Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hermansky-Pudlak syndrome 4 protein

Gene

HPS4

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

Functioni

Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38 (PubMed:23084991).1 Publication

GO - Molecular functioni

  • guanyl-nucleotide exchange factor activity Source: UniProtKB-KW
  • protein dimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB

GO - Biological processi

  • blood coagulation Source: Ensembl
  • hemostasis Source: UniProtKB
  • lysosome organization Source: UniProtKB
  • melanocyte differentiation Source: Ensembl
  • melanosome assembly Source: UniProtKB
  • positive regulation of eye pigmentation Source: UniProtKB
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • protein stabilization Source: UniProtKB
  • protein targeting Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100099-MONOMER.
ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
Hermansky-Pudlak syndrome 4 protein
Alternative name(s):
Light-ear protein homolog
Gene namesi
Name:HPS4
Synonyms:KIAA1667
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:15844. HPS4.

Subcellular locationi

GO - Cellular componenti

  • BLOC-3 complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • lysosome Source: UniProtKB
  • melanosome Source: UniProtKB
  • membrane Source: UniProtKB
  • platelet dense granule Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Hermansky-Pudlak syndrome 4 (HPS4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.
See also OMIM:614073

Keywords - Diseasei

Albinism, Hermansky-Pudlak syndrome

Organism-specific databases

DisGeNETi89781.
MalaCardsiHPS4.
MIMi614073. phenotype.
OpenTargetsiENSG00000100099.
Orphaneti231500. Hermansky-Pudlak syndrome with pulmonary fibrosis.
PharmGKBiPA29434.

Polymorphism and mutation databases

DMDMi21362617.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000840521 – 708Hermansky-Pudlak syndrome 4 proteinAdd BLAST708

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei355PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9NQG7.
PaxDbiQ9NQG7.
PeptideAtlasiQ9NQG7.
PRIDEiQ9NQG7.

PTM databases

iPTMnetiQ9NQG7.
PhosphoSitePlusiQ9NQG7.

Expressioni

Gene expression databases

BgeeiENSG00000100099.
CleanExiHS_HPS4.
ExpressionAtlasiQ9NQG7. baseline and differential.
GenevisibleiQ9NQG7. HS.

Organism-specific databases

HPAiCAB033106.
HPA050189.

Interactioni

Subunit structurei

Component of the biogenesis of lysosome-related organelles complex-3 (or BLOC-3), a heterodimer of HPS1 and HPS4 (PubMed:20048159, PubMed:23084991). HPS4 and the BLOC-3 complex interact with the GTP-bound form of RAB9A and RAB9B but not with the GDP-bound form of RAB9A and RAB9B. The BLOC-3 complex does not interact with RAB5A, RAB7A and RAB27A (PubMed:20048159).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HPS1Q9290215EBI-704377,EBI-704347

GO - Molecular functioni

  • protein dimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • Rab GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi124600. 1 interactor.
IntActiQ9NQG7. 2 interactors.
STRINGi9606.ENSP00000338457.

Structurei

3D structure databases

ProteinModelPortaliQ9NQG7.
SMRiQ9NQG7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Phylogenomic databases

eggNOGiENOG410II2Z. Eukaryota.
ENOG4110KSY. LUCA.
GeneTreeiENSGT00390000007349.
HOVERGENiHBG031612.
InParanoidiQ9NQG7.
KOiK20194.
OMAiQAVSLMH.
OrthoDBiEOG091G0T3D.
PhylomeDBiQ9NQG7.
TreeFamiTF332819.

