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Protein

HCLS1-associated protein X-1

Gene

HAX1

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

Functioni

Recruits the Arp2/3 complex to the cell cortex and regulates reorganization of the cortical actin cytoskeleton via its interaction with KCNC3 and the Arp2/3 complex (PubMed:26997484). Slows down the rate of inactivation of KCNC3 channels (PubMed:26997484). Promotes GNA13-mediated cell migration. Involved in the clathrin-mediated endocytosis pathway. May be involved in internalization of ABC transporters such as ABCB11. May inhibit CASP9 and CASP3. Promotes cell survival. May regulate intracellular calcium pools.7 Publications

GO - Molecular functioni

  • interleukin-1 binding Source: UniProtKB
  • protein N-terminus binding Source: UniProtKB

GO - Biological processi

  • cellular response to cytokine stimulus Source: BHF-UCL
  • negative regulation of apoptotic process Source: UniProtKB
  • positive regulation of actin cytoskeleton reorganization Source: BHF-UCL
  • positive regulation of granulocyte differentiation Source: BHF-UCL
  • positive regulation of peptidyl-serine phosphorylation Source: BHF-UCL
  • positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  • positive regulation of protein kinase B signaling Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • regulation of actin filament polymerization Source: BHF-UCL
  • regulation of apoptotic process Source: ParkinsonsUK-UCL
  • regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
  • regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL

Enzyme and pathway databases

SIGNORiO00165

Names & Taxonomyi

Protein namesi
Recommended name:
HCLS1-associated protein X-1
Alternative name(s):
HS1-associating protein X-1
Short name:
HAX-1
HS1-binding protein 1
Short name:
HSP1BP-1
Gene namesi
Name:HAX1
Synonyms:HS1BP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143575.14
HGNCiHGNC:16915 HAX1
MIMi605998 gene
neXtProtiNX_O00165

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Mitochondrion, Nucleus, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Neutropenia, severe congenital 3, autosomal recessive (SCN3)4 Publications
The disease is caused by mutations affecting the gene represented in this entry. The clinical phenotype due to HAX1 deficiency appears to depend on the localization of the mutations and their influence on the transcript variants. Mutations affecting exclusively isoform 1 are associated with isolated congenital neutropenia, whereas mutations affecting both isoform 1 and isoform 5 are associated with additional neurologic symptoms (PubMed:18337561).1 Publication
Disease descriptionA disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. Some patients affected by severe congenital neutropenia type 3 have neurological manifestations such as psychomotor retardation and seizures.
See also OMIM:610738
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064514130L → R in SCN3. 1 PublicationCorresponds to variant dbSNP:rs179363871EnsemblClinVar.1
Natural variantiVAR_062259141F → L in SCN3; mild form. 1 PublicationCorresponds to variant dbSNP:rs179363870EnsemblClinVar.1
Natural variantiVAR_064515172V → I in SCN3. 1 PublicationCorresponds to variant dbSNP:rs141970914EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10456
MalaCardsiHAX1
MIMi610738 phenotype
OpenTargetsiENSG00000143575
Orphaneti99749 Kostmann syndrome
PharmGKBiPA142671700

Polymorphism and mutation databases

BioMutaiHAX1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000839062 – 279HCLS1-associated protein X-1Add BLAST278

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei189PhosphoserineCombined sources1
Modified residuei192PhosphoserineCombined sources1

Post-translational modificationi

Proteolytically cleaved by caspase-3 during apoptosis.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei127 – 128Cleavage; by caspase-32

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO00165
MaxQBiO00165
PaxDbiO00165
PeptideAtlasiO00165
PRIDEiO00165
ProteomicsDBi47750
47751 [O00165-2]
47752 [O00165-3]
47753 [O00165-4]
47754 [O00165-5]
47755 [O00165-6]
TopDownProteomicsiO00165-2 [O00165-2]

PTM databases

iPTMnetiO00165
PhosphoSitePlusiO00165

Miscellaneous databases

PMAP-CutDBiO00165

Expressioni

Tissue specificityi

Ubiquitous. Up-regulated in oral cancers.2 Publications

Gene expression databases

BgeeiENSG00000143575
CleanExiHS_HAX1
ExpressionAtlasiO00165 baseline and differential
GenevisibleiO00165 HS

