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Protein

Afadin

Gene

Mllt4

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

Functioni

Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. May play a key role in the organization of epithelial structures of the embryonic ectoderm.

GO - Molecular functioni

  • LIM domain binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

ReactomeiR-RNO-418990. Adherens junctions interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Afadin
Alternative name(s):
Protein Af-6
Gene namesi
Name:Mllt4
Synonyms:Af6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi708561. Mllt4.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: RGD
  • cytosol Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell junction

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 18291829AfadinPRO_0000215920Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei216 – 2161PhosphoserineBy similarity
Modified residuei246 – 2461PhosphoserineBy similarity
Modified residuei391 – 3911PhosphoserineCombined sources
Modified residuei512 – 5121PhosphoserineCombined sources
Modified residuei557 – 5571PhosphoserineBy similarity
Modified residuei1090 – 10901PhosphoserineCombined sources
Modified residuei1114 – 11141PhosphoserineBy similarity
Modified residuei1133 – 11331PhosphoserineBy similarity
Modified residuei1147 – 11471PhosphoserineCombined sources
Modified residuei1150 – 11501PhosphoserineCombined sources
Modified residuei1179 – 11791PhosphoserineBy similarity
Modified residuei1189 – 11891PhosphoserineCombined sources
Modified residuei1218 – 12181PhosphothreonineBy similarity
Modified residuei1239 – 12391PhosphothreonineBy similarity
Modified residuei1282 – 12821PhosphoserineCombined sources
Modified residuei1506 – 15061PhosphoserineCombined sources
Modified residuei1517 – 15171PhosphoserineCombined sources
Modified residuei1701 – 17011PhosphoserineBy similarity
Modified residuei1726 – 17261PhosphoserineCombined sources
Modified residuei1779 – 17791PhosphoserineCombined sources
Modified residuei1804 – 18041PhosphoserineCombined sources
Modified residuei1812 – 18121N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PRIDEiO35889.

PTM databases

iPTMnetiO35889.
PhosphoSiteiO35889.

Expressioni

Tissue specificityi

Isoform 1 is widely expressed, including in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Isoform 2 is mainly expressed in the brain.1 Publication

Interactioni

Subunit structurei

Homodimer. Interacts with F-actin, nectin and NECTIN3. Essential for the association of nectin and E-cadherin. Isoform 2/s-afadin does not interact with F-actin. Interacts with ZO-1 and occludin, but probably in an indirect manner. Interacts with RIT1, RIT2, NRXN1 and BCR (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Ctnna1P262312EBI-6654073,EBI-647895From a different organism.
DBN1Q166433EBI-6654073,EBI-351394From a different organism.
Ssx2ipQ8VC664EBI-6654073,EBI-6654049From a different organism.

GO - Molecular functioni

  • LIM domain binding Source: RGD

Protein-protein interaction databases

BioGridi247803. 1 interaction.
IntActiO35889. 12 interactions.
MINTiMINT-135600.

Structurei

3D structure databases

ProteinModelPortaliO35889.
SMRiO35889. Positions 249-348, 381-502, 1008-1103.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini39 – 13395Ras-associating 1PROSITE-ProRule annotationAdd
BLAST
Domaini246 – 348103Ras-associating 2PROSITE-ProRule annotationAdd
BLAST
Domaini441 – 50767FHAAdd
BLAST
Domaini668 – 915248DilutePROSITE-ProRule annotationAdd
BLAST
Domaini1014 – 110087PDZPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili146 – 18641Sequence analysisAdd
BLAST
Coiled coili1417 – 145438Sequence analysisAdd
BLAST
Coiled coili1530 – 156435Sequence analysisAdd
BLAST
Coiled coili1600 – 167273Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1353 – 139947Pro-richAdd
BLAST
Compositional biasi1683 – 171331Pro-richAdd
BLAST
Compositional biasi1739 – 17424Poly-Asp

Sequence similaritiesi

Contains 1 dilute domain.PROSITE-ProRule annotation
Contains 1 FHA domain.Curated
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
Contains 2 Ras-associating domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

HOGENOMiHOG000008041.
HOVERGENiHBG050463.
InParanoidiO35889.
KOiK05702.
PhylomeDBiO35889.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
2.60.200.20. 1 hit.
InterProiIPR002710. Dilute_dom.
IPR000253. FHA_dom.
IPR001478. PDZ.
IPR000159. RA_dom.
IPR008984. SMAD_FHA_domain.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF01843. DIL. 1 hit.
PF00498. FHA. 1 hit.
PF00595. PDZ. 1 hit.
PF00788. RA. 2 hits.
[Graphical view]
SMARTiSM01132. DIL. 1 hit.
SM00240. FHA. 1 hit.
SM00228. PDZ. 1 hit.
SM00314. RA. 2 hits.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF54236. SSF54236. 2 hits.
PROSITEiPS51126. DILUTE. 1 hit.
PS50106. PDZ. 1 hit.
PS50200. RA. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: O35889-1) [UniParc]FASTAAdd to basket

