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O97799

- KIT_CANFA

UniProt

O97799 - KIT_CANFA

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Protein
Mast/stem cell growth factor receptor Kit
Gene
KIT
Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1 By similarity.

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulationi

Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi571 – 5711Magnesium By similarity
Sitei571 – 5711Interaction with SH2B2/APS By similarity
Binding sitei626 – 6261ATP By similarity
Active sitei795 – 7951Proton acceptor By similarity
Binding sitei799 – 7991ATP By similarity
Metal bindingi800 – 8001Magnesium By similarity
Metal bindingi813 – 8131Magnesium By similarity
Sitei939 – 9391Important for interaction with phosphotyrosine-binding proteins By similarity
Sitei939 – 9391Interaction with SH2B2/APS By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi599 – 6068ATP By similarity
Nucleotide bindingi674 – 6807ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cytokine binding Source: UniProtKB
  3. metal ion binding Source: UniProtKB-KW
  4. receptor signaling protein tyrosine kinase activity Source: InterPro
  5. stem cell factor receptor activity Source: Ensembl
  6. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. Fc receptor signaling pathway Source: UniProtKB
  2. Kit signaling pathway Source: UniProtKB
  3. T cell differentiation Source: UniProtKB
  4. actin cytoskeleton reorganization Source: UniProtKB
  5. activation of MAPK activity Source: UniProtKB
  6. cell chemotaxis Source: UniProtKB
  7. cellular response to thyroid hormone stimulus Source: Ensembl
  8. cytokine-mediated signaling pathway Source: UniProtKB
  9. dendritic cell cytokine production Source: UniProtKB
  10. detection of mechanical stimulus involved in sensory perception of sound Source: UniProtKB
  11. digestive tract development Source: UniProtKB
  12. ectopic germ cell programmed cell death Source: Ensembl
  13. embryonic hemopoiesis Source: UniProtKB
  14. erythrocyte differentiation Source: UniProtKB
  15. erythropoietin-mediated signaling pathway Source: UniProtKB
  16. glycosphingolipid metabolic process Source: Ensembl
  17. immature B cell differentiation Source: UniProtKB
  18. inflammatory response Source: UniProtKB
  19. lamellipodium assembly Source: UniProtKB
  20. lymphoid progenitor cell differentiation Source: Ensembl
  21. male gonad development Source: Ensembl
  22. mast cell chemotaxis Source: Ensembl
  23. mast cell cytokine production Source: UniProtKB
  24. mast cell degranulation Source: UniProtKB
  25. mast cell differentiation Source: UniProtKB
  26. megakaryocyte development Source: UniProtKB
  27. melanocyte adhesion Source: UniProtKB
  28. melanocyte differentiation Source: UniProtKB
  29. melanocyte migration Source: UniProtKB
  30. myeloid progenitor cell differentiation Source: Ensembl
  31. negative regulation of programmed cell death Source: Ensembl
  32. ovarian follicle development Source: UniProtKB
  33. peptidyl-tyrosine phosphorylation Source: UniProtKB
  34. pigmentation Source: UniProtKB
  35. positive regulation of cell proliferation Source: Ensembl
  36. positive regulation of gene expression Source: Ensembl
  37. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  38. positive regulation of tyrosine phosphorylation of Stat1 protein Source: Ensembl
  39. positive regulation of tyrosine phosphorylation of Stat3 protein Source: Ensembl
  40. positive regulation of tyrosine phosphorylation of Stat5 protein Source: Ensembl
  41. protein autophosphorylation Source: Ensembl
  42. regulation of cell shape Source: UniProtKB
  43. regulation of developmental pigmentation Source: Ensembl
  44. response to radiation Source: Ensembl
  45. spermatid development Source: Ensembl
  46. spermatogenesis Source: UniProtKB
  47. stem cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 1154.
ReactomeiREACT_174426. Signaling by SCF-KIT.
REACT_175504. Regulation of KIT signaling.
REACT_226965. Constitutive PI3K/AKT Signaling in Cancer.

Protein family/group databases

MEROPSiI43.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Mast/stem cell growth factor receptor Kit (EC:2.7.10.1)
Short name:
SCFR
Alternative name(s):
Proto-oncogene c-Kit
Tyrosine-protein kinase Kit
CD_antigen: CD117
Gene namesi
Name:KIT
OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
ProteomesiUP000002254: Chromosome 13

