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Q9H2C0

- GAN_HUMAN

UniProt

Q9H2C0 - GAN_HUMAN

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Protein

Gigaxonin

Gene

GAN

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

Functioni

Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. May act as a substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB. Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival.4 Publications

Pathwayi

GO - Biological processi

  1. cell death Source: UniProtKB-KW
  2. protein ubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Gigaxonin
Alternative name(s):
Kelch-like protein 16
Gene namesi
Name:GAN
Synonyms:GAN1, KLHL16
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:4137. GAN.

Subcellular locationi

GO - Cellular componenti

  1. Cul3-RING ubiquitin ligase complex Source: UniProtKB
  2. cytoplasm Source: UniProtKB
  3. cytoskeleton Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Giant axonal neuropathy 1, autosomal recessive (GAN1) [MIM:256850]: A severe autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. Axonal loss and the presence of giant axonal swellings filled with neurofilaments on nerve biopsies are the hallmarks of this neurodegenerative disorder.5 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151R → S in GAN1; no effect on binding to TBCB. 1 Publication
VAR_010759
Natural varianti51 – 511A → P in GAN1. 1 Publication
VAR_054113
Natural varianti52 – 521S → G in GAN1. 1 Publication
VAR_010760
Natural varianti79 – 791S → L in GAN1. 1 Publication
VAR_010761
Natural varianti82 – 821V → F in GAN1; no effect on binding to TBCB. 1 Publication
VAR_010762
Natural varianti86 – 861I → F in GAN1. 1 Publication
VAR_015680
Natural varianti89 – 891Y → C in GAN1. 1 Publication
VAR_054114
Natural varianti138 – 1381R → H in GAN1. 1 Publication
VAR_010763
Natural varianti195 – 1951V → F in GAN1. 1 Publication
VAR_054115
Natural varianti269 – 2691R → Q in GAN1. 2 Publications
VAR_010764
Natural varianti309 – 3091L → R in GAN1. 1 Publication
VAR_010765
Natural varianti315 – 3151P → L in GAN1. 1 Publication
Corresponds to variant rs144486241 [ dbSNP | Ensembl ].
VAR_054116
Natural varianti368 – 3681G → R in GAN1. 2 Publications
VAR_015681
Natural varianti423 – 4231I → T in GAN1. 2 Publications
VAR_015560
Natural varianti474 – 4741G → R in GAN1. 1 Publication
VAR_054117
Natural varianti486 – 4861E → K in GAN1. 1 Publication
VAR_010757
Natural varianti545 – 5451R → C in GAN1; complete loss of binding to TBCB. 1 Publication
VAR_010766
Natural varianti545 – 5451R → H in GAN1. 1 Publication
VAR_054118
Natural varianti570 – 5701C → Y in GAN1. 1 Publication
VAR_010767

Keywords - Diseasei

Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

MIMi256850. phenotype.
Orphaneti643. Giant axonal neuropathy.
PharmGKBiPA28550.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 597597GigaxoninPRO_0000119070Add
BLAST

Post-translational modificationi

Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and RBX1 and probably targeted for proteasome-independent degradation.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ9H2C0.
PaxDbiQ9H2C0.
PRIDEiQ9H2C0.

PTM databases

PhosphoSiteiQ9H2C0.

Expressioni

Tissue specificityi

Expressed in brain, heart and muscle.1 Publication

Gene expression databases

BgeeiQ9H2C0.
CleanExiHS_GAN.
GenevestigatoriQ9H2C0.

Organism-specific databases

HPAiCAB011825.
HPA049473.

Interactioni

Subunit structurei

Interacts with TBCB. Interacts with CUL3. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with UBA1. Interacts (via Kelch domains) with MAP1B (via C-terminus) and MAP1S (via C-terminus).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP1BP468213EBI-764342,EBI-764611
TBCBQ994263EBI-764342,EBI-764356
UBA1P223145EBI-764342,EBI-709688

Protein-protein interaction databases

BioGridi113800. 10 interactions.
IntActiQ9H2C0. 8 interactions.
MINTiMINT-243055.
STRINGi9606.ENSP00000248272.

