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O15303

- GRM6_HUMAN

UniProt

O15303 - GRM6_HUMAN

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Protein

Metabotropic glutamate receptor 6

Gene

GRM6

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

Functioni

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca2+ uptake. Required for normal vision.By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei154 – 1541GlutamateBy similarity
Binding sitei225 – 2251GlutamateBy similarity
Binding sitei307 – 3071GlutamateBy similarity
Binding sitei400 – 4001GlutamateBy similarity

GO - Molecular functioni

  1. glutamate receptor activity Source: UniProtKB
  2. G-protein coupled receptor activity Source: UniProtKB
  3. group III metabotropic glutamate receptor activity Source: RefGenome
  4. protein homodimerization activity Source: UniProtKB

GO - Biological processi

  1. adenylate cyclase-inhibiting G-protein coupled glutamate receptor signaling pathway Source: RefGenome
  2. detection of light stimulus involved in visual perception Source: UniProtKB
  3. detection of visible light Source: ProtInc
  4. G-protein coupled glutamate receptor signaling pathway Source: UniProtKB
  5. locomotory behavior Source: Ensembl
  6. positive regulation of calcium ion import Source: UniProtKB
  7. regulation of synaptic transmission, glutamatergic Source: RefGenome
  8. retina development in camera-type eye Source: Ensembl
  9. synaptic transmission Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Sensory transduction, Vision

Enzyme and pathway databases

ReactomeiREACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
REACT_19231. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Metabotropic glutamate receptor 6
Short name:
mGluR6
Gene namesi
Name:GRM6
Synonyms:GPRC1F, MGLUR6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:4598. GRM6.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication. Golgi apparatus membrane 1 Publication; Multi-pass membrane protein 1 Publication. Cell projectiondendrite By similarity
Note: Subject to trafficking from the endoplasmic reticulum to the Golgi apparatus and then to the cell membrane.

GO - Cellular componenti

  1. cell projection Source: UniProtKB-KW
  2. endoplasmic reticulum membrane Source: UniProtKB
  3. Golgi membrane Source: UniProtKB
  4. integral component of plasma membrane Source: UniProtKB
  5. new growing cell tip Source: Ensembl
  6. plasma membrane Source: Reactome
  7. presynaptic membrane Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Night blindness, congenital stationary, 1B (CSNB1B) [MIM:257270]: A non-progressive retinal disorder characterized by impaired night vision. Congenital stationary night blindness type 1B is an autosomal recessive form associated with a negative electroretinogram waveform. Patients are night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system. ERGs in response to single brief flashes of light have clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicate a markedly reduced on response and a nearly normal OFF response. There is no subjective delay in the perception of suddenly appearing white vs black objects on a gray background.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti46 – 461P → L in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_069817
Natural varianti58 – 581G → R in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_069818
Natural varianti150 – 1501G → S in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_030756
Natural varianti405 – 4051I → T in CSNB1B; abolishes expression at the cell membrane. 1 Publication
VAR_069819
Natural varianti522 – 5221C → Y in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_069820
Natural varianti781 – 7811E → K in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_030757

Keywords - Diseasei

Congenital stationary night blindness, Disease mutation

Organism-specific databases

MIMi257270. phenotype.
Orphaneti215. Congenital stationary night blindness.
PharmGKBiPA28995.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence AnalysisAdd
BLAST
Chaini25 – 877853Metabotropic glutamate receptor 6PRO_0000012934Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi57 ↔ 99By similarity
Disulfide bondi244 ↔ 536By similarity
Glycosylationi296 – 2961N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi367 ↔ 383By similarity
Disulfide bondi423 ↔ 430By similarity
Glycosylationi451 – 4511N-linked (GlcNAc...)Sequence Analysis
Glycosylationi479 – 4791N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi518 ↔ 537By similarity
Disulfide bondi522 ↔ 540By similarity
Disulfide bondi543 ↔ 555By similarity
Disulfide bondi558 ↔ 571By similarity
Glycosylationi567 – 5671N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO15303.
PRIDEiO15303.

