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Q86TH1

- ATL2_HUMAN

UniProt

Q86TH1 - ATL2_HUMAN

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Protein
ADAMTS-like protein 2
Gene
ADAMTSL2, KIAA0605
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

GO - Molecular functioni

  1. metalloendopeptidase activity Source: InterPro
  2. protein binding Source: BHF-UCL
  3. zinc ion binding Source: InterPro

GO - Biological processi

  1. negative regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_200626. O-glycosylation of TSR domain-containing proteins.
SignaLinkiQ86TH1.

Names & Taxonomyi

Protein namesi
Recommended name:
ADAMTS-like protein 2
Short name:
ADAMTSL-2
Gene namesi
Synonyms:KIAA0605
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 9

Organism-specific databases

HGNCiHGNC:14631. ADAMTSL2.

Subcellular locationi

Secreted Reviewed prediction

GO - Cellular componenti

  1. proteinaceous extracellular matrix Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Geleophysic dysplasia 1 (GPHYSD1) [MIM:231050]: An autosomal recessive disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501W → C in GPHYSD1. 1 Publication
VAR_066543
Natural varianti72 – 721R → Q in GPHYSD1. 1 Publication
VAR_066544
Natural varianti113 – 1131R → H in GPHYSD1; leads to the reduced secretion of the mutated protein. 1 Publication
VAR_054874
Natural varianti114 – 1141E → K in GPHYSD1. 2 Publications
VAR_054875
Natural varianti147 – 1471P → L in GPHYSD1; leads to the reduced secretion of the mutated protein. 1 Publication
VAR_054876
Natural varianti159 – 1591R → W in GPHYSD1. 1 Publication
VAR_066545
Natural varianti165 – 1651A → T in GPHYSD1. 1 Publication
VAR_066546
Natural varianti171 – 1711C → R in GPHYSD1. 1 Publication
VAR_066547
Natural varianti221 – 2211R → C in GPHYSD1. 1 Publication
VAR_066548
Natural varianti239 – 2391A → T in GPHYSD1. 1 Publication
VAR_066549
Natural varianti383 – 39210Missing in GPHYSD1.
VAR_066550
Natural varianti593 – 5931R → C in GPHYSD1. 1 Publication
VAR_066551
Natural varianti635 – 6351S → L in GPHYSD1. 1 Publication
VAR_066552
Natural varianti811 – 8111G → R in GPHYSD1; leads to the reduced secretion of the mutated protein. 1 Publication
VAR_054877
Natural varianti906 – 9061P → L in GPHYSD1. 1 Publication
VAR_066553

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

MIMi231050. phenotype.
Orphaneti2623. Geleophysic dysplasia.
PharmGKBiPA134920655.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222 Reviewed prediction
Add
BLAST
Chaini23 – 951929ADAMTS-like protein 2
PRO_0000249682Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi59 ↔ 100 By similarity
Disulfide bondi63 ↔ 105 By similarity
Disulfide bondi74 ↔ 90 By similarity
Glycosylationi87 – 871N-linked (GlcNAc...) Reviewed prediction
Glycosylationi367 – 3671N-linked (GlcNAc...) Reviewed prediction
Glycosylationi428 – 4281N-linked (GlcNAc...) (complex)1 Publication
Glycosylationi475 – 4751N-linked (GlcNAc...) Reviewed prediction
Glycosylationi511 – 5111N-linked (GlcNAc...) Reviewed prediction
Glycosylationi524 – 5241N-linked (GlcNAc...) Reviewed prediction
Glycosylationi533 – 5331N-linked (GlcNAc...) Reviewed prediction
Glycosylationi544 – 5441N-linked (GlcNAc...) Reviewed prediction
Glycosylationi731 – 7311N-linked (GlcNAc...) Reviewed prediction
Glycosylationi807 – 8071N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Glycosylated By similarity. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion By similarity.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ86TH1.
PRIDEiQ86TH1.

PTM databases

PhosphoSiteiQ86TH1.

