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Q8NFM7

- I17RD_HUMAN

UniProt

Q8NFM7 - I17RD_HUMAN

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Protein
Interleukin-17 receptor D
Gene
IL17RD, IL17RLM, SEF, UNQ6115/PRO20026
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation. May inhibit FGF-induced FGFR1 tyrosine phosphorylation. Regulates the nuclear ERK signaling pathway by spatially blocking nuclear translocation of activated ERK without inhibiting cytoplasmic phosphorylation of ERK. Mediates JNK activation and may be involved in apoptosis. Might have a role in the early stages of fate specification of GnRH-secreting neurons By similarity.3 Publications

GO - Biological processi

  1. signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiREACT_9470. Signaling by FGFR.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-17 receptor D
Short name:
IL-17 receptor D
Short name:
IL-17RD
Alternative name(s):
IL17Rhom
Interleukin-17 receptor-like protein
Sef homolog
Short name:
hSef
Gene namesi
Name:IL17RD
Synonyms:IL17RLM, SEF
ORF Names:UNQ6115/PRO20026
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:17616. IL17RD.

Subcellular locationi

Golgi apparatus membrane; Single-pass type I membrane protein. Cell membrane; Single-pass type I membrane protein
Note: Predominantly associated with the Golgi apparatus and is partially translocated to the plasma membrane upon stimulation.1 Publication
Isoform 4 : Cytoplasm 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini17 – 299283Extracellular Reviewed prediction
Add
BLAST
Transmembranei300 – 32021Helical; Reviewed prediction
Add
BLAST
Topological domaini321 – 739419Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. Golgi apparatus Source: HPA
  2. Golgi membrane Source: UniProtKB-SubCell
  3. integral component of membrane Source: UniProtKB-KW
  4. nucleus Source: HPA
  5. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 18 with or without anosmia (HH18) [MIM:615267]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
Note: The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in IL17RD also have a heterozygous mutation in another HH-associated gene including FGFR1 and KISS1R (1 Publication).1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1311K → T in HH18; results in decreased expression at the cell surface and reduced activity. 1 Publication
Corresponds to variant rs184758350 [ dbSNP | Ensembl ].
VAR_069936
Natural varianti162 – 1621K → R in HH18; results in decreased expression at the cell surface. 1 Publication
VAR_069937
Natural varianti306 – 3061P → S in HH18; reduced activity. 1 Publication
VAR_069938
Natural varianti379 – 3791Y → C in HH18; rare variant associated with susceptibility to disease; some patients have a second mutation in the HH-associated gene FGFR1; reduced activity. 1 Publication
Corresponds to variant rs369641068 [ dbSNP | Ensembl ].
VAR_069939
Natural varianti468 – 4681S → L in HH18; reduced activity. 1 Publication
VAR_069940
Natural varianti577 – 5771P → Q in HH18; reduced activity. 1 Publication
VAR_069941
Natural varianti735 – 7351A → V in HH18; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene KISS1R; results in decreased expression at the cell surface. 1 Publication
VAR_069942

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

MIMi615267. phenotype.
Orphaneti478. Kallmann syndrome.
PharmGKBiPA134993407.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1616 Reviewed prediction
Add
BLAST
Chaini17 – 739723Interleukin-17 receptor D
PRO_0000041871Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi19 – 191N-linked (GlcNAc...) Reviewed prediction
Glycosylationi55 – 551N-linked (GlcNAc...) Reviewed prediction
Glycosylationi62 – 621N-linked (GlcNAc...) Reviewed prediction
Glycosylationi80 – 801N-linked (GlcNAc...) Reviewed prediction
Glycosylationi137 – 1371N-linked (GlcNAc...) Reviewed prediction
Glycosylationi171 – 1711N-linked (GlcNAc...) Reviewed prediction
Glycosylationi206 – 2061N-linked (GlcNAc...) Reviewed prediction
Glycosylationi277 – 2771N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8NFM7.
PRIDEiQ8NFM7.

PTM databases

PhosphoSiteiQ8NFM7.

Expressioni

Tissue specificityi

Expressed in umbilical vein endothelial cells and in several highly vascularized tissues such as kidney, colon, skeletal muscle, heart and small intestine. Highly expressed in ductal epithelial cells of salivary glands, seminal vesicles and the collecting tubules of the kidney. Isoform 1 is also highly expressed in both fetal and adult brain, pituitary, tonsils, spleen, adenoids, fetal kidney, liver, testes and ovary. Isoform 1 is also expressed at moderate levels in primary aortic endothelial cells and adrenal medulla, and at low levels in adrenal cortex. Isoform 4 is specifically and highly expressed in pituitary, fetal brain and umbilical vein endothelial cells.1 Publication

Gene expression databases

ArrayExpressiQ8NFM7.
BgeeiQ8NFM7.
CleanExiHS_IL17RD.
GenevestigatoriQ8NFM7.