Also known as: l-afadin, p205

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
MSAGGRDEER RKLADIIHHW NANRLDLFEI SQPTEDLEFH GVMRFYFQDK
60 70 80 90 100
AAGNFATKCI RVSSTATTQD VIETLAEKFR PDMRMLSSPK YSLYEVHVSG
110 120 130 140 150
ERRLDIDEKP LVVQLNWNKD DREGRFVLKN ENDAIPAKKA QSNGPEKQEK
160 170 180 190 200
EGVIQNFKRT LSKKEKKEKK KREKEALRQA SDKEERPSQG DDSENSRLAA
210 220 230 240 250
EVYKDMPETS FTRTISNPEV VMKRRRQQKL EKRMQEFRSS DGRPDSGGTL
260 270 280 290 300
RIYADSLKPN IPYKTILLST TDPADFAVAE SLEKYGLEKE NPKDYCIARV
310 320 330 340 350
MLPPGAQHSD ERGAKEIILD DDECPLQIFR EWPSDKGILV FQLKRRPPDY
360 370 380 390 400
IPKKMKKHVE GKPLKGKDRA DGSGYGSALP PEKLPYLVEL SPGRRNHFAY
410 420 430 440 450
YSYHTYEDGS DSRDKPKLYR LQLSVTEVGT EKFDDNSIQL FGPGIQPHHC
460 470 480 490 500
DLTNMDGVVT VTPRSMDAET YVDGQRISET TMLQSGMRLQ FGTSHVFKFV
510 520 530 540 550
DPIQDHVLSK RSVDGGLMVK GPRHKPGAVQ ETTFELGGDI HSGTALPASR
560 570 580 590 600
STTRLDSDRV SSASSTAERG MVKPMIRLDQ EQDYRRRESR TQDAAGPELM
610 620 630 640 650
LPASIEFRES SEDSFLSAII NYTNSSTVHF KLSPTYVLYM ACRYVLSSQH
660 670 680 690 700
RPDISPTERT HKAIAVVNKM VSMMEGVIQE VDQVDQKQKN IAGALAFWMA
710 720 730 740 750
NASELLNFIK QDRDLSRITL DAQDVLAHLV QMAFKYLVHC LQSELNNYMP
760 770 780 790 800
AFLDDPEENS LQRPKIDDVL HTLTGAMSLL RRCRVNAALT IQLFSQLFHF
810 820 830 840 850
INMWLFNRLV TDPDSGLCSH YWGAIIRQQL GHIEAWAEKQ GLELAADCHL
860 870 880 890 900
SRIVQATTLL TMDKYVPDDI PNINSTCFKL NSLQLQALLQ NYHCAPDEPF
910 920 930 940 950
IPTDLIENVV AVAENTADEL ARSDGRDVQL EEDPDLQLPF LLPEDGYSCD
960 970 980 990 1000
VVRNIPNGLQ EFLDPLCQRG FCRLVPHTRS PGTWTIYFEG ADYESHLMRE
1010 1020 1030 1040 1050
NTELTQPLRK EPEVITVTLK KQNGMGLSIV AAKGAGQDKL GIYVKSVVKG
1060 1070 1080 1090 1100
GAADVDGRLA AGDQLLSVDG RSLVGLSQER AAELMTRTSS VVTLEVAKQG
1110 1120 1130 1140 1150
AIYHGLATLL NQPSPMMQRI SDRRGSGKPR PKSEGFELYN NSAQNGSPES
1160 1170 1180 1190 1200
PQMPWTEYSE PKKLPGDDRL MKNRADHRSS PNVANQPPSP GGKSPYTSGT
1210 1220 1230 1240 1250
AAKITSVSTG NLCTEEQTPP PRPEAYPIPT QTYTREYFTF PASKSQDRMA
1260 1270 1280 1290 1300
PVQNQWPNYE EKPHMHTESD HASIAIQRVT RSQEELREEK VYQLERHRVE
1310 1320 1330 1340 1350
SGMDRKCDSD MWINQSSSVE SSTSSQEHLN HSSKSVTPAS TLTKSGPGRW
1360 1370 1380 1390 1400
KTPAAVLPTP VAVSQPIRTD LPPPPPPPPA HYTSDFDGIS MDLPLPPPPA
1410 1420 1430 1440 1450
NQAAPQSAQV AAAERKKREE HQRWYEKEKA RLEEERERKR REQERKLGQM
1460 1470 1480 1490 1500
RTQSLNPASF SPLATQAKPE KPSTLQRPQE TVIRELQPQQ QPRTIERRDL
1510 1520 1530 1540 1550
QYITISKEEL SSGDSLSPDP WKRDAREKLE KQQQMHIVDM LSKEIHELQN
1560 1570 1580 1590 1600
KGDRTAEESD RLRKLMLEWQ FQKRLQESKQ KDEDDDEEED DDVDTMLIMQ
1610 1620 1630 1640 1650
RLEAERRARL QDEERRRQQQ LEEMRKREVE DRVRQEEDGR HQEEERVKRD
1660 1670 1680 1690 1700
AEEKRRQEEG YYSRLEAERR RQHEEAARRL LEPEEPGLSR PPLPQDYEPP
1710 1720 1730 1740 1750
SQSSAPSAPP PPPQRNASYL KTQVLSPDSL FTAKFVAYDD DDEEENYVPA
1760 1770 1780 1790 1800
GPNSYSGSAG TTAGTYDAPR DTREKLSRSQ DADLPGSSGA PENLTFRERQ
1810 1820
RLFSQGQDVS DKVKASRKLT ELENELNTK
Length:1,829
Mass (Da):207,678
Last modified:January 1, 1998 - v1
Checksum:i45C597A82F109D6F
GO
Isoform 2 (identifier: O35889-2) [UniParc]FASTAAdd to basket

