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Q96E52

- OMA1_HUMAN

UniProt

Q96E52 - OMA1_HUMAN

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Protein

Metalloendopeptidase OMA1, mitochondrial

Gene
OMA1, MPRP1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Metalloprotease that is part of the quality control system in the inner membrane of mitochondria. Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion. Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions.1 Publication

Cofactori

Binds 1 zinc ion per subunit Reviewed prediction.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi327 – 3271Zinc; catalytic By similarity
Active sitei328 – 3281 By similarity
Metal bindingi331 – 3311Zinc; catalytic Inferred
Metal bindingi392 – 3921Zinc; catalytic By similarity

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. metalloendopeptidase activity Source: UniProtKB

GO - Biological processi

  1. cristae formation Source: Ensembl
  2. diet induced thermogenesis Source: UniProtKB
  3. energy homeostasis Source: UniProtKB
  4. glucose metabolic process Source: UniProtKB
  5. lipid metabolic process Source: UniProtKB
  6. misfolded or incompletely synthesized protein catabolic process Source: UniProtKB
  7. mitochondrial protein processing Source: Ensembl
  8. negative regulation of mitochondrial fusion Source: UniProtKB
  9. response to stress Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiM48.017.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloendopeptidase OMA1, mitochondrial (EC:3.4.24.-)
Alternative name(s):
Metalloprotease-related protein 1
Short name:
MPRP-1
Overlapping with the m-AAA protease 1 homolog
Gene namesi
Name:OMA1
Synonyms:MPRP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:29661. OMA1.

Subcellular locationi

Mitochondrion inner membrane; Multi-pass membrane protein Inferred 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei196 – 21621Helical; Reviewed predictionAdd
BLAST
Transmembranei341 – 36121Helical; Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. mitochondrial inner membrane Source: UniProtKB-SubCell
  3. mitochondrial membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi331 – 3311H → A: Abolishes ability to cleave OPA1 at S1 position. 1 Publication

Organism-specific databases

PharmGKBiPA134911478.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 1313Mitochondrion Reviewed predictionAdd
BLAST
Chaini14 – 524511Metalloendopeptidase OMA1, mitochondrialPRO_0000302809Add
BLAST

Post-translational modificationi

In normal conditions, cleaved into an inactive 40 kDa form. Following CCCP treatment that induces loss of mitochondrial membrane potential, the 40 kDa form is reduced in favor of an active 60 kDa form.1 Publication

Proteomic databases

MaxQBiQ96E52.
PaxDbiQ96E52.
PRIDEiQ96E52.

PTM databases

PhosphoSiteiQ96E52.

Expressioni

Tissue specificityi

Widely expressed, with strong expression in the heart, skeletal muscle, kidney and liver.1 Publication

Gene expression databases

BgeeiQ96E52.
CleanExiHS_OMA1.
GenevestigatoriQ96E52.

Organism-specific databases

HPAiHPA055120.

Interactioni

Protein-protein interaction databases

IntActiQ96E52. 1 interaction.
STRINGi9606.ENSP00000360270.

Structurei

3D structure databases

ProteinModelPortaliQ96E52.
SMRiQ96E52. Positions 282-455.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M48 family.

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0501.
HOVERGENiHBG096685.
InParanoidiQ96E52.
OMAiKLSMKHF.
PhylomeDBiQ96E52.
TreeFamiTF329133.

Family and domain databases

InterProiIPR001915. Peptidase_M48.
[Graphical view]
PfamiPF01435. Peptidase_M48. 1 hit.
[Graphical view]
PROSITEiPS00142. ZINC_PROTEASE. 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: Q96E52-1) [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