Organism-specific databases

HPAiHPA055141
HPA075289

Interactioni

Subunit structurei

Interacts with ABCB1, ABCB4 and ABCB11 (By similarity). Directly associates with HCLS1/HS1, through binding to its N-terminal region (PubMed:9058808). Interacts with CTTN (By similarity). Interacts with PKD2 (PubMed:10760273). Interacts with GNA13 (PubMed:15339924). Interacts with CASP9 (PubMed:16857965). Interacts with ITGB6 (PubMed:17545607). Interacts with PLN and ATP2A2; these interactions are inhibited by calcium (PubMed:17241641, PubMed:18971376). Interacts with GRB7 (PubMed:20665473). Interacts (via C-terminus) with XIAP/BIRC4 (via BIR 2 domain and BIR 3 domain) and this interaction blocks ubiquitination of XIAP/BIRC4 (PubMed:20171186). Interacts with TPC2 (PubMed:24188827). Interacts with KCNC3 (PubMed:26997484). Interacts with XPO1 (PubMed:23164465).By similarity12 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • interleukin-1 binding Source: UniProtKB
  • protein N-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115719, 127 interactors
CORUMiO00165
DIPiDIP-36771N
IntActiO00165, 109 interactors
MINTiO00165
STRINGi9606.ENSP00000329002

Structurei

3D structure databases

ProteinModelPortaliO00165
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 41Required for localization in mitochondriaBy similarityAdd BLAST40
Regioni114 – 279Involved in HCLS1 bindingAdd BLAST166
Regioni175 – 206Involved in CASP9 bindingAdd BLAST32
Regioni176 – 247Involved in GNA13 bindingAdd BLAST72
Regioni183 – 279Required for localization in sarcoplasmic reticulumBy similarityAdd BLAST97
Regioni184 – 279Involved in PKD2 bindingAdd BLAST96
Regioni203 – 245Involved in ATP2A2 bindingAdd BLAST43
Regioni203 – 225Involved in PLN bindingAdd BLAST23
Regioni270 – 279Required for ITGB6 binding10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi30 – 40Asp/Glu-rich (highly acidic)Add BLAST11

Sequence similaritiesi

Belongs to the HAX1 family.Curated

Phylogenomic databases

eggNOGiENOG410IJQ0 Eukaryota
ENOG411211U LUCA
GeneTreeiENSGT00390000018324
HOVERGENiHBG002991
InParanoidiO00165
KOiK16220
OMAiPKPAPDW
OrthoDBiEOG091G0MK9
PhylomeDBiO00165
TreeFamiTF328619

Family and domain databases

InterProiView protein in InterPro
IPR017248 HAX-1
PIRSFiPIRSF037634 HS1-associating_X-1, 1 hit

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O00165-1) [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
MSLFDLFRGF FGFPGPRSHR DPFFGGMTRD EDDDEEEEEE GGSWGRGNPR
60 70 80 90 100
FHSPQHPPEE FGFGFSFSPG GGIRFHDNFG FDDLVRDFNS IFSDMGAWTL
110 120 130 140 150
PSHPPELPGP ESETPGERLR EGQTLRDSML KYPDSHQPRI FGGVLESDAR
160 170 180 190 200
SESPQPAPDW GSQRPFHRFD DVWPMDPHPR TREDNDLDSQ VSQEGLGPVL
210 220 230 240 250
QPQPKSYFKS ISVTKITKPD GIVEERRTVV DSEGRTETTV TRHEADSSPR
260 270
GDPESPRPPA LDDAFSILDL FLGRWFRSR
Length:279
Mass (Da):31,621
Last modified:January 23, 2002 - v2
Checksum:i87EEF0C46857704B
GO
Isoform 2 (identifier: O00165-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     105-105: P → PANTCHLSA

Show »
Length:287
Mass (Da):32,418
Checksum:i762F6F8897C11AB9
GO
Isoform 3 (identifier: O00165-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: Missing.

Show »
Length:253
Mass (Da):28,646
Checksum:iA7F85EF8A7E6E0AB
GO
Isoform 4 (identifier: O00165-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     106-124: ELPGPESETPGERLREGQT → GVWLSLRGNLWFLVGWWVK
     125-279: Missing.

