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Protein

Artemin

Gene

ARTN

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

Functioni

Ligand for the GFR-alpha-3-RET receptor complex but can also activate the GFR-alpha-1-RET receptor complex. Supports the survival of sensory and sympathetic peripheral neurons in culture and also supports the survival of dopaminergic neurons of the ventral mid-brain. Strong attractant of gut hematopoietic cells thus promoting the formation Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue.2 Publications

GO - Molecular functioni

  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiR-HSA-419037. NCAM1 interactions.
R-HSA-5673001. RAF/MAP kinase cascade.
SIGNORiQ5T4W7.

Names & Taxonomyi

Protein namesi
Recommended name:
Artemin
Alternative name(s):
Enovin
Neublastin
Gene namesi
Name:ARTN
Synonyms:EVN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:727. ARTN.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA25017.

Polymorphism and mutation databases

BioMutaiARTN.
DMDMi74744994.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3939Sequence analysisAdd
BLAST
Propeptidei40 – 10768Sequence analysisPRO_0000240286Add
BLAST
Chaini108 – 220113ArteminPRO_0000240287Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi123 ↔ 1881 Publication
Disulfide bondi150 ↔ 2161 Publication
Disulfide bondi154 ↔ 2181 Publication
Disulfide bondi187 – 187Interchain1 Publication
Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ5T4W7.
PRIDEiQ5T4W7.
TopDownProteomicsiQ5T4W7-3. [Q5T4W7-3]

PTM databases

iPTMnetiQ5T4W7.

Expressioni

Tissue specificityi

Ubiquitous. Expressed at high levels in peripheral tissues including prostate, placenta, pancreas, heart, kidney, pituitary gland, lung and testis. Expressed at low levels in the brain.2 Publications

Developmental stagei

Expressed during embryogenesis. High level expression seen in fetal kidney and lung while a low level expression seen in the fetal brain.1 Publication

Gene expression databases

BgeeiQ5T4W7.
CleanExiHS_ARTN.
ExpressionAtlasiQ5T4W7. baseline and differential.
GenevisibleiQ5T4W7. HS.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Binds to RET (By similarity).By similarity

GO - Molecular functioni

  • receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi114510. 1 interaction.
DIPiDIP-29113N.
STRINGi9606.ENSP00000387435.

Structurei

Secondary structure

1
220
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi122 – 13110Combined sources
Helixi132 – 1354Combined sources
Beta strandi136 – 1383Combined sources
Beta strandi144 – 1518Combined sources
Helixi155 – 1573Combined sources
Helixi160 – 17011Combined sources
Beta strandi178 – 1803Combined sources
Beta strandi187 – 19913Combined sources
Beta strandi205 – 21915Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ASKX-ray1.55A/B108-220[»]
2GH0X-ray1.92C/D122-220[»]
2GYRX-ray2.60A/B/C/D/E/F122-220[»]
2GYZX-ray1.76A122-220[»]
ProteinModelPortaliQ5T4W7.
SMRiQ5T4W7. Positions 120-220.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ5T4W7.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi45 – 10056Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the TGF-beta family. GDNF subfamily.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J0YD. Eukaryota.
ENOG4111W7C. LUCA.
GeneTreeiENSGT00520000055559.
HOGENOMiHOG000220877.
HOVERGENiHBG080137.
InParanoidiQ5T4W7.
OMAiISQPCCR.
OrthoDBiEOG7TXKK8.
PhylomeDBiQ5T4W7.
TreeFamiTF332366.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
[Graphical view]
PfamiPF00019. TGF_beta. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5T4W7-1) [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
MELGLGGLST LSHCPWPRQQ PALWPTLAAL ALLSSVAEAS LGSAPRSPAP
60 70 80 90 100
REGPPPVLAS PAGHLPGGRT ARWCSGRARR PPPQPSRPAP PPPAPPSALP
110 120 130 140 150
RGGRAARAGG PGSRARAAGA RGCRLRSQLV PVRALGLGHR SDELVRFRFC
160 170 180 190 200
SGSCRRARSP HDLSLASLLG AGALRPPPGS RPVSQPCCRP TRYEAVSFMD
210 220
VNSTWRTVDR LSATACGCLG
Length:220
Mass (Da):22,878
Last modified:December 21, 2004 - v1
Checksum:iC61B65EF3A51FEE4
GO
Isoform 2 (identifier: Q5T4W7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MELGLGGLSTLSHCPWPRQ → MPGLISARGQPLLEVLPPQAHLGALFLPEAPLGLSA

