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Protein

Ankyrin repeat domain-containing protein 27

Gene

ANKRD27

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

Functioni

May be a guanine exchange factor (GEF) for Rab21, Rab32 and Rab38 and regulate endosome dynamics (PubMed:16525121, PubMed:18477474). May regulate the participation of VAMP7 in membrane fusion events; in vitro inhibits VAMP7-mediated SNARE complex formation by trapping VAMP7 in a closed, fusogenically inactive conformation (PubMed:23104059). Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with Rab32, Rab38 and VAMP7 (By similarity). Involved in the regulation of neurite growth; the function seems to require its GEF activity, probably towards Rab21, and VAMP7 but not Rab32/38 (By similarity). Proposed to be involved in Golgi sorting of VAMP7 and transport of VAMP7 vesicles to the cell surface; the function seems to implicate kinesin heavy chain isoform 5 proteins, GOLGA4, RAB21 and MACF1 (PubMed:22705394). Required for the colocalization of VAMP7 and Rab21, probably on TGN sites (PubMed:19745841). Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with VPS29 (PubMed:24856514). Regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (By similarity).By similarity3 Publications2 Publications

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB-KW
  • guanyl-nucleotide exchange factor activity Source: MGI
  • Rab GTPase binding Source: UniProtKB
  • SNARE binding Source: GO_Central

GO - Biological processi

  • early endosome to late endosome transport Source: MGI
  • endosome to melanosome transport Source: Ensembl
  • negative regulation of SNARE complex assembly Source: UniProtKB
  • neuron projection morphogenesis Source: GO_Central
  • positive regulation of dendrite morphogenesis Source: Ensembl
  • protein transport Source: UniProtKB-KW
  • retrograde transport, endosome to plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Guanine-nucleotide releasing factor

Keywords - Biological processi

Protein transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105186-MONOMER.
ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
Ankyrin repeat domain-containing protein 27
Alternative name(s):
VPS9 domain-containing protein
Gene namesi
Name:ANKRD27
ORF Names:PP12899
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:25310. ANKRD27.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • cytosol Source: GOC
  • early endosome Source: UniProtKB
  • late endosome Source: UniProtKB
  • lysosome Source: UniProtKB
  • melanosome Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • neuron projection Source: GO_Central
  • plasma membrane Source: UniProtKB
  • transport vesicle Source: GO_Central
  • tubular endosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi432H → A: Disrupts interaction with VPS29; when associated with A-434. 1 Publication1
Mutagenesisi434L → A: Disrupts interaction with VPS29; when associated with A-432. 1 Publication1
Mutagenesisi509Q → A: Disrupts interaction with RAB32. 1 Publication1
Mutagenesisi513L → D: Disrupts interaction with RAB32. 1 Publication1
Mutagenesisi546K → D: Impairs interaction with RAB32. 1 Publication1
Mutagenesisi550Y → A: Impairs interaction with RAB32. 1 Publication1
Mutagenesisi679D → A: Disrupts interaction with VAMP7. 1 Publication1
Mutagenesisi681D → A: Disrupts interaction with VAMP7. 1 Publication1
Mutagenesisi684M → D: Disrupts interaction with VAMP7. 1 Publication1
Mutagenesisi687Y → S: Disrupts interaction with VAMP7. 1 Publication1
Mutagenesisi712H → A: Disrupts interaction with VPS29; when associated with A-714. 1 Publication1
Mutagenesisi714L → A: Disrupts interaction with VPS29; when associated with A-712. 1 Publication1

Organism-specific databases

DisGeNETi84079.
OpenTargetsiENSG00000105186.
PharmGKBiPA134893411.

Polymorphism and mutation databases

BioMutaiANKRD27.
DMDMi125987706.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002745561 – 1050Ankyrin repeat domain-containing protein 27Add BLAST1050

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei962PhosphoserineCombined sources1
Modified residuei970PhosphoserineCombined sources1
Modified residuei1023PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96NW4.
MaxQBiQ96NW4.
PaxDbiQ96NW4.
PeptideAtlasiQ96NW4.
PRIDEiQ96NW4.

