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P42702

- LIFR_HUMAN

UniProt

P42702 - LIFR_HUMAN

Protein

Leukemia inhibitory factor receptor

Gene

LIFR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells.

    GO - Molecular functioni

    1. ciliary neurotrophic factor receptor binding Source: BHF-UCL
    2. growth factor binding Source: BHF-UCL
    3. leukemia inhibitory factor receptor activity Source: MGI

    GO - Biological processi

    1. cell surface receptor signaling pathway Source: ProtInc
    2. ciliary neurotrophic factor-mediated signaling pathway Source: BHF-UCL
    3. cytokine-mediated signaling pathway Source: MGI
    4. leukemia inhibitory factor signaling pathway Source: BHF-UCL
    5. oncostatin-M-mediated signaling pathway Source: GOC
    6. positive regulation of cell proliferation Source: BHF-UCL
    7. response to cytokine Source: BHF-UCL

    Keywords - Molecular functioni

    Receptor

    Enzyme and pathway databases

    SignaLinkiP42702.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Leukemia inhibitory factor receptor
    Short name:
    LIF receptor
    Short name:
    LIF-R
    Alternative name(s):
    CD_antigen: CD118
    Gene namesi
    Name:LIFR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:6597. LIFR.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell
    2. integral component of plasma membrane Source: ProtInc

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Stueve-Wiedemann syndrome (STWS) [MIM:601559]: Severe autosomal recessive condition and belongs to the group of the bent-bone dysplasias. SWS is characterized by bowing of the lower limbs, with internal cortical thickening, wide metaphyses with abnormal trabecular pattern, and camptodactyly. Additional features include feeding and swallowing difficulties, as well as respiratory distress and hyperthermic episodes, which cause death in the first months of life. The rare survivors develop progressive scoliosis, spontaneous fractures, bowing of the lower limbs, with prominent joints and dysautonomia symptoms, including temperature instability, absent corneal and patellar reflexes, and smooth tongue.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti279 – 2791S → P in STWS. 1 Publication
    VAR_025666
    A chromosomal aberration involving LIFR is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(5;8)(p13;q12) with PLAG1.

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi601559. phenotype.
    Orphaneti3206. Stuve-Wiedemann syndrome.
    PharmGKBiPA30371.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 4444Sequence AnalysisAdd
    BLAST
    Chaini45 – 10971053Leukemia inhibitory factor receptorPRO_0000010902Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi55 ↔ 651 Publication
    Glycosylationi64 – 641N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi82 ↔ 901 Publication
    Glycosylationi85 – 851N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi131 – 1311N-linked (GlcNAc...)1 Publication
    Glycosylationi143 – 1431N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi191 – 1911N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi213 ↔ 2701 Publication
    Glycosylationi243 – 2431N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi303 – 3031N-linked (GlcNAc...)1 Publication
    Disulfide bondi341 ↔ 3511 Publication
    Glycosylationi390 – 3901N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi407 – 4071N-linked (GlcNAc...)1 Publication
    Glycosylationi426 – 4261N-linked (GlcNAc...)1 Publication
    Glycosylationi445 – 4451N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi466 ↔ 5111 Publication
    Glycosylationi481 – 4811N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi489 – 4891N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi572 – 5721N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi652 – 6521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi663 – 6631N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi680 – 6801N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi729 – 7291N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi787 – 7871N-linked (GlcNAc...)Sequence Analysis
    Modified residuei927 – 9271Phosphoserine1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiP42702.
    PaxDbiP42702.
    PRIDEiP42702.

    PTM databases

    PhosphoSiteiP42702.

    Expressioni

    Gene expression databases

    ArrayExpressiP42702.
    BgeeiP42702.
    CleanExiHS_LIFR.
    GenevestigatoriP42702.

    Organism-specific databases

    HPAiCAB010252.
    HPA004478.

    Interactioni

    Subunit structurei

    Heterodimer composed of LIFR and IL6ST. The heterodimer formed by LIFR and IL6ST interacts with the complex formed by CNTF and CNTFR.1 Publication

    Protein-protein interaction databases

    BioGridi110165. 7 interactions.
    DIPiDIP-5770N.
    MINTiMINT-1352123.
    STRINGi9606.ENSP00000263409.