Family and domain databases

InterProiIPR026091. HPS4.
[Graphical view]
PANTHERiPTHR14407. PTHR14407. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9NQG7-1) [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
MATSTSTEAK SASWWNYFFL YDGSKVKEEG DPTRAGICYF YPSQTLLDQQ
60 70 80 90 100
ELLCGQIAGV VRCVSDISDS PPTLVRLRKL KFAIKVDGDY LWVLGCAVEL
110 120 130 140 150
PDVSCKRFLD QLVGFFNFYN GPVSLAYENC SQEELSTEWD TFIEQILKNT
160 170 180 190 200
SDLHKIFNSL WNLDQTKVEP LLLLKAARIL QTCQRSPHIL AGCILYKGLI
210 220 230 240 250
VSTQLPPSLT AKVLLHRTAP QEQRLPTGED APQEHGAALP PNVQIIPVFV
260 270 280 290 300
TKEEAISLHE FPVEQMTRSL ASPAGLQDGS AQHHPKGGST SALKENATGH
310 320 330 340 350
VESMAWTTPD PTSPDEACPD GRKENGCLSG HDLESIRPAG LHNSARGEVL
360 370 380 390 400
GLSSSLGKEL VFLQEELDLS EIHIPEAQEV EMASGHFAFL HVPVPDGRAP
410 420 430 440 450
YCKASLSASS SLEPTPPEDT AISSLRPPSA PEMLTQHGAQ EQLEDHPGHS
460 470 480 490 500
SQAPIPRADP LPRRTRRPLL LPRLDPGQRG NKLPTGEQGL DEDVDGVCES
510 520 530 540 550
HAAPGLECSS GSANCQGAGP SADGISSRLT PAESCMGLVR MNLYTHCVKG
560 570 580 590 600
LVLSLLAEEP LLGDSAAIEE VYHSSLASLN GLEVHLKETL PRDEAASTSS
610 620 630 640 650
TYNFTHYDRI QSLLMANLPQ VATPQDRRFL QAVSLMHSEF AQLPALYEMT
660 670 680 690 700
VRNASTAVYA CCNPIQETYF QQLAPAARSS GFPNPQDGAF SLSGKAKQKL

LKHGVNLL
Length:708
Mass (Da):76,919
Last modified:June 6, 2002 - v2
Checksum:iE47BCF49FC78830A
GO
Isoform 2 (identifier: Q9NQG7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     236-236: G → GKWMLWSFKNRVTHQNPNG
     463-510: RRTRRPLLLP...HAAPGLECSS → KSTVLFSGGC...FFDSMRQTAG
     511-708: Missing.

Note: No experimental confirmation available.
Show »
Length:528
Mass (Da):58,067
Checksum:i59CCB0697F2192EA
GO
Isoform 3 (identifier: Q9NQG7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MATSTSTEAKSASW → MAPLCSLAR

Note: No experimental confirmation available.
Show »
Length:703
Mass (Da):76,423
Checksum:iC73D3EE841604112
GO
Isoform 4 (identifier: Q9NQG7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MATSTSTEAKSASW → MAPLCSLAR
     236-236: G → GKWMLWSFKNRVTHQNPNG

Note: No experimental confirmation available.
Show »
Length:721
Mass (Da):78,648
Checksum:i60F5499DBDBAF003
GO

Sequence cautioni

The sequence BAB33337 differs from that shown. Intron retention.Curated
The sequence BAB33337 differs from that shown. Reason: Frameshift at position 237.Curated
The sequence BC035614 differs from that shown. Intron retention.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti168V → A (PubMed:15489334).Curated1
Sequence conflicti430A → V in BAB71540 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025006229E → G.3 PublicationsCorresponds to variant rs713998dbSNPEnsembl.1
Natural variantiVAR_024158443L → V.1 PublicationCorresponds to variant rs2014410dbSNPEnsembl.1
Natural variantiVAR_025007552V → M.3 PublicationsCorresponds to variant rs5752330dbSNPEnsembl.1
Natural variantiVAR_024159606H → Y.3 PublicationsCorresponds to variant rs1894706dbSNPEnsembl.1
Natural variantiVAR_021836625Q → H.2 PublicationsCorresponds to variant rs1894704dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0170821 – 14MATST…KSASW → MAPLCSLAR in isoform 3 and isoform 4. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_003880236G → GKWMLWSFKNRVTHQNPNG in isoform 2 and isoform 4. 2 Publications1
Alternative sequenceiVSP_003881463 – 510RRTRR…LECSS → KSTVLFSGGCVKGSDTQLCV PGLVWYLEPQFYYVIVRHFF DSMRQTAG in isoform 2. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_003882511 – 708Missing in isoform 2. 1 PublicationAdd BLAST198

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY043416 mRNA. Translation: AAK95330.1.
AL365512 mRNA. Translation: CAB97208.1.
AK057648 mRNA. Translation: BAB71540.1.
AL713795 mRNA. Translation: CAD28549.1.
Z99714 Genomic DNA. Translation: CAI17880.1.
Z99714 Genomic DNA. Translation: CAQ09361.1.
BC035614 mRNA. No translation available.
AB051454 mRNA. Translation: BAB33337.1. Sequence problems.
CCDSiCCDS13835.1. [Q9NQG7-1]
CCDS46677.1. [Q9NQG7-3]
RefSeqiNP_071364.4. NM_022081.5. [Q9NQG7-1]
NP_690054.1. NM_152841.2. [Q9NQG7-3]
XP_016884531.1. XM_017029042.1. [Q9NQG7-1]
XP_016884532.1. XM_017029043.1. [Q9NQG7-1]
XP_016884533.1. XM_017029044.1. [Q9NQG7-1]
UniGeneiHs.474436.

Genome annotation databases

EnsembliENST00000336873; ENSP00000338457; ENSG00000100099. [Q9NQG7-1]
ENST00000398145; ENSP00000381213; ENSG00000100099. [Q9NQG7-1]
ENST00000402105; ENSP00000384185; ENSG00000100099. [Q9NQG7-3]
GeneIDi89781.
KEGGihsa:89781.
UCSCiuc003aci.5. human. [Q9NQG7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Mutations of the HPS4 gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY043416 mRNA. Translation: AAK95330.1.
AL365512 mRNA. Translation: CAB97208.1.
AK057648 mRNA. Translation: BAB71540.1.
AL713795 mRNA. Translation: CAD28549.1.
Z99714 Genomic DNA. Translation: CAI17880.1.
Z99714 Genomic DNA. Translation: CAQ09361.1.
BC035614 mRNA. No translation available.
AB051454 mRNA. Translation: BAB33337.1. Sequence problems.
CCDSiCCDS13835.1. [Q9NQG7-1]
CCDS46677.1. [Q9NQG7-3]
RefSeqiNP_071364.4. NM_022081.5. [Q9NQG7-1]
NP_690054.1. NM_152841.2. [Q9NQG7-3]
XP_016884531.1. XM_017029042.1. [Q9NQG7-1]
XP_016884532.1. XM_017029043.1. [Q9NQG7-1]
XP_016884533.1. XM_017029044.1. [Q9NQG7-1]
UniGeneiHs.474436.

3D structure databases

ProteinModelPortaliQ9NQG7.
SMRiQ9NQG7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124600. 1 interactor.
IntActiQ9NQG7. 2 interactors.
STRINGi9606.ENSP00000338457.

PTM databases

iPTMnetiQ9NQG7.
PhosphoSitePlusiQ9NQG7.

Polymorphism and mutation databases

DMDMi21362617.

Proteomic databases

MaxQBiQ9NQG7.
PaxDbiQ9NQG7.
PeptideAtlasiQ9NQG7.
PRIDEiQ9NQG7.

Protocols and materials databases

DNASUi89781.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336873; ENSP00000338457; ENSG00000100099. [Q9NQG7-1]
ENST00000398145; ENSP00000381213; ENSG00000100099. [Q9NQG7-1]
ENST00000402105; ENSP00000384185; ENSG00000100099. [Q9NQG7-3]
GeneIDi89781.
KEGGihsa:89781.
UCSCiuc003aci.5. human. [Q9NQG7-1]

Organism-specific databases

CTDi89781.
DisGeNETi89781.
GeneCardsiHPS4.
GeneReviewsiHPS4.
HGNCiHGNC:15844. HPS4.
HPAiCAB033106.
HPA050189.
MalaCardsiHPS4.
MIMi606682. gene.
614073. phenotype.
neXtProtiNX_Q9NQG7.
OpenTargetsiENSG00000100099.
Orphaneti231500. Hermansky-Pudlak syndrome with pulmonary fibrosis.
PharmGKBiPA29434.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410II2Z. Eukaryota.
ENOG4110KSY. LUCA.
GeneTreeiENSGT00390000007349.
HOVERGENiHBG031612.
InParanoidiQ9NQG7.
KOiK20194.
OMAiQAVSLMH.
OrthoDBiEOG091G0T3D.
PhylomeDBiQ9NQG7.
TreeFamiTF332819.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100099-MONOMER.
ReactomeiR-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.

Miscellaneous databases

ChiTaRSiHPS4. human.
GeneWikiiHPS4.
GenomeRNAii89781.
PROiQ9NQG7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100099.
CleanExiHS_HPS4.
ExpressionAtlasiQ9NQG7. baseline and differential.
GenevisibleiQ9NQG7. HS.

Family and domain databases

InterProiIPR026091. HPS4.
[Graphical view]
PANTHERiPTHR14407. PTHR14407. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiHPS4_HUMAN
AccessioniPrimary (citable) accession number: Q9NQG7
Secondary accession number(s): B1AHQ4
, Q5H8V6, Q96LX6, Q9BY93, Q9UH37, Q9UH38
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: June 6, 2002
Last modified: November 30, 2016
This is version 136 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: 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

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.