PTM databases

iPTMnetiQ96NW4.
PhosphoSitePlusiQ96NW4.

Expressioni

Gene expression databases

BgeeiENSG00000105186.
CleanExiHS_ANKRD27.
ExpressionAtlasiQ96NW4. baseline and differential.
GenevisibleiQ96NW4. HS.

Organism-specific databases

HPAiHPA042769.

Interactioni

Subunit structurei

Interacts with RAB21 (GDP-bound form), VPS29, RAB32 (GTP-bound form), RAB38 (GTP-bound form), VAMP7, KIF5A, KIF5C, GOLGA4. Interacts with low affinity with RAB5. ANKRD27:RAB32 heterodimers can homodimerize to form tetramers. Can interact with RAB38 or RAB32, VPS29 and VAMP7 simultaneously (PubMed:16525121, PubMed:18477474, PubMed:19745841, PubMed:22705394, PubMed:23104059, PubMed:24856514, PubMed:21808068). A decreased interaction with RAB32 seen in the presence of SGSM2 (PubMed:21808068).7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GOLGA4Q134392EBI-6125599,EBI-1037845
KIF5AQ128404EBI-6125599,EBI-713468
Kif5aP331752EBI-6125599,EBI-349710From a different organism.
Vamp7Q9JHW54EBI-6125599,EBI-919936From a different organism.

GO - Molecular functioni

  • Rab GTPase binding Source: UniProtKB
  • SNARE binding Source: GO_Central

Protein-protein interaction databases

BioGridi123874. 14 interactors.
DIPiDIP-57614N.
IntActiQ96NW4. 11 interactors.
MINTiMINT-1198049.
STRINGi9606.ENSP00000304292.

Structurei

Secondary structure

11050
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi466 – 473Combined sources8
Helixi476 – 484Combined sources9
Helixi499 – 506Combined sources8
Helixi509 – 517Combined sources9
Helixi532 – 538Combined sources7
Helixi542 – 551Combined sources10
Beta strandi552 – 554Combined sources3
Helixi568 – 574Combined sources7
Helixi578 – 586Combined sources9
Helixi601 – 604Combined sources4
Helixi608 – 615Combined sources8
Helixi668 – 678Combined sources11
Helixi682 – 689Combined sources8
Helixi747 – 753Combined sources7
Helixi759 – 765Combined sources7
Helixi780 – 787Combined sources8
Helixi790 – 798Combined sources9
Helixi813 – 819Combined sources7
Helixi823 – 825Combined sources3
Helixi826 – 831Combined sources6
Helixi846 – 852Combined sources7
Helixi856 – 864Combined sources9
Helixi880 – 882Combined sources3
Helixi888 – 892Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4B93X-ray2.00B659-921[»]
4CYMX-ray2.80D/E/F450-640[»]
4CZ2X-ray2.97D/E/F450-640[»]
ProteinModelPortaliQ96NW4.
SMRiQ96NW4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini233 – 371VPS9PROSITE-ProRule annotationAdd BLAST139
Repeati396 – 426ANK 1Add BLAST31
Repeati462 – 491ANK 2Add BLAST30
Repeati495 – 524ANK 3Add BLAST30
Repeati528 – 560ANK 4Add BLAST33
Repeati564 – 593ANK 5Add BLAST30
Repeati597 – 627ANK 6Add BLAST31
Repeati668 – 698ANK 7Add BLAST31
Repeati743 – 772ANK 8Add BLAST30
Repeati776 – 805ANK 9Add BLAST30
Repeati809 – 838ANK 10Add BLAST30
Repeati842 – 871ANK 11Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 372Sufficient for GEF activity towards RAB211 PublicationAdd BLAST372
Regioni396 – 460Sufficient for interaction with VPS291 PublicationAdd BLAST65
Regioni451 – 730Interaction with RAB32By similarityAdd BLAST280
Regioni451 – 600Interaction with RAB38By similarity1 PublicationAdd BLAST150
Regioni658 – 707Required for interaction with VAMP7By similarity2 PublicationsAdd BLAST50
Regioni692 – 746Sufficient for interaction with VPS291 PublicationAdd BLAST55

Sequence similaritiesi

Contains 11 ANK repeats.PROSITE-ProRule annotation
Contains 1 VPS9 domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IQ81. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00780000121977.
HOGENOMiHOG000033958.
HOVERGENiHBG080845.
InParanoidiQ96NW4.
KOiK20175.
OMAiIDCLFKH.
OrthoDBiEOG091G07HY.
PhylomeDBiQ96NW4.
TreeFamiTF351261.