    Structurei

    Secondary structure

    1
    1097
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi55 – 595
    Beta strandi62 – 665
    Beta strandi71 – 733
    Beta strandi79 – 835
    Beta strandi85 – 873
    Beta strandi89 – 979
    Beta strandi104 – 1063
    Beta strandi110 – 1134
    Beta strandi145 – 1473
    Turni148 – 1514
    Beta strandi152 – 1598
    Helixi161 – 1633
    Beta strandi169 – 18113
    Beta strandi183 – 19210
    Helixi194 – 1963
    Beta strandi199 – 2068
    Beta strandi216 – 22510
    Beta strandi231 – 2333
    Beta strandi242 – 2443
    Beta strandi254 – 2563
    Beta strandi258 – 2625
    Beta strandi267 – 2715
    Beta strandi277 – 2848
    Beta strandi293 – 2953
    Beta strandi297 – 3015
    Beta strandi312 – 3209
    Beta strandi322 – 3309
    Beta strandi337 – 3459
    Beta strandi348 – 3547
    Helixi363 – 3653
    Beta strandi368 – 3736
    Turni374 – 3763
    Beta strandi379 – 3824
    Beta strandi393 – 3986
    Beta strandi406 – 4138
    Beta strandi418 – 4258
    Helixi427 – 4304
    Beta strandi437 – 4415
    Beta strandi444 – 4485
    Beta strandi451 – 4544
    Beta strandi467 – 4715
    Beta strandi473 – 4753
    Beta strandi479 – 4813
    Beta strandi488 – 4914
    Beta strandi501 – 5044
    Beta strandi506 – 5105

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3E0GX-ray3.10A52-534[»]
    ProteinModelPortaliP42702.
    SMRiP42702. Positions 52-822.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP42702.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini45 – 833789ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini859 – 1097239CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei834 – 85825HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini49 – 13890Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini335 – 434100Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini435 – 534100Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini538 – 62992Fibronectin type-III 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini627 – 71993Fibronectin type-III 5PROSITE-ProRule annotationAdd
    BLAST
    Domaini724 – 833110Fibronectin type-III 6PROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi519 – 5235WSXWS motif
    Motifi869 – 8779Box 1 motif

    Domaini

    The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
    The box 1 motif is required for JAK interaction and/or activation.

    Sequence similaritiesi

    Contains 6 fibronectin type-III domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG147644.
    HOGENOMiHOG000113324.
    HOVERGENiHBG006266.
    InParanoidiP42702.
    KOiK05058.
    OMAiFYPDIPN.
    OrthoDBiEOG7V49XP.
    PhylomeDBiP42702.
    TreeFamiTF338122.

    Family and domain databases

    Gene3Di2.60.40.10. 5 hits.
    InterProiIPR003961. Fibronectin_type3.
    IPR003529. Hematopoietin_rcpt_Gp130_CS.
    IPR013783. Ig-like_fold.
    [Graphical view]
    PfamiPF00041. fn3. 1 hit.
    [Graphical view]
    SMARTiSM00060. FN3. 5 hits.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 4 hits.
    PROSITEiPS50853. FN3. 5 hits.
    PS01353. HEMATOPO_REC_L_F2. 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: P42702-1) [UniParc]FASTAAdd to Basket

    Also known as: Membrane

    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

    MMDIYVCLKR PSWMVDNKRM RTASNFQWLL STFILLYLMN QVNSQKKGAP     50
    HDLKCVTNNL QVWNCSWKAP SGTGRGTDYE VCIENRSRSC YQLEKTSIKI 100
    PALSHGDYEI TINSLHDFGS STSKFTLNEQ NVSLIPDTPE ILNLSADFST 150
    STLYLKWNDR GSVFPHRSNV IWEIKVLRKE SMELVKLVTH NTTLNGKDTL 200
    HHWSWASDMP LECAIHFVEI RCYIDNLHFS GLEEWSDWSP VKNISWIPDS 250
    QTKVFPQDKV ILVGSDITFC CVSQEKVLSA LIGHTNCPLI HLDGENVAIK 300
    IRNISVSASS GTNVVFTTED NIFGTVIFAG YPPDTPQQLN CETHDLKEII 350
    CSWNPGRVTA LVGPRATSYT LVESFSGKYV RLKRAEAPTN ESYQLLFQML 400
    PNQEIYNFTL NAHNPLGRSQ STILVNITEK VYPHTPTSFK VKDINSTAVK 450
    LSWHLPGNFA KINFLCEIEI KKSNSVQEQR NVTIKGVENS SYLVALDKLN 500
    PYTLYTFRIR CSTETFWKWS KWSNKKQHLT TEASPSKGPD TWREWSSDGK 550
    NLIIYWKPLP INEANGKILS YNVSCSSDEE TQSLSEIPDP QHKAEIRLDK 600
    NDYIISVVAK NSVGSSPPSK IASMEIPNDD LKIEQVVGMG KGILLTWHYD 650
    PNMTCDYVIK WCNSSRSEPC LMDWRKVPSN STETVIESDE FRPGIRYNFF 700
    LYGCRNQGYQ LLRSMIGYIE ELAPIVAPNF TVEDTSADSI LVKWEDIPVE 750
    ELRGFLRGYL FYFGKGERDT SKMRVLESGR SDIKVKNITD ISQKTLRIAD 800
    LQGKTSYHLV LRAYTDGGVG PEKSMYVVTK ENSVGLIIAI LIPVAVAVIV 850
    GVVTSILCYR KREWIKETFY PDIPNPENCK ALQFQKSVCE GSSALKTLEM 900
    NPCTPNNVEV LETRSAFPKI EDTEIISPVA ERPEDRSDAE PENHVVVSYC 950
    PPIIEEEIPN PAADEAGGTA QVIYIDVQSM YQPQAKPEEE QENDPVGGAG 1000
    YKPQMHLPIN STVEDIAAEE DLDKTAGYRP QANVNTWNLV SPDSPRSIDS 1050
    NSEIVSFGSP CSINSRQFLI PPKDEDSPKS NGGGWSFTNF FQNKPND 1097
    Length:1,097
    Mass (Da):123,743
    Last modified:November 1, 1995 - v1
    Checksum:iC8602897E359FCE5
    GO
    Isoform 2 (identifier: P42702-2)

    Also known as: Secreted

    Sequence is not available

    Note: No experimental confirmation available.

    Length:
    Mass (Da):

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti116 – 1161H → Y.
    Corresponds to variant rs3729734 [ dbSNP | Ensembl ].
    VAR_029109
    Natural varianti279 – 2791S → P in STWS. 1 Publication
    VAR_025666
    Natural varianti578 – 5781D → N.
    Corresponds to variant rs3729740 [ dbSNP | Ensembl ].
    VAR_029110
    Natural varianti633 – 6331I → M.
    Corresponds to variant rs2303743 [ dbSNP | Ensembl ].
    VAR_021996
    Natural varianti664 – 6641S → L.
    Corresponds to variant rs3729744 [ dbSNP | Ensembl ].
    VAR_038626
    Natural varianti785 – 7851V → I.
    Corresponds to variant rs3110234 [ dbSNP | Ensembl ].
    VAR_029111
    Natural varianti1068 – 10681F → L in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036166

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X61615 mRNA. Translation: CAA43805.1.
    U66563 mRNA. Translation: AAB61897.1.
    CCDSiCCDS3927.1. [P42702-1]
    PIRiS17308.
    RefSeqiNP_001121143.1. NM_001127671.1. [P42702-1]
    NP_002301.1. NM_002310.5. [P42702-1]
    UniGeneiHs.133421.

    Genome annotation databases

    EnsembliENST00000263409; ENSP00000263409; ENSG00000113594. [P42702-1]
    ENST00000453190; ENSP00000398368; ENSG00000113594. [P42702-1]
    GeneIDi3977.
    KEGGihsa:3977.
    UCSCiuc003jli.2. human. [P42702-1]

    Polymorphism databases

    DMDMi1170784.

    Keywords - Coding sequence diversityi

    Alternative splicing, Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X61615 mRNA. Translation: CAA43805.1 .
    U66563 mRNA. Translation: AAB61897.1 .
    CCDSi CCDS3927.1. [P42702-1 ]
    PIRi S17308.
    RefSeqi NP_001121143.1. NM_001127671.1. [P42702-1 ]
    NP_002301.1. NM_002310.5. [P42702-1 ]
    UniGenei Hs.133421.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3E0G X-ray 3.10 A 52-534 [» ]
    ProteinModelPortali P42702.
    SMRi P42702. Positions 52-822.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110165. 7 interactions.
    DIPi DIP-5770N.
    MINTi MINT-1352123.
    STRINGi 9606.ENSP00000263409.

    PTM databases

    PhosphoSitei P42702.

    Polymorphism databases

    DMDMi 1170784.

    Proteomic databases

    MaxQBi P42702.
    PaxDbi P42702.
    PRIDEi P42702.

    Protocols and materials databases

    DNASUi 3977.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000263409 ; ENSP00000263409 ; ENSG00000113594 . [P42702-1 ]
    ENST00000453190 ; ENSP00000398368 ; ENSG00000113594 . [P42702-1 ]
    GeneIDi 3977.
    KEGGi hsa:3977.
    UCSCi uc003jli.2. human. [P42702-1 ]

    Organism-specific databases

    CTDi 3977.
    GeneCardsi GC05M038475.
    HGNCi HGNC:6597. LIFR.
    HPAi CAB010252.
    HPA004478.
    MIMi 151443. gene.
    601559. phenotype.
    neXtProti NX_P42702.
    Orphaneti 3206. Stuve-Wiedemann syndrome.
    PharmGKBi PA30371.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG147644.
    HOGENOMi HOG000113324.
    HOVERGENi HBG006266.
    InParanoidi P42702.
    KOi K05058.
    OMAi FYPDIPN.
    OrthoDBi EOG7V49XP.
    PhylomeDBi P42702.
    TreeFami TF338122.

    Enzyme and pathway databases

    SignaLinki P42702.

    Miscellaneous databases

    EvolutionaryTracei P42702.
    GeneWikii Leukemia_inhibitory_factor_receptor.
    GenomeRNAii 3977.
    NextBioi 15588.
    PROi P42702.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P42702.
    Bgeei P42702.
    CleanExi HS_LIFR.
    Genevestigatori P42702.

    Family and domain databases

    Gene3Di 2.60.40.10. 5 hits.
    InterProi IPR003961. Fibronectin_type3.
    IPR003529. Hematopoietin_rcpt_Gp130_CS.
    IPR013783. Ig-like_fold.
    [Graphical view ]
    Pfami PF00041. fn3. 1 hit.
    [Graphical view ]
    SMARTi SM00060. FN3. 5 hits.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 4 hits.
    PROSITEi PS50853. FN3. 5 hits.
    PS01353. HEMATOPO_REC_L_F2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130."
      Gearing D.P., Thut C.J., Vanden Bos T., Gimpel S.D., Delaney P.B., King J., Price V., Cosman D., Beckmann M.P.
      EMBO J. 10:2839-2848(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Placenta.
    2. "Human LIF receptor 3' non-coding region."
      Wang Z., Melmed S.
      Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 942-1097.
    3. "The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter."
      Voz M.L., Astrom A.-K., Kas K., Mark J., Stenman G., Van de Ven W.J.M.
      Oncogene 16:1409-1416(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHROMOSOMAL TRANSLOCATION WITH PLAG1.
    4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-927, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    5. "Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex."
      Skiniotis G., Lupardus P.J., Martick M., Walz T., Garcia K.C.
      Mol. Cell 31:737-748(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 52-534, IDENTIFICATION IN A COMPLEX WITH IL6ST; CNTF AND CNTFR, GLYCOSYLATION AT ASN-131; ASN-303; ASN-407 AND ASN-426, DISULFIDE BONDS, ELECTRON MICROSCOPY, SUBUNIT.
    6. Cited for: VARIANT STWS PRO-279.
    7. Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-1068.

    Entry informationi

    Entry nameiLIFR_HUMAN
    AccessioniPrimary (citable) accession number: P42702
    Secondary accession number(s): Q6LCD9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 142 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 cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3