Also known as: s-afadin, p190

The sequence of this isoform differs from the canonical sequence as follows:
     679-685: Missing.
     1609-1609: R → RQTAMPAISVLDL
     1655-1658: RRQE → VMVL
     1659-1829: Missing.

Show »
Length:1,663
Mass (Da):188,981
Checksum:i65C54B0ED2D0C74C
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei679 – 6857Missing in isoform 2. 1 PublicationVSP_011726
Alternative sequencei1609 – 16091R → RQTAMPAISVLDL in isoform 2. 1 PublicationVSP_011727
Alternative sequencei1655 – 16584RRQE → VMVL in isoform 2. 1 PublicationVSP_011728
Alternative sequencei1659 – 1829171Missing in isoform 2. 1 PublicationVSP_011729Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83231 mRNA. Translation: AAC53391.1.
U83230 mRNA. Translation: AAC53390.1.
PIRiT41751.
T42092.
RefSeqiNP_037349.1. NM_013217.2. [O35889-1]
UniGeneiRn.58.

Genome annotation databases

GeneIDi26955.
KEGGirno:26955.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83231 mRNA. Translation: AAC53391.1.
U83230 mRNA. Translation: AAC53390.1.
PIRiT41751.
T42092.
RefSeqiNP_037349.1. NM_013217.2. [O35889-1]
UniGeneiRn.58.

3D structure databases

ProteinModelPortaliO35889.
SMRiO35889. Positions 249-348, 381-502, 1008-1103.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247803. 1 interaction.
IntActiO35889. 12 interactions.
MINTiMINT-135600.

PTM databases

iPTMnetiO35889.
PhosphoSiteiO35889.

Proteomic databases

PRIDEiO35889.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi26955.
KEGGirno:26955.

Organism-specific databases

CTDi4301.
RGDi708561. Mllt4.

Phylogenomic databases

HOGENOMiHOG000008041.
HOVERGENiHBG050463.
InParanoidiO35889.
KOiK05702.
PhylomeDBiO35889.

Enzyme and pathway databases

ReactomeiR-RNO-418990. Adherens junctions interactions.

Miscellaneous databases

PROiO35889.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
2.60.200.20. 1 hit.
InterProiIPR002710. Dilute_dom.
IPR000253. FHA_dom.
IPR001478. PDZ.
IPR000159. RA_dom.
IPR008984. SMAD_FHA_domain.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF01843. DIL. 1 hit.
PF00498. FHA. 1 hit.
PF00595. PDZ. 1 hit.
PF00788. RA. 2 hits.
[Graphical view]
SMARTiSM01132. DIL. 1 hit.
SM00240. FHA. 1 hit.
SM00228. PDZ. 1 hit.
SM00314. RA. 2 hits.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF54236. SSF54236. 2 hits.
PROSITEiPS51126. DILUTE. 1 hit.
PS50106. PDZ. 1 hit.
PS50200. RA. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Afadin: a novel actin filament-binding protein with one PDZ domain localized at cadherin-based cell-to-cell adherens junction."
    Mandai K., Nakanishi H., Satoh A., Obaishi H., Wada M., Nishioka H., Itoh M., Mizoguchi A., Aoki T., Fujimoto T., Matsuda Y., Tsukita S., Takai Y.
    J. Cell Biol. 139:517-528(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH F-ACTIN.
    Tissue: Brain.
  2. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391; SER-512; SER-1090; SER-1147; SER-1150; SER-1189; SER-1282; SER-1506; SER-1517; SER-1726; SER-1779 AND SER-1804, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiAFAD_RAT
AccessioniPrimary (citable) accession number: O35889
Secondary accession number(s): O35890
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: January 1, 1998
Last modified: June 8, 2016
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Isoform 1 increases the viscosity of F-actin in a dose-dependent manner. Isoform 1 causes F-actin to associate into bundles and meshworks.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, 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.