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 527500Extracellular Reviewed prediction
Add
BLAST
Transmembranei528 – 54821Helical; Reviewed prediction
Add
BLAST
Topological domaini549 – 979431Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. external side of plasma membrane Source: Ensembl
  2. extracellular space Source: Ensembl
  3. integral component of membrane Source: UniProtKB-KW
  4. mast cell granule Source: GOC
  5. nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727 Reviewed prediction
Add
BLAST
Chaini28 – 979952Mast/stem cell growth factor receptor Kit
PRO_0000016751Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi60 ↔ 99 By similarity
Glycosylationi96 – 961N-linked (GlcNAc...) Reviewed prediction
Glycosylationi132 – 1321N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi138 ↔ 188 By similarity
Glycosylationi147 – 1471N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi153 ↔ 185 By similarity
Disulfide bondi235 ↔ 293 By similarity
Glycosylationi286 – 2861N-linked (GlcNAc...) Reviewed prediction
Glycosylationi296 – 2961N-linked (GlcNAc...) Reviewed prediction
Glycosylationi303 – 3031N-linked (GlcNAc...) Reviewed prediction
Glycosylationi355 – 3551N-linked (GlcNAc...) Reviewed prediction
Glycosylationi370 – 3701N-linked (GlcNAc...) Reviewed prediction
Glycosylationi403 – 4031N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi431 ↔ 494 By similarity
Glycosylationi466 – 4661N-linked (GlcNAc...) Reviewed prediction
Glycosylationi489 – 4891N-linked (GlcNAc...) Reviewed prediction
Modified residuei550 – 5501Phosphotyrosine; by autocatalysis By similarity
Modified residuei556 – 5561Phosphotyrosine; by autocatalysis By similarity
Modified residuei571 – 5711Phosphotyrosine; by autocatalysis By similarity
Modified residuei573 – 5731Phosphotyrosine; by autocatalysis By similarity
Modified residuei706 – 7061Phosphotyrosine; by autocatalysis By similarity
Modified residuei724 – 7241Phosphotyrosine; by autocatalysis By similarity
Modified residuei733 – 7331Phosphotyrosine; by autocatalysis By similarity
Modified residuei744 – 7441Phosphoserine; by PKC/PRKCA By similarity
Modified residuei749 – 7491Phosphoserine; by PKC/PRKCA By similarity
Modified residuei824 – 8241Phosphoserine By similarity
Modified residuei826 – 8261Phosphotyrosine; by autocatalysis By similarity
Modified residuei894 – 8941Phosphoserine By similarity
Modified residuei903 – 9031Phosphotyrosine; by autocatalysis By similarity
Modified residuei939 – 9391Phosphotyrosine; by autocatalysis By similarity
Modified residuei962 – 9621Phosphoserine By similarity

Post-translational modificationi

Ubiquitinated by SOCS6 By similarity. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation By similarity.
Autophosphorylated on tyrosine residues. KITLG/SCF binding promotes autophosphorylation. Phosphorylated tyrosine residues are important for interaction with specific binding partners By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3 catalytic subunit. Interacts (via phosphorylated tyrosine) with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). Interacts with LYN and FES/FPS. Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with PLCG1. Interacts with DOK1 and TEC By similarity.

Structurei

3D structure databases

ProteinModelPortaliO97799.
SMRiO97799. Positions 35-510, 550-930.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 11486Ig-like C2-type 1
Add
BLAST
Domaini123 – 20785Ig-like C2-type 2
Add
BLAST
Domaini214 – 31198Ig-like C2-type 3
Add
BLAST
Domaini320 – 41394Ig-like C2-type 4
Add
BLAST
Domaini416 – 51095Ig-like C2-type 5
Add
BLAST
Domaini592 – 940349Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni571 – 5733Important for interaction with phosphotyrosine-binding proteins By similarity

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00720000108490.
HOGENOMiHOG000112008.
HOVERGENiHBG004335.
InParanoidiO97799.
KOiK05091.
OMAiYFCPGTE.
OrthoDBiEOG7S7SCZ.
TreeFamiTF325768.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR027263. SCGF_receptor.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PfamiPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500951. SCGF_recepter. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O97799-1) [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

