O15244 (S22A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 110.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Solute carrier family 22 member 2 Alternative name(s): Organic cation transporter 2 Short name=hOCT2 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 555 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity. Ref.1 Ref.2 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 |
| Subcellular location | Membrane; Multi-pass membrane protein Potential. |
| Tissue specificity | Mainly expressed in kidney. Localized at the luminal membrane and basolateral membrane of kidney distal tubule and proximal tubules. To a lower extent, expressed in neurons of the cerebral cortex and in various subcortical nuclei (at protein levels). Also detected in secretory phase endometrium; in scattered cells in the stroma. Ref.1 Ref.8 Ref.10 Ref.22 |
| Induction | May be down-regulated in diabetic patients. Ref.13 |
| Sequence similarities | Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification] |
| Biophysicochemical properties | Kinetic parameters: KM=1 mM for agmatine Ref.2 Ref.8 Ref.9 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 KM=95 µM for amiloride KM=24 µM for ASP KM=34 µM for memantine KM=27 µM for amantadine KM=1.38 mM for metformin KM=1.9 mM for noradrenaline KM=1.9 mM for norepinephrine KM=1.3 mM for histamine KM=0.39 mM for dopamine KM=0.08 mM for serotonine KM=72.6 µM for cimetidine (at pH 7.4 and 37 degrees Celsius) KM=56.1 µM for famotidine KM=65.2 µM for ranitidine KM=431 µM for TEA (isoform 1) KM=63 µM for TEA (isoform 2) Vmax=3770 pmol/min/mg enzyme for TEA uptake (isoform 1) Vmax=314 pmol/min/mg enzyme for TEA uptake (isoform 2) Vmax=11.9 nmol/min/mg enzyme for metformin uptake Vmax=2170 pmol/min/mg enzyme for cimetidine uptake Vmax=204 pmol/min/mg enzyme for famotidine uptake Vmax=265 pmol/min/mg enzyme for ranitidine uptake |
Ontologies
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O15244-1) 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 2 (identifier: O15244-2) Also known as: OCT2-A; The sequence of this isoform differs from the canonical sequence as follows: 427-483: DLQWLKIIIS...CDIGGIITPF → GKFQVKLESY...SEQIHMASLL 484-555: Missing. | ||||||
| Isoform 3 (identifier: O15244-3) The sequence of this isoform differs from the canonical sequence as follows: 225-242: ITEFVGRRYRRTVGIFYQ → SKNVCACNCENKATSLPK 243-555: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 555 | 555 | Solute carrier family 22 member 2 | PRO_0000320957 | |||||
Regions | |||||||||
| Topological domain | 1 – 22 | 22 | Cytoplasmic Potential | ||||||
| Transmembrane | 23 – 43 | 21 | Helical; Potential | ||||||
| Topological domain | 44 – 150 | 107 | Extracellular Potential | ||||||
| Transmembrane | 151 – 171 | 21 | Helical; Potential | ||||||
| Topological domain | 172 – 177 | 6 | Cytoplasmic Potential | ||||||
| Transmembrane | 178 – 198 | 21 | Helical; Potential | ||||||
| Topological domain | 199 – 208 | 10 | Extracellular Potential | ||||||
| Transmembrane | 209 – 229 | 21 | Helical; Potential | ||||||
| Topological domain | 230 – 238 | 9 | Cytoplasmic Potential | ||||||
| Transmembrane | 239 – 259 | 21 | Helical; Potential | ||||||
| Topological domain | 260 – 263 | 4 | Extracellular Potential | ||||||
| Transmembrane | 264 – 284 | 21 | Helical; Potential | ||||||
| Topological domain | 285 – 348 | 64 | Cytoplasmic Potential | ||||||
| Transmembrane | 349 – 369 | 21 | Helical; Potential | ||||||
| Topological domain | 370 – 375 | 6 | Extracellular Potential | ||||||
| Transmembrane | 376 – 396 | 21 | Helical; Potential | ||||||
| Topological domain | 397 – 414 | 18 | Cytoplasmic Potential | ||||||
| Transmembrane | 415 – 435 | 21 | Helical; Potential | ||||||
| Topological domain | 436 – 441 | 6 | Extracellular Potential | ||||||
| Transmembrane | 442 – 462 | 21 | Helical; Potential | ||||||
| Topological domain | 463 – 464 | 2 | Cytoplasmic Potential | ||||||
| Transmembrane | 465 – 485 | 21 | Helical; Potential | ||||||
| Topological domain | 486 – 494 | 9 | Extracellular Potential | ||||||
| Transmembrane | 495 – 515 | 21 | Helical; Potential | ||||||
| Topological domain | 516 – 555 | 40 | Cytoplasmic Potential | ||||||
Sites | |||||||||
| Site | 451 | 1 | Involved in recognition of organic cations and participates in structural changes that occur during translocation of organic cations By similarity | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 72 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 225 – 242 | 18 | ITEFV…GIFYQ → SKNVCACNCENKATSLPK in isoform 3. | VSP_031771 | |||||
| Alternative sequence | 243 – 555 | 313 | Missing in isoform 3. | VSP_031772 | |||||