Structurei

Secondary structure

1
597
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi12 – 2211Combined sources
Beta strandi32 – 365Combined sources
Beta strandi39 – 435Combined sources
Helixi45 – 517Combined sources
Helixi53 – 619Combined sources
Beta strandi72 – 743Combined sources
Helixi80 – 9011Combined sources
Turni99 – 1013Combined sources
Helixi102 – 11110Combined sources
Helixi115 – 1228Combined sources
Helixi135 – 1439Combined sources
Helixi147 – 16418Combined sources
Helixi168 – 1714Combined sources
Helixi175 – 1839Combined sources
Helixi196 – 1994Combined sources
Turni200 – 2023Combined sources
Turni211 – 2133Combined sources
Helixi214 – 22411Combined sources
Helixi231 – 2366Combined sources
Helixi241 – 2455Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2PPIX-ray2.40A6-126[»]
3HVEX-ray2.80A/B1-254[»]
ProteinModelPortaliQ9H2C0.
SMRiQ9H2C0. Positions 3-554.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H2C0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 9970BTBPROSITE-ProRule annotationAdd
BLAST
Domaini134 – 236103BACKAdd
BLAST
Repeati274 – 32653Kelch 1Add
BLAST
Repeati327 – 37448Kelch 2Add
BLAST
Repeati376 – 42146Kelch 3Add
BLAST
Repeati422 – 46847Kelch 4Add
BLAST
Repeati470 – 52253Kelch 5Add
BLAST
Repeati528 – 57447Kelch 6Add
BLAST

Sequence similaritiesi

Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
Contains 6 Kelch repeats.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiNOG274392.
GeneTreeiENSGT00760000119153.
HOGENOMiHOG000290709.
HOVERGENiHBG005802.
InParanoidiQ9H2C0.
KOiK10453.
OMAiIQGSEMV.
OrthoDBiEOG7P2XRJ.
PhylomeDBiQ9H2C0.
TreeFamiTF329218.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
3.30.710.10. 1 hit.
InterProiIPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR017096. Kelch-like_gigaxonin-typ.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
[Graphical view]
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 5 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9H2C0-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAEGSAVSDP QHAARLLRAL SSFREESRFC DAHLVLDGEE IPVQKNILAA
60 70 80 90 100
ASPYIRTKLN YNPPKDDGST YKIELEGISV MVMREILDYI FSGQIRLNED
110 120 130 140 150
TIQDVVQAAD LLLLTDLKTL CCEFLEGCIA AENCIGIRDF ALHYCLHHVH
160 170 180 190 200
YLATEYLETH FRDVSSTEEF LELSPQKLKE VISLEKLNVG NERYVFEAVI
210 220 230 240 250
RWIAHDTEIR KVHMKDVMSA LWVSGLDSSY LREQMLNEPL VREIVKECSN
260 270 280 290 300
IPLSQPQQGE AMLANFKPRG YSECIVTVGG EERVSRKPTA AMRCMCPLYD
310 320 330 340 350
PNRQLWIELA PLSMPRINHG VLSAEGFLFV FGGQDENKQT LSSGEKYDPD
360 370 380 390 400
ANTWTALPPM NEARHNFGIV EIDGMLYILG GEDGEKELIS MECYDIYSKT
410 420 430 440 450
WTKQPDLTMV RKIGCYAAMK KKIYAMGGGS YGKLFESVEC YDPRTQQWTA
460 470 480 490 500
ICPLKERRFG AVACGVAMEL YVFGGVRSRE DAQGSEMVTC KSEFYHDEFK
510 520 530 540 550
RWIYLNDQNL CIPASSSFVY GAVPIGASIY VIGDLDTGTN YDYVREFKRS
560 570 580 590
TGTWHHTKPL LPSDLRRTGC AALRIANCKL FRLQLQQGLF RIRVHSP
Length:597
Mass (Da):67,638
Last modified:March 1, 2001 - v1
Checksum:i4B6ECFA6849880C7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151R → S in GAN1; no effect on binding to TBCB. 1 Publication
VAR_010759
Natural varianti51 – 511A → P in GAN1. 1 Publication
VAR_054113
Natural varianti52 – 521S → G in GAN1. 1 Publication
VAR_010760
Natural varianti79 – 791S → L in GAN1. 1 Publication
VAR_010761
Natural varianti82 – 821V → F in GAN1; no effect on binding to TBCB. 1 Publication
VAR_010762
Natural varianti86 – 861I → F in GAN1. 1 Publication
VAR_015680
Natural varianti89 – 891Y → C in GAN1. 1 Publication
VAR_054114
Natural varianti138 – 1381R → H in GAN1. 1 Publication
VAR_010763
Natural varianti195 – 1951V → F in GAN1. 1 Publication
VAR_054115
Natural varianti269 – 2691R → Q in GAN1. 2 Publications
VAR_010764
Natural varianti309 – 3091L → R in GAN1. 1 Publication
VAR_010765
Natural varianti315 – 3151P → L in GAN1. 1 Publication
Corresponds to variant rs144486241 [ dbSNP | Ensembl ].
VAR_054116
Natural varianti368 – 3681G → R in GAN1. 2 Publications
VAR_015681
Natural varianti423 – 4231I → T in GAN1. 2 Publications
VAR_015560
Natural varianti474 – 4741G → R in GAN1. 1 Publication
VAR_054117
Natural varianti486 – 4861E → K in GAN1. 1 Publication
VAR_010757
Natural varianti545 – 5451R → C in GAN1; complete loss of binding to TBCB. 1 Publication
VAR_010766
Natural varianti545 – 5451R → H in GAN1. 1 Publication
VAR_054118
Natural varianti570 – 5701C → Y in GAN1. 1 Publication
VAR_010767