Organism-specific databases

HPAiHPA039577.
HPA043550.

Interactioni

Subunit structurei

Interacts with MAP3K7 By similarity. Self-associates. Interacts with FGFR1, FGFR2 and phosphorylated MAP2K1 or MAP2K2. Associates with a MAP2K1/2-MAPK1/3 complex.3 Publications

Protein-protein interaction databases

BioGridi120132. 1 interaction.
STRINGi9606.ENSP00000296318.

Structurei

3D structure databases

ProteinModelPortaliQ8NFM7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini355 – 509155SEFIR
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi695 – 7006Poly-Ser

Sequence similaritiesi

Contains 1 SEFIR domain.

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG45649.
HOVERGENiHBG081777.
InParanoidiQ8NFM7.
KOiK05167.
OMAiSTKYKLM.
OrthoDBiEOG7P8P7V.
PhylomeDBiQ8NFM7.
TreeFamiTF329644.

Family and domain databases

InterProiIPR013568. SEFIR.
IPR000157. TIR_dom.
[Graphical view]
PfamiPF08357. SEFIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51534. SEFIR. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8NFM7-1) [UniParc]FASTAAdd to Basket

Also known as: hSef-a, IL17RLM-L, Long

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

MAPWLQLCSV FFTVNACLNG SQLAVAAGGS GRARGADTCG WRGVGPASRN    50
SGLYNITFKY DNCTTYLNPV GKHVIADAQN ITISQYACHD QVAVTILWSP 100
GALGIEFLKG FRVILEELKS EGRQCQQLIL KDPKQLNSSF KRTGMESQPF 150
LNMKFETDYF VKVVPFPSIK NESNYHPFFF RTRACDLLLQ PDNLACKPFW 200
KPRNLNISQH GSDMQVSFDH APHNFGFRFF YLHYKLKHEG PFKRKTCKQE 250
QTTETTSCLL QNVSPGDYII ELVDDTNTTR KVMHYALKPV HSPWAGPIRA 300
VAITVPLVVI SAFATLFTVM CRKKQQENIY SHLDEESSES STYTAALPRE 350
RLRPRPKVFL CYSSKDGQNH MNVVQCFAYF LQDFCGCEVA LDLWEDFSLC 400
REGQREWVIQ KIHESQFIIV VCSKGMKYFV DKKNYKHKGG GRGSGKGELF 450
LVAVSAIAEK LRQAKQSSSA ALSKFIAVYF DYSCEGDVPG ILDLSTKYRL 500
MDNLPQLCSH LHSRDHGLQE PGQHTRQGSR RNYFRSKSGR SLYVAICNMH 550
QFIDEEPDWF EKQFVPFHPP PLRYREPVLE KFDSGLVLND VMCKPGPESD 600
FCLKVEAAVL GATGPADSQH ESQHGGLDQD GEARPALDGS AALQPLLHTV 650
KAGSPSDMPR DSGIYDSSVP SSELSLPLME GLSTDQTETS SLTESVSSSS 700
GLGEEEPPAL PSKLLSSGSC KADLGCRSYT DELHAVAPL 739
Length:739
Mass (Da):82,411
Last modified:February 20, 2007 - v3
Checksum:i7A2B45818DBD6E44
GO
Isoform 2 (identifier: Q8NFM7-2) [UniParc]FASTAAdd to Basket

Also known as: "IL17RLM-S, Short

The sequence of this isoform differs from the canonical sequence as follows:
     1-144: Missing.