Expressioni

Gene expression databases

ArrayExpressiQ86TH1.
BgeeiQ86TH1.
CleanExiHS_ADAMTSL2.
GenevestigatoriQ86TH1.

Organism-specific databases

HPAiHPA045634.

Interactioni

Subunit structurei

Interacts with LTBP1.1 Publication

Protein-protein interaction databases

BioGridi115068. 1 interaction.
IntActiQ86TH1. 2 interactions.
MINTiMINT-8417703.
STRINGi9606.ENSP00000346478.

Structurei

3D structure databases

ProteinModelPortaliQ86TH1.
SMRiQ86TH1. Positions 50-236.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini47 – 10660TSP type-1 1
Add
BLAST
Domaini564 – 61855TSP type-1 2
Add
BLAST
Domaini622 – 68665TSP type-1 3
Add
BLAST
Domaini688 – 73649TSP type-1 4
Add
BLAST
Domaini737 – 79559TSP type-1 5
Add
BLAST
Domaini797 – 85155TSP type-1 6
Add
BLAST
Domaini853 – 90856TSP type-1 7
Add
BLAST
Domaini912 – 95039PLAC
Add
BLAST

Sequence similaritiesi

Contains 1 PLAC domain.
Contains 7 TSP type-1 domains.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG299441.
HOGENOMiHOG000116076.
HOVERGENiHBG079685.
InParanoidiQ86TH1.
OrthoDBiEOG74N5FZ.
PhylomeDBiQ86TH1.
TreeFamiTF316874.

Family and domain databases

InterProiIPR010294. ADAM_spacer1.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR010909. PLAC.
IPR000884. Thrombospondin_1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF08686. PLAC. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view]
PRINTSiPR01857. ADAMTSFAMILY.
SMARTiSM00209. TSP1. 7 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 7 hits.
PROSITEiPS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q86TH1-1 [UniParc]FASTAAdd to Basket

« Hide

MDGRWQCSCW AWFLLVLAVV AGDTVSTGST DNSPTSNSLE GGTDATAFWW    50
GEWTKWTACS RSCGGGVTSQ ERHCLQQRRK SVPGPGNRTC TGTSKRYQLC 100
RVQECPPDGR SFREEQCVSF NSHVYNGRTH QWKPLYPDDY VHISSKPCDL 150
HCTTVDGQRQ LMVPARDGTS CKLTDLRGVC VSGKCEPIGC DGVLFSTHTL 200
DKCGICQGDG SSCTHVTGNY RKGNAHLGYS LVTHIPAGAR DIQIVERKKS 250
ADVLALADEA GYYFFNGNYK VDSPKNFNIA GTVVKYRRPM DVYETGIEYI 300
VAQGPTNQGL NVMVWNQNGK SPSITFEYTL LQPPHESRPQ PIYYGFSESA 350
ESQGLDGAGL MGFVPHNGSL YGQASSERLG LDNRLFGHPG LDMELGPSQG 400
QETNEVCEQA GGGACEGPPR GKGFRDRNVT GTPLTGDKDD EEVDTHFASQ 450
EFFSANAISD QLLGAGSDLK DFTLNETVNS IFAQGAPRSS LAESFFVDYE 500
ENEGAGPYLL NGSYLELSSD RVANSSSEAP FPNVSTSLLT SAGNRTHKAR 550
TRPKARKQGV SPADMYRWKL SSHEPCSATC TTGVMSAYAM CVRYDGVEVD 600
DSYCDALTRP EPVHEFCAGR ECQPRWETSS WSECSRTCGE GYQFRVVRCW 650
KMLSPGFDSS VYSDLCEAAE AVRPEERKTC RNPACGPQWE MSEWSECTAK 700
CGERSVVTRD IRCSEDEKLC DPNTRPVGEK NCTGPPCDRQ WTVSDWGPCS 750
GSCGQGRTIR HVYCKTSDGR VVPESQCQME TKPLAIHPCG DKNCPAHWLA 800
QDWERCNTTC GRGVKKRLVL CMELANGKPQ TRSGPECGLA KKPPEESTCF 850
ERPCFKWYTS PWSECTKTCG VGVRMRDVKC YQGTDIVRGC DPLVKPVGRQ 900
ACDLQPCPTE PPDDSCQDQP GTNCALAIKV NLCGHWYYSK ACCRSCRPPH 950
S 951
Length:951
Mass (Da):104,621
Last modified:June 1, 2003 - v1
Checksum:i93A9B0DC5BAB6CC7
GO