PTM databases

PhosphoSiteiO15303.

Expressioni

Tissue specificityi

Detected in melanocytes.1 Publication

Gene expression databases

BgeeiO15303.
CleanExiHS_GRM6.
GenevestigatoriO15303.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000231188.

Structurei

3D structure databases

ProteinModelPortaliO15303.
SMRiO15303. Positions 32-851.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 585561ExtracellularSequence AnalysisAdd
BLAST
Topological domaini609 – 62214CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini644 – 65411ExtracellularSequence AnalysisAdd
BLAST
Topological domaini674 – 69724CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini719 – 74830ExtracellularSequence AnalysisAdd
BLAST
Topological domaini771 – 78313CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini807 – 81913ExtracellularSequence AnalysisAdd
BLAST
Topological domaini846 – 87732CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei586 – 60823Helical; Name=1Sequence AnalysisAdd
BLAST
Transmembranei623 – 64321Helical; Name=2Sequence AnalysisAdd
BLAST
Transmembranei655 – 67319Helical; Name=3Sequence AnalysisAdd
BLAST
Transmembranei698 – 71821Helical; Name=4Sequence AnalysisAdd
BLAST
Transmembranei749 – 77022Helical; Name=5Sequence AnalysisAdd
BLAST
Transmembranei784 – 80623Helical; Name=6Sequence AnalysisAdd
BLAST
Transmembranei820 – 84526Helical; Name=7Sequence AnalysisAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni175 – 1773Glutamate bindingBy similarity

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG295200.
GeneTreeiENSGT00760000118884.
HOGENOMiHOG000218635.
HOVERGENiHBG107965.
InParanoidiO15303.
KOiK04608.
OMAiVCIAQSI.
OrthoDBiEOG7Z0JXG.
PhylomeDBiO15303.
TreeFamiTF313240.

Family and domain databases

InterProiIPR001828. ANF_lig-bd_rcpt.
IPR000337. GPCR_3.
IPR011500. GPCR_3_9-Cys_dom.
IPR017978. GPCR_3_C.
IPR017979. GPCR_3_CS.
IPR000162. GPCR_3_mtglu_rcpt.
IPR000112. GPCR_3_mtglu_rcpt_6.
IPR028082. Peripla_BP_I.
[Graphical view]
PfamiPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view]
PRINTSiPR00248. GPCRMGR.
PR01056. MTABOTROPC6R.
PR00593. MTABOTROPICR.
SUPFAMiSSF53822. SSF53822. 1 hit.
PROSITEiPS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O15303 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MARPRRAREP LLVALLPLAW LAQAGLARAA GSVRLAGGLT LGGLFPVHAR
60 70 80 90 100
GAAGRACGQL KKEQGVHRLE AMLYALDRVN ADPELLPGVR LGARLLDTCS
110 120 130 140 150
RDTYALEQAL SFVQALIRGR GDGDEVGVRC PGGVPPLRPA PPERVVAVVG
160 170 180 190 200
ASASSVSIMV ANVLRLFAIP QISYASTAPE LSDSTRYDFF SRVVPPDSYQ
210 220 230 240 250
AQAMVDIVRA LGWNYVSTLA SEGNYGESGV EAFVQISREA GGVCIAQSIK
260 270 280 290 300
IPREPKPGEF SKVIRRLMET PNARGIIIFA NEDDIRRVLE AARQANLTGH
310 320 330 340 350
FLWVGSDSWG AKTSPILSLE DVAVGAITIL PKRASIDGFD QYFMTRSLEN
360 370 380 390 400
NRRNIWFAEF WEENFNCKLT SSGTQSDDST RKCTGEERIG RDSTYEQEGK
410 420 430 440 450
VQFVIDAVYA IAHALHSMHQ ALCPGHTGLC PAMEPTDGRM LLQYIRAVRF
460 470 480 490 500
NGSAGTPVMF NENGDAPGRY DIFQYQATNG SASSGGYQAV GQWAETLRLD
510 520 530 540 550
VEALQWSGDP HEVPSSLCSL PCGPGERKKM VKGVPCCWHC EACDGYRFQV
560 570 580 590 600
DEFTCEACPG DMRPTPNHTG CRPTPVVRLS WSSPWAAPPL LLAVLGIVAT
610 620 630 640 650
TTVVATFVRY NNTPIVRASG RELSYVLLTG IFLIYAITFL MVAEPGAAVC
660 670 680 690 700
AARRLFLGLG TTLSYSALLT KTNRIYRIFE QGKRSVTPPP FISPTSQLVI
710 720 730 740 750
TFSLTSLQVV GMIAWLGARP PHSVIDYEEQ RTVDPEQARG VLKCDMSDLS
760 770 780 790 800
LIGCLGYSLL LMVTCTVYAI KARGVPETFN EAKPIGFTMY TTCIIWLAFV
810 820 830 840 850
PIFFGTAQSA EKIYIQTTTL TVSLSLSASV SLGMLYVPKT YVILFHPEQN
860 870
VQKRKRSLKA TSTVAAPPKG EDAEAHK
Length:877
Mass (Da):95,468
Last modified:June 16, 2009 - v2
Checksum:i2AB27C5627B388C6
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti46 – 461P → L in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_069817
Natural varianti58 – 581G → R in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_069818
Natural varianti59 – 591Q → P No effect on location at the cell membrane. 2 Publications
Corresponds to variant rs2645329 [ dbSNP | Ensembl ].
VAR_059310
Natural varianti150 – 1501G → S in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_030756
Natural varianti191 – 1911S → F in a breast cancer sample; somatic mutation. 1 Publication
VAR_036195
Natural varianti227 – 2271E → V.
Corresponds to variant rs17078898 [ dbSNP | Ensembl ].
VAR_055876
Natural varianti236 – 2361I → F.
Corresponds to variant rs17078896 [ dbSNP | Ensembl ].
VAR_055877
Natural varianti405 – 4051I → T in CSNB1B; abolishes expression at the cell membrane. 1 Publication
VAR_069819
Natural varianti522 – 5221C → Y in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_069820
Natural varianti712 – 7121M → V.
Corresponds to variant rs17078877 [ dbSNP | Ensembl ].
VAR_055878
Natural varianti781 – 7811E → K in CSNB1B; abolishes expression at the cell membrane. 2 Publications
VAR_030757
Natural varianti807 – 8071A → V.
Corresponds to variant rs17078874 [ dbSNP | Ensembl ].
VAR_055879
Natural varianti817 – 8171T → S.
Corresponds to variant rs17078857 [ dbSNP | Ensembl ].
VAR_055880

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U82083 Genomic DNA. Translation: AAB82068.1.
AC104117 Genomic DNA. No translation available.
CCDSiCCDS4442.1.
RefSeqiNP_000834.2. NM_000843.3.
UniGeneiHs.248131.

Genome annotation databases

EnsembliENST00000231188; ENSP00000231188; ENSG00000113262.
ENST00000517717; ENSP00000430767; ENSG00000113262.
GeneIDi2916.
KEGGihsa:2916.
UCSCiuc003mjr.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U82083 Genomic DNA. Translation: AAB82068.1 .
AC104117 Genomic DNA. No translation available.
CCDSi CCDS4442.1.
RefSeqi NP_000834.2. NM_000843.3.
UniGenei Hs.248131.

3D structure databases

ProteinModelPortali O15303.
SMRi O15303. Positions 32-851.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000231188.

Chemistry

BindingDBi O15303.
ChEMBLi CHEMBL4573.
GuidetoPHARMACOLOGYi 294.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei O15303.

Proteomic databases

PaxDbi O15303.
PRIDEi O15303.

Protocols and materials databases

DNASUi 2916.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000231188 ; ENSP00000231188 ; ENSG00000113262 .
ENST00000517717 ; ENSP00000430767 ; ENSG00000113262 .
GeneIDi 2916.
KEGGi hsa:2916.
UCSCi uc003mjr.3. human.

Organism-specific databases

CTDi 2916.
GeneCardsi GC05M178392.
H-InvDB HIX0024983.
HGNCi HGNC:4598. GRM6.
MIMi 257270. phenotype.
604096. gene.
neXtProti NX_O15303.
Orphaneti 215. Congenital stationary night blindness.
PharmGKBi PA28995.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG295200.
GeneTreei ENSGT00760000118884.
HOGENOMi HOG000218635.
HOVERGENi HBG107965.
InParanoidi O15303.
KOi K04608.
OMAi VCIAQSI.
OrthoDBi EOG7Z0JXG.
PhylomeDBi O15303.
TreeFami TF313240.

Enzyme and pathway databases

Reactomei REACT_18319. Class C/3 (Metabotropic glutamate/pheromone receptors).
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

GeneWikii Metabotropic_glutamate_receptor_6.
GenomeRNAii 2916.
NextBioi 11559.
PROi O15303.
SOURCEi Search...

Gene expression databases

Bgeei O15303.
CleanExi HS_GRM6.
Genevestigatori O15303.

Family and domain databases

InterProi IPR001828. ANF_lig-bd_rcpt.
IPR000337. GPCR_3.
IPR011500. GPCR_3_9-Cys_dom.
IPR017978. GPCR_3_C.
IPR017979. GPCR_3_CS.
IPR000162. GPCR_3_mtglu_rcpt.
IPR000112. GPCR_3_mtglu_rcpt_6.
IPR028082. Peripla_BP_I.
[Graphical view ]
Pfami PF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF07562. NCD3G. 1 hit.
[Graphical view ]
PRINTSi PR00248. GPCRMGR.
PR01056. MTABOTROPC6R.
PR00593. MTABOTROPICR.
SUPFAMi SSF53822. SSF53822. 1 hit.
PROSITEi PS00979. G_PROTEIN_RECEP_F3_1. 1 hit.
PS00980. G_PROTEIN_RECEP_F3_2. 1 hit.
PS00981. G_PROTEIN_RECEP_F3_3. 1 hit.
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6."
    Hashimoto T., Inazawa J., Okamoto N., Tagawa Y., Bessho Y., Honda Y., Nakanishi S.
    Eur. J. Neurosci. 9:1226-1235(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-59.
  2. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes."
    Devi S., Markandeya Y., Maddodi N., Dhingra A., Vardi N., Balijepalli R.C., Setaluri V.
    Pigment Cell Melanoma Res. 26:348-356(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  4. "Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6."
    Dryja T.P., McGee T.L., Berson E.L., Fishman G.A., Sandberg M.A., Alexander K.R., Derlacki D.J., Rajagopalan A.S.
    Proc. Natl. Acad. Sci. U.S.A. 102:4884-4889(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CSNB1B SER-150 AND LYS-781.
  5. Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-191.
  6. "Night blindness-associated mutations in the ligand-binding, cysteine-rich, and intracellular domains of the metabotropic glutamate receptor 6 abolish protein trafficking."
    Zeitz C., Forster U., Neidhardt J., Feil S., Kalin S., Leifert D., Flor P.J., Berger W.
    Hum. Mutat. 28:771-780(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781, VARIANT PRO-59, CHARACTERIZATION OF VARIANT PRO-59, CHARACTERIZATION OF VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781, SUBUNIT, SUBCELLULAR LOCATION.
  7. Cited for: VARIANTS CSNB1B LEU-46; ARG-58 AND TYR-522.

Entry informationi

Entry nameiGRM6_HUMAN
AccessioniPrimary (citable) accession number: O15303
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 16, 2009
Last modified: October 29, 2014
This is version 123 of the entry and version 2 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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 5
    Human chromosome 5: 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3