Show »
Length:595
Mass (Da):66,817
Checksum:i12307ED8AA4B4041
GO
Isoform 3 (identifier: Q8NFM7-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MAPWLQLCSVFFTVNACLNGSQLAVAAGGSGRARGADTCGWR → MPRASASGVPALFVSGEQ

Show »
Length:715
Mass (Da):79,871
Checksum:i27564B1A6F365EF6
GO
Isoform 4 (identifier: Q8NFM7-4) [UniParc]FASTAAdd to Basket

Also known as: hSef-b

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MAPWLQLCSVFFTVNACLNGSQLAVAAGGSGRARGADTCGWR → MDYRQSWPWQ

Show »
Length:707
Mass (Da):79,463
Checksum:i116027A2BD48902D
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1311K → T in HH18; results in decreased expression at the cell surface and reduced activity. 1 Publication
Corresponds to variant rs184758350 [ dbSNP | Ensembl ].
VAR_069936
Natural varianti162 – 1621K → R in HH18; results in decreased expression at the cell surface. 1 Publication
VAR_069937
Natural varianti255 – 2551T → M.6 Publications
Corresponds to variant rs6780995 [ dbSNP | Ensembl ].
VAR_023478
Natural varianti301 – 3011V → M.
Corresponds to variant rs17057718 [ dbSNP | Ensembl ].
VAR_023479
Natural varianti306 – 3061P → S in HH18; reduced activity. 1 Publication
VAR_069938
Natural varianti379 – 3791Y → C in HH18; rare variant associated with susceptibility to disease; some patients have a second mutation in the HH-associated gene FGFR1; reduced activity. 1 Publication
Corresponds to variant rs369641068 [ dbSNP | Ensembl ].
VAR_069939
Natural varianti468 – 4681S → L in HH18; reduced activity. 1 Publication
VAR_069940
Natural varianti577 – 5771P → Q in HH18; reduced activity. 1 Publication
VAR_069941
Natural varianti735 – 7351A → V in HH18; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene KISS1R; results in decreased expression at the cell surface. 1 Publication
VAR_069942

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 144144Missing in isoform 2.
VSP_015582Add
BLAST
Alternative sequencei1 – 4242MAPWL…TCGWR → MPRASASGVPALFVSGEQ in isoform 3.
VSP_015583Add
BLAST
Alternative sequencei1 – 4242MAPWL…TCGWR → MDYRQSWPWQ in isoform 4.
VSP_015584Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti223 – 2231H → HGSDMQVSFDHAPH in CAB61408. 1 Publication
Sequence conflicti248 – 2481K → E in AAM74077. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF494208 mRNA. Translation: AAM74077.1.
AF494211 mRNA. Translation: AAM74080.1.
AY489047 mRNA. Translation: AAS15051.2.
AF458067 mRNA. Translation: AAM77571.1.
AY358774 mRNA. Translation: AAQ89134.1.
AL133097 mRNA. Translation: CAB61408.1.
AL833913 mRNA. Translation: CAD38769.1.
BC111702 mRNA. Translation: AAI11703.2.
CCDSiCCDS2880.2. [Q8NFM7-1]
PIRiT42695.
RefSeqiNP_060033.3. NM_017563.3. [Q8NFM7-1]
XP_006713272.1. XM_006713209.1. [Q8NFM7-2]
UniGeneiHs.150725.

Genome annotation databases

EnsembliENST00000296318; ENSP00000296318; ENSG00000144730. [Q8NFM7-1]
ENST00000320057; ENSP00000322250; ENSG00000144730. [Q8NFM7-2]
ENST00000427856; ENSP00000399209; ENSG00000144730. [Q8NFM7-3]
ENST00000463523; ENSP00000417516; ENSG00000144730. [Q8NFM7-2]
GeneIDi54756.
KEGGihsa:54756.
UCSCiuc003dik.3. human. [Q8NFM7-3]
uc003dil.3. human. [Q8NFM7-1]

Polymorphism databases

DMDMi126302555.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF494208 mRNA. Translation: AAM74077.1 .
AF494211 mRNA. Translation: AAM74080.1 .
AY489047 mRNA. Translation: AAS15051.2 .
AF458067 mRNA. Translation: AAM77571.1 .
AY358774 mRNA. Translation: AAQ89134.1 .
AL133097 mRNA. Translation: CAB61408.1 .
AL833913 mRNA. Translation: CAD38769.1 .
BC111702 mRNA. Translation: AAI11703.2 .
CCDSi CCDS2880.2. [Q8NFM7-1 ]
PIRi T42695.
RefSeqi NP_060033.3. NM_017563.3. [Q8NFM7-1 ]
XP_006713272.1. XM_006713209.1. [Q8NFM7-2 ]
UniGenei Hs.150725.

3D structure databases

ProteinModelPortali Q8NFM7.
ModBasei Search...

Protein-protein interaction databases

BioGridi 120132. 1 interaction.
STRINGi 9606.ENSP00000296318.

PTM databases

PhosphoSitei Q8NFM7.

Polymorphism databases

DMDMi 126302555.

