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Protein

Kinase D-interacting substrate of 220 kDa

Gene

Kidins220

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation. May play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4. In cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in neurotrophin- and ephrin-mediated neuronal outgrowth and in axon guidance during neural development and in neuronal regeneration.4 Publications

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB
  • protein kinase binding Source: RGD
  • protein kinase regulator activity Source: RGD

GO - Biological processi

  • activation of MAPKK activity Source: Reactome
  • cellular response to nerve growth factor stimulus Source: UniProtKB
  • nerve growth factor signaling pathway Source: UniProtKB
  • positive regulation of neuron projection development Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Neurogenesis

Enzyme and pathway databases

ReactomeiR-RNO-170984. ARMS-mediated activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Kinase D-interacting substrate of 220 kDa
Alternative name(s):
Ankyrin repeat-rich membrane-spanning protein
Gene namesi
Name:Kidins220
Synonyms:Arms
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi619949. Kidins220.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 499499CytoplasmicSequence analysisAdd
BLAST
Transmembranei500 – 52021HelicalSequence analysisAdd
BLAST
Topological domaini521 – 5244ExtracellularSequence analysis
Transmembranei525 – 54521HelicalSequence analysisAdd
BLAST
Topological domaini546 – 659114CytoplasmicSequence analysisAdd
BLAST
Transmembranei660 – 68021HelicalSequence analysisAdd
BLAST
Topological domaini681 – 6855ExtracellularSequence analysis
Transmembranei686 – 70621HelicalSequence analysisAdd
BLAST
Topological domaini707 – 17621056CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytosol Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
  • late endosome Source: UniProtKB
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi918 – 9181S → A: Loss of phosphorylation. 1 Publication
Mutagenesisi1760 – 17601S → D: Loss of binding to PDZ domain of SNTA1 and SNTB2. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 17621762Kinase D-interacting substrate of 220 kDaPRO_0000322120Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei882 – 8821PhosphoserineBy similarity
Modified residuei885 – 8851PhosphoserineBy similarity
Modified residuei914 – 9141PhosphothreonineBy similarity
Modified residuei918 – 9181Phosphoserine; by PKDCombined sources1 Publication
Modified residuei1163 – 11631PhosphoserineBy similarity
Modified residuei1288 – 12881PhosphoserineBy similarity
Modified residuei1344 – 13441PhosphoserineBy similarity
Modified residuei1351 – 13511PhosphoserineBy similarity
Modified residuei1353 – 13531PhosphoserineBy similarity
Modified residuei1354 – 13541PhosphoserineBy similarity
Modified residuei1357 – 13571PhosphoserineBy similarity
Modified residuei1513 – 15131PhosphoserineCombined sources
Modified residuei1518 – 15181PhosphoserineCombined sources
Modified residuei1547 – 15471PhosphoserineBy similarity
Modified residuei1566 – 15661PhosphoserineBy similarity
Modified residuei1615 – 16151PhosphoserineBy similarity
Modified residuei1625 – 16251PhosphoserineBy similarity
Modified residuei1671 – 16711PhosphothreonineBy similarity
Modified residuei1673 – 16731PhosphoserineBy similarity
Modified residuei1676 – 16761PhosphothreonineBy similarity

Post-translational modificationi

Tyrosine phosphorylated by NTRK1, NTRK2, EPHB2 and EPHA4. Phosphorylation at Ser-918 is induced by phorbol ester treatment. Phosphorylation by NTRK2 is induced by brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5. Phosphorylation by NTRK1 is induced by nerve growth factor (NGF).4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9EQG6.
PRIDEiQ9EQG6.

PTM databases

iPTMnetiQ9EQG6.
PhosphoSiteiQ9EQG6.
SwissPalmiQ9EQG6.

Expressioni

Tissue specificityi

Expressed in developing nervous system and in highly plastic areas of the adult brain. Also expressed in neuroendocrine cells, where it concentrates at the tip of neurites. Expressed in developing muscle and is concentrated at the neuromuscular junction (NMS). SNTA1 can regulate its localization in the NMS.3 Publications

Developmental stagei

Expressed in postmitotic neurons during the stage of development in which extensive axon pathfinding is occurring. At embryonic day 14 (E14), expressed in both spinal cord and dorsal root ganglia. Present on the sarcolemma in postnstal day 1 (P1) gastrocnemius muscle. By P8, becomes more concentrated at the junctional sites and by P21, colocalizes with acetylcholine receptor clusters.2 Publications

Interactioni

Subunit structurei

Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a nerve growth factor (NGF)-dependent manner. Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation. Isoform 2 interacts (via C-terminal domain) with MAGI2 isoform 1 (via PDZ domain). Interacts with NTRK1, NTRK2, NTRK3, ERKL and NGFR. Can form a ternary complex with NGFR and NTRK1 and this complex is affected by the expression levels of KIDINS220/ARMS. An increase in KIDINS220/ARMS expression leads to a decreased association of NGFR and NTRK1. Interacts with SNTA1 and SNTB2 and binds to their PDZ domains. Interacts with EPHA4 and PRKD1.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CRKLP461092EBI-976654,EBI-910From a different organism.