Show »
Length:124
Mass (Da):14,235
Checksum:iB59B40DC8DF641E3
GO
Isoform 5 (identifier: O00165-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-65: Missing.

Show »
Length:231
Mass (Da):26,100
Checksum:i25EF194EC019C474
GO
Isoform 6 (identifier: O00165-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     85-264: VRDFNSIFSD...SPRPPALDDA → NFQVLSQRHL...SPNPISRASL
     265-279: Missing.

Show »
Length:191
Mass (Da):21,801
Checksum:iE9D736737D3F978F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25G → V in BAG62359 (Ref. 3) Curated1
Sequence conflicti45G → R in AAB51196 (PubMed:9058808).Curated1
Sequence conflicti201Q → T in AAB51196 (PubMed:9058808).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06225849P → S. Corresponds to variant dbSNP:rs11556344Ensembl.1
Natural variantiVAR_064514130L → R in SCN3. 1 PublicationCorresponds to variant dbSNP:rs179363871EnsemblClinVar.1
Natural variantiVAR_062259141F → L in SCN3; mild form. 1 PublicationCorresponds to variant dbSNP:rs179363870EnsemblClinVar.1
Natural variantiVAR_062260151S → G1 PublicationCorresponds to variant dbSNP:rs17851425Ensembl.1
Natural variantiVAR_064515172V → I in SCN3. 1 PublicationCorresponds to variant dbSNP:rs141970914EnsemblClinVar.1
Natural variantiVAR_062261278S → P. Corresponds to variant dbSNP:rs1804715Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0385361 – 26Missing in isoform 3. 2 PublicationsAdd BLAST26
Alternative sequenceiVSP_03854318 – 65Missing in isoform 5. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_03854485 – 264VRDFN…ALDDA → NFQVLSQRHLVRDYGRDRHF GTQCLSIQIVTSPGSLGGSW RVMQEVNPPNQHQTGAPRGH FIGLMMYGLWTPILEPERTM ILIPRFPRRVLARFYSPSPN PISRASL in isoform 6. 1 PublicationAdd BLAST180
Alternative sequenceiVSP_038537105P → PANTCHLSA in isoform 2. 2 Publications1
Alternative sequenceiVSP_038538106 – 124ELPGP…REGQT → GVWLSLRGNLWFLVGWWVK in isoform 4. 3 PublicationsAdd BLAST19
Alternative sequenceiVSP_038539125 – 279Missing in isoform 4. 3 PublicationsAdd BLAST155
Alternative sequenceiVSP_038545265 – 279Missing in isoform 6. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68566 mRNA Translation: AAB51196.1
EU190982 mRNA Translation: ABW73998.1
EU190983 mRNA Translation: ABW73999.1
AK290626 mRNA Translation: BAF83315.1
AK294298 mRNA Translation: BAG57580.1
AK300676 mRNA Translation: BAG62359.1
AL354980 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53212.1
BC005240 mRNA Translation: AAH05240.1
BC014314 mRNA Translation: AAH14314.1
BC015209 mRNA Translation: AAH15209.1
BC016730 mRNA Translation: AAH16730.1
CCDSiCCDS1064.1 [O00165-1]
CCDS44230.1 [O00165-5]
RefSeqiNP_001018238.1, NM_001018837.1 [O00165-5]
NP_006109.2, NM_006118.3 [O00165-1]
UniGeneiHs.199625

Genome annotation databases

EnsembliENST00000328703; ENSP00000329002; ENSG00000143575 [O00165-1]
ENST00000447768; ENSP00000403848; ENSG00000143575 [O00165-6]
ENST00000457918; ENSP00000411448; ENSG00000143575 [O00165-5]
ENST00000483970; ENSP00000435088; ENSG00000143575 [O00165-2]
GeneIDi10456
KEGGihsa:10456
UCSCiuc001fes.5 human [O00165-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHAX1_HUMAN
AccessioniPrimary (citable) accession number: O00165
Secondary accession number(s): A8W4W9
, A8W4X0, B4DUJ7, Q5VYD5, Q5VYD7, Q96AU4, Q9BS80
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2002
Last modified: June 20, 2018
This is version 172 of the entry and version 2 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

Complete proteome, Direct protein sequencing, Reference proteome

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