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UniProtKB - Q5T4F4 (ZFY27_HUMAN)

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Protein

Protrudin

Gene

ZFYVE27

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

Functioni

Key regulator of RAB11-dependent vesicular trafficking during neurite extension through polarized membrane transport (PubMed:17082457). Promotes axonal elongation and contributes to the establishment of neuronal cell polarity (By similarity). Involved in nerve growth factor-induced neurite formation in VAPA-dependent manner (PubMed:19289470). Contributes to both the formation and stabilization of the tubular ER network (PubMed:24668814). Involved in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections (PubMed:23969831). Acts as an adapter protein and facilitates the interaction of KIF5A with VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 and the ZFYVE27-KIF5A complex contributes to the transport of these proteins in neurons. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a KIF5A/B-dependent manner (PubMed:21976701).By similarity5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri344 – 410FYVE-typePROSITE-ProRule annotationAdd BLAST67

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein self-association Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • endoplasmic reticulum tubular network formation Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • neurotrophin TRK receptor signaling pathway Source: UniProtKB
  • positive regulation of axon extension Source: UniProtKB
  • protein localization to plasma membrane Source: UniProtKB
  • vesicle-mediated transport Source: UniProtKB
Complete GO annotation...

Keywordsi

LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Protrudin
Alternative name(s):
Spastic paraplegia 33 protein1 Publication
Zinc finger FYVE domain-containing protein 27
Gene namesi
Name:ZFYVE27
Synonyms:SPG331 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:26559. ZFYVE27.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 66Cytoplasmic1 PublicationAdd BLAST66
Transmembranei67 – 87HelicalSequence analysisAdd BLAST21
Topological domaini88Lumenal1 Publication1
Transmembranei89 – 109HelicalSequence analysisAdd BLAST21
Topological domaini110 – 187Cytoplasmic1 PublicationAdd BLAST78
Transmembranei188 – 208HelicalSequence analysisAdd BLAST21
Topological domaini209 – 411Extracellular1 PublicationAdd BLAST203

GO - Cellular componenti

  • axon Source: UniProtKB
  • dendrite Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum tubular network Source: UniProtKB
  • growth cone membrane Source: UniProtKB
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • recycling endosome membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Endoplasmic reticulum, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 33, autosomal dominant (SPG33)4 Publications
The disease is caused by mutations affecting the gene represented in this entry. According to PubMed:18606302, the properties of the variant Val-191 and its frequency in some populations raise doubts on the implication of that gene in the disease.
Disease descriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
See also OMIM:610244
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027269191G → V in SPG33; no effect on its function in the regulation of ER morphology and stability, no effect on its localization to ER but according to PubMed:16826525 an aberrant subcellular localization to cell membrane seen, altered interaction with SPAST, increased susceptibility to ER stress, no effect on its interaction with REEP1, REEP5 and ATL1 and increased protein stabilty. 4 PublicationsCorresponds to variant dbSNP:rs35077384Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi13L → A: Alters interaction with RAB11A; when associated with A-49. 1 Publication1
Mutagenesisi49I → A: Alters interaction with RAB11A; when associated with A-13. 1 Publication1
Mutagenesisi289D → A: Loss of interaction with VAPA and loss of function in cell projections formation. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi118813.
MalaCardsiZFYVE27.
MIMi610244. phenotype.
OpenTargetsiENSG00000155256.
PharmGKBiPA134863310.

Polymorphism and mutation databases

BioMutaiZFYVE27.
DMDMi74744927.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002456011 – 411ProtrudinAdd BLAST411

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi209N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Phosphorylated. Phosphorylation is induced by NGF through the MAPK/ERK pathway and modulates interaction with RAB11A.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ5T4F4.
PaxDbiQ5T4F4.
PeptideAtlasiQ5T4F4.
PRIDEiQ5T4F4.

PTM databases

iPTMnetiQ5T4F4.
PhosphoSitePlusiQ5T4F4.