Family and domain databases

Gene3Di1.25.40.20. 6 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR003123. VPS9.
[Graphical view]
PfamiPF12796. Ank_2. 3 hits.
PF13606. Ank_3. 1 hit.
PF02204. VPS9. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 8 hits.
SM00167. VPS9. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 3 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 8 hits.
PS51205. VPS9. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q96NW4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALYDEDLLK NPFYLALQKC RPDLCSKVAQ IHGIVLVPCK GSLSSSIQST
60 70 80 90 100
CQFESYILIP VEEHFQTLNG KDVFIQGNRI KLGAGFACLL SVPILFEETF
110 120 130 140 150
YNEKEESFSI LCIAHPLEKR ESSEEPLAPS DPFSLKTIED VREFLGRHSE
160 170 180 190 200
RFDRNIASFH RTFRECERKS LRHHIDSANA LYTKCLQQLL RDSHLKMLAK
210 220 230 240 250
QEAQMNLMKQ AVEIYVHHEI YNLIFKYVGT MEASEDAAFN KITRSLQDLQ
260 270 280 290 300
QKDIGVKPEF SFNIPRAKRE LAQLNKCTSP QQKLVCLRKV VQLITQSPSQ
310 320 330 340 350
RVNLETMCAD DLLSVLLYLL VKTEIPNWMA NLSYIKNFRF SSLAKDELGY
360 370 380 390 400
CLTSFEAAIE YIRQGSLSAK PPESEGFGDR LFLKQRMSLL SQMTSSPTDC
410 420 430 440 450
LFKHIASGNQ KEVERLLSQE DHDKDTVQKM CHPLCFCDDC EKLVSGRLND
460 470 480 490 500
PSVVTPFSRD DRGHTPLHVA AVCGQASLID LLVSKGAMVN ATDYHGATPL
510 520 530 540 550
HLACQKGYQS VTLLLLHYKA SAEVQDNNGN TPLHLACTYG HEDCVKALVY
560 570 580 590 600
YDVESCRLDI GNEKGDTPLH IAARWGYQGV IETLLQNGAS TEIQNRLKET
610 620 630 640 650
PLKCALNSKI LSVMEAYHLS FERRQKSSEA PVQSPQRSVD SISQESSTSS
660 670 680 690 700
FSSMSASSRQ EETKKDYREV EKLLRAVADG DLEMVRYLLE WTEEDLEDAE
710 720 730 740 750
DTVSAADPEF CHPLCQCPKC APAQKRLAKV PASGLGVNVT SQDGSSPLHV
760 770 780 790 800
AALHGRADLI PLLLKHGANA GARNADQAVP LHLACQQGHF QVVKCLLDSN
810 820 830 840 850
AKPNKKDLSG NTPLIYACSG GHHELVALLL QHGASINASN NKGNTALHEA
860 870 880 890 900
VIEKHVFVVE LLLLHGASVQ VLNKRQRTAV DCAEQNSKIM ELLQVVPSCV
910 920 930 940 950
ASLDDVAETD RKEYVTVKIR KKWNSKLYDL PDEPFTRQFY FVHSAGQFKG
960 970 980 990 1000
KTSREIMARD RSVPNLTEGS LHEPGRQSVT LRQNNLPAQS GSHAAEKGNS
1010 1020 1030 1040 1050
DWPERPGLTQ TGPGHRRMLR RHTVEDAVVS QGPEAAGPLS TPQEVSASRS
Length:1,050
Mass (Da):116,984
Last modified:February 6, 2007 - v2
Checksum:iC47A96AA15E420F9
GO