MSFICGLQSA ARNHVFFRFN SLSNWRKCNT LASTSRGCHQ VQVNHIVNKY    50
QGLGVNQCDR WSFLPGNFHF YSTFNNKRTG GLSSTKSKEI WRITSKCTVW 100
NDAFSRQLLI KEVTAVPSLS VLHPLSPASI RAIRNFHTSP RFQAAPVPLL 150
LMILKPVQKL FAIIVGRGIR KWWQALPPNK KEVVKENIRK NKWKLFLGLS 200
SFGLLFVVFY FTHLEVSPIT GRSKLLLLGK EQFRLLSELE YEAWMEEFKN 250
DMLTEKDARY LAVKEVLCHL IECNKDVPGI SQINWVIHVV DSPIINAFVL 300
PNGQMFVFTG FLNSVTDIHQ LSFLLGHEIA HAVLGHAAEK AGMVHLLDFL 350
GMIFLTMIWA ICPRDSLALL CQWIQSKLQE YMFNRPYSRK LEAEADKIGL 400
LLAAKACADI RASSVFWQQM EFVDSLHGQP KMPEWLSTHP SHGNRVEYLD 450
RLIPQALKIR EMCNCPPLSN PDPRLLFKLS TKHFLEESEK EDLNITKKQK 500
MDTLPIQKQE QIPLTYIVEK RTGS 524
Length:524
Mass (Da):60,120
Last modified:December 1, 2001 - v1
Checksum:iF8F9B37489B0EFF1
GO
Isoform 2 (identifier: Q96E52-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     456-524: ALKIREMCNC...TYIVEKRTGS → LVREEKFIEQPEQIAELTLNSFIQNTEICRS

Note: No experimental confirmation available.

Show »
Length:486
Mass (Da):55,744
Checksum:iF2D48060E2D25826
GO

Sequence cautioni

The sequence BAC03583.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
The sequence CAI13522.1 differs from that shown. Reason: Erroneous gene model prediction.
The sequence CAI13523.1 differs from that shown. Reason: Erroneous gene model prediction.
The sequence CAI13524.1 differs from that shown. Reason: Erroneous gene model prediction.
The sequence CAI13525.1 differs from that shown. Reason: Erroneous gene model prediction.
The sequence CAI13526.1 differs from that shown. Reason: Erroneous gene model prediction.
The sequence CAI22238.1 differs from that shown. Reason: Erroneous gene model prediction.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti67 – 671N → K.
Corresponds to variant rs34466938 [ dbSNP | Ensembl ].
VAR_034958
Natural varianti69 – 691H → Y in a patient with amyotrophic lateral sclerosis. 1 Publication
Corresponds to variant rs75220198 [ dbSNP | Ensembl ].
VAR_065755
Natural varianti117 – 1171P → L.1 Publication
Corresponds to variant rs17117720 [ dbSNP | Ensembl ].
VAR_034959
Natural varianti211 – 2111F → C.
Corresponds to variant rs17117699 [ dbSNP | Ensembl ].
VAR_034960
Natural varianti226 – 2261L → V in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035708
Natural varianti272 – 2721E → G in a patient with amyotrophic lateral sclerosis. 1 Publication
VAR_065756
Natural varianti329 – 3291I → L.1 Publication
Corresponds to variant rs17117678 [ dbSNP | Ensembl ].
VAR_034961
Natural varianti365 – 3651D → Y.1 Publication
Corresponds to variant rs77980955 [ dbSNP | Ensembl ].
VAR_065757

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei456 – 52469ALKIR…KRTGS → LVREEKFIEQPEQIAELTLN SFIQNTEICRS in isoform 2. VSP_027958Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB048348 mRNA. Translation: BAC79381.1.
AL365187 Genomic DNA. Translation: CAI13522.1. Sequence problems.
AL365187 Genomic DNA. Translation: CAI13523.1. Sequence problems.
AL365187 Genomic DNA. Translation: CAI13524.1. Sequence problems.
AL365187 Genomic DNA. Translation: CAI13525.1. Sequence problems.
AL365187, AL109845 Genomic DNA. Translation: CAI13526.1. Sequence problems.
AL109845, AL365187 Genomic DNA. Translation: CAI22238.1. Sequence problems.
AL365187, AL109845 Genomic DNA. Translation: CAI13527.1.
AL109845, AL365187 Genomic DNA. Translation: CAI22239.1.
CH471059 Genomic DNA. Translation: EAX06631.1.
CH471059 Genomic DNA. Translation: EAX06632.1.
CH471059 Genomic DNA. Translation: EAX06633.1.
BC012915 mRNA. Translation: AAH12915.1.
AK091101 mRNA. Translation: BAC03583.1. Different initiation.
CCDSiCCDS608.1. [Q96E52-1]
RefSeqiNP_660286.1. NM_145243.3. [Q96E52-1]
UniGeneiHs.425769.

