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P40225

- TPO_HUMAN

UniProt

P40225 - TPO_HUMAN

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Protein

Thrombopoietin

Gene

THPO

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

Functioni

Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.

GO - Molecular functioni

  1. growth factor activity Source: ProtInc

GO - Biological processi

  1. blood coagulation Source: Reactome
  2. cell proliferation Source: ProtInc
  3. multicellular organismal development Source: ProtInc
  4. myeloid cell differentiation Source: Ensembl
  5. platelet activation Source: Reactome
  6. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  7. positive regulation of megakaryocyte differentiation Source: UniProtKB
  8. positive regulation of protein kinase B signaling Source: UniProtKB
  9. positive regulation of protein phosphorylation Source: UniProtKB
  10. thrombopoietin-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Hormone

Enzyme and pathway databases

ReactomeiREACT_278. Platelet Aggregation (Plug Formation).
SignaLinkiP40225.

Names & Taxonomyi

Protein namesi
Recommended name:
Thrombopoietin
Alternative name(s):
C-mpl ligand
Short name:
ML
Megakaryocyte colony-stimulating factor
Megakaryocyte growth and development factor
Short name:
MGDF
Myeloproliferative leukemia virus oncogene ligand
Gene namesi
Name:THPO
Synonyms:MGDF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:11795. THPO.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Thrombocythemia 1 (THCYT1) [MIM:187950]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Organism-specific databases

MIMi187950. phenotype.
Orphaneti71493. Familial thrombocytosis.
397692. Hereditary aplastic anemia.
329319. Hereditary thrombocytosis with transverse limb defect.
PharmGKBiPA36506.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Add
BLAST
Chaini22 – 353332ThrombopoietinPRO_0000008411Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi22 – 221O-linked (GalNAc...)1 Publication
Disulfide bondi28 ↔ 172
Disulfide bondi50 ↔ 106
Glycosylationi58 – 581O-linked (GalNAc...)1 Publication
Glycosylationi131 – 1311O-linked (GalNAc...)1 Publication
Glycosylationi179 – 1791O-linked (GalNAc...)1 Publication
Glycosylationi180 – 1801O-linked (GalNAc...)1 Publication
Glycosylationi184 – 1841O-linked (GalNAc...)1 Publication
Glycosylationi197 – 1971N-linked (GlcNAc...) (complex)1 Publication
Glycosylationi206 – 2061N-linked (GlcNAc...) (complex)1 Publication
Glycosylationi213 – 2131O-linked (GalNAc...)1 Publication
Glycosylationi234 – 2341N-linked (GlcNAc...) (complex)1 Publication
Glycosylationi255 – 2551N-linked (GlcNAc...) (complex)1 Publication
Glycosylationi265 – 2651O-linked (GalNAc...)1 Publication
Glycosylationi340 – 3401N-linked (GlcNAc...)Sequence Analysis
Glycosylationi348 – 3481N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP40225.
PRIDEiP40225.

PTM databases

PhosphoSiteiP40225.

Miscellaneous databases

PMAP-CutDBP40225.

Expressioni

Gene expression databases

BgeeiP40225.
CleanExiHS_THPO.
ExpressionAtlasiP40225. baseline and differential.
GenevestigatoriP40225.

Interactioni

Protein-protein interaction databases

BioGridi112922. 3 interactions.
DIPiDIP-5729N.
IntActiP40225. 3 interactions.
STRINGi9606.ENSP00000204615.

Structurei

Secondary structure

1
353
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi32 – 4514Combined sources
Helixi46 – 483Combined sources
Beta strandi49 – 524Combined sources
Beta strandi60 – 634Combined sources
Helixi70 – 745Combined sources
Helixi77 – 9822Combined sources
Turni99 – 1013Combined sources
Beta strandi104 – 1063Combined sources
Helixi107 – 1104Combined sources
Helixi113 – 12917Combined sources
Beta strandi139 – 1435Combined sources
Helixi145 – 1473Combined sources
Helixi148 – 15710Combined sources
Turni158 – 1603Combined sources
Helixi161 – 1633Combined sources
Beta strandi165 – 1673Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1V7MX-ray2.51V/X22-184[»]
1V7NX-ray3.30V/X/Y/Z22-184[»]
ProteinModelPortaliP40225.
SMRiP40225. Positions 28-172.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP40225.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi285 – 33753Pro-richAdd
BLAST

Domaini

Two-domain structure with an erythropoietin-like N-terminal and a Ser/Pro/Thr-rich C-terminal.