| Alternative sequence | 427 – 483 | 57 | DLQWL…IITPF → GKFQVKLESYLQDPGERECH GPLIGKPCNLSSKSIWKDKL EGSIWDPSEQIHMASLL in isoform 2. | VSP_031773 | |||||
| Alternative sequence | 484 – 555 | 72 | Missing in isoform 2. | VSP_031774 | |||||
| Natural variant | 54 | 1 | P → S. Ref.23 Corresponds to variant rs8177504 [ dbSNP | Ensembl ]. | VAR_039322 | |||||
| Natural variant | 165 | 1 | M → I Lower Vmax. Ref.23 | VAR_039323 | |||||
| Natural variant | 201 | 1 | T → M. Ref.24 | VAR_039324 | |||||
| Natural variant | 270 | 1 | S → A Increased Ki value for TBA inhibition of MPP. Ref.1 Ref.2 Ref.3 Ref.6 Ref.23 Ref.24 Corresponds to variant rs316019 [ dbSNP | Ensembl ]. | VAR_039325 | |||||
| Natural variant | 297 | 1 | A → G. Corresponds to variant rs8177513 [ dbSNP | Ensembl ]. | VAR_039326 | |||||
| Natural variant | 400 | 1 | R → C Lower Vmax and reduced Ki value for TBA inhibition of MPP. Ref.23 Corresponds to variant rs8177516 [ dbSNP | Ensembl ]. | VAR_039327 | |||||
| Natural variant | 432 | 1 | K → Q Lower Km value for MPP and reduced Ki value for TBA inhibition of MPP. Ref.23 Corresponds to variant rs8177517 [ dbSNP | Ensembl ]. | VAR_039328 | |||||
| Natural variant | 463 | 1 | R → K. Corresponds to variant rs3907239 [ dbSNP | Ensembl ]. | VAR_039329 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning and characterization of two human polyspecific organic cation transporters." Gorboulev V., Ulzheimer J.C., Akhoundova A., Ulzheimer-Teuber I., Karbach U., Quester S., Baumann C., Lang F., Busch A.E., Koepsell H. DNA Cell Biol. 16:871-881(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, VARIANT ALA-270. Tissue: Kidney cortex. |
| [2] | "cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney." Urakami Y., Akazawa M., Saito H., Okuda M., Inui K. J. Am. Soc. Nephrol. 13:1703-1710(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT ALA-270. Tissue: Kidney. |
| [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ALA-270. Tissue: Kidney. |
| [4] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "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] (ISOFORMS 1 AND 3), VARIANT ALA-270. Tissue: Colon and Kidney. |
| [7] | "Gene structures of the human non-neuronal monoamine transporters EMT and OCT2." Gruendemann D., Schoemig E. Hum. Genet. 106:627-635(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-138. |
| [8] | "Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine." Busch A.E., Karbach U., Miska D., Gorboulev V., Akhoundova A., Volk C., Arndt P., Ulzheimer J.C., Sonders M.S., Baumann C., Waldegger S., Lang F., Koepsell H. Mol. Pharmacol. 54:342-352(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. |
| [9] | "Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules." Urakami Y., Okuda M., Masuda S., Akazawa M., Saito H., Inui K. Pharm. Res. 18:1528-1534(2001) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES. |
| [10] | "Gene expression levels and immunolocalization of organic ion transporters in the human kidney." Motohashi H., Sakurai Y., Saito H., Masuda S., Urakami Y., Goto M., Fukatsu A., Ogawa O., Inui K. J. Am. Soc. Nephrol. 13:866-874(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [11] | "Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2)." Grundemann D., Hahne C., Berkels R., Schomig E. J. Pharmacol. Exp. Ther. 304:810-817(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES. |
| [12] | "Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A)." Motohashi H., Uwai Y., Hiramoto K., Okuda M., Inui K. Eur. J. Pharmacol. 503:25-30(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [13] | "Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2." Ciarimboli G., Ludwig T., Lang D., Pavenstaedt H., Koepsell H., Piechota H.J., Haier J., Jaehde U., Zisowsky J., Schlatter E. Am. J. Pathol. 167:1477-1484(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION. |
| [14] | "Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1." Kimura N., Masuda S., Tanihara Y., Ueo H., Okuda M., Katsura T., Inui K. Drug Metab. Pharmacokinet. 20:379-386(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES. |
| [15] | "A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters." Tahara H., Kusuhara H., Endou H., Koepsell H., Imaoka T., Fuse E., Sugiyama Y. J. Pharmacol. Exp. Ther. 315:337-345(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES. |
| [16] | "Metformin transport by renal basolateral organic cation transporter hOCT2." Kimura N., Okuda M., Inui K. Pharm. Res. 22:255-259(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES. |