Expressioni

Gene expression databases

BgeeiENSG00000155256.
GenevisibleiQ5T4F4. HS.

Organism-specific databases

HPAiHPA037523.
HPA069876.

Interactioni

Subunit structurei

Can form homooligomers (monomers, dimers and tetramers) (PubMed:23969831). Interacts with RAB11A (GDP-bound form); regulates RAB11A (PubMed:17082457). Interacts with FKBP8; may negatively regulate ZFYVE27 phosphorylation (PubMed:17082457, PubMed:18459960). Interacts with VAPA (via MSP domain); may regulate ZFYVE27 retention in the endoplasmic reticulum and its function in cell projections formation (PubMed:19289470, PubMed:21976701). Interacts with VAPB (via MSP domain) (PubMed:19289470, PubMed:21976701). Interacts with REEP1, REEP5 and ATL1 (PubMed:24668814, PubMed:23969831). Interacts with ATL2, ATL3 and SPAST (PubMed:23969831). Interacts with KIF5A and RTN3 (PubMed:21976701). Interacts with RAB11B (GDP-bound form), SURF4, KIF5B and KIF5C (By similarity).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein self-association Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi125623. 21 interactors.
DIPiDIP-61530N.
IntActiQ5T4F4. 7 interactors.
STRINGi9606.ENSP00000348593.

Structurei

Secondary structure

1411
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi351 – 353Combined sources3
Beta strandi359 – 361Combined sources3
Beta strandi367 – 369Combined sources3
Turni375 – 377Combined sources3
Beta strandi380 – 382Combined sources3
Turni385 – 387Combined sources3
Beta strandi399 – 401Combined sources3
Helixi403 – 410Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X4UNMR-A341-411[»]
ProteinModelPortaliQ5T4F4.
SMRiQ5T4F4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ5T4F4.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 205Sufficient for localization to endoplasmic reticulum tubular network and for interactions with REEP1, REEP5, ATL1, ATL2, ATL3 and SPAST2 PublicationsAdd BLAST205
Regioni1 – 92Sufficient for homooligomerization1 PublicationAdd BLAST92
Regioni51 – 64Necessary for interaction with RAB11A and function in neurite outgrowth1 PublicationAdd BLAST14
Regioni271 – 361Necessary for interaction with KIF5A1 PublicationAdd BLAST91
Regioni286 – 292Necessary for interaction with VAPA and function in cell projections formation7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi246 – 249Poly-Pro4

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri344 – 410FYVE-typePROSITE-ProRule annotationAdd BLAST67

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJBT. Eukaryota.
ENOG4111KCR. LUCA.
GeneTreeiENSGT00390000013298.
HOGENOMiHOG000155785.
HOVERGENiHBG054907.
InParanoidiQ5T4F4.
KOiK19368.
OMAiRCCSFKV.
OrthoDBiEOG091G0QCA.
PhylomeDBiQ5T4F4.
TreeFamiTF331044.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
PfamiView protein in Pfam
PF01363. FYVE. 1 hit.
SMARTiView protein in SMART
SM00064. FYVE. 1 hit.
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiView protein in PROSITE
PS50178. ZF_FYVE. 1 hit.