Sequence similaritiesi

Belongs to the EPO/TPO family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG84342.
GeneTreeiENSGT00390000006294.
HOVERGENiHBG002468.
InParanoidiP40225.
KOiK06854.
OMAiEQSKAQD.
OrthoDBiEOG7PVWPW.
PhylomeDBiP40225.
TreeFamiTF338084.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003978. Thrombopoeitin.
[Graphical view]
PANTHERiPTHR10560. PTHR10560. 1 hit.
PfamiPF00758. EPO_TPO. 1 hit.
[Graphical view]
PRINTSiPR01485. THROMBOPTN.
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00817. EPO_TPO. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P40225-1) [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.

« Hide

        10         20         30         40         50
MELTELLLVV MLLLTARLTL SSPAPPACDL RVLSKLLRDS HVLHSRLSQC
60 70 80 90 100
PEVHPLPTPV LLPAVDFSLG EWKTQMEETK AQDILGAVTL LLEGVMAARG
110 120 130 140 150
QLGPTCLSSL LGQLSGQVRL LLGALQSLLG TQLPPQGRTT AHKDPNAIFL
160 170 180 190 200
SFQHLLRGKV RFLMLVGGST LCVRRAPPTT AVPSRTSLVL TLNELPNRTS
210 220 230 240 250
GLLETNFTAS ARTTGSGLLK WQQGFRAKIP GLLNQTSRSL DQIPGYLNRI
260 270 280 290 300
HELLNGTRGL FPGPSRRTLG APDISSGTSD TGSLPPNLQP GYSPSPTHPP
310 320 330 340 350
TGQYTLFPLP PTLPTPVVQL HPLLPDPSAP TPTPTSPLLN TSYTHSQNLS

QEG
Length:353
Mass (Da):37,823
Last modified:February 1, 1995 - v1
Checksum:iF0AB5449B72E5526
GO
Isoform 2 (identifier: P40225-2) [UniParc]FASTAAdd to Basket

Also known as: TPO-2

The sequence of this isoform differs from the canonical sequence as follows:
     133-136: Missing.

Show »
Length:349
Mass (Da):37,387
Checksum:iC7348E1148DAA58C
GO
Isoform 3 (identifier: P40225-3) [UniParc]FASTAAdd to Basket

Also known as: Truncated

The sequence of this isoform differs from the canonical sequence as follows:
     160-198: Missing.

Show »
Length:314
Mass (Da):33,604
Checksum:i183A09670C9FAEE4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti46 – 461R → K in AAB03392. 1 PublicationCurated
Sequence conflicti46 – 461R → K in AAB03393. 1 PublicationCurated
Sequence conflicti46 – 461R → K in AAB03394. 1 PublicationCurated
Sequence conflicti76 – 761M → MSQ in AAA74083. (PubMed:7822271)Curated
Sequence conflicti113 – 1131Q → E in AAA50553. (PubMed:8020099)Curated
Sequence conflicti131 – 1311T → P in AAA74083. (PubMed:7822271)Curated
Sequence conflicti277 – 2771G → E in AAB03393. 1 PublicationCurated
Sequence conflicti277 – 2771G → E in AAB03394. 1 PublicationCurated
Sequence conflicti346 – 3461S → C in AAB03393. 1 PublicationCurated
Sequence conflicti346 – 3461S → C in AAB03394. 1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti14 – 141L → P.
Corresponds to variant rs1042346 [ dbSNP | Ensembl ].
VAR_011795
Natural varianti116 – 1161G → E.
Corresponds to variant rs1126665 [ dbSNP | Ensembl ].
VAR_011796

