRY. Tissue: T-cell. |
| [8] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1165 AND SER-1184, MASS SPECTROMETRY. Tissue: Epithelium. |
| [9] | "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-1090, MASS SPECTROMETRY. Tissue: Epithelium. |
| [10] | "A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1681, MASS SPECTROMETRY. Tissue: Epithelium. |
| [11] | "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J.Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-94, MASS SPECTROMETRY. |
| [12] | "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction." Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R. Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed: 17693683] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1165, MASS SPECTROMETRY. |
| [13] | "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-1679, MASS SPECTROMETRY. |
| [14] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-1090; SER-1165; THR-1215 AND SER-1704, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1698 AND SER-1718 (ISOFORM 3), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1779 AND SER-1799 (ISOFORM 4), PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1789 AND SER-1809 (ISOFORM 5), MASS SPECTROMETRY. |
| [15] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [16] | "Solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr." Zhou H., Xu Y., Yang Y., Huang A., Wu J., Shi Y. J. Biol. Chem. 280:13841-13847(2005) [PubMed: 15684424] [Abstract] Cited for: STRUCTURE BY NMR OF 987-1077 IN COMPLEX WITH NRXN1 AND BCR. |
| [17] | "Structure of AF-6 PDZ domain." Joshi M., Boisguerin P., Leitner D., Volkmer-Engert R., Moelling K., Schade M., Schmieder P., Krause G., Oschkinat H. Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 985-1078. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| U02478 mRNA. Translation: AAC50059.1. AB011399 Genomic DNA. Translation: BAA32483.1. AB011399 Genomic DNA. Translation: BAA32484.1. AB011399 Genomic DNA. Translation: BAA32485.1. AL009178, AL731868, AL049698 Genomic DNA. Translation: CAI20900.1. AL731868, AL009178, AL049698 Genomic DNA. Translation: CAI40824.1. AL049698, AL009178, AL731868 Genomic DNA. Translation: CAI42812.1. AL161973 mRNA. Translation: CAB82312.1. Frameshift. | |||||||||||||||||||||||||||||||
| IPI | IPI00023461. IPI00216505. IPI00398718. IPI00552765. IPI00759546. | ||||||||||||||||||||||||||||||
| PIR | T47137. | ||||||||||||||||||||||||||||||
| RefSeq | NP_001035090.1. NP_005927.2. | ||||||||||||||||||||||||||||||
| UniGene | Hs.644024 Hs.715090 | ||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
| SMR | P55196. Positions 248-347, 373-487. | ||||||||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||
| IntAct | P55196. 6 interactions. | ||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||
| PhosphoSite | P55196. | ||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||
| PRIDE | P55196. | ||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||
| Ensembl | ENSG00000130396. Homo sapiens. [Contig view] | ||||||||||||||||||||||||||||||
| GeneID | 4301. | ||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||
| GeneCards | GC06P167970. GC06P168046. | ||||||||||||||||||||||||||||||
| HGNC | HGNC:7137. MLLT4. | ||||||||||||||||||||||||||||||
| MIM | 159559. gene. | ||||||||||||||||||||||||||||||
| PharmGKB | PA30853. | ||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||
| HOVERGEN | P55196. | ||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||
| ArrayExpress | P55196. | ||||||||||||||||||||||||||||||
| Bgee | P55196. | ||||||||||||||||||||||||||||||
| CleanEx | HS_MLLT4. | ||||||||||||||||||||||||||||||
| GermOnline | ENSG00000130396. Homo sapiens. | ||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||
| InterPro | IPR018444. Dil_domain. IPR002710. Dilute. IPR000253. FHA. IPR001478. PDZ/DHR/GLGF. IPR000159. Ras-assoc. [Graphical view] | ||||||||||||||||||||||||||||||
| Pfam | PF01843. DIL. 1 hit. PF00498. FHA. 1 hit. PF00595. PDZ. 1 hit. PF00788. RA. 2 hits. [Graphical view] | ||||||||||||||||||||||||||||||
| ProDom | PD003376. DIL. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||||||||||||||||||||
| SMART | SM00240. FHA. 1 hit. SM00228. PDZ. 1 hit. SM00314. RA. 2 hits. [Graphical view] | ||||||||||||||||||||||||||||||
| PROSITE | PS51126. DILUTE. 1 hit. PS50006. FHA_DOMAIN. False negative. PS50106. PDZ. 1 hit. PS50200. RA. 2 hits. [Graphical view] | ||||||||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||||||||
| NextBio | 16931. | ||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||
Entry information
| Entry name | AFAD_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P55196 Secondary accession number(s): O75087 Q9NU92 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