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5T4F4-1) [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
MQTSEREGSG PELSPSVMPE APLESPPFPT KSPAFDLFNL VLSYKRLEIY 
        60         70         80         90        100
LEPLKDAGDG VRYLLRWQMP LCSLLTCLGL NVLFLTLNEG AWYSVGALMI 
       110        120        130        140        150
SVPALLGYLQ EVCRARLPDS ELMRRKYHSV RQEDLQRGRL SRPEAVAEVK 
       160        170        180        190        200
SFLIQLEAFL SRLCCTCEAA YRVLHWENPV VSSQFYGALL GTVCMLYLLP 
       210        220        230        240        250
LCWVLTLLNS TLFLGNVEFF RVVSEYRASL QQRMNPKQEE HAFESPPPPD 
       260        270        280        290        300
VGGKDGLMDS TPALTPTEDL TPGSVEEAEE AEPDEEFKDA IEETHLVVLE 
       310        320        330        340        350
DDEGAPCPAE DELALQDNGF LSKNEVLRSK VSRLTERLRK RYPTNNFGNC 
       360        370        380        390        400
TGCSATFSVL KKRRSCSNCG NSFCSRCCSF KVPKSSMGAT APEAQRETVF 
       410 
VCASCNQTLS K
Length:411
Mass (Da):45,843
Last modified:December 21, 2004 - v1
Checksum:i5B86C64A398033D2
GO
Isoform 2 (identifier: Q5T4F4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     294-300: Missing.

Show »
Length:404
Mass (Da):45,052
Checksum:i0FA0436DAE7716D7
GO
Isoform 3 (identifier: Q5T4F4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     268-268: E → ESLSSQ

Show »
Length:416
Mass (Da):46,346
Checksum:iBF488D2456C6B924
GO
Isoform 4 (identifier: Q5T4F4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: Missing.
     268-268: E → ESLSSQ
     294-300: Missing.
     349-356: NCTGCSAT → VTGAGSS
     357-411: Missing.

Show »
Length:285
Mass (Da):31,744
Checksum:i977E99E1E5857BDD
GO
Isoform 5 (identifier: Q5T4F4-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     66-152: RWQMPLCSLL...PEAVAEVKSF → S
     294-300: Missing.

Show »
Length:318
Mass (Da):35,205
Checksum:i1E3E1DF487779DEB
GO
Isoform 6 (identifier: Q5T4F4-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     67-184: Missing.
     294-300: Missing.

Note: No experimental confirmation available.
Show »
Length:286
Mass (Da):31,612
Checksum:iC4F817D0A286151B
GO
Isoform 7 (identifier: Q5T4F4-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: Missing.
     268-268: E → ESLSSQ
     294-300: Missing.

Note: No experimental confirmation available.
Show »
Length:311
Mass (Da):34,681
Checksum:i3035EAF2EF4EEA53
GO
Isoform 8 (identifier: Q5T4F4-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-89: Missing.
     294-300: Missing.

Note: No experimental confirmation available.
Show »
Length:372
Mass (Da):41,417
Checksum:i0D235A6E1A98B2E2
GO

Sequence cautioni

The sequence CAD38913 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti50Y → N in AAH30621 (PubMed:15489334).Curated1
Sequence conflicti218E → G in BAC11260 (PubMed:14702039).Curated1
Sequence conflicti222V → F in BAH13112 (PubMed:14702039).Curated1
Sequence conflicti340K → R in BAH13112 (PubMed:14702039).Curated1
Sequence conflicti387M → A in BAH13112 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02700282V → I. Corresponds to variant dbSNP:rs17108378Ensembl.1
Natural variantiVAR_027003138G → V3 PublicationsCorresponds to variant dbSNP:rs10882993Ensembl.1
Natural variantiVAR_027269191G → V in SPG33; no effect on its function in the regulation of ER morphology and stability, no effect on its localization to ER but according to PubMed:16826525 an aberrant subcellular localization to cell membrane seen, altered interaction with SPAST, increased susceptibility to ER stress, no effect on its interaction with REEP1, REEP5 and ATL1 and increased protein stabilty. 4 PublicationsCorresponds to variant dbSNP:rs35077384Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0452651 – 98Missing in isoform 7. 1 PublicationAdd BLAST98
Alternative sequenceiVSP_0197511 – 68Missing in isoform 4. 1 PublicationAdd BLAST68
Alternative sequenceiVSP_04605158 – 89Missing in isoform 8. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_01975266 – 152RWQMP…EVKSF → S in isoform 5. 1 PublicationAdd BLAST87
Alternative sequenceiVSP_04526667 – 184Missing in isoform 6. 1 PublicationAdd BLAST118
Alternative sequenceiVSP_019753268E → ESLSSQ in isoform 3, isoform 4 and isoform 7. 2 Publications1
Alternative sequenceiVSP_019754294 – 300Missing in isoform 2, isoform 4, isoform 5, isoform 6, isoform 7 and isoform 8. 1 Publication7
Alternative sequenceiVSP_019755349 – 356NCTGCSAT → VTGAGSS in isoform 4. 1 Publication8
Alternative sequenceiVSP_019756357 – 411Missing in isoform 4. 1 PublicationAdd BLAST55

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK057481 mRNA. Translation: BAB71506.1.
AK097945 mRNA. Translation: BAC05200.1.
AK074876 mRNA. Translation: BAC11260.1.
AK296295 mRNA. Translation: BAH12306.1.
AK296588 mRNA. Translation: BAH12390.1.
AK299735 mRNA. Translation: BAH13112.1.
AL358938 Genomic DNA. Translation: CAI14270.1.
AL358938 Genomic DNA. Translation: CAI14271.1.
AL358938 Genomic DNA. Translation: CAI14272.1.
BC030621 mRNA. Translation: AAH30621.2.
AL834235 mRNA. Translation: CAD38913.2. Different initiation.
CCDSiCCDS31262.1. [Q5T4F4-3]
CCDS31263.1. [Q5T4F4-1]
CCDS31264.1. [Q5T4F4-2]
CCDS53562.1. [Q5T4F4-8]
CCDS53563.1. [Q5T4F4-5]
CCDS53564.1. [Q5T4F4-6]
CCDS53565.1. [Q5T4F4-7]
RefSeqiNP_001002261.1. NM_001002261.3. [Q5T4F4-3]
NP_001002262.1. NM_001002262.3. [Q5T4F4-2]
NP_001167590.1. NM_001174119.1. [Q5T4F4-8]
NP_001167591.1. NM_001174120.1. [Q5T4F4-5]
NP_001167592.1. NM_001174121.1. [Q5T4F4-7]
NP_001167593.1. NM_001174122.1. [Q5T4F4-6]
NP_653189.3. NM_144588.6. [Q5T4F4-1]
XP_005269559.1. XM_005269502.3. [Q5T4F4-3]
XP_005269560.1. XM_005269503.3. [Q5T4F4-3]
XP_005269561.1. XM_005269504.3. [Q5T4F4-1]
XP_005269563.1. XM_005269506.3. [Q5T4F4-2]
UniGeneiHs.744075.

Genome annotation databases

EnsembliENST00000337540; ENSP00000337993; ENSG00000155256. [Q5T4F4-8]
ENST00000357540; ENSP00000350148; ENSG00000155256. [Q5T4F4-5]
ENST00000359980; ENSP00000353069; ENSG00000155256. [Q5T4F4-2]
ENST00000370610; ENSP00000359642; ENSG00000155256. [Q5T4F4-7]
ENST00000370613; ENSP00000359646; ENSG00000155256. [Q5T4F4-6]
ENST00000393677; ENSP00000377282; ENSG00000155256. [Q5T4F4-1]
ENST00000423811; ENSP00000409594; ENSG00000155256. [Q5T4F4-3]
GeneIDi118813.
KEGGihsa:118813.
UCSCiuc001kol.3. human. [Q5T4F4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.

Entry informationi

Entry nameiZFY27_HUMAN
AccessioniPrimary (citable) accession number: Q5T4F4
Secondary accession number(s): B7Z3S0
, B7Z404, B7Z626, G8JLC3, G8JLF0, J3KP98, Q5T4F1, Q5T4F2, Q5T4F3, Q8N1K0, Q8N6D6, Q8NCA0, Q8NDE4, Q96M08
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: December 21, 2004
Last modified: June 7, 2017
This is version 130 of the entry and version 1 of the sequence. See 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 10
    Human chromosome 10: 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