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei133 – 1364Missing in isoform 2. 1 PublicationVSP_001450
Alternative sequencei160 – 19839Missing in isoform 3. CuratedVSP_001451Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33410 mRNA. Translation: AAA59857.1.
U11025 mRNA. Translation: AAA50553.1.
L36051 Genomic DNA. Translation: AAC37568.1.
L36052 mRNA. Translation: AAC37566.1.
D32046 Genomic DNA. Translation: BAA06807.1.
S76771 Genomic DNA. Translation: AAB33390.1.
D32047 mRNA. Translation: BAA21930.1.
U59493 mRNA. Translation: AAB03392.1.
U59494 mRNA. Translation: AAB03393.1.
U59495 mRNA. Translation: AAB03394.1.
U17071 Genomic DNA. Translation: AAA74083.1.
BC130322 mRNA. Translation: AAI30323.1.
BC136338 mRNA. Translation: AAI36339.1.
BC143982 mRNA. Translation: AAI43983.1.
CCDSiCCDS3265.1. [P40225-1]
CCDS54693.1. [P40225-2]
PIRiG02729.
I59281. I80105.
RefSeqiNP_000451.1. NM_000460.3. [P40225-1]
NP_001171068.1. NM_001177597.2. [P40225-2]
NP_001171069.1. NM_001177598.2.
NP_001276926.1. NM_001289997.1.
NP_001276927.1. NM_001289998.1. [P40225-1]
NP_001276932.1. NM_001290003.1.
NP_001276951.1. NM_001290022.1. [P40225-2]
NP_001276955.1. NM_001290026.1.
NP_001276956.1. NM_001290027.1.
NP_001276957.1. NM_001290028.1. [P40225-1]
UniGeneiHs.1166.
Hs.734657.

Genome annotation databases

EnsembliENST00000204615; ENSP00000204615; ENSG00000090534. [P40225-1]
ENST00000445696; ENSP00000410763; ENSG00000090534. [P40225-2]
GeneIDi7066.
KEGGihsa:7066.
UCSCiuc003fol.1. human. [P40225-1]
uc003fom.2. human. [P40225-2]

Polymorphism databases

DMDMi730982.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

R&D Systems' cytokine source book: Thrombopoietin

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33410 mRNA. Translation: AAA59857.1 .
U11025 mRNA. Translation: AAA50553.1 .
L36051 Genomic DNA. Translation: AAC37568.1 .
L36052 mRNA. Translation: AAC37566.1 .
D32046 Genomic DNA. Translation: BAA06807.1 .
S76771 Genomic DNA. Translation: AAB33390.1 .
D32047 mRNA. Translation: BAA21930.1 .
U59493 mRNA. Translation: AAB03392.1 .
U59494 mRNA. Translation: AAB03393.1 .
U59495 mRNA. Translation: AAB03394.1 .
U17071 Genomic DNA. Translation: AAA74083.1 .
BC130322 mRNA. Translation: AAI30323.1 .
BC136338 mRNA. Translation: AAI36339.1 .
BC143982 mRNA. Translation: AAI43983.1 .
CCDSi CCDS3265.1. [P40225-1 ]
CCDS54693.1. [P40225-2 ]
PIRi G02729.
I59281. I80105.
RefSeqi NP_000451.1. NM_000460.3. [P40225-1 ]
NP_001171068.1. NM_001177597.2. [P40225-2 ]
NP_001171069.1. NM_001177598.2.
NP_001276926.1. NM_001289997.1.
NP_001276927.1. NM_001289998.1. [P40225-1 ]
NP_001276932.1. NM_001290003.1.
NP_001276951.1. NM_001290022.1. [P40225-2 ]
NP_001276955.1. NM_001290026.1.
NP_001276956.1. NM_001290027.1.
NP_001276957.1. NM_001290028.1. [P40225-1 ]
UniGenei Hs.1166.
Hs.734657.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1V7M X-ray 2.51 V/X 22-184 [» ]
1V7N X-ray 3.30 V/X/Y/Z 22-184 [» ]
ProteinModelPortali P40225.
SMRi P40225. Positions 28-172.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112922. 3 interactions.
DIPi DIP-5729N.
IntActi P40225. 3 interactions.
STRINGi 9606.ENSP00000204615.

Chemistry

ChEMBLi CHEMBL1293256.

PTM databases

PhosphoSitei P40225.

Polymorphism databases

DMDMi 730982.

Proteomic databases

PaxDbi P40225.
PRIDEi P40225.

Protocols and materials databases

DNASUi 7066.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000204615 ; ENSP00000204615 ; ENSG00000090534 . [P40225-1 ]
ENST00000445696 ; ENSP00000410763 ; ENSG00000090534 . [P40225-2 ]
GeneIDi 7066.
KEGGi hsa:7066.
UCSCi uc003fol.1. human. [P40225-1 ]
uc003fom.2. human. [P40225-2 ]

Organism-specific databases

CTDi 7066.
GeneCardsi GC03M184089.
HGNCi HGNC:11795. THPO.
MIMi 187950. phenotype.
600044. gene.
neXtProti NX_P40225.
Orphaneti 71493. Familial thrombocytosis.
397692. Hereditary aplastic anemia.
329319. Hereditary thrombocytosis with transverse limb defect.
PharmGKBi PA36506.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG84342.
GeneTreei ENSGT00390000006294.
HOVERGENi HBG002468.
InParanoidi P40225.
KOi K06854.
OMAi EQSKAQD.
OrthoDBi EOG7PVWPW.
PhylomeDBi P40225.
TreeFami TF338084.

Enzyme and pathway databases

Reactomei REACT_278. Platelet Aggregation (Plug Formation).
SignaLinki P40225.

Miscellaneous databases

ChiTaRSi THPO. human.
EvolutionaryTracei P40225.
GeneWikii Thrombopoietin.
GenomeRNAii 7066.
NextBioi 27627.
PMAP-CutDB P40225.
PROi P40225.
SOURCEi Search...

Gene expression databases

Bgeei P40225.
CleanExi HS_THPO.
ExpressionAtlasi P40225. baseline and differential.
Genevestigatori P40225.

Family and domain databases

Gene3Di 1.20.1250.10. 1 hit.
InterProi IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003978. Thrombopoeitin.
[Graphical view ]
PANTHERi PTHR10560. PTHR10560. 1 hit.
Pfami PF00758. EPO_TPO. 1 hit.
[Graphical view ]
PRINTSi PR01485. THROMBOPTN.
SUPFAMi SSF47266. SSF47266. 1 hit.
PROSITEi PS00817. EPO_TPO. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Fetal liver.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Fetal liver.
  3. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
  4. "Molecular cloning and chromosomal localization of the human thrombopoietin gene."
    Sohma Y., Akahori H., Seki N., Hori T.-A., Ogami K., Kawamura K., Miyazaki H.
    FEBS Lett. 353:57-61(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
  5. "Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin."
    Gurney A.L., Kuang W.-J., Xie M.-H., Malloy B.E., Eaton D.L., de Sauvage F.J.
    Blood 85:981-988(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
  6. "Purification and characterization of thrombopoietin."
    Kato T., Ogami K., Shimada Y., Iwamatsu A., Sohma Y., Akahori H., Horie K., Kokubo A., Kudo Y., Maeda E., Kobayashi K., Ohashi H., Ozawa T., Inoue H., Kawamura K., Miyazaki H.
    J. Biochem. 118:229-236(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Liver.
  7. "Cloning and characterization of the human megakaryocyte growth and development factor (MGDF) gene."
    Chang M., McNinch J., Basu R., Shutter J., Hsu R., Perkins C., Mar V., Suggs S., Welcher A., Li L., Lu H., Bartley T., Hunt P., Martin F., Samal B., Bogenberger J.
    J. Biol. Chem. 270:511-514(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    Tissue: Placenta.
  8. "Cloning and sequencing of human thrombopoietin."
    Im S.H., Lee W.S., Chung K.H.
    Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
  9. "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 2).
    Tissue: Brain and Testis.
  10. "An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia."
    Wiestner A., Schlemper R.J., van der Maas A.P.C., Skoda R.C.
    Nat. Genet. 18:49-52(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISEASE.
  11. "Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246."
    Hoffman R.C., Andersen H., Walker K., Krakover J.D., Patel S., Stamm M.R., Osborn S.G.
    Biochemistry 35:14849-14861(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS, GLYCOSYLATION AT SER-22; THR-58; THR-131; THR-179; THR-180; SER-184; ASN-197; ASN-206; THR-213; ASN-234; ASN-255 AND SER-265.
  12. "Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment."
    Feese M.D., Tamada T., Kato Y., Maeda Y., Hirose M., Matsukura Y., Shigematsu H., Muto T., Matsumoto A., Watarai H., Ogami K., Tahara T., Kato T., Miyazaki H., Kuroki R.
    Proc. Natl. Acad. Sci. U.S.A. 101:1816-1821(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 22-184 IN COMPLEX WITH ANTIBODY, DISULFIDE BONDS.

Entry informationi

Entry nameiTPO_HUMAN
AccessioniPrimary (citable) accession number: P40225
Secondary accession number(s): A1L3Y0
, B7ZLR8, B9EGA8, Q13020, Q15790, Q15791, Q15792
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 26, 2014
This is version 146 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 3
    Human chromosome 3: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3