Proteomic databases

PaxDbi Q8NFM7.
PRIDEi Q8NFM7.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000296318 ; ENSP00000296318 ; ENSG00000144730 . [Q8NFM7-1 ]
ENST00000320057 ; ENSP00000322250 ; ENSG00000144730 . [Q8NFM7-2 ]
ENST00000427856 ; ENSP00000399209 ; ENSG00000144730 . [Q8NFM7-3 ]
ENST00000463523 ; ENSP00000417516 ; ENSG00000144730 . [Q8NFM7-2 ]
GeneIDi 54756.
KEGGi hsa:54756.
UCSCi uc003dik.3. human. [Q8NFM7-3 ]
uc003dil.3. human. [Q8NFM7-1 ]

Organism-specific databases

CTDi 54756.
GeneCardsi GC03M057124.
H-InvDB HIX0003391.
HGNCi HGNC:17616. IL17RD.
HPAi HPA039577.
HPA043550.
MIMi 606807. gene.
615267. phenotype.
neXtProti NX_Q8NFM7.
Orphaneti 478. Kallmann syndrome.
PharmGKBi PA134993407.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG45649.
HOVERGENi HBG081777.
InParanoidi Q8NFM7.
KOi K05167.
OMAi STKYKLM.
OrthoDBi EOG7P8P7V.
PhylomeDBi Q8NFM7.
TreeFami TF329644.

Enzyme and pathway databases

Reactomei REACT_9470. Signaling by FGFR.

Miscellaneous databases

ChiTaRSi IL17RD. human.
GenomeRNAii 54756.
NextBioi 57378.
PROi Q8NFM7.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8NFM7.
Bgeei Q8NFM7.
CleanExi HS_IL17RD.
Genevestigatori Q8NFM7.

Family and domain databases

InterProi IPR013568. SEFIR.
IPR000157. TIR_dom.
[Graphical view ]
Pfami PF08357. SEFIR. 1 hit.
[Graphical view ]
SUPFAMi SSF52200. SSF52200. 1 hit.
PROSITEi PS51534. SEFIR. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "hSef inhibits PC-12 cell differentiation by interfering with Ras-mitogen-activated protein kinase MAPK signaling."
    Xiong S.Q., Zhao Q.H., Rong Z., Huang G.R., Huang Y., Chen P.L., Zhang S., Liu L., Chang Z.J.
    J. Biol. Chem. 278:50273-50282(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT MET-255, FUNCTION, INTERACTION WITH FGFR1 AND FGFR2.
  2. "Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity."
    Preger E., Ziv I., Shabtay A., Sher I., Tsang M., Dawid I.B., Altuvia Y., Ron D.
    Proc. Natl. Acad. Sci. U.S.A. 101:1229-1234(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANT MET-255, SUBCELLULAR LOCATION.
    Tissue: Testis.
  3. "Identification of novel IL-17 related receptors."
    Gilbert J.M., Gorman D.M.
    Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-255.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT MET-255.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT MET-255.
    Tissue: Testis.
  6. "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 4), VARIANT MET-255.
  7. "A novel interleukin-17 receptor-like protein identified in human umbilical vein endothelial cells antagonizes basic fibroblast growth factor-induced signaling."
    Yang R.-B., Domingos Ng C.K., Wasserman S.M., Koemueves L.G., Gerritsen M.E., Topper J.N.
    J. Biol. Chem. 278:33232-33238(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, HOMOOLIGOMERIZATION, INTERACTION WITH FGFR1.
  8. "Sef is a spatial regulator for Ras/MAP kinase signaling."
    Torii S., Kusakabe M., Yamamoto T., Maekawa M., Nishida E.
    Dev. Cell 7:33-44(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MAP2K1/2, IDENTIFICATION IN A COMPLEX WITH MAP2K1/2 AND MAPK1/3.
  9. Cited for: VARIANTS HH18 THR-131; ARG-162; SER-306; CYS-379; LEU-468; GLN-577 AND VAL-735, CHARACTERIZATION OF VARIANTS HH18 THR-131; ARG-162; SER-306; CYS-379; LEU-468; GLN-577 AND VAL-735.

Entry informationi

Entry nameiI17RD_HUMAN
AccessioniPrimary (citable) accession number: Q8NFM7
Secondary accession number(s): Q2NKP7
, Q58EZ7, Q6RVF4, Q6UWI5, Q8N113, Q8NFS0, Q9UFA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: February 20, 2007
Last modified: September 3, 2014
This is version 98 of the entry and version 3 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 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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