MRGARGAWDF LCVLLLLLLL GVQTGSSQPS VSPGEPSLPS IHPAKSELIV    50
SVGDELRLSC TDPGFVKWTF ETLGQLNENT HNEWITEKAE AGHTGNYTCT 100
NRDGLSRSIY VFVRDPAKLF LVDLPLYGKE GNDTLVRCPL TDPEVTNYSL 150
RGCEGKPLPK DLTFVADPKA GITIRNVKRE YHRLCLHCSA DQKGRTVLSK 200
KFTLKVRAAI RAVPVVSVSK TSSLLKEGEA FSVMCFIKDV SSFVDSMWIK 250
ENSQQTNAQT QSNSWHHGDF NFERQEKLII SSARVNDSGV FMCYANNTFG 300
SANVTTTLEV VDKGFINIFP MMSTTIFVND GENVDLIVEY EAYPKPEHQQ 350
WIYMNRTFTD KWEDYPKSDN ESNIRYVSEL HLTRLKGNEG GTYTFQVSNS 400
DVNSSVTFNV YVNTKPEILT HESLTNGMLQ CVVAGFPEPA VDWYFCPGAE 450
QRCSVPIGPM DVQMQNSSLS PSGKLVVQSS IDYSAFKHNG TVECRAYNNV 500
GRSSAFFNFA FKGNSKEQIH PHTLFTPLLI GFVIAAGMMC IIVMILTYKY 550
LQKPMYEVQW KVVEEINGNN YVYIDPTQLP YDHKWEFPRN RLSFGKTLGA 600
GAFGKVVEAT AYGLIKSDAA MTVAVKMLKP SAHLTEREAL MSELKVLSYL 650
GNHMNIVNLL GACTVGGPTL VITEYCCYGD LLNFLRRKRD SFICSKQEDH 700
GEVALYKNLL HSKESSCSDS TNEYMDMKPG VSYVVPTKAD KRRSARIGSY 750
IERDVTPAIM EDDELALDLE DLLSFSYQVA KGMAFLASKN CIHRDLAARN 800
ILLTHGRITK ICDFGLARDI KNDSNYVVKG NARLPVKWMA PESIFNCVYT 850
FESDVWSYGI FLWELFSLGS SPYPGMPVDS KFYKMIKEGF RMLSPEHAPA 900
EMYDIMKTCW DADPLKRPTF KQIVQLIEKQ ISDSTNHIYS NLANCSPNPE 950
RPVVDHSVRI NSVGSSASST QPLLVHEDV 979
Length:979
Mass (Da):109,753
Last modified:September 5, 2006 - v2
Checksum:i46C30D5DEB8E33D3
GO
Isoform 2 (identifier: O97799-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     512-515: Missing.

Show »
Length:975
Mass (Da):109,367
Checksum:iD845FADB06231FD9
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei512 – 5154Missing in isoform 2.
VSP_020224

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti23 – 231Q → R in AAD02327. 1 Publication
Sequence conflicti332 – 3321E → Q in AAD02327. 1 Publication
Sequence conflicti442 – 4421D → G in AAD02327. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF044249 mRNA. Translation: AAD02327.1.
AF448148 mRNA. Translation: AAL40833.1.
AY296484 mRNA. Translation: AAP51178.1.
AY313776 mRNA. Translation: AAP76390.1.
RefSeqiNP_001003181.1. NM_001003181.1.
XP_005628025.1. XM_005627968.1. [O97799-1]
UniGeneiCfa.184.

Genome annotation databases

EnsembliENSCAFT00000049830; ENSCAFP00000039467; ENSCAFG00000002065. [O97799-2]
GeneIDi403811.
KEGGicfa:403811.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF044249 mRNA. Translation: AAD02327.1 .
AF448148 mRNA. Translation: AAL40833.1 .
AY296484 mRNA. Translation: AAP51178.1 .
AY313776 mRNA. Translation: AAP76390.1 .
RefSeqi NP_001003181.1. NM_001003181.1.
XP_005628025.1. XM_005627968.1. [O97799-1 ]
UniGenei Cfa.184.

3D structure databases

ProteinModelPortali O97799.
SMRi O97799. Positions 35-510, 550-930.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

MEROPSi I43.001.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSCAFT00000049830 ; ENSCAFP00000039467 ; ENSCAFG00000002065 . [O97799-2 ]
GeneIDi 403811.
KEGGi cfa:403811.

Organism-specific databases

CTDi 3815.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00720000108490.
HOGENOMi HOG000112008.
HOVERGENi HBG004335.
InParanoidi O97799.
KOi K05091.
OMAi YFCPGTE.
OrthoDBi EOG7S7SCZ.
TreeFami TF325768.

Enzyme and pathway databases

BRENDAi 2.7.10.1. 1154.
Reactomei REACT_174426. Signaling by SCF-KIT.
REACT_175504. Regulation of KIT signaling.
REACT_226965. Constitutive PI3K/AKT Signaling in Cancer.

Miscellaneous databases

NextBioi 20817307.

Family and domain databases

Gene3Di 2.60.40.10. 5 hits.
InterProi IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR027263. SCGF_receptor.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view ]
Pfami PF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view ]
PIRSFi PIRSF500951. SCGF_recepter. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTi SM00409. IG. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 2 hits.
PROSITEi PS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Clustering of activating mutations in c-KIT's juxtamembrane coding region in canine mast cell neoplasms."
    Ma Y., Longley B.J., Wang X., Blount J.L., Langley K., Caughey G.H.
    J. Invest. Dermatol. 112:165-170(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  2. Zemke D., Yuzbasiyan-Gurkan V.
    Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Characterization of an isoform and RH mapping of canine c-kit."
    Tsai K.L., Guyon R., Murphy K.E.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).

Entry informationi

Entry nameiKIT_CANFA
AccessioniPrimary (citable) accession number: O97799
Secondary accession number(s): Q7YRV7, Q8WN23
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 5, 2006
Last modified: September 3, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions By similarity.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi