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Protein

Ubiquitin carboxyl-terminal hydrolase MINDY-1

Gene

FAM63A

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

Functioni

Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins. Has exodeubiquitinase activity and has a preference for long polyubiquitin chains. May play a regulatory role at the level of protein turnover.1 Publication

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei137Nucleophile1 Publication1
Active sitei319Proton acceptor1 Publication1

GO - Molecular functioni

  • cysteine-type carboxypeptidase activity Source: UniProtKB
  • Lys48-specific deubiquitinase activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase MINDY-11 Publication (EC:3.4.19.121 Publication)
Alternative name(s):
Deubiquitinating enzyme MINDY-11 Publication
Protein FAM63A
Gene namesi
Name:FAM63A
Synonyms:KIAA1390
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:25648. FAM63A.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: HPA
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi131Q → A or E: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi137C → A: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi209D → A: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi210V → A: Greatly impairs ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi240W → A: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi258Y → A: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi263E → A: Greatly impairs ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi263E → R: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi315F → A: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi319H → A: Abolishes ubiquitin hydrolase activity. 1 Publication1
Mutagenesisi415 – 416LA → AG: Decreases association of proteins with 'Lys-48'-linked conjugated ubiquitin. 1 Publication2

Organism-specific databases

DisGeNETi55793.
OpenTargetsiENSG00000143409.
PharmGKBiPA142671872.

Polymorphism and mutation databases

BioMutaiFAM63A.
DMDMi311033379.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003440371 – 469Ubiquitin carboxyl-terminal hydrolase MINDY-1Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei103PhosphoserineCombined sources1
Modified residuei441PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8N5J2.
MaxQBiQ8N5J2.
PaxDbiQ8N5J2.
PeptideAtlasiQ8N5J2.
PRIDEiQ8N5J2.
TopDownProteomicsiQ8N5J2-2. [Q8N5J2-2]

PTM databases

iPTMnetiQ8N5J2.
PhosphoSitePlusiQ8N5J2.

Expressioni

Gene expression databases

BgeeiENSG00000143409.
CleanExiHS_FAM63A.
ExpressionAtlasiQ8N5J2. baseline and differential.
GenevisibleiQ8N5J2. HS.

Organism-specific databases

HPAiHPA028351.
HPA028358.
HPA061086.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
FLJ13057Q53SE73EBI-372322,EBI-10172181

Protein-protein interaction databases

BioGridi120906. 11 interactors.
IntActiQ8N5J2. 4 interactors.
STRINGi9606.ENSP00000354669.

Structurei

Secondary structure

1469
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi113 – 121Combined sources9
Beta strandi124 – 129Combined sources6
Helixi137 – 148Combined sources12
Beta strandi160 – 162Combined sources3
Helixi163 – 174Combined sources12
Helixi188 – 206Combined sources19
Beta strandi208 – 210Combined sources3
Helixi224 – 231Combined sources8
Beta strandi236 – 239Combined sources4
Helixi247 – 253Combined sources7
Helixi258 – 270Combined sources13
Helixi274 – 289Combined sources16
Turni290 – 292Combined sources3
Helixi296 – 305Combined sources10
Beta strandi311 – 316Combined sources6
Beta strandi319 – 326Combined sources8
Beta strandi329 – 333Combined sources5
Helixi337 – 339Combined sources3
Beta strandi347 – 349Combined sources3
Beta strandi353 – 355Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JKNX-ray3.00A110-384[»]
5JQSX-ray2.65A110-384[»]
ProteinModelPortaliQ8N5J2.
SMRiQ8N5J2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni388 – 426Ubiquitin-binding domain (UBD)1 PublicationAdd BLAST39

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi386 – 431Gln-richAdd BLAST46

Sequence similaritiesi

Belongs to the peptidase MINDY family. FAM63 subfamily.Curated

Phylogenomic databases

eggNOGiKOG2427. Eukaryota.
ENOG41102GM. LUCA.
GeneTreeiENSGT00390000016607.
HOVERGENiHBG054318.
InParanoidiQ8N5J2.
OMAiVIPENHE.
OrthoDBiEOG091G0C4Y.
PhylomeDBiQ8N5J2.
TreeFamiTF314589.

Family and domain databases

InterProiIPR007518. MINDY.
IPR033979. MINDY_domain.
[Graphical view]
PANTHERiPTHR18063. PTHR18063. 1 hit.
PfamiPF04424. DUF544. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N5J2-1) [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
MEYHQPEDPA PGKAGTAEAV IPENHEVLAG PDEHPQDTDA RDADGEARER
60 70 80 90 100
EPADQALLPS QCGDNLESPL PEASSAPPGP TLGTLPEVET IRACSMPQEL
110 120 130 140 150
PQSPRTRQPE PDFYCVKWIP WKGEQTPIIT QSTNGPCPLL AIMNILFLQW
160 170 180 190 200
KVKLPPQKEV ITSDELMAHL GNCLLSIKPQ EKSEGLQLNF QQNVDDAMTV
210 220 230 240 250
LPKLATGLDV NVRFTGVSDF EYTPECSVFD LLGIPLYHGW LVDPQSPEAV
260 270 280 290 300
RAVGKLSYNQ LVERIITCKH SSDTNLVTEG LIAEQFLETT AAQLTYHGLC
310 320 330 340 350
ELTAAAKEGE LSVFFRNNHF STMTKHKSHL YLLVTDQGFL QEEQVVWESL
360 370 380 390 400
HNVDGDSCFC DSDFHLSHSL GKGPGAEGGS GSPETQLQVD QDYLIALSLQ
410 420 430 440 450
QQQPRGPLGL TDLELAQQLQ QEEYQQQQAA QPVRMRTRVL SLQGRGATSG
460
RPAGERRQRP KHESDCILL
Length:469
Mass (Da):51,778
Last modified:November 2, 2010 - v2
Checksum:iFEB658BAF8A878C6
GO
Isoform 2 (identifier: Q8N5J2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-142: Missing.

Show »
Length:327
Mass (Da):36,458
Checksum:iA0B153B6B2217B7A
GO
Isoform 3 (identifier: Q8N5J2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLLGPPPFNESTKPSPSPCHSFASQAWLRQVPEVSKHLQCPSAKSLLTM

Show »
Length:517
Mass (Da):56,991
Checksum:i6BBA4F7A62BF16FD
GO
Isoform 4 (identifier: Q8N5J2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-95: Missing.

Show »
Length:374
Mass (Da):41,833
Checksum:i49C3DA92F5491B1A
GO

Sequence cautioni

The sequence BAA92628 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti287L → P in BAA92104 (PubMed:14702039).Curated1
Sequence conflicti367S → R in BAA92104 (PubMed:14702039).Curated1
Isoform 3 (identifier: Q8N5J2-3)
Sequence conflicti44K → E in BAG63364 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_044541385T → K.4 PublicationsCorresponds to variant rs2925741dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0347151 – 142Missing in isoform 2. 1 PublicationAdd BLAST142
Alternative sequenceiVSP_0370761 – 95Missing in isoform 4. 1 PublicationAdd BLAST95
Alternative sequenceiVSP_0370771M → MLLGPPPFNESTKPSPSPCH SFASQAWLRQVPEVSKHLQC PSAKSLLTM in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037811 mRNA. Translation: BAA92628.1. Different initiation.
AK002142 mRNA. Translation: BAA92104.1.
AK125493 mRNA. Translation: BAG54206.1.
AK125959 mRNA. Translation: BAG54270.1.
AK301946 mRNA. Translation: BAG63364.1.
AK303962 mRNA. Translation: BAG64886.1.
AL590133 Genomic DNA. Translation: CAI13336.1.
CH471121 Genomic DNA. Translation: EAW53491.1.
CH471121 Genomic DNA. Translation: EAW53492.1.
CH471121 Genomic DNA. Translation: EAW53493.1.
CH471121 Genomic DNA. Translation: EAW53495.1.
BC032321 mRNA. Translation: AAH32321.1.
CCDSiCCDS30854.1. [Q8N5J2-2]
CCDS53361.1. [Q8N5J2-3]
CCDS55635.1. [Q8N5J2-4]
CCDS976.1. [Q8N5J2-1]
RefSeqiNP_001035307.1. NM_001040217.2.
NP_001156730.1. NM_001163258.1.
NP_001156731.1. NM_001163259.1.
NP_001156732.1. NM_001163260.1.
NP_001306927.1. NM_001319998.1.
NP_060849.2. NM_018379.4.
XP_016857261.1. XM_017001772.1. [Q8N5J2-1]
XP_016857266.1. XM_017001777.1. [Q8N5J2-3]
UniGeneiHs.743952.

Genome annotation databases

EnsembliENST00000312210; ENSP00000310923; ENSG00000143409. [Q8N5J2-2]
ENST00000361738; ENSP00000354669; ENSG00000143409. [Q8N5J2-3]
ENST00000361936; ENSP00000354814; ENSG00000143409. [Q8N5J2-1]
ENST00000493834; ENSP00000437174; ENSG00000143409. [Q8N5J2-4]
ENST00000622754; ENSP00000481304; ENSG00000143409. [Q8N5J2-1]
GeneIDi55793.
KEGGihsa:55793.
UCSCiuc001ewd.4. human. [Q8N5J2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037811 mRNA. Translation: BAA92628.1. Different initiation.
AK002142 mRNA. Translation: BAA92104.1.
AK125493 mRNA. Translation: BAG54206.1.
AK125959 mRNA. Translation: BAG54270.1.
AK301946 mRNA. Translation: BAG63364.1.
AK303962 mRNA. Translation: BAG64886.1.
AL590133 Genomic DNA. Translation: CAI13336.1.
CH471121 Genomic DNA. Translation: EAW53491.1.
CH471121 Genomic DNA. Translation: EAW53492.1.
CH471121 Genomic DNA. Translation: EAW53493.1.
CH471121 Genomic DNA. Translation: EAW53495.1.
BC032321 mRNA. Translation: AAH32321.1.
CCDSiCCDS30854.1. [Q8N5J2-2]
CCDS53361.1. [Q8N5J2-3]
CCDS55635.1. [Q8N5J2-4]
CCDS976.1. [Q8N5J2-1]
RefSeqiNP_001035307.1. NM_001040217.2.
NP_001156730.1. NM_001163258.1.
NP_001156731.1. NM_001163259.1.
NP_001156732.1. NM_001163260.1.
NP_001306927.1. NM_001319998.1.
NP_060849.2. NM_018379.4.
XP_016857261.1. XM_017001772.1. [Q8N5J2-1]
XP_016857266.1. XM_017001777.1. [Q8N5J2-3]
UniGeneiHs.743952.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JKNX-ray3.00A110-384[»]
5JQSX-ray2.65A110-384[»]
ProteinModelPortaliQ8N5J2.
SMRiQ8N5J2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120906. 11 interactors.
IntActiQ8N5J2. 4 interactors.
STRINGi9606.ENSP00000354669.

PTM databases

iPTMnetiQ8N5J2.
PhosphoSitePlusiQ8N5J2.

Polymorphism and mutation databases

BioMutaiFAM63A.
DMDMi311033379.

Proteomic databases

EPDiQ8N5J2.
MaxQBiQ8N5J2.
PaxDbiQ8N5J2.
PeptideAtlasiQ8N5J2.
PRIDEiQ8N5J2.
TopDownProteomicsiQ8N5J2-2. [Q8N5J2-2]

Protocols and materials databases

DNASUi55793.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312210; ENSP00000310923; ENSG00000143409. [Q8N5J2-2]
ENST00000361738; ENSP00000354669; ENSG00000143409. [Q8N5J2-3]
ENST00000361936; ENSP00000354814; ENSG00000143409. [Q8N5J2-1]
ENST00000493834; ENSP00000437174; ENSG00000143409. [Q8N5J2-4]
ENST00000622754; ENSP00000481304; ENSG00000143409. [Q8N5J2-1]
GeneIDi55793.
KEGGihsa:55793.
UCSCiuc001ewd.4. human. [Q8N5J2-1]

Organism-specific databases

CTDi55793.
DisGeNETi55793.
GeneCardsiFAM63A.
H-InvDBHIX0001041.
HGNCiHGNC:25648. FAM63A.
HPAiHPA028351.
HPA028358.
HPA061086.
neXtProtiNX_Q8N5J2.
OpenTargetsiENSG00000143409.
PharmGKBiPA142671872.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2427. Eukaryota.
ENOG41102GM. LUCA.
GeneTreeiENSGT00390000016607.
HOVERGENiHBG054318.
InParanoidiQ8N5J2.
OMAiVIPENHE.
OrthoDBiEOG091G0C4Y.
PhylomeDBiQ8N5J2.
TreeFamiTF314589.

Miscellaneous databases

ChiTaRSiFAM63A. human.
GenomeRNAii55793.
PROiQ8N5J2.

Gene expression databases

BgeeiENSG00000143409.
CleanExiHS_FAM63A.
ExpressionAtlasiQ8N5J2. baseline and differential.
GenevisibleiQ8N5J2. HS.

Family and domain databases

InterProiIPR007518. MINDY.
IPR033979. MINDY_domain.
[Graphical view]
PANTHERiPTHR18063. PTHR18063. 1 hit.
PfamiPF04424. DUF544. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFA63A_HUMAN
AccessioniPrimary (citable) accession number: Q8N5J2
Secondary accession number(s): B3KWP4
, B3KWV8, B4DXF2, B4E1S4, D3DV09, J3KP53, Q5SZF0, Q9NUL9, Q9P2F7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: November 2, 2010
Last modified: November 30, 2016
This is version 112 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 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Peptidase families
    Classification of peptidase families and list of entries
  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.