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF291673 mRNA. Translation: AAG35311.1.
BC044840 mRNA. Translation: AAH44840.1.
CCDSiCCDS10935.1.
RefSeqiNP_071324.1. NM_022041.3.
UniGeneiHs.112569.

Genome annotation databases

EnsembliENST00000568107; ENSP00000476795; ENSG00000261609.
GeneIDi8139.
KEGGihsa:8139.
UCSCiuc002fgo.3. human.

Polymorphism databases

DMDMi13626745.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Inherited peripheral neuropathies mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF291673 mRNA. Translation: AAG35311.1 .
BC044840 mRNA. Translation: AAH44840.1 .
CCDSi CCDS10935.1.
RefSeqi NP_071324.1. NM_022041.3.
UniGenei Hs.112569.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2PPI X-ray 2.40 A 6-126 [» ]
3HVE X-ray 2.80 A/B 1-254 [» ]
ProteinModelPortali Q9H2C0.
SMRi Q9H2C0. Positions 3-554.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113800. 10 interactions.
IntActi Q9H2C0. 8 interactions.
MINTi MINT-243055.
STRINGi 9606.ENSP00000248272.

PTM databases

PhosphoSitei Q9H2C0.

Polymorphism databases

DMDMi 13626745.

Proteomic databases

MaxQBi Q9H2C0.
PaxDbi Q9H2C0.
PRIDEi Q9H2C0.

Protocols and materials databases

DNASUi 8139.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000568107 ; ENSP00000476795 ; ENSG00000261609 .
GeneIDi 8139.
KEGGi hsa:8139.
UCSCi uc002fgo.3. human.

Organism-specific databases

CTDi 8139.
GeneCardsi GC16P081348.
GeneReviewsi GAN.
HGNCi HGNC:4137. GAN.
HPAi CAB011825.
HPA049473.
MIMi 256850. phenotype.
605379. gene.
neXtProti NX_Q9H2C0.
Orphaneti 643. Giant axonal neuropathy.
PharmGKBi PA28550.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG274392.
GeneTreei ENSGT00760000119153.
HOGENOMi HOG000290709.
HOVERGENi HBG005802.
InParanoidi Q9H2C0.
KOi K10453.
OMAi IQGSEMV.
OrthoDBi EOG7P2XRJ.
PhylomeDBi Q9H2C0.
TreeFami TF329218.