Sequence cautioni

The sequence BAA25531.2 differs from that shown. Reason: Erroneous initiation.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501W → C in GPHYSD1. 1 Publication
VAR_066543
Natural varianti72 – 721R → Q in GPHYSD1. 1 Publication
VAR_066544
Natural varianti113 – 1131R → H in GPHYSD1; leads to the reduced secretion of the mutated protein. 1 Publication
VAR_054874
Natural varianti114 – 1141E → K in GPHYSD1. 2 Publications
VAR_054875
Natural varianti147 – 1471P → L in GPHYSD1; leads to the reduced secretion of the mutated protein. 1 Publication
VAR_054876
Natural varianti159 – 1591R → W in GPHYSD1. 1 Publication
VAR_066545
Natural varianti165 – 1651A → T in GPHYSD1. 1 Publication
VAR_066546
Natural varianti171 – 1711C → R in GPHYSD1. 1 Publication
VAR_066547
Natural varianti221 – 2211R → C in GPHYSD1. 1 Publication
VAR_066548
Natural varianti239 – 2391A → T in GPHYSD1. 1 Publication
VAR_066549
Natural varianti364 – 3641V → I.1 Publication
Corresponds to variant rs35767802 [ dbSNP | Ensembl ].
VAR_046011
Natural varianti383 – 39210Missing in GPHYSD1.
VAR_066550
Natural varianti593 – 5931R → C in GPHYSD1. 1 Publication
VAR_066551
Natural varianti635 – 6351S → L in GPHYSD1. 1 Publication
VAR_066552
Natural varianti811 – 8111G → R in GPHYSD1; leads to the reduced secretion of the mutated protein. 1 Publication
VAR_054877
Natural varianti906 – 9061P → L in GPHYSD1. 1 Publication
VAR_066553

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti59 – 591C → F in BAA25531. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB011177 mRNA. Translation: BAA25531.2. Different initiation.
BX324209, BX629352, BX649571 Genomic DNA. Translation: CAI17317.1.
BX649571, BX324209, BX629352 Genomic DNA. Translation: CAI18773.1.
BX629352, BX324209, BX649571 Genomic DNA. Translation: CAI23592.1.
BC050544 mRNA. Translation: AAH50544.1.
CCDSiCCDS6976.1.
PIRiT00260.
RefSeqiNP_001138792.1. NM_001145320.1.
NP_055509.2. NM_014694.3.
XP_005272296.1. XM_005272239.1.
XP_006717400.1. XM_006717337.1.
UniGeneiHs.522543.

Genome annotation databases

EnsembliENST00000354484; ENSP00000346478; ENSG00000197859.
ENST00000393060; ENSP00000376780; ENSG00000197859.
GeneIDi9719.
KEGGihsa:9719.
UCSCiuc004cei.3. human.

Polymorphism databases

DMDMi74750384.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB011177 mRNA. Translation: BAA25531.2 . Different initiation.
BX324209 , BX629352 , BX649571 Genomic DNA. Translation: CAI17317.1 .
BX649571 , BX324209 , BX629352 Genomic DNA. Translation: CAI18773.1 .
BX629352 , BX324209 , BX649571 Genomic DNA. Translation: CAI23592.1 .
BC050544 mRNA. Translation: AAH50544.1 .
CCDSi CCDS6976.1.
PIRi T00260.
RefSeqi NP_001138792.1. NM_001145320.1.
NP_055509.2. NM_014694.3.
XP_005272296.1. XM_005272239.1.
XP_006717400.1. XM_006717337.1.
UniGenei Hs.522543.

