P51636
- CAV2_HUMAN
UniProt
P51636 - CAV2_HUMAN
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Protein
Caveolin-2
Gene
CAV2
Organism
Homo sapiens (Human)
Status
Functioni
May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity).By similarity
GO - Molecular functioni
- D1 dopamine receptor binding Source: BHF-UCL
- protein homodimerization activity Source: MGI
GO - Biological processi
- caveola assembly Source: BHF-UCL
- endoplasmic reticulum organization Source: UniProtKB
- mitochondrion organization Source: UniProtKB
- negative regulation of endothelial cell proliferation Source: UniProtKB
- negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
- positive regulation of dopamine receptor signaling pathway Source: BHF-UCL
- positive regulation of endothelial cell proliferation Source: Ensembl
- protein oligomerization Source: Ensembl
- regulation of mitosis Source: BHF-UCL
- skeletal muscle fiber development Source: UniProtKB
- synaptic transmission Source: Ensembl
- vesicle docking Source: BHF-UCL
- vesicle fusion Source: BHF-UCL
- vesicle organization Source: BHF-UCL
Enzyme and pathway databases
SignaLinki | P51636. |
Names & Taxonomyi
Protein namesi | Recommended name: Caveolin-2 |
Gene namesi | Name:CAV2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi | UP000005640: Chromosome 7 |
Organism-specific databases
HGNCi | HGNC:1528. CAV2. |
Subcellular locationi
Nucleus. Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein. Cell membrane; Peripheral membrane protein. Membrane › caveola; Peripheral membrane protein
Note: Potential hairpin-like structure in the membrane. Membrane protein of caveolae. Tyr-19-phosphorylated form is enriched at sites of cell-cell contact and is translocated to the nucleus in complex with MAPK1 in response to insulin (By similarity). Tyr-27-phosphorylated form is located both in the cytoplasm and plasma membrane. CAV1-mediated Ser-23-phosphorylated form locates to the plasma membrane. Ser-36-phosphorylated form resides in intracellular compartments.By similarity
Note: Potential hairpin-like structure in the membrane. Membrane protein of caveolae. Tyr-19-phosphorylated form is enriched at sites of cell-cell contact and is translocated to the nucleus in complex with MAPK1 in response to insulin (By similarity). Tyr-27-phosphorylated form is located both in the cytoplasm and plasma membrane. CAV1-mediated Ser-23-phosphorylated form locates to the plasma membrane. Ser-36-phosphorylated form resides in intracellular compartments.By similarity
GO - Cellular componenti
- acrosomal membrane Source: Ensembl
- caveola Source: BHF-UCL
- cell surface Source: Ensembl
- cytoplasmic vesicle Source: MGI
- cytosol Source: Ensembl
- extrinsic component of cytoplasmic side of plasma membrane Source: BHF-UCL
- Golgi apparatus Source: BHF-UCL
- integral component of plasma membrane Source: MGI
- intracellular Source: BHF-UCL
- lipid particle Source: Ensembl
- membrane Source: BHF-UCL
- membrane raft Source: HGNC
- nucleus Source: UniProtKB-KW
- perinuclear region of cytoplasm Source: BHF-UCL
- plasma membrane Source: BHF-UCL
- protein complex Source: MGI
- transport vesicle Source: LIFEdb
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Golgi apparatus, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | Actions |
---|---|---|---|---|---|---|
Mutagenesisi | 19 – 19 | 1 | Y → A: Greatly reduced Src-mediated phosphorylation and binding of RASA1, SRC and NCK1. Completely eliminates Src-mediated tyrosine phosphorylation and binding to RASA1, SRC and NCK1; when associated with A-27. 1 Publication | |||
Mutagenesisi | 23 – 23 | 1 | S → A: Abolishes phosphorylation. 1 Publication | |||
Mutagenesisi | 27 – 27 | 1 | Y → A: Greatly reduced Src-mediated phosphorylation and binding of RASA1, SRC and NCK1. Completely eliminates Src-mediated phosphorylation and binding of RASA1, SRC and NCK1; when associated with A-19. 1 Publication | |||
Mutagenesisi | 36 – 36 | 1 | S → A: Abolishes phosphorylation. 1 Publication |
Organism-specific databases
PharmGKBi | PA26108. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | Actions |
---|---|---|---|---|---|---|
Chaini | 1 – 162 | 162 | Caveolin-2 | PRO_0000004772 | Add BLAST |
Amino acid modifications
Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | Actions |
---|---|---|---|---|---|---|
Modified residuei | 19 – 19 | 1 | Phosphotyrosine; by SRC2 Publications | |||
Modified residuei | 23 – 23 | 1 | Phosphoserine1 Publication | |||
Modified residuei | 27 – 27 | 1 | Phosphotyrosine; by SRC1 Publication | |||
Modified residuei | 36 – 36 | 1 | Phosphoserine1 Publication |
Post-translational modificationi
Phosphorylated on serine and tyrosine residues. CAV1 promotes phosphorylation on Ser-23 which then targets the complex to the plasma membrane, lipid rafts and caveolae. Phosphorylation on Ser-36 appears to modulate mitosis in endothelial cells (By similarity). Phosphorylation on both Tyr-19 and Tyr-27 is required for insulin-induced 'Ser-727' phosphorylation of STAT3 and its activation. Phosphorylation on Tyr-19 is required for insulin-induced phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine phosphorylation is induced by both EGF and insulin (By similarity).By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
MaxQBi | P51636. |
PaxDbi | P51636. |
PRIDEi | P51636. |
PTM databases
PhosphoSitei | P51636. |
Expressioni
Tissue specificityi
Expressed in endothelial cells, smooth muscle cells, skeletal myoblasts and fibroblasts.1 Publication
Gene expression databases
Bgeei | P51636. |
CleanExi | HS_CAV2. |
ExpressionAtlasi | P51636. baseline and differential. |
Genevestigatori | P51636. |
Organism-specific databases
HPAi | CAB013488. HPA044810. |
Interactioni
Subunit structurei
Monomer or homodimer. Interacts with CAV1; the interaction forms a stable heterooligomeric complex that is required for targeting to lipid rafts and for caveolae formation. Tyrosine phosphorylated forms do not form heterooligomers with the Tyr-19-phosphorylated form existing as a monomer or dimer, and the Tyr-27-form as a monomer only. Interacts (tyrosine phosphorylated form) with the SH2 domain-containing proteins, RASA1, NCK1 and SRC. Interacts (tyrosine phosphorylated form) with INSR, the interaction (Tyr-27-phosphorylated form) is increased on insulin stimulation. Interacts (Tyr-19 phosphorylated form) with MAPK1 (phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with STAT3; the interaction is increased on insulin-induced tyrosine phosphorylation leading to STAT activation (By similarity).By similarity
Protein-protein interaction databases
BioGridi | 107306. 12 interactions. |
DIPi | DIP-34929N. |
IntActi | P51636. 6 interactions. |
MINTi | MINT-1403441. |
STRINGi | 9606.ENSP00000222693. |
Structurei
3D structure databases
ProteinModelPortali | P51636. |
ModBasei | Search... |
MobiDBi | Search... |
Topological domain
Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | Actions |
---|---|---|---|---|---|---|
Topological domaini | 1 – 86 | 86 | CytoplasmicSequence Analysis | Add BLAST | ||
Topological domaini | 108 – 162 | 55 | CytoplasmicSequence Analysis | Add BLAST |
Intramembrane
Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | Actions |
---|---|---|---|---|---|---|
Intramembranei | 87 – 107 | 21 | HelicalSequence Analysis | Add BLAST |
Family & Domainsi
Sequence similaritiesi
Belongs to the caveolin family.Curated
Phylogenomic databases
eggNOGi | NOG74268. |
GeneTreei | ENSGT00390000014924. |
HOGENOMi | HOG000036550. |
HOVERGENi | HBG003422. |
InParanoidi | P51636. |
KOi | K12958. |
OMAi | STHSFDK. |
OrthoDBi | EOG7V1FSD. |
PhylomeDBi | P51636. |
TreeFami | TF315736. |
Family and domain databases
InterProi | IPR001612. Caveolin. IPR018361. Caveolin_CS. [Graphical view] |
PANTHERi | PTHR10844. PTHR10844. 1 hit. |
Pfami | PF01146. Caveolin. 1 hit. [Graphical view] |
PROSITEi | PS01210. CAVEOLIN. 1 hit. [Graphical view] |
Sequences (3)i
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative initiation. Align
Isoform Alpha (identifier: P51636-1) [UniParc]FASTAAdd to Basket
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.
10 20 30 40 50
MGLETEKADV QLFMDDDSYS HHSGLEYADP EKFADSDQDR DPHRLNSHLK
60 70 80 90 100
LGFEDVIAEP VTTHSFDKVW ICSHALFEIS KYVMYKFLTV FLAIPLAFIA
110 120 130 140 150
GILFATLSCL HIWILMPFVK TCLMVLPSVQ TIWKSVTDVI IAPLCTSVGR
160
CFSSVSLQLS QD
Isoform Beta (identifier: P51636-2) [UniParc]FASTAAdd to Basket
The sequence of this isoform differs from the canonical sequence as follows:
1-13: Missing.
Note: Produced by alternative initiation.
Show »Natural variant
Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | Actions |
---|---|---|---|---|---|---|
Natural varianti | 130 – 130 | 1 | Q → E. Corresponds to variant rs8940 [ dbSNP | Ensembl ]. | VAR_012071 |
Alternative sequence
Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | Actions |
---|---|---|---|---|---|---|
Alternative sequencei | 1 – 13 | 13 | Missing in isoform Beta. Curated | VSP_018696 | Add BLAST | |
Alternative sequencei | 51 – 112 | 62 | LGFED…SCLHI → DFNAFCKDLPNGSAFSADNM EECDRCYHCSIVYERRTMLL FCQPATEPGLNTWTPGLEIG IL in isoform C. 1 Publication | VSP_038114 | Add BLAST | |
Alternative sequencei | 113 – 162 | 50 | Missing in isoform C. 1 Publication | VSP_038115 | Add BLAST |
Sequence databases
Select the link destinations: EMBL GenBank DDBJ Links Updated | AF035752 mRNA. Translation: AAB88492.1. AJ133269 Genomic DNA. Translation: CAB63653.1. BT007051 mRNA. Translation: AAP35700.1. BC005256 mRNA. Translation: AAH05256.1. AJ242718 Genomic DNA. Translation: CAB65090.1. AK310786 mRNA. No translation available. CH236947 Genomic DNA. Translation: EAL24361.1. |
CCDSi | CCDS5765.1. [P51636-3] CCDS5766.1. [P51636-1] |
RefSeqi | NP_001193676.1. NM_001206747.1. [P51636-2] NP_001193677.1. NM_001206748.1. NP_001224.1. NM_001233.4. [P51636-1] NP_937855.1. NM_198212.2. [P51636-3] |
UniGenei | Hs.212332. Hs.603096. |
Genome annotation databases
Ensembli | ENST00000222693; ENSP00000222693; ENSG00000105971. [P51636-1] ENST00000343213; ENSP00000345679; ENSG00000105971. [P51636-3] |
GeneIDi | 858. |
KEGGi | hsa:858. |
UCSCi | uc003vid.3. human. [P51636-1] uc003vie.3. human. [P51636-3] uc022akj.1. human. [P51636-2] |
Keywords - Coding sequence diversityi
Alternative initiation, Alternative splicing, PolymorphismCross-referencesi
Web resourcesi
Wikipedia
Caveolin entry |
Sequence databases
Select the link destinations:
EMBL GenBank DDBJ Links Updated
|
AF035752
mRNA. Translation: AAB88492.1
. AJ133269 Genomic DNA. Translation: CAB63653.1 . BT007051 mRNA. Translation: AAP35700.1 . BC005256 mRNA. Translation: AAH05256.1 . AJ242718 Genomic DNA. Translation: CAB65090.1 . AK310786 mRNA. No translation available. CH236947 Genomic DNA. Translation: EAL24361.1 . |
CCDSi | CCDS5765.1.
[P51636-3
] CCDS5766.1. [P51636-1 ] |
RefSeqi | NP_001193676.1.
NM_001206747.1.
[P51636-2
] NP_001193677.1. NM_001206748.1. NP_001224.1. NM_001233.4. [P51636-1 ] NP_937855.1. NM_198212.2. [P51636-3 ] |
UniGenei | Hs.212332. Hs.603096. |
3D structure databases
ProteinModelPortali | P51636.
|
ModBasei | Search...
|
MobiDBi | Search...
|
Protein-protein interaction databases
BioGridi | 107306.
12 interactions. |
DIPi | DIP-34929N.
|
IntActi | P51636.
6 interactions. |
MINTi | MINT-1403441.
|
STRINGi | 9606.ENSP00000222693.
|
PTM databases
PhosphoSitei | P51636.
|
Proteomic databases
MaxQBi | P51636.
|
PaxDbi | P51636.
|
PRIDEi | P51636.
|
Protocols and materials databases
DNASUi | 858.
|
Structural Biology Knowledgebase | Search...
|
Genome annotation databases
Ensembli | ENST00000222693
; ENSP00000222693
; ENSG00000105971
. [P51636-1
] ENST00000343213 ; ENSP00000345679 ; ENSG00000105971 . [P51636-3 ] |
GeneIDi | 858.
|
KEGGi | hsa:858.
|
UCSCi | uc003vid.3.
human. [P51636-1
] uc003vie.3. human. [P51636-3 ] uc022akj.1. human. [P51636-2 ] |
Organism-specific databases
CTDi | 858.
|
GeneCardsi | GC07P115926.
|
HGNCi | HGNC:1528.
CAV2. |
HPAi | CAB013488.
HPA044810. |
MIMi | 601048.
gene. |
neXtProti | NX_P51636.
|
PharmGKBi | PA26108.
|
GenAtlasi | Search...
|
Phylogenomic databases
eggNOGi | NOG74268.
|
GeneTreei | ENSGT00390000014924.
|
HOGENOMi | HOG000036550.
|
HOVERGENi | HBG003422.
|
InParanoidi | P51636.
|
KOi | K12958.
|
OMAi | STHSFDK.
|
OrthoDBi | EOG7V1FSD.
|
PhylomeDBi | P51636.
|
TreeFami | TF315736.
|
Enzyme and pathway databases
SignaLinki | P51636.
|
Miscellaneous databases
ChiTaRSi | CAV2.
human. |
GeneWikii | Caveolin_2.
|
GenomeRNAii | 858.
|
NextBioi | 3560.
|
PROi | P51636.
|
SOURCEi | Search...
|
Gene expression databases
Bgeei | P51636.
|
CleanExi | HS_CAV2.
|
ExpressionAtlasi | P51636.
baseline and differential. |
Genevestigatori | P51636.
|
Family and domain databases
InterProi | IPR001612.
Caveolin. IPR018361. Caveolin_CS. [Graphical view ] |
PANTHERi | PTHR10844.
PTHR10844. 1 hit. |
Pfami | PF01146.
Caveolin. 1 hit. [Graphical view ] |
PROSITEi | PS01210.
CAVEOLIN. 1 hit. [Graphical view ] |
ProtoNeti | Search...
|
Publicationsi
- "Identification, sequence, and expression of caveolin-2 defines a caveolin gene family."
Scherer P.E., Okamoto T., Chun M., Nishimoto I., Lodish H.F., Lisanti M.P.
Proc. Natl. Acad. Sci. U.S.A. 93:131-135(1996) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). - "Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo."
Scherer P.E., Lewis R.Y., Volonte D., Engelman J.A., Galbiati F., Couet J., Kohtz D.S., van Donselaar E., Peters P., Lisanti M.P.
J. Biol. Chem. 272:29337-29346(1997) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), INTERACTION WITH CAV1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. - "Sequence and detailed organization of the human caveolin-1 and -2 genes located near the D7S522 locus (7q31.1). Methylation of a CpG island in the 5' promoter region of the caveolin-1 gene in human breast cancer cell lines."
Engelman J.A., Zhang X.L., Lisanti M.P.
FEBS Lett. 448:221-230(1999) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. - "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databasesCited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). - "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 C).Tissue: Hepatoma. - "Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. - "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] (ISOFORM ALPHA).Tissue: Kidney. - "Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes."
Li S., Galbiati F., Volonte D., Sargiacomo M., Engelman J.A., Das K., Scherer P.E., Lisanti M.P.
FEBS Lett. 434:127-134(1998) [PubMed] [Europe PMC] [Abstract]Cited for: INTERACTION WITH CAV1, ALTERNATIVE PRODUCTS, SUBCELLULAR LOCATION. - "Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho-caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains associated with lipid rafts/caveolae, but no longer forms a high molecular mass hetero-oligomer with caveolin-1."
Lee H., Park D.S., Wang X.B., Scherer P.E., Schwartz P.E., Lisanti M.P.
J. Biol. Chem. 277:34556-34567(2002) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT TYR-19, SUBCELLULAR LOCATION, INTERACTION WITH CAV1; SRC; RASA1 AND NCK1. - "Tyrosine phosphorylation of caveolin-2 at residue 27: differences in the spatial and temporal behavior of phospho-Cav-2 (pY19 and pY27)."
Wang X.B., Lee H., Capozza F., Marmon S., Sotgia F., Brooks J.W., Campos-Gonzalez R., Lisanti M.P.
Biochemistry 43:13694-13706(2004) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT TYR-19 AND TYR-27, SUBCELLULAR LOCATION, INTERACTION WITH CAV1; NCK1; RASA1 AND SRC, FUNCTION, MUTAGENESIS OF TYR-19 AND TYR-27. - "Serine 23 and 36 phosphorylation of caveolin-2 is differentially regulated by targeting to lipid raft/caveolae and in mitotic endothelial cells."
Sowa G., Xie L., Xu L., Sessa W.C.
Biochemistry 47:101-111(2008) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT SER-23 AND SER-36, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-23 AND SER-36. - "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] [Europe PMC] [Abstract]Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].Tissue: Cervix carcinoma. - "Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Entry informationi
Entry namei | CAV2_HUMAN | ||||||||
Accessioni | P51636Primary (citable) accession number: P51636 Secondary accession number(s): A4D0U2, Q9UGM7 | ||||||||
Entry historyi |
| ||||||||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- Human chromosome 7Human chromosome 7: entries, gene names and cross-references to MIM
- Human entries with polymorphisms or disease mutationsList of human entries with polymorphisms or disease mutations
- Human polymorphisms and disease mutationsIndex of human polymorphisms and disease mutations
- MIM cross-referencesOnline Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
- SIMILARITY commentsIndex of protein domains and families