Genome annotation databases

EnsembliENST00000358603; ENSP00000351417; ENSG00000162600. [Q96E52-2]
ENST00000371226; ENSP00000360270; ENSG00000162600. [Q96E52-1]
GeneIDi115209.
KEGGihsa:115209.
UCSCiuc001cyx.1. human. [Q96E52-2]
uc001cyy.3. human. [Q96E52-1]

Polymorphism databases

DMDMi74751828.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB048348 mRNA. Translation: BAC79381.1 .
AL365187 Genomic DNA. Translation: CAI13522.1 . Sequence problems.
AL365187 Genomic DNA. Translation: CAI13523.1 . Sequence problems.
AL365187 Genomic DNA. Translation: CAI13524.1 . Sequence problems.
AL365187 Genomic DNA. Translation: CAI13525.1 . Sequence problems.
AL365187 , AL109845 Genomic DNA. Translation: CAI13526.1 . Sequence problems.
AL109845 , AL365187 Genomic DNA. Translation: CAI22238.1 . Sequence problems.
AL365187 , AL109845 Genomic DNA. Translation: CAI13527.1 .
AL109845 , AL365187 Genomic DNA. Translation: CAI22239.1 .
CH471059 Genomic DNA. Translation: EAX06631.1 .
CH471059 Genomic DNA. Translation: EAX06632.1 .
CH471059 Genomic DNA. Translation: EAX06633.1 .
BC012915 mRNA. Translation: AAH12915.1 .
AK091101 mRNA. Translation: BAC03583.1 . Different initiation.
CCDSi CCDS608.1. [Q96E52-1 ]
RefSeqi NP_660286.1. NM_145243.3. [Q96E52-1 ]
UniGenei Hs.425769.

3D structure databases

ProteinModelPortali Q96E52.
SMRi Q96E52. Positions 282-455.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q96E52. 1 interaction.
STRINGi 9606.ENSP00000360270.

Protein family/group databases

MEROPSi M48.017.

PTM databases

PhosphoSitei Q96E52.

Polymorphism databases

DMDMi 74751828.

Proteomic databases

MaxQBi Q96E52.
PaxDbi Q96E52.
PRIDEi Q96E52.

Protocols and materials databases

DNASUi 115209.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000358603 ; ENSP00000351417 ; ENSG00000162600 . [Q96E52-2 ]
ENST00000371226 ; ENSP00000360270 ; ENSG00000162600 . [Q96E52-1 ]
GeneIDi 115209.
KEGGi hsa:115209.
UCSCi uc001cyx.1. human. [Q96E52-2 ]
uc001cyy.3. human. [Q96E52-1 ]

Organism-specific databases

CTDi 115209.
GeneCardsi GC01M058881.
H-InvDB HIX0077405.
HGNCi HGNC:29661. OMA1.
HPAi HPA055120.
neXtProti NX_Q96E52.
PharmGKBi PA134911478.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0501.
HOVERGENi HBG096685.
InParanoidi Q96E52.
OMAi KLSMKHF.
PhylomeDBi Q96E52.
TreeFami TF329133.

Miscellaneous databases

GenomeRNAii 115209.
NextBioi 79540.
PROi Q96E52.

Gene expression databases

Bgeei Q96E52.
CleanExi HS_OMA1.
Genevestigatori Q96E52.

Family and domain databases

InterProi IPR001915. Peptidase_M48.
[Graphical view ]
Pfami PF01435. Peptidase_M48. 1 hit.
[Graphical view ]
PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a human cDNA sequence which encodes a novel membrane-associated protein containing a zinc metalloprotease motif."
    Bao Y.-C., Tsuruga H., Hirai M., Yasuda K., Yokoi N., Kitamura T., Kumagai H.
    DNA Res. 10:123-128(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] (ISOFORM 1).
    Tissue: Liver.
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 160-524 (ISOFORM 2).
    Tissue: Substantia nigra.
  6. "Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells."
    Head B., Griparic L., Amiri M., Gandre-Babbe S., van der Bliek A.M.
    J. Cell Biol. 187:959-966(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, MUTAGENESIS OF HIS-331.
  7. Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-226.
  8. "Resequencing of 29 candidate genes in patients with familial and sporadic amyotrophic lateral sclerosis."
    Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D., Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A., Rouleau G.A.
    Arch. Neurol. 68:587-593(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TYR-69; LEU-117; GLY-272; LEU-329 AND TYR-365.

Entry informationi

Entry nameiOMA1_HUMAN
AccessioniPrimary (citable) accession number: Q96E52
Secondary accession number(s): D3DQ54
, Q5T3G6, Q5T3G7, Q5T3G8, Q5T3G9, Q5T3H0, Q8NBB3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 108 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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