Sequence cautioni

The sequence BAB70755 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti160 – 175HRTFR…LRHHI → LIEHSENARERASVTT in AAQ04657 (PubMed:15498874).CuratedAdd BLAST16

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030317657S → G.1 PublicationCorresponds to variant rs2287669dbSNPEnsembl.1
Natural variantiVAR_030318761P → R.1 PublicationCorresponds to variant rs2302970dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136784 mRNA. Translation: CAB66718.1.
AK054561 mRNA. Translation: BAB70755.1. Different initiation.
BC050529 mRNA. Translation: AAH50529.1.
AF447882 mRNA. Translation: AAQ04657.1.
AL834335 mRNA. Translation: CAD39003.1.
CCDSiCCDS32986.1.
RefSeqiNP_115515.2. NM_032139.2.
XP_006723475.1. XM_006723412.2.
UniGeneiHs.59236.

Genome annotation databases

EnsembliENST00000306065; ENSP00000304292; ENSG00000105186.
GeneIDi84079.
KEGGihsa:84079.
UCSCiuc002ntn.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136784 mRNA. Translation: CAB66718.1.
AK054561 mRNA. Translation: BAB70755.1. Different initiation.
BC050529 mRNA. Translation: AAH50529.1.
AF447882 mRNA. Translation: AAQ04657.1.
AL834335 mRNA. Translation: CAD39003.1.
CCDSiCCDS32986.1.
RefSeqiNP_115515.2. NM_032139.2.
XP_006723475.1. XM_006723412.2.
UniGeneiHs.59236.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4B93X-ray2.00B659-921[»]
4CYMX-ray2.80D/E/F450-640[»]
4CZ2X-ray2.97D/E/F450-640[»]
ProteinModelPortaliQ96NW4.
SMRiQ96NW4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123874. 14 interactors.
DIPiDIP-57614N.
IntActiQ96NW4. 11 interactors.
MINTiMINT-1198049.
STRINGi9606.ENSP00000304292.

PTM databases

iPTMnetiQ96NW4.
PhosphoSitePlusiQ96NW4.

Polymorphism and mutation databases

BioMutaiANKRD27.
DMDMi125987706.

Proteomic databases

EPDiQ96NW4.
MaxQBiQ96NW4.
PaxDbiQ96NW4.
PeptideAtlasiQ96NW4.
PRIDEiQ96NW4.

Protocols and materials databases

DNASUi84079.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306065; ENSP00000304292; ENSG00000105186.
GeneIDi84079.
KEGGihsa:84079.
UCSCiuc002ntn.2. human.

Organism-specific databases

CTDi84079.
DisGeNETi84079.
GeneCardsiANKRD27.
HGNCiHGNC:25310. ANKRD27.
HPAiHPA042769.
neXtProtiNX_Q96NW4.
OpenTargetsiENSG00000105186.
PharmGKBiPA134893411.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQ81. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00780000121977.
HOGENOMiHOG000033958.
HOVERGENiHBG080845.
InParanoidiQ96NW4.
KOiK20175.
OMAiIDCLFKH.
OrthoDBiEOG091G07HY.
PhylomeDBiQ96NW4.
TreeFamiTF351261.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105186-MONOMER.
ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Miscellaneous databases

ChiTaRSiANKRD27. human.
GeneWikiiANKRD27.
GenomeRNAii84079.
PROiQ96NW4.

Gene expression databases

BgeeiENSG00000105186.
CleanExiHS_ANKRD27.
ExpressionAtlasiQ96NW4. baseline and differential.
GenevisibleiQ96NW4. HS.

Family and domain databases

Gene3Di1.25.40.20. 6 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR003123. VPS9.
[Graphical view]
PfamiPF12796. Ank_2. 3 hits.
PF13606. Ank_3. 1 hit.
PF02204. VPS9. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 8 hits.
SM00167. VPS9. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 3 hits.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 8 hits.
PS51205. VPS9. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiANR27_HUMAN
AccessioniPrimary (citable) accession number: Q96NW4
Secondary accession number(s): Q71MF5
, Q86UC3, Q8ND80, Q9H0I4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: November 30, 2016
This is version 120 of the entry and version 2 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 19
    Human chromosome 19: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.