GO - Molecular functioni

  • PDZ domain binding Source: UniProtKB
  • protein kinase binding Source: RGD

Protein-protein interaction databases

IntActiQ9EQG6. 5 interactions.
MINTiMINT-7187897.
STRINGi10116.ENSRNOP00000063889.

Structurei

3D structure databases

ProteinModelPortaliQ9EQG6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati4 – 3330ANK 1Add
BLAST
Repeati37 – 6630ANK 2Add
BLAST
Repeati70 – 9930ANK 3Add
BLAST
Repeati103 – 13230ANK 4Add
BLAST
Repeati136 – 16530ANK 5Add
BLAST
Repeati169 – 19830ANK 6Add
BLAST
Repeati202 – 23130ANK 7Add
BLAST
Repeati235 – 26430ANK 8Add
BLAST
Repeati268 – 29730ANK 9Add
BLAST
Repeati301 – 33030ANK 10Add
BLAST
Repeati334 – 36330ANK 11Add
BLAST
Repeati367 – 39630ANK 12Add
BLAST
Domaini440 – 953514KAP NTPaseAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1089 – 10924Mediates interaction with CRKL
Regioni1758 – 17625Mediates interaction with SNTA1

Domaini

The transmembrane domain mediates interaction with NTRK1.1 Publication

Sequence similaritiesi

Contains 12 ANK repeats.PROSITE-ProRule annotation
Contains 1 KAP NTPase domain.Curated

Keywords - Domaini

ANK repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0502. Eukaryota.
COG0666. LUCA.
InParanoidiQ9EQG6.
KOiK12460.
PhylomeDBiQ9EQG6.

Family and domain databases

Gene3Di1.25.40.20. 4 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011646. KAP_P-loop.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF12796. Ank_2. 3 hits.
PF07693. KAP_NTPase. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 11 hits.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 10 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9EQG6-1) [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
MSVLISQSVI NYVEEENIPA LKALLEKCKD VDERNECGQT PLMLAAEQGN
60 70 80 90 100
VEIVKELLKN GANCNLEDLD NWTALISASK EGHIHIVEEL LKSGASLEHR
110 120 130 140 150
DMGGWTALMW ACYKGRTDVV ELLLSHGANP SVTGLYSVYP IIWAAGRGHA
160 170 180 190 200
DIVHLLLQNG AKVNCSDKYG TTPLVWAARK GHLECVKHLL AMGADVDQEG
210 220 230 240 250
ANSMTALIVA VKGGYTQSVK EILKRNPNVN LTDKDGNTAL MIASKEGHIE
260 270 280 290 300
IVQDLLDAGT YVNIPDRSGD TVLIGAVRGG HVEIVRALLQ KYADIDIRGQ
310 320 330 340 350
DNKTALYWAV EKGNATMVRD ILQCNPDTEI CTKDGETPLI KATKMRNIEV
360 370 380 390 400
VELLLDKGAK VSAVDKKGDT PLHVAIRGRS RRLAELLLRN PKDGRLLYRP
410 420 430 440 450
NKAGETPYNI DCSHQKSILT QIFGARHLSP TETDGDMLGY DLYSSALADI
460 470 480 490 500
LSEPTMQPPI CVGLYAQWGS GKSFLLKKLE DEMKTFAGQQ TEPLFQFSWL
510 520 530 540 550
IVFLTLLLCG GLGLVFAFTV DTNLAIAISL SFLALIYIFF IVIYFGGRRE
560 570 580 590 600
GESWNWAWAL STRLARHIGY LELLFKLMFV NPPELPEQTT KALPVRFLFT
610 620 630 640 650
DYNRLSSVGG ETSLAEMIAT LSDACEREFG FLATRLFRVF RTEESQGKKK
660 670 680 690 700
WKKTCCLPSF VIFLFIVGCI IAGITLLAIF RVDPKHLTVN AILISIASVV
710 720 730 740 750
GLAFVLNCRT WWQVLDSLLN SQRKRLHSAA SKLHKLKSEG FMKVLKCEVE
760 770 780 790 800
LMARMAKTID SFTQNQTRLV VIIDGLDACE QDKVLQMLDT VRVLFSKGPF
810 820 830 840 850
IAIFASDPHI IIKAINQNLN SVLRDSNING HDYMRNIVHL PVFLNSRGLS
860 870 880 890 900
NARKFLVTSA TNGDITCSDT TGTQEDTDRR VSQNSLGEMT KLGSKTALNR
910 920 930 940 950
RDTYRRRQMQ RTITRQMSFD LTKLLVTEDW FSDISPQTMR RLLNIVSVTG
960 970 980 990 1000
RLLRANQITF NWDRLASWIN LTEQWPYRTS WLILYLEETE GLPDQMTLKT
1010 1020 1030 1040 1050
IYERISKNIP TTKDVEPLLE IDGDIRNFEV FLSSRTPVLV ARDVKTFLPC
1060 1070 1080 1090 1100
TVNLDPKLRE IIADVRAARE QINIGGLAYP PLPLHEGPPR PPSGYSQPAS
1110 1120 1130 1140 1150
VCSSASFNGP FPGGVVSPQP HSSYYSGLSG PQHPFYNRPF FAPYLYTPRY
1160 1170 1180 1190 1200
YPGGSQHLIS RSSVKTSLPR DQNNGLPCDS GFNKQRQAAV PATGSSLLLS
1210 1220 1230 1240 1250
SMTVDVVCEK LRQIEGLDQS MMPQYCTTIK KANINGRVLS QCNIDELKKE
1260 1270 1280 1290 1300
MAMNFGDWHL FRSMVLEMRS VESQVVPEDP RFLNENSSAP VPHGESARRS
1310 1320 1330 1340 1350
SHTELPLTEL SSQTPYTLNF SFEELNTLGL DEGAPRHSNL SWQSQTRRTP
1360 1370 1380 1390 1400
SLSSLNSQDS SIEISKLTDK VQAEYRDAYR EYIAQMSQLE GGTGSSTISG
1410 1420 1430 1440 1450
RSSPHSTYYI GQSSSGGSIH STLEQERGKE GELKQEDGRK SFLMKRGDVI
1460 1470 1480 1490 1500
DYSSSGVSTN EASPLDPITE EDEKSDQSGS KLLPGKKSSE RPSLFQTDLK
1510 1520 1530 1540 1550
LKGGGLRYQK LPSDEDESGT EESDNTPLLK DDKDKKAEGK AERVCKSPEH
1560 1570 1580 1590 1600
SAEPIRTFIK AKEYLSDALL DKKDSSDSGV RSNESSPNHS LHNEAADDSQ
1610 1620 1630 1640 1650
LEKANLIELE DEGHSGKRGM PHSLSGLQDP IIARMSICSE DKKSPSECSL
1660 1670 1680 1690 1700
IASSPEESWP ACQKAYNLNR TPSTVTLNNN TAPTNRANQN FDEIEGIRET
1710 1720 1730 1740 1750
SQVILRPGPS PNPTAVQNEN LKSMAHKRSQ RSSYTRLSKD ASELHAASSE
1760
STGFGEERES IL
Length:1,762
Mass (Da):195,716
Last modified:October 1, 2001 - v2
Checksum:i0CB2689A571F8AE4
GO
Isoform 2 (identifier: Q9EQG6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     135-135: L → LQ
     1139-1187: Missing.

Show »
Length:1,714
Mass (Da):190,272
Checksum:i95EEEB55C2AF0E99
GO

Sequence cautioni

The sequence AAG34167 differs from that shown. Reason: Frameshift at positions 1521, 1523 and 1549. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti519 – 5191T → P in AAG34167 (PubMed:11150334).Curated
Sequence conflicti1001 – 10011I → M in AAG34167 (PubMed:11150334).Curated
Sequence conflicti1220 – 12201S → N in AAG34167 (PubMed:11150334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei135 – 1351L → LQ in isoform 2. 1 PublicationVSP_031868
Alternative sequencei1139 – 118749Missing in isoform 2. 1 PublicationVSP_031869Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF239045 mRNA. Translation: AAG35185.2.
AF313464 mRNA. Translation: AAG34167.1. Frameshift.
RefSeqiNP_446247.1. NM_053795.1. [Q9EQG6-1]
UniGeneiRn.21470.

Genome annotation databases

GeneIDi116478.
KEGGirno:116478.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF239045 mRNA. Translation: AAG35185.2.
AF313464 mRNA. Translation: AAG34167.1. Frameshift.
RefSeqiNP_446247.1. NM_053795.1. [Q9EQG6-1]
UniGeneiRn.21470.

3D structure databases

ProteinModelPortaliQ9EQG6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9EQG6. 5 interactions.
MINTiMINT-7187897.
STRINGi10116.ENSRNOP00000063889.

PTM databases

iPTMnetiQ9EQG6.
PhosphoSiteiQ9EQG6.
SwissPalmiQ9EQG6.

Proteomic databases

PaxDbiQ9EQG6.
PRIDEiQ9EQG6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi116478.
KEGGirno:116478.

Organism-specific databases

CTDi57498.
RGDi619949. Kidins220.

Phylogenomic databases

eggNOGiKOG0502. Eukaryota.
COG0666. LUCA.
InParanoidiQ9EQG6.
KOiK12460.
PhylomeDBiQ9EQG6.

Enzyme and pathway databases

ReactomeiR-RNO-170984. ARMS-mediated activation.

Miscellaneous databases

PROiQ9EQG6.

Family and domain databases

Gene3Di1.25.40.20. 4 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011646. KAP_P-loop.
IPR013761. SAM/pointed.
[Graphical view]
PfamiPF12796. Ank_2. 3 hits.
PF07693. KAP_NTPase. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 11 hits.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 10 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKDIS_RAT
AccessioniPrimary (citable) accession number: Q9EQG6
Secondary accession number(s): Q9ERD4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: October 1, 2001
Last modified: September 7, 2016
This is version 97 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.