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Q8N335

- GPD1L_HUMAN

UniProt

Q8N335 - GPD1L_HUMAN

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Protein
Glycerol-3-phosphate dehydrogenase 1-like protein
Gene
GPD1L, KIAA0089
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium current; cardiac sodium current may also be reduced due to alterations of NAD(H) balance induced by DPD1L.2 Publications

Catalytic activityi

sn-glycerol 3-phosphate + NAD+ = glycerone phosphate + NADH.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei43 – 431NAD By similarity
Binding sitei99 – 991NAD By similarity
Binding sitei122 – 1221Substrate By similarity
Binding sitei155 – 1551NAD; via amide nitrogen
Active sitei206 – 2061Proton acceptor
Binding sitei271 – 2711NAD By similarity
Binding sitei298 – 2981NAD; via amide nitrogen
Binding sitei300 – 3001NAD By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi12 – 176NAD

GO - Molecular functioni

  1. NAD binding Source: InterPro
  2. glycerol-3-phosphate dehydrogenase [NAD+] activity Source: UniProtKB-EC
  3. ion channel binding Source: BHF-UCL
  4. sodium channel regulator activity Source: BHF-UCL

GO - Biological processi

  1. NAD metabolic process Source: BHF-UCL
  2. NADH metabolic process Source: Ensembl
  3. carbohydrate metabolic process Source: InterPro
  4. cellular lipid metabolic process Source: Reactome
  5. glycerol-3-phosphate catabolic process Source: InterPro
  6. glycerophospholipid biosynthetic process Source: Reactome
  7. negative regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  8. negative regulation of protein kinase C signaling Source: BHF-UCL
  9. phosphatidic acid biosynthetic process Source: Reactome
  10. phospholipid metabolic process Source: Reactome
  11. positive regulation of protein localization to cell surface Source: BHF-UCL
  12. positive regulation of sodium ion transport Source: BHF-UCL
  13. regulation of heart rate Source: BHF-UCL
  14. regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
  15. regulation of ventricular cardiac muscle cell membrane depolarization Source: BHF-UCL
  16. small molecule metabolic process Source: Reactome
  17. triglyceride biosynthetic process Source: Reactome
  18. ventricular cardiac muscle cell action potential Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD

Enzyme and pathway databases

ReactomeiREACT_1190. Triglyceride Biosynthesis.
REACT_120906. Synthesis of PA.

Names & Taxonomyi

Protein namesi
Recommended name:
Glycerol-3-phosphate dehydrogenase 1-like protein (EC:1.1.1.8)
Short name:
GPD1-L
Gene namesi
Name:GPD1L
Synonyms:KIAA0089
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:28956. GPD1L.

Subcellular locationi

Cytoplasm
Note: Localized to the region of the plasma membrane.1 Publication

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. extracellular vesicular exosome Source: UniProt
  3. glycerol-3-phosphate dehydrogenase complex Source: InterPro
  4. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Brugada syndrome 2 (BRGDA2) [MIM:611777]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti280 – 2801A → V in BRGDA2; decreased enzymatic activity; affects SCN5A membrane expression; reduction of sodium current when coexpressed with SCN5A in HEK cells. 3 Publications
VAR_044047
Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti83 – 831E → K in SIDS; decreased enzymatic activity and significant reduction of sodium current when coexpressed with SCN5A in HEK cells. 2 Publications
VAR_044044
Natural varianti124 – 1241I → V in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. 1 Publication
Corresponds to variant rs72552293 [ dbSNP | Ensembl ].
VAR_044045
Natural varianti273 – 2731R → C in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. 1 Publication
VAR_044046

Keywords - Diseasei

Brugada syndrome, Disease mutation

Organism-specific databases

MIMi272120. phenotype.
611777. phenotype.
Orphaneti130. Brugada syndrome.
PharmGKBiPA134986345.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 351351Glycerol-3-phosphate dehydrogenase 1-like protein
PRO_0000286511Add
BLAST

Proteomic databases

MaxQBiQ8N335.
PaxDbiQ8N335.
PeptideAtlasiQ8N335.
PRIDEiQ8N335.

PTM databases

PhosphoSiteiQ8N335.

Expressioni

Tissue specificityi

Most highly expressed in heart tissue, with lower levels in the skeletal muscle, kidney, lung and other organs.1 Publication

Gene expression databases

ArrayExpressiQ8N335.
BgeeiQ8N335.
CleanExiHS_GPD1L.
GenevestigatoriQ8N335.

Organism-specific databases

HPAiHPA035284.

Interactioni

Subunit structurei

Interacts with SCN5A.1 Publication

Protein-protein interaction databases

BioGridi116783. 3 interactions.
STRINGi9606.ENSP00000282541.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi8 – 114
Helixi15 – 2814
Beta strandi38 – 414
Helixi52 – 598
Turni63 – 653
Beta strandi75 – 795
Helixi81 – 855
Beta strandi89 – 935
Helixi97 – 993
Helixi100 – 1078
Beta strandi116 – 1194
Beta strandi124 – 1274
Beta strandi130 – 1334
Helixi134 – 1429
Beta strandi144 – 1529
Helixi155 – 1595
Beta strandi164 – 1696
Helixi173 – 18311
Beta strandi188 – 1947
Helixi196 – 21823
Helixi223 – 24422
Beta strandi245 – 2473
Helixi251 – 2544
Turni257 – 2593
Helixi260 – 26910
Helixi271 – 28212
Helixi286 – 2949
Helixi301 – 31515
Helixi318 – 3203
Helixi322 – 33211
Helixi339 – 3457

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2PLAX-ray2.51A/B1-349[»]
ProteinModelPortaliQ8N335.
SMRiQ8N335. Positions 4-346.

Miscellaneous databases

EvolutionaryTraceiQ8N335.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni271 – 2722Substrate binding

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0240.
HOGENOMiHOG000246855.
HOVERGENiHBG003669.
InParanoidiQ8N335.
KOiK00006.
OMAiKIFCKGQ.
PhylomeDBiQ8N335.
TreeFamiTF300836.

Family and domain databases

Gene3Di1.10.1040.10. 1 hit.
3.40.50.720. 1 hit.
InterProiIPR008927. 6-PGluconate_DH_C-like.
IPR013328. DH_multihelical.
IPR006168. G3P_DH_NAD-dep.
IPR006109. G3P_DH_NAD-dep_C.
IPR017751. G3P_DH_NAD-dep_euk.
IPR011128. G3P_DH_NAD-dep_N.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR11728. PTHR11728. 1 hit.
PfamiPF07479. NAD_Gly3P_dh_C. 1 hit.
PF01210. NAD_Gly3P_dh_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000114. Glycerol-3-P_dh. 1 hit.
PRINTSiPR00077. GPDHDRGNASE.
SUPFAMiSSF48179. SSF48179. 1 hit.
TIGRFAMsiTIGR03376. glycerol3P_DH. 1 hit.

Sequencei

Sequence statusi: Complete.

Q8N335-1 [UniParc]FASTAAdd to Basket

« Hide

MAAAPLKVCI VGSGNWGSAV AKIIGNNVKK LQKFASTVKM WVFEETVNGR    50
KLTDIINNDH ENVKYLPGHK LPENVVAMSN LSEAVQDADL LVFVIPHQFI 100
HRICDEITGR VPKKALGITL IKGIDEGPEG LKLISDIIRE KMGIDISVLM 150
GANIANEVAA EKFCETTIGS KVMENGLLFK ELLQTPNFRI TVVDDADTVE 200
LCGALKNIVA VGAGFCDGLR CGDNTKAAVI RLGLMEMIAF ARIFCKGQVS 250
TATFLESCGV ADLITTCYGG RNRRVAEAFA RTGKTIEELE KEMLNGQKLQ 300
GPQTSAEVYR ILKQKGLLDK FPLFTAVYQI CYESRPVQEM LSCLQSHPEH 350
T 351
Length:351
Mass (Da):38,419
Last modified:October 1, 2002 - v1
Checksum:i74C3B27EEB41DE89
GO

Sequence cautioni

The sequence BAA07648.1 differs from that shown. Reason: Erroneous initiation.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti83 – 831E → K in SIDS; decreased enzymatic activity and significant reduction of sodium current when coexpressed with SCN5A in HEK cells. 2 Publications
VAR_044044
Natural varianti124 – 1241I → V in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. 1 Publication
Corresponds to variant rs72552293 [ dbSNP | Ensembl ].
VAR_044045
Natural varianti178 – 1781L → F.
Corresponds to variant rs35447795 [ dbSNP | Ensembl ].
VAR_032114
Natural varianti273 – 2731R → C in SIDS; significant reduction of sodium current when coexpressed with SCN5A in HEK cells. 1 Publication
VAR_044046
Natural varianti280 – 2801A → V in BRGDA2; decreased enzymatic activity; affects SCN5A membrane expression; reduction of sodium current when coexpressed with SCN5A in HEK cells. 3 Publications
VAR_044047

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D42047 mRNA. Translation: BAA07648.1. Different initiation.
AK292808 mRNA. Translation: BAF85497.1.
CH471055 Genomic DNA. Translation: EAW64422.1.
BC006168 mRNA. Translation: AAH06168.1.
BC028726 mRNA. Translation: AAH28726.1.
CCDSiCCDS33729.1.
RefSeqiNP_055956.1. NM_015141.3.
UniGeneiHs.82432.

Genome annotation databases

EnsembliENST00000282541; ENSP00000282541; ENSG00000152642.
GeneIDi23171.
KEGGihsa:23171.
UCSCiuc003cew.3. human.

Polymorphism databases

DMDMi74750945.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D42047 mRNA. Translation: BAA07648.1 . Different initiation.
AK292808 mRNA. Translation: BAF85497.1 .
CH471055 Genomic DNA. Translation: EAW64422.1 .
BC006168 mRNA. Translation: AAH06168.1 .
BC028726 mRNA. Translation: AAH28726.1 .
CCDSi CCDS33729.1.
RefSeqi NP_055956.1. NM_015141.3.
UniGenei Hs.82432.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2PLA X-ray 2.51 A/B 1-349 [» ]
ProteinModelPortali Q8N335.
SMRi Q8N335. Positions 4-346.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116783. 3 interactions.
STRINGi 9606.ENSP00000282541.

PTM databases

PhosphoSitei Q8N335.

Polymorphism databases

DMDMi 74750945.

Proteomic databases

MaxQBi Q8N335.
PaxDbi Q8N335.
PeptideAtlasi Q8N335.
PRIDEi Q8N335.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000282541 ; ENSP00000282541 ; ENSG00000152642 .
GeneIDi 23171.
KEGGi hsa:23171.
UCSCi uc003cew.3. human.

Organism-specific databases

CTDi 23171.
GeneCardsi GC03P032123.
GeneReviewsi GPD1L.
HGNCi HGNC:28956. GPD1L.
HPAi HPA035284.
MIMi 272120. phenotype.
611777. phenotype.
611778. gene.
neXtProti NX_Q8N335.
Orphaneti 130. Brugada syndrome.
PharmGKBi PA134986345.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0240.
HOGENOMi HOG000246855.
HOVERGENi HBG003669.
InParanoidi Q8N335.
KOi K00006.
OMAi KIFCKGQ.
PhylomeDBi Q8N335.
TreeFami TF300836.

Enzyme and pathway databases

Reactomei REACT_1190. Triglyceride Biosynthesis.
REACT_120906. Synthesis of PA.

Miscellaneous databases

ChiTaRSi GPD1L. human.
EvolutionaryTracei Q8N335.
GenomeRNAii 23171.
NextBioi 44579.
PROi Q8N335.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8N335.
Bgeei Q8N335.
CleanExi HS_GPD1L.
Genevestigatori Q8N335.

Family and domain databases

Gene3Di 1.10.1040.10. 1 hit.
3.40.50.720. 1 hit.
InterProi IPR008927. 6-PGluconate_DH_C-like.
IPR013328. DH_multihelical.
IPR006168. G3P_DH_NAD-dep.
IPR006109. G3P_DH_NAD-dep_C.
IPR017751. G3P_DH_NAD-dep_euk.
IPR011128. G3P_DH_NAD-dep_N.
IPR016040. NAD(P)-bd_dom.
[Graphical view ]
PANTHERi PTHR11728. PTHR11728. 1 hit.
Pfami PF07479. NAD_Gly3P_dh_C. 1 hit.
PF01210. NAD_Gly3P_dh_N. 1 hit.
[Graphical view ]
PIRSFi PIRSF000114. Glycerol-3-P_dh. 1 hit.
PRINTSi PR00077. GPDHDRGNASE.
SUPFAMi SSF48179. SSF48179. 1 hit.
TIGRFAMsi TIGR03376. glycerol3P_DH. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1."
    Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.
    DNA Res. 2:37-43(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Bone marrow.
  2. "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].
  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].
    Tissue: Brain and Placenta.
  5. "GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A."
    Valdivia C.R., Ueda K., Ackerman M.J., Makielski J.C.
    Am. J. Physiol. 297:H1446-H1452(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS LYS-83 AND VAL-280, INTERACTION WITH SCN5A.
  6. Cited for: FUNCTION, CHARACTERIZATION OF VARIANT VAL-280.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "Crystal structure of human glycerol-3-phosphate dehydrogenase 1-like protein."
    Structural genomics consortium (SGC)
    Submitted (MAY-2007) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 1-349 IN COMPLEX WITH NAD AND PHOSPHATE IONS.
  9. "Molecular and functional characterization of novel glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) mutations in sudden infant death syndrome."
    Van Norstrand D.W., Valdivia C.R., Tester D.J., Ueda K., London B., Makielski J.C., Ackerman M.J.
    Circulation 116:2253-2259(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SIDS LYS-83; VAL-124 AND CYS-273, CHARACTERIZATION OF VARIANTS SIDS LYS-83; VAL-124 AND CYS-273.
  10. "Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias."
    London B., Michalec M., Mehdi H., Zhu X., Kerchner L., Sanyal S., Viswanathan P.C., Pfahnl A.E., Shang L.L., Madhusudanan M., Baty C.J., Lagana S., Aleong R., Gutmann R., Ackerman M.J., McNamara D.M., Weiss R., Dudley S.C. Jr.
    Circulation 116:2260-2268(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT BRGDA2 VAL-280, CHARACTERIZATION OF VARIANT BRGDA2 VAL-280.

Entry informationi

Entry nameiGPD1L_HUMAN
AccessioniPrimary (citable) accession number: Q8N335
Secondary accession number(s): A8K9U3, Q14702, Q9BRM5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: October 1, 2002
Last modified: September 3, 2014
This is version 111 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

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