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P43003

- EAA1_HUMAN

UniProt

P43003 - EAA1_HUMAN

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Protein

Excitatory amino acid transporter 1

Gene

SLC1A3

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

Functioni

Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.

GO - Molecular functioni

  1. glutamate binding Source: Ensembl
  2. high-affinity glutamate transmembrane transporter activity Source: Ensembl
  3. L-glutamate transmembrane transporter activity Source: BHF-UCL
  4. sodium:dicarboxylate symporter activity Source: InterPro

GO - Biological processi

  1. auditory behavior Source: Ensembl
  2. cell morphogenesis involved in neuron differentiation Source: Ensembl
  3. cranial nerve development Source: Ensembl
  4. D-aspartate import Source: UniProtKB
  5. gamma-aminobutyric acid biosynthetic process Source: Ensembl
  6. glutamate biosynthetic process Source: Ensembl
  7. ion transport Source: Reactome
  8. L-glutamate import Source: UniProtKB
  9. neuromuscular process controlling balance Source: Ensembl
  10. neurotransmitter uptake Source: ProtInc
  11. positive regulation of synaptic transmission Source: Ensembl
  12. response to antibiotic Source: Ensembl
  13. response to drug Source: Ensembl
  14. response to light stimulus Source: Ensembl
  15. response to wounding Source: Ensembl
  16. sensory perception of sound Source: Ensembl
  17. synaptic transmission Source: ProtInc
  18. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Symport, Transport

Enzyme and pathway databases

ReactomeiREACT_13639. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
REACT_19397. Transport of inorganic cations/anions and amino acids/oligopeptides.

Protein family/group databases

TCDBi2.A.23.2.6. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Excitatory amino acid transporter 1
Alternative name(s):
Sodium-dependent glutamate/aspartate transporter 1
Short name:
GLAST-1
Solute carrier family 1 member 3
Gene namesi
Name:SLC1A3
Synonyms:EAAT1, GLAST, GLAST1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:10941. SLC1A3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4747CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei48 – 6821HelicalSequence AnalysisAdd
BLAST
Transmembranei91 – 11121HelicalSequence AnalysisAdd
BLAST
Transmembranei123 – 14523HelicalSequence AnalysisAdd
BLAST
Topological domaini146 – 23792ExtracellularSequence AnalysisAdd
BLAST
Transmembranei238 – 26023HelicalSequence AnalysisAdd
BLAST
Transmembranei281 – 30222HelicalSequence AnalysisAdd
BLAST
Transmembranei319 – 34022HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell projection Source: Ensembl
  2. cell surface Source: Ensembl
  3. fibril Source: Ensembl
  4. integral component of membrane Source: UniProtKB-KW
  5. membrane Source: ProtInc
  6. neuronal cell body Source: Ensembl
  7. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Episodic ataxia 6 (EA6) [MIM:612656]: A disorder characterized by episodic ataxia, seizures, migraine and alternating hemiplegia.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti290 – 2901P → R in EA6. 1 Publication
VAR_031733

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi612656. phenotype.
Orphaneti2131. Alternating hemiplegia of childhood.
209967. Episodic ataxia type 6.
PharmGKBiPA35828.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 542542Excitatory amino acid transporter 1PRO_0000202057Add
BLAST

Post-translational modificationi

Glycosylated.

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP43003.
PaxDbiP43003.
PRIDEiP43003.

PTM databases

PhosphoSiteiP43003.

Expressioni

Tissue specificityi

Highly expressed in cerebellum, but also found in frontal cortex, hippocampus and basal ganglia.

Gene expression databases

BgeeiP43003.
CleanExiHS_SLC1A3.
ExpressionAtlasiP43003. baseline and differential.
GenevestigatoriP43003.

Organism-specific databases

HPAiCAB002573.
HPA037467.
HPA037468.

Interactioni

Protein-protein interaction databases

BioGridi112398. 2 interactions.
IntActiP43003. 1 interaction.
MINTiMINT-5004226.
STRINGi9606.ENSP00000265113.

Structurei

3D structure databases

ProteinModelPortaliP43003.
SMRiP43003. Positions 55-494.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1301.
GeneTreeiENSGT00760000119117.
HOGENOMiHOG000208776.
HOVERGENiHBG000080.
InParanoidiP43003.
KOiK05614.
OMAiTLRPYRM.
OrthoDBiEOG7RV9G2.
PhylomeDBiP43003.
TreeFamiTF315206.

Family and domain databases

Gene3Di1.10.3860.10. 2 hits.
InterProiIPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view]
PANTHERiPTHR11958. PTHR11958. 1 hit.
PfamiPF00375. SDF. 1 hit.
[Graphical view]
PRINTSiPR00173. EDTRNSPORT.
SUPFAMiSSF118215. SSF118215. 2 hits.
PROSITEiPS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P43003-1) [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
MTKSNGEEPK MGGRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF
60 70 80 90 100
VLLTVTAVIV GTILGFTLRP YRMSYREVKY FSFPGELLMR MLQMLVLPLI
110 120 130 140 150
ISSLVTGMAA LDSKASGKMG MRAVVYYMTT TIIAVVIGII IVIIIHPGKG
160 170 180 190 200
TKENMHREGK IVRVTAADAF LDLIRNMFPP NLVEACFKQF KTNYEKRSFK
210 220 230 240 250
VPIQANETLV GAVINNVSEA METLTRITEE LVPVPGSVNG VNALGLVVFS
260 270 280 290 300
MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP VGILFLIAGK
310 320 330 340 350
IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG
360 370 380 390 400
GLLQALITAL GTSSSSATLP ITFKCLEENN GVDKRVTRFV LPVGATINMD
410 420 430 440 450
GTALYEALAA IFIAQVNNFE LNFGQIITIS ITATAASIGA AGIPQAGLVT
460 470 480 490 500
MVIVLTSVGL PTDDITLIIA VDWFLDRLRT TTNVLGDSLG AGIVEHLSRH
510 520 530 540
ELKNRDVEMG NSVIEENEMK KPYQLIAQDN ETEKPIDSET KM
Length:542
Mass (Da):59,572
Last modified:November 1, 1995 - v1
Checksum:i6E9F62D35A3A5A29
GO
Isoform 2 (identifier: P43003-2) [UniParc]FASTAAdd to Basket

Also known as: EAAT1ex9skip

The sequence of this isoform differs from the canonical sequence as follows:
     430-475: SITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFL → R

Note: Expressed throughout the CNS, both in gray matter and axonal tracts, at levels ranging between 10% and 20% of isoform 1. Localizes to ER, has no functional glutamate uptake activity, and exerts a dominant negative effect isoform 1.

Show »
Length:497
Mass (Da):55,149
Checksum:i7C21EC2B467E1C11
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti366 – 3661S → CT(PubMed:8218410)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti219 – 2191E → D.
Corresponds to variant rs2032892 [ dbSNP | Ensembl ].
VAR_011877
Natural varianti290 – 2901P → R in EA6. 1 Publication
VAR_031733

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei430 – 47546SITAT…VDWFL → R in isoform 2. 1 PublicationVSP_043913Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19158 mRNA. No translation available.
U03504 mRNA. Translation: AAA50428.1.
D26443 mRNA. Translation: BAA05462.1.
Z31713
, Z31703, Z31704, Z31705, Z31706, Z31707, Z31708, Z31709, Z31710 Genomic DNA. Translation: CAA83507.1.
AY954110 mRNA. Translation: AAY28724.1.
AK312304 mRNA. Translation: BAG35230.1.
AC008957 Genomic DNA. No translation available.
AC010631 Genomic DNA. No translation available.
CH471119 Genomic DNA. Translation: EAW55945.1.
CCDSiCCDS3919.1. [P43003-1]
CCDS54844.1. [P43003-2]
PIRiS38353.
RefSeqiNP_001160167.1. NM_001166695.2. [P43003-2]
NP_001276869.1. NM_001289940.1.
NP_004163.3. NM_004172.4. [P43003-1]
XP_005248399.1. XM_005248342.1. [P43003-1]
XP_006714551.1. XM_006714488.1. [P43003-1]
UniGeneiHs.481918.

Genome annotation databases

EnsembliENST00000265113; ENSP00000265113; ENSG00000079215. [P43003-1]
ENST00000381918; ENSP00000371343; ENSG00000079215. [P43003-2]
GeneIDi6507.
KEGGihsa:6507.
UCSCiuc003jkj.4. human. [P43003-1]
uc010iuy.3. human. [P43003-2]

Polymorphism databases

DMDMi1169458.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19158 mRNA. No translation available.
U03504 mRNA. Translation: AAA50428.1 .
D26443 mRNA. Translation: BAA05462.1 .
Z31713
, Z31703 , Z31704 , Z31705 , Z31706 , Z31707 , Z31708 , Z31709 , Z31710 Genomic DNA. Translation: CAA83507.1 .
AY954110 mRNA. Translation: AAY28724.1 .
AK312304 mRNA. Translation: BAG35230.1 .
AC008957 Genomic DNA. No translation available.
AC010631 Genomic DNA. No translation available.
CH471119 Genomic DNA. Translation: EAW55945.1 .
CCDSi CCDS3919.1. [P43003-1 ]
CCDS54844.1. [P43003-2 ]
PIRi S38353.
RefSeqi NP_001160167.1. NM_001166695.2. [P43003-2 ]
NP_001276869.1. NM_001289940.1.
NP_004163.3. NM_004172.4. [P43003-1 ]
XP_005248399.1. XM_005248342.1. [P43003-1 ]
XP_006714551.1. XM_006714488.1. [P43003-1 ]
UniGenei Hs.481918.

3D structure databases

ProteinModelPortali P43003.
SMRi P43003. Positions 55-494.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112398. 2 interactions.
IntActi P43003. 1 interaction.
MINTi MINT-5004226.
STRINGi 9606.ENSP00000265113.

Chemistry

BindingDBi P43003.
ChEMBLi CHEMBL3085.
GuidetoPHARMACOLOGYi 868.

Protein family/group databases

TCDBi 2.A.23.2.6. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

PTM databases

PhosphoSitei P43003.

Polymorphism databases

DMDMi 1169458.

Proteomic databases

MaxQBi P43003.
PaxDbi P43003.
PRIDEi P43003.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000265113 ; ENSP00000265113 ; ENSG00000079215 . [P43003-1 ]
ENST00000381918 ; ENSP00000371343 ; ENSG00000079215 . [P43003-2 ]
GeneIDi 6507.
KEGGi hsa:6507.
UCSCi uc003jkj.4. human. [P43003-1 ]
uc010iuy.3. human. [P43003-2 ]

Organism-specific databases

CTDi 6507.
GeneCardsi GC05P036606.
HGNCi HGNC:10941. SLC1A3.
HPAi CAB002573.
HPA037467.
HPA037468.
MIMi 600111. gene.
612656. phenotype.
neXtProti NX_P43003.
Orphaneti 2131. Alternating hemiplegia of childhood.
209967. Episodic ataxia type 6.
PharmGKBi PA35828.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1301.
GeneTreei ENSGT00760000119117.
HOGENOMi HOG000208776.
HOVERGENi HBG000080.
InParanoidi P43003.
KOi K05614.
OMAi TLRPYRM.
OrthoDBi EOG7RV9G2.
PhylomeDBi P43003.
TreeFami TF315206.

Enzyme and pathway databases

Reactomei REACT_13639. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
REACT_19397. Transport of inorganic cations/anions and amino acids/oligopeptides.

Miscellaneous databases

ChiTaRSi SLC1A3. human.
GeneWikii Glutamate_aspartate_transporter.
GenomeRNAii 6507.
NextBioi 25301.
PROi P43003.
SOURCEi Search...

Gene expression databases

Bgeei P43003.
CleanExi HS_SLC1A3.
ExpressionAtlasi P43003. baseline and differential.
Genevestigatori P43003.

Family and domain databases

Gene3Di 1.10.3860.10. 2 hits.
InterProi IPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view ]
PANTHERi PTHR11958. PTHR11958. 1 hit.
Pfami PF00375. SDF. 1 hit.
[Graphical view ]
PRINTSi PR00173. EDTRNSPORT.
SUPFAMi SSF118215. SSF118215. 2 hits.
PROSITEi PS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of a glutamate transporter cDNA from human cerebellum."
    Shashidharan P., Plaitakis A.
    Biochim. Biophys. Acta 1216:161-164(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Cerebellum.
  2. "Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex."
    Arriza J.L., Fairman W.A., Wendy A., Wadiche J.I., Murdoch G.H., Kavanaugh M.P., Amara S.G.
    J. Neurosci. 14:5559-5569(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain cortex.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  4. "Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12."
    Stoffel W., Sasse J., Dueker M., Mueller R., Hofmann K.O., Fink T., Lichter P.
    FEBS Lett. 386:189-193(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake."
    Vallejo-Illarramendi A., Domercq M., Matute C.
    J. Neurochem. 95:341-348(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  6. "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] (ISOFORM 1).
    Tissue: Cerebellum.
  7. "The DNA sequence and comparative analysis of human chromosome 5."
    Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
    , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
    Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. "Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures."
    Jen J.C., Wan J., Palos T.P., Howard B.D., Baloh R.W.
    Neurology 65:529-534(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT EA6 ARG-290.

Entry informationi

Entry nameiEAA1_HUMAN
AccessioniPrimary (citable) accession number: P43003
Secondary accession number(s): B2R5T3, Q4JCQ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: October 29, 2014
This is version 137 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 5
    Human chromosome 5: 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