Enzyme and pathway databases

UniPathwayi UPA00143 .
Reactomei REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSi GAN. human.
EvolutionaryTracei Q9H2C0.
GeneWikii Gigaxonin.
GenomeRNAii 8139.
NextBioi 30807.
PROi Q9H2C0.
SOURCEi Search...

Gene expression databases

Bgeei Q9H2C0.
CleanExi HS_GAN.
Genevestigatori Q9H2C0.

Family and domain databases

Gene3Di 2.120.10.80. 1 hit.
3.30.710.10. 1 hit.
InterProi IPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR017096. Kelch-like_gigaxonin-typ.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
[Graphical view ]
Pfami PF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 3 hits.
[Graphical view ]
PIRSFi PIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTi SM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 5 hits.
[Graphical view ]
SUPFAMi SSF54695. SSF54695. 1 hit.
PROSITEi PS50097. BTB. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy."
    Bomont P., Cavalier L., Blondeau F., Ben-Hamida C., Belal S., Tazir M., Demir E., Topaloglu H., Korinthenberg R., Tueysuez B., Landrieu P., Hentati F., Koenig M.
    Nat. Genet. 26:370-374(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GAN1 SER-15; GLY-52; LEU-79; PHE-82; HIS-138; GLN-269; ARG-309; LYS-486; CYS-545 AND TYR-570.
    Tissue: Brain.
  2. "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].
    Tissue: Placenta.
  3. "Microtubule-associated protein 1B: a neuronal binding partner for gigaxonin."
    Ding J., Liu J.-J., Kowal A.S., Nardine T., Bhattacharya P., Lee A., Yang Y.
    J. Cell Biol. 158:427-433(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MAP1B, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  4. "Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."
    Furukawa M., He Y.J., Borchers C., Xiong Y.
    Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CUL3.
  5. "Gigaxonin interacts with tubulin folding cofactor B and controls its degradation through the ubiquitin-proteasome pathway."
    Wang W., Ding J., Allen E., Zhu P., Zhang L., Vogel H., Yang Y.
    Curr. Biol. 15:2050-2055(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TBCB, CHARACTERIZATION OF VARIANTS GAN1 SER-15; PHE-82 AND CYS-545.
  6. "Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway."
    Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M.
    J. Biol. Chem. 280:30091-30099(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH CUL3 AND RBX1, UBIQUITINATION.
  7. "Gigaxonin-controlled degradation of MAP1B light chain is critical to neuronal survival."
    Allen E., Ding J., Wang W., Pramanik S., Chou J., Yau V., Yang Y.
    Nature 438:224-228(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH UBA1 AND MAP1B.
  8. "Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level."
    Wang X.J., Zhang D.D.
    PLoS ONE 4:E5492-E5492(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  9. "Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases."
    Zhuang M., Calabrese M.F., Liu J., Waddell M.B., Nourse A., Hammel M., Miller D.J., Walden H., Duda D.M., Seyedin S.N., Hoggard T., Harper J.W., White K.P., Schulman B.A.
    Mol. Cell 36:39-50(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-254.
  10. "Structure of the BTB (tramtrack and bric a brac) domain of human gigaxonin."
    Structural genomics consortium (SGC)
    Submitted (JUL-2011) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 6-126.
  11. "Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene."
    Kuhlenbaumer G., Young P., Oberwittler C., Hunermund G., Schirmacher A., Domschke K., Ringelstein B., Stogbauer F.
    Neurology 58:1273-1276(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT GAN1 THR-423.
  12. Cited for: VARIANTS GAN1 PHE-86; GLN-269 AND ARG-368.
  13. "New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy."
    Houlden H., Groves M., Miedzybrodzka Z., Roper H., Willis T., Winer J., Cole G., Reilly M.M.
    J. Neurol. Neurosurg. Psych. 78:1267-1270(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS GAN1 PRO-51 AND LEU-315.
  14. Cited for: VARIANTS GAN1 CYS-89; PHE-195; ARG-368; THR-423; ARG-474 AND HIS-545.

Entry informationi

Entry nameiGAN_HUMAN
AccessioniPrimary (citable) accession number: Q9H2C0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: March 1, 2001
Last modified: November 26, 2014
This is version 140 of the entry and version 1 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. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  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