3D structure databases

ProteinModelPortali Q86TH1.
SMRi Q86TH1. Positions 50-236.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 115068. 1 interaction.
IntActi Q86TH1. 2 interactions.
MINTi MINT-8417703.
STRINGi 9606.ENSP00000346478.

PTM databases

PhosphoSitei Q86TH1.

Polymorphism databases

DMDMi 74750384.

Proteomic databases

PaxDbi Q86TH1.
PRIDEi Q86TH1.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000354484 ; ENSP00000346478 ; ENSG00000197859 .
ENST00000393060 ; ENSP00000376780 ; ENSG00000197859 .
GeneIDi 9719.
KEGGi hsa:9719.
UCSCi uc004cei.3. human.

Organism-specific databases

CTDi 9719.
GeneCardsi GC09P136397.
GeneReviewsi ADAMTSL2.
H-InvDB HIX0170293.
HGNCi HGNC:14631. ADAMTSL2.
HPAi HPA045634.
MIMi 231050. phenotype.
612277. gene.
neXtProti NX_Q86TH1.
Orphaneti 2623. Geleophysic dysplasia.
PharmGKBi PA134920655.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG299441.
HOGENOMi HOG000116076.
HOVERGENi HBG079685.
InParanoidi Q86TH1.
OrthoDBi EOG74N5FZ.
PhylomeDBi Q86TH1.
TreeFami TF316874.

Enzyme and pathway databases

Reactomei REACT_200626. O-glycosylation of TSR domain-containing proteins.
SignaLinki Q86TH1.

Miscellaneous databases

ChiTaRSi ADAMTSL2. human.
GenomeRNAii 9719.
NextBioi 36549.
PROi Q86TH1.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q86TH1.
Bgeei Q86TH1.
CleanExi HS_ADAMTSL2.
Genevestigatori Q86TH1.

Family and domain databases

InterProi IPR010294. ADAM_spacer1.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR010909. PLAC.
IPR000884. Thrombospondin_1_rpt.
[Graphical view ]
Pfami PF05986. ADAM_spacer1. 1 hit.
PF08686. PLAC. 1 hit.
PF00090. TSP_1. 5 hits.
[Graphical view ]
PRINTSi PR01857. ADAMTSFAMILY.
SMARTi SM00209. TSP1. 7 hits.
[Graphical view ]
SUPFAMi SSF82895. SSF82895. 7 hits.
PROSITEi PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
    Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-364.
    Tissue: Brain.
  2. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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: PNS.
  4. Cited for: GLYCOSYLATION AT ASN-428.
  5. "ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation."
    Le Goff C., Morice-Picard F., Dagoneau N., Wang L.W., Perrot C., Crow Y.J., Bauer F., Flori E., Prost-Squarcioni C., Krakow D., Ge G., Greenspan D.S., Bonnet D., Le Merrer M., Munnich A., Apte S.S., Cormier-Daire V.
    Nat. Genet. 40:1119-1123(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS GPHYSD1 HIS-113; LYS-114; LEU-147 AND ARG-811, CHARACTERIZATION OF VARIANTS HIS-113; LEU-147 AND ARG-811, INTERACTION WITH LTBP1.
  6. Cited for: VARIANTS GPHYSD1 CYS-50; GLN-72; LYS-114; TRP-159; THR-165; ARG-171; CYS-221; THR-239; 383-ASN--ASP-392 DEL; CYS-593; LEU-635 AND LEU-906.

Entry informationi

Entry nameiATL2_HUMAN
AccessioniPrimary (citable) accession number: Q86TH1
Secondary accession number(s): B1B0D5, O60345
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: June 1, 2003
Last modified: September 3, 2014
This is version 95 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

Miscellaneous

There is a significant increase in total and active TGFB1 in the culture medium as well as nuclear localization of phosphorylated SMAD2 in fibroblasts from individuals with geleophysic dysplasia.

Caution

Although strongly similar to members of the ADAMTS family it lacks the metalloprotease and disintegrin-like domains which are typical of that family.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi