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P18089

- ADA2B_HUMAN

UniProt

P18089 - ADA2B_HUMAN

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Protein

Alpha-2B adrenergic receptor

Gene

ADRA2B

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

Functioni

Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei92 – 921Implicated in ligand bindingBy similarity
Sitei176 – 1761Implicated in catechol agonist bindingBy similarity
Sitei180 – 1801Implicated in catechol agonist bindingBy similarity

GO - Molecular functioni

  1. alpha2-adrenergic receptor activity Source: BHF-UCL
  2. epinephrine binding Source: BHF-UCL

GO - Biological processi

  1. activation of MAPK activity by adrenergic receptor signaling pathway Source: BHF-UCL
  2. activation of protein kinase B activity Source: BHF-UCL
  3. angiogenesis Source: Ensembl
  4. blood coagulation Source: Reactome
  5. cell-cell signaling Source: ProtInc
  6. epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway Source: BHF-UCL
  7. female pregnancy Source: Ensembl
  8. G-protein coupled receptor signaling pathway Source: ProtInc
  9. MAPK cascade Source: Ensembl
  10. negative regulation of epinephrine secretion Source: BHF-UCL
  11. negative regulation of norepinephrine secretion Source: BHF-UCL
  12. platelet activation Source: Reactome
  13. positive regulation of blood pressure Source: Ensembl
  14. positive regulation of neuron differentiation Source: BHF-UCL
  15. positive regulation of uterine smooth muscle contraction Source: Ensembl
  16. regulation of vascular smooth muscle contraction Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_16927. Adrenoceptors.
REACT_19180. Adrenaline signalling through Alpha-2 adrenergic receptor.
REACT_19231. G alpha (i) signalling events.
REACT_19333. G alpha (z) signalling events.
SignaLinkiP18089.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-2B adrenergic receptor
Alternative name(s):
Alpha-2 adrenergic receptor subtype C2
Alpha-2B adrenoreceptor
Short name:
Alpha-2B adrenoceptor
Short name:
Alpha-2BAR
Gene namesi
Name:ADRA2B
Synonyms:ADRA2L1, ADRA2RL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:282. ADRA2B.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Note: Interaction with RAB26 mediates transport from the Golgi to the cell membrane.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1212ExtracellularBy similarityAdd
BLAST
Transmembranei13 – 3826Helical; Name=1By similarityAdd
BLAST
Topological domaini39 – 4810CytoplasmicBy similarity
Transmembranei49 – 6921Helical; Name=2By similarityAdd
BLAST
Topological domaini70 – 8617ExtracellularBy similarityAdd
BLAST
Transmembranei87 – 10721Helical; Name=3By similarityAdd
BLAST
Topological domaini108 – 12821CytoplasmicBy similarityAdd
BLAST
Transmembranei129 – 14921Helical; Name=4By similarityAdd
BLAST
Topological domaini150 – 17223ExtracellularBy similarityAdd
BLAST
Transmembranei173 – 19321Helical; Name=5By similarityAdd
BLAST
Topological domaini194 – 369176CytoplasmicBy similarityAdd
BLAST
Transmembranei370 – 39324Helical; Name=6By similarityAdd
BLAST
Topological domaini394 – 4029ExtracellularBy similarity
Transmembranei403 – 42321Helical; Name=7By similarityAdd
BLAST
Topological domaini424 – 44724CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

Orphaneti86814. Benign adult familial myoclonic epilepsy.
PharmGKBiPA36.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 447447Alpha-2B adrenergic receptorPRO_0000069094Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi85 ↔ 164PROSITE-ProRule annotation
Lipidationi439 – 4391S-palmitoyl cysteineSequence Analysis

Keywords - PTMi

Disulfide bond, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP18089.
PRIDEiP18089.

Expressioni

Gene expression databases

BgeeiP18089.
CleanExiHS_ADRA2B.
GenevestigatoriP18089.

Interactioni

Subunit structurei

Interacts with RAB26.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
RAB26Q9ULW54EBI-9077302,EBI-958239

Protein-protein interaction databases

BioGridi106660. 3 interactions.
IntActiP18089. 1 interaction.
STRINGi9606.ENSP00000387281.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CVAmodel-A97-128[»]
ProteinModelPortaliP18089.
SMRiP18089. Positions 22-438.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi294 – 30815Asp/Glu-rich (acidic)Add
BLAST

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG249628.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP18089.
KOiK04139.
OrthoDBiEOG7J9VPT.
PhylomeDBiP18089.
TreeFamiTF316350.

Family and domain databases

Gene3Di1.20.1070.10. 2 hits.
InterProiIPR002233. ADR_fam.
IPR000207. ADRA2B_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24248:SF26. PTHR24248:SF26. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01103. ADRENERGICR.
PR00559. ADRENRGCA2BR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P18089-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDHQDPYSVQ ATAAIAAAIT FLILFTIFGN ALVILAVLTS RSLRAPQNLF
60 70 80 90 100
LVSLAAADIL VATLIIPFSL ANELLGYWYF RRTWCEVYLA LDVLFCTSSI
110 120 130 140 150
VHLCAISLDR YWAVSRALEY NSKRTPRRIK CIILTVWLIA AVISLPPLIY
160 170 180 190 200
KGDQGPQPRG RPQCKLNQEA WYILASSIGS FFAPCLIMIL VYLRIYLIAK
210 220 230 240 250
RSNRRGPRAK GGPGQGESKQ PRPDHGGALA SAKLPALASV ASAREVNGHS
260 270 280 290 300
KSTGEKEEGE TPEDTGTRAL PPSWAALPNS GQGQKEGVCG ASPEDEAEEE
310 320 330 340 350
EEEEEECEPQ AVPVSPASAC SPPLQQPQGS RVLATLRGQV LLGRGVGAIG
360 370 380 390 400
GQWWRRRAQL TREKRFTFVL AVVIGVFVLC WFPFFFSYSL GAICPKHCKV
410 420 430 440
PHGLFQFFFW IGYCNSSLNP VIYTIFNQDF RRAFRRILCR PWTQTAW
Length:447
Mass (Da):49,566
Last modified:April 16, 2014 - v3
Checksum:iB33D4B5B719C1C45
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti359 – 3602QL → HV in AAA51666. (PubMed:2164221)Curated
Sequence conflicti359 – 3602QL → HV no nucleotide entry (PubMed:2172775)Curated

Polymorphismi

A rare polymorphic frameshift in position 448 produces a protein of 542 residues.
The gene is polymorphic at position 300. The sequence shown here is found with a frequency of 0.31 in Caucasians and 0.12 in African-Americans. It exhibits impaired phosphorylation and desensitization by GRKs compared to the sequence including a stretch of glutamic acid at that position.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti211 – 2111G → A.1 Publication
Corresponds to variant rs9333568 [ dbSNP | Ensembl ].
VAR_025099
Natural varianti300 – 3001E → EEEE.5 Publications
VAR_070775
Natural varianti373 – 3731V → I.
Corresponds to variant rs29000569 [ dbSNP | Ensembl ].
VAR_033462
Natural varianti376 – 3761V → G.1 Publication
VAR_025100
Natural varianti376 – 3761V → I.
Corresponds to variant rs29000569 [ dbSNP | Ensembl ].
VAR_033463

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34041 Genomic DNA. Translation: AAA51666.1.
AF316895 Genomic DNA. Translation: AAK01635.1.
AF005900 Genomic DNA. Translation: AAB62558.1.
AY548167 Genomic DNA. Translation: AAS55646.1.
DQ057076 Genomic DNA. Translation: AAY43127.1.
AC092603 Genomic DNA. Translation: AAX93218.1.
M38742 Genomic DNA. Translation: AAA62823.1.
PIRiA37223.
RefSeqiNP_000673.2. NM_000682.6.
UniGeneiHs.247686.

Genome annotation databases

GeneIDi151.
KEGGihsa:151.
UCSCiuc021vlh.1. human.

Polymorphism databases

DMDMi27151763.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34041 Genomic DNA. Translation: AAA51666.1 .
AF316895 Genomic DNA. Translation: AAK01635.1 .
AF005900 Genomic DNA. Translation: AAB62558.1 .
AY548167 Genomic DNA. Translation: AAS55646.1 .
DQ057076 Genomic DNA. Translation: AAY43127.1 .
AC092603 Genomic DNA. Translation: AAX93218.1 .
M38742 Genomic DNA. Translation: AAA62823.1 .
PIRi A37223.
RefSeqi NP_000673.2. NM_000682.6.
UniGenei Hs.247686.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2CVA model - A 97-128 [» ]
ProteinModelPortali P18089.
SMRi P18089. Positions 22-438.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106660. 3 interactions.
IntActi P18089. 1 interaction.
STRINGi 9606.ENSP00000387281.

Chemistry

BindingDBi P18089.
ChEMBLi CHEMBL2095158.
DrugBanki DB00543. Amoxapine.
DB00182. Amphetamine.
DB00714. Apomorphine.
DB00964. Apraclonidine.
DB01238. Aripiprazole.
DB06216. Asenapine.
DB00217. Bethanidine.
DB00484. Brimonidine.
DB01200. Bromocriptine.
DB00248. Cabergoline.
DB01136. Carvedilol.
DB00477. Chlorpromazine.
DB00575. Clonidine.
DB00363. Clozapine.
DB01151. Desipramine.
DB01142. Doxepin.
DB04855. Dronedarone.
DB06262. Droxidopa.
DB01363. Ephedra.
DB00668. Epinephrine.
DB01049. Ergoloid mesylate.
DB00696. Ergotamine.
DB00292. Etomidate.
DB00800. Fenoldopam.
DB00629. Guanabenz.
DB01018. Guanfacine.
DB00589. Lisuride.
DB00408. Loxapine.
DB00934. Maprotiline.
DB01365. Mephentermine.
DB01577. Methamphetamine.
DB01403. Methotrimeprazine.
DB06148. Mianserin.
DB00368. Norepinephrine.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00935. Oxymetazoline.
DB01267. Paliperidone.
DB01186. Pergolide.
DB00925. Phenoxybenzamine.
DB00413. Pramipexole.
DB00457. Prazosin.
DB01224. Quetiapine.
DB00734. Risperidone.
DB00268. Ropinirole.
DB05271. Rotigotine.
DB00697. Tizanidine.
DB00797. Tolazoline.
DB00726. Trimipramine.
DB06694. Xylometazoline.
DB01392. Yohimbine.
DB00246. Ziprasidone.
GuidetoPHARMACOLOGYi 26.

Protein family/group databases

GPCRDBi Search...

Polymorphism databases

DMDMi 27151763.

Proteomic databases

PaxDbi P18089.
PRIDEi P18089.

Protocols and materials databases

DNASUi 151.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 151.
KEGGi hsa:151.
UCSCi uc021vlh.1. human.

Organism-specific databases

CTDi 151.
GeneCardsi GC02M096778.
H-InvDB HIX0161945.
HGNCi HGNC:282. ADRA2B.
MIMi 104260. gene.
neXtProti NX_P18089.
Orphaneti 86814. Benign adult familial myoclonic epilepsy.
PharmGKBi PA36.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG249628.
HOGENOMi HOG000239242.
HOVERGENi HBG106962.
InParanoidi P18089.
KOi K04139.
OrthoDBi EOG7J9VPT.
PhylomeDBi P18089.
TreeFami TF316350.

Enzyme and pathway databases

Reactomei REACT_16927. Adrenoceptors.
REACT_19180. Adrenaline signalling through Alpha-2 adrenergic receptor.
REACT_19231. G alpha (i) signalling events.
REACT_19333. G alpha (z) signalling events.
SignaLinki P18089.

Miscellaneous databases

GeneWikii Alpha-2B_adrenergic_receptor.
GenomeRNAii 151.
NextBioi 599.
PROi P18089.
SOURCEi Search...

Gene expression databases

Bgeei P18089.
CleanExi HS_ADRA2B.
Genevestigatori P18089.

Family and domain databases

Gene3Di 1.20.1070.10. 2 hits.
InterProi IPR002233. ADR_fam.
IPR000207. ADRA2B_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24248:SF26. PTHR24248:SF26. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR01103. ADRENERGICR.
PR00559. ADRENRGCA2BR.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2."
    Lomasney J.W., Lorenz W., Allen L.F., King K., Regan J.W., Yang-Feng T.L., Caron M.G., Lefkowitz R.J.
    Proc. Natl. Acad. Sci. U.S.A. 87:5094-5098(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
  2. "Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor."
    Weinshank R.L., Zgombick J.M., Macchi M., Adham N., Lichtblau H., Branchek T.A., Hartig P.R.
    Mol. Pharmacol. 38:681-688(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
  3. "Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization."
    Small K.M., Brown K.M., Forbes S.L., Liggett S.B.
    J. Biol. Chem. 276:4917-4922(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene."
    Cayla C., Heinonen P., Viikari L., Schaak S., Snapir A., Bouloumie A., Karvonen M.K., Pesonen U., Scheinin M., Paris H.
    Biochem. Pharmacol. 67:469-478(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
  5. "Isolation of complete coding sequence for adrenergic receptor alpha 2B (ADRA2B)."
    Kopatz S.A., Aronstam R.S., Sharma S.V.
    Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-GLU-GLU-300 INS.
  6. SeattleSNPs variation discovery resource
    Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-211; GLU-GLU-GLU-300 INS AND GLY-376, FRAMESHIFT POLYMORPHISM.
  7. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans."
    Chang A.C., Ho T.F., Chang N.-C.A.
    Biochem. Biophys. Res. Commun. 172:817-823(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-386, VARIANT GLU-GLU-GLU-300 INS.
  9. "Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi."
    Li C., Fan Y., Lan T.H., Lambert N.A., Wu G.
    J. Biol. Chem. 287:42784-42794(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RAB26, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiADA2B_HUMAN
AccessioniPrimary (citable) accession number: P18089
Secondary accession number(s): Q4TUH9, Q53RF2, Q9BZK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: April 16, 2014
Last modified: October 29, 2014
This is version 154 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3