Show »
Length:237
Mass (Da):24,471
Checksum:i11C64C4B510CE3AB
GO
Isoform 3 (identifier: Q5T4W7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     21-21: P → APLGLSAQP

Show »
Length:228
Mass (Da):23,616
Checksum:i568BFD09EE05D0FC
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti19 – 191Q → R.3 Publications
Corresponds to variant rs2242637 [ dbSNP | Ensembl ].
VAR_026718

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1919MELGL…PWPRQ → MPGLISARGQPLLEVLPPQA HLGALFLPEAPLGLSA in isoform 2. 1 PublicationVSP_019335Add
BLAST
Alternative sequencei21 – 211P → APLGLSAQP in isoform 3. 1 PublicationVSP_019336

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF109401 mRNA. Translation: AAC98690.1.
AF115765 Genomic DNA. Translation: AAD13109.1.
AF115765 Genomic DNA. Translation: AAD13110.1.
AJ245628 Genomic DNA. Translation: CAB52396.1.
AF120274 mRNA. Translation: AAD21075.1.
AL357079 Genomic DNA. Translation: CAI16797.1.
CH471059 Genomic DNA. Translation: EAX07074.1.
CH471059 Genomic DNA. Translation: EAX07077.1.
CH471059 Genomic DNA. Translation: EAX07079.1.
CH471059 Genomic DNA. Translation: EAX07078.1.
CH471059 Genomic DNA. Translation: EAX07080.1.
BC062375 mRNA. Translation: AAH62375.1.
CCDSiCCDS501.1. [Q5T4W7-1]
CCDS502.1. [Q5T4W7-3]
RefSeqiNP_001129687.1. NM_001136215.1. [Q5T4W7-3]
NP_476431.2. NM_057090.2. [Q5T4W7-3]
NP_476432.2. NM_057091.2. [Q5T4W7-1]
XP_006711087.1. XM_006711024.1. [Q5T4W7-2]
XP_011540704.1. XM_011542402.1. [Q5T4W7-2]
UniGeneiHs.632404.

Genome annotation databases

EnsembliENST00000372354; ENSP00000361429; ENSG00000117407. [Q5T4W7-1]
ENST00000372359; ENSP00000361434; ENSG00000117407. [Q5T4W7-1]
ENST00000414809; ENSP00000387435; ENSG00000117407. [Q5T4W7-3]
ENST00000438616; ENSP00000391998; ENSG00000117407. [Q5T4W7-2]
ENST00000498139; ENSP00000436727; ENSG00000117407. [Q5T4W7-3]
GeneIDi9048.
KEGGihsa:9048.
UCSCiuc001cks.4. human. [Q5T4W7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF109401 mRNA. Translation: AAC98690.1.
AF115765 Genomic DNA. Translation: AAD13109.1.
AF115765 Genomic DNA. Translation: AAD13110.1.
AJ245628 Genomic DNA. Translation: CAB52396.1.
AF120274 mRNA. Translation: AAD21075.1.
AL357079 Genomic DNA. Translation: CAI16797.1.
CH471059 Genomic DNA. Translation: EAX07074.1.
CH471059 Genomic DNA. Translation: EAX07077.1.
CH471059 Genomic DNA. Translation: EAX07079.1.
CH471059 Genomic DNA. Translation: EAX07078.1.
CH471059 Genomic DNA. Translation: EAX07080.1.
BC062375 mRNA. Translation: AAH62375.1.
CCDSiCCDS501.1. [Q5T4W7-1]
CCDS502.1. [Q5T4W7-3]
RefSeqiNP_001129687.1. NM_001136215.1. [Q5T4W7-3]
NP_476431.2. NM_057090.2. [Q5T4W7-3]
NP_476432.2. NM_057091.2. [Q5T4W7-1]
XP_006711087.1. XM_006711024.1. [Q5T4W7-2]
XP_011540704.1. XM_011542402.1. [Q5T4W7-2]
UniGeneiHs.632404.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ASKX-ray1.55A/B108-220[»]
2GH0X-ray1.92C/D122-220[»]
2GYRX-ray2.60A/B/C/D/E/F122-220[»]
2GYZX-ray1.76A122-220[»]
ProteinModelPortaliQ5T4W7.
SMRiQ5T4W7. Positions 120-220.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114510. 1 interaction.
DIPiDIP-29113N.
STRINGi9606.ENSP00000387435.

PTM databases

iPTMnetiQ5T4W7.

Polymorphism and mutation databases

BioMutaiARTN.
DMDMi74744994.

Proteomic databases

PaxDbiQ5T4W7.
PRIDEiQ5T4W7.
TopDownProteomicsiQ5T4W7-3. [Q5T4W7-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372354; ENSP00000361429; ENSG00000117407. [Q5T4W7-1]
ENST00000372359; ENSP00000361434; ENSG00000117407. [Q5T4W7-1]
ENST00000414809; ENSP00000387435; ENSG00000117407. [Q5T4W7-3]
ENST00000438616; ENSP00000391998; ENSG00000117407. [Q5T4W7-2]
ENST00000498139; ENSP00000436727; ENSG00000117407. [Q5T4W7-3]
GeneIDi9048.
KEGGihsa:9048.
UCSCiuc001cks.4. human. [Q5T4W7-1]

Organism-specific databases

CTDi9048.
GeneCardsiARTN.
HGNCiHGNC:727. ARTN.
MIMi603886. gene.
neXtProtiNX_Q5T4W7.
PharmGKBiPA25017.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J0YD. Eukaryota.
ENOG4111W7C. LUCA.
GeneTreeiENSGT00520000055559.
HOGENOMiHOG000220877.
HOVERGENiHBG080137.
InParanoidiQ5T4W7.
OMAiISQPCCR.
OrthoDBiEOG7TXKK8.
PhylomeDBiQ5T4W7.
TreeFamiTF332366.

Enzyme and pathway databases

ReactomeiR-HSA-419037. NCAM1 interactions.
R-HSA-5673001. RAF/MAP kinase cascade.
SIGNORiQ5T4W7.

Miscellaneous databases

EvolutionaryTraceiQ5T4W7.
GeneWikiiArtemin.
GenomeRNAii9048.
PROiQ5T4W7.
SOURCEiSearch...

Gene expression databases

BgeeiQ5T4W7.
CleanExiHS_ARTN.
ExpressionAtlasiQ5T4W7. baseline and differential.
GenevisibleiQ5T4W7. HS.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
[Graphical view]
PfamiPF00019. TGF_beta. 1 hit.
[Graphical view]
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex."
    Baloh R.H., Tansey M.G., Lampe P.A., Fahrner T.J., Enomoto H., Simburger K.S., Leitner M.L., Araki T., Johnson E.M. Jr., Milbrandt J.
    Neuron 21:1291-1302(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, VARIANT ARG-19.
  2. "Enovin, a member of the glial cell-line-derived neurotrophic factor (GDNF) family with growth promoting activity on neuronal cells. Existence and tissue-specific expression of different splice variants."
    Masure S., Geerts H., Cik M., Hoefnagel E., Van Den Kieboom G., Tuytelaars A., Harris S., Lesage A.S.J., Leysen J.E., van der Helm L., Verhasselt P., Yon J., Gordon R.D.
    Eur. J. Biochem. 266:892-902(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), FUNCTION, TISSUE SPECIFICITY, VARIANT ARG-19.
  3. "In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin."
    Rosenblad C., Gronborg M., Hansen C., Blom N., Meyer M., Johansen J., Dago L., Kirik D., Patel U.A., Lundberg C., Trono D., Bjoerklund A., Johansen T.E.
    Mol. Cell. Neurosci. 15:199-214(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-19.
    Tissue: Brain.
  4. "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].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  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 3).
    Tissue: Brain.
  7. "Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors."
    Wang X., Baloh R.H., Milbrandt J., Garcia K.C.
    Structure 14:1083-1092(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 122-220 IN COMPLEX WITH GFRA3, DISULFIDE BONDS, SUBUNIT.

Entry informationi

Entry nameiARTN_HUMAN
AccessioniPrimary (citable) accession number: Q5T4W7
Secondary accession number(s): D3DPY1
, D3DPY3, O95441, O96030, Q6P6A3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: December 21, 2004
Last modified: July 6, 2016
This is version 102 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 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. 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.