| [17] | "Characterization of regulatory mechanisms and states of human organic cation transporter 2." Biermann J., Lang D., Gorboulev V., Koepsell H., Sindic A., Schroter R., Zvirbliene A., Pavenstadt H., Schlatter E., Ciarimboli G. Am. J. Physiol. 290:C1521-C1531(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES. |
| [18] | "Organic cation transporters are determinants of oxaliplatin cytotoxicity." Zhang S., Lovejoy K.S., Shima J.E., Lagpacan L.L., Shu Y., Lapuk A., Chen Y., Komori T., Gray J.W., Chen X., Lippard S.J., Giacomini K.M. Cancer Res. 66:8847-8857(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [19] | "Interactions of fluoroquinolone antibacterials, DX-619 and levofloxacin, with creatinine transport by renal organic cation transporter hOCT2." Okuda M., Kimura N., Inui K. Drug Metab. Pharmacokinet. 21:432-436(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [20] | "Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family)." Yonezawa A., Masuda S., Yokoo S., Katsura T., Inui K. J. Pharmacol. Exp. Ther. 319:879-886(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [21] | "Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity." Yokoo S., Yonezawa A., Masuda S., Fukatsu A., Katsura T., Inui K. Biochem. Pharmacol. 74:477-487(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [22] | "The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua." Bottalico B., Noskova V., Pilka R., Larsson I., Domanski H., Casslen B., Hansson S.R. Mol. Reprod. Dev. 74:1303-1311(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [23] | "Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function." Leabman M.K., Huang C.C., Kawamoto M., Johns S.J., Stryke D., Ferrin T.E., DeYoung J., Taylor T., Clark A.G., Herskowitz I., Giacomini K.M. Pharmacogenetics 12:395-405(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-54, CHARACTERIZATION OF VARIANTS ILE-165; ALA-270; CYS-400 AND GLN-432. |
| [24] | "Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin." Shikata E., Yamamoto R., Takane H., Shigemasa C., Ikeda T., Otsubo K., Ieiri I. J. Hum. Genet. 52:117-122(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MET-201 AND ALA-270. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | X98333 mRNA. Translation: CAA66978.1. AB075951 mRNA. Translation: BAC02720.1. AK290787 mRNA. Translation: BAF83476.1. AL162582 Genomic DNA. Translation: CAI20003.1. CH471051 Genomic DNA. Translation: EAW47602.1. BC030978 mRNA. Translation: AAH30978.1. BC039899 mRNA. Translation: AAH39899.1. AJ251885 Genomic DNA. Translation: CAB96133.1. |
| IPI | IPI00017625. IPI00448803. IPI00885027. |
| RefSeq | NP_003049.2. NM_003058.3. |
| UniGene | Hs.436385. |
3D structure databases | |
| ProteinModelPortal | O15244. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | O15244. 8 interactions. |
| STRING | 9606.ENSP00000355920. |
PTM databases | |
| PhosphoSite | O15244. |
Proteomic databases | |
| PaxDb | O15244. |
| PRIDE | O15244. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000366953; ENSP00000355920; ENSG00000112499. |
| GeneID | 6582. |
| KEGG | hsa:6582. |
| UCSC | uc003qtf.3. human. uc003qth.2. human. |
Organism-specific databases | |
| CTD | 6582. |
| GeneCards | GC06M160592. |
| H-InvDB | HIX0025014. |
| HGNC | HGNC:10966. SLC22A2. |
| HPA | HPA008567. |
| MIM | 602608. gene. |
| neXtProt | NX_O15244. |
| PharmGKB | PA331. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG0477. |
| HOGENOM | HOG000234568. |
| HOVERGEN | HBG061545. |
| InParanoid | O15244. |
| KO | K08199. |
| OMA | KAGWLIS. |
| OrthoDB | EOG4S4PG6. |
| PhylomeDB | O15244. |
Enzyme and pathway databases | |
| Reactome | REACT_111217. Metabolism. REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules. REACT_20679. Amine compound SLC transporters. |
Gene expression databases | |
| ArrayExpress | O15244. |
| Bgee | O15244. |
| CleanEx | HS_SLC22A2. |
| Genevestigator | O15244. |
Family and domain databases | |
| InterPro | IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004749. Orgcat_transp. IPR005828. Sub_transporter. IPR005829. Sugar_transporter_CS. [Graphical view] |
| Pfam | PF00083. Sugar_tr. 1 hit. [Graphical view] |
| SUPFAM | SSF103473. MFS_gen_substrate_transporter. 1 hit. |
| TIGRFAMs | TIGR00898. 2A0119. 1 hit. |
| PROSITE | PS50850. MFS. 1 hit. PS00216. SUGAR_TRANSPORT_1. 2 hits. PS00217. SUGAR_TRANSPORT_2. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChEMBL | CHEMBL1743122. |
| GenomeRNAi | 6582. |
| NextBio | 25613. |
| SOURCE | Search... |
Entry information
| Entry name | S22A2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O15244 Secondary accession number(s): Q5T7Q6 Q9NQB9 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
