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Protein

Hematopoietic lineage cell-specific protein

Gene

HCLS1

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

Functioni

Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression.

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL

GO - Biological processi

  • actin filament polymerization Source: InterPro
  • cellular response to cytokine stimulus Source: BHF-UCL
  • erythrocyte differentiation Source: UniProtKB
  • intracellular signal transduction Source: ProtInc
  • negative regulation of leukocyte apoptotic process Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • positive regulation of actin cytoskeleton reorganization Source: BHF-UCL
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of granulocyte differentiation Source: BHF-UCL
  • positive regulation of macrophage differentiation Source: Ensembl
  • 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 factor import into nucleus Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: UniProtKB
  • regulation of actin filament polymerization Source: BHF-UCL
  • regulation of transcription, DNA-templated Source: ProtInc
  • response to hormone Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180353-MONOMER.
SIGNORiP14317.

Names & Taxonomyi

Protein namesi
Recommended name:
Hematopoietic lineage cell-specific protein
Alternative name(s):
Hematopoietic cell-specific LYN substrate 1
LckBP1
p75
Gene namesi
Name:HCLS1
Synonyms:HS1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:4844. HCLS1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • membrane Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi3059.
OpenTargetsiENSG00000180353.
PharmGKBiPA29220.

Polymorphism and mutation databases

BioMutaiHCLS1.
DMDMi317373440.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000839211 – 486Hematopoietic lineage cell-specific proteinAdd BLAST486

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei41N6-acetyllysineCombined sources1
Modified residuei123N6-acetyllysineCombined sources1
Modified residuei140PhosphotyrosineBy similarity1
Modified residuei192N6-acetyllysineCombined sources1
Modified residuei198PhosphotyrosineCombined sources1
Modified residuei222Phosphotyrosine; by FGR2 Publications1
Modified residuei241N6-acetyllysineCombined sources1
Modified residuei275PhosphoserineCombined sources1
Modified residuei308PhosphothreonineCombined sources1
Modified residuei378Phosphotyrosine; by SYK and FESBy similarity1
Modified residuei397Phosphotyrosine; by SYK and FESBy similarity1

Post-translational modificationi

Phosphorylated by FES (By similarity). Phosphorylated by LYN, FYN and FGR after cross-linking of surface IgM on B-cells. Phosphorylation by LYN, FYN and FGR requires prior phosphorylation by SYK or FES.By similarity3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP14317.
MaxQBiP14317.
PaxDbiP14317.
PeptideAtlasiP14317.
PRIDEiP14317.

PTM databases

iPTMnetiP14317.
PhosphoSitePlusiP14317.

Miscellaneous databases

PMAP-CutDBP14317.

Expressioni

Tissue specificityi

Expressed only in tissues and cells of hematopoietic origin.

Developmental stagei

Expressed in early stage of myeloid and erythroid differentiation.

Gene expression databases

BgeeiENSG00000180353.
CleanExiHS_HCLS1.
ExpressionAtlasiP14317. baseline and differential.
GenevisibleiP14317. HS.

Organism-specific databases

HPAiHPA019143.

Interactioni

Subunit structurei

Associates with the SH2 and SH3 domains of LCK. Binding to he LCK SH3 domain occurs constitutively, while binding to the LCK SH2 domain occurs only upon TCR stimulation. A similar binding pattern was observed with LYN, but not with FYN in which the FYN SH2 region associates upon TCR stimulation but the FYN SH3 region does not associate regardless of TCR stimulation. Directly associates with HAX1, through binding to its C-terminal region. Interacts with HS1BP3. Interacts with FES/FPS (By similarity). Interacts (via SH2 domain) with FGR. Forms a multiprotein complex with LYN and ANKRD54 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SH2D4AQ9H7886EBI-750369,EBI-747035
TERF1P542742EBI-750369,EBI-710997
WIPF1O435162EBI-750369,EBI-346356

GO - Molecular functioni

  • protein kinase binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi109309. 25 interactors.
IntActiP14317. 16 interactors.
MINTiMINT-1343660.
STRINGi9606.ENSP00000320176.

Structurei

3D structure databases

ProteinModelPortaliP14317.
SMRiP14317.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati79 – 115Cortactin 1Add BLAST37
Repeati116 – 152Cortactin 2Add BLAST37
Repeati153 – 189Cortactin 3Add BLAST37
Repeati190 – 212Cortactin 4; truncatedAdd BLAST23
Domaini428 – 486SH3PROSITE-ProRule annotationAdd BLAST59

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni27 – 66Involved in HAX-1 bindingAdd BLAST40

Sequence similaritiesi

Contains 4 cortactin repeats.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiENOG410IFV2. Eukaryota.
ENOG410XTAK. LUCA.
GeneTreeiENSGT00530000062953.
HOGENOMiHOG000006523.
HOVERGENiHBG005994.
InParanoidiP14317.
KOiK06106.
OMAiEMDRHEQ.
OrthoDBiEOG091G0CPX.
PhylomeDBiP14317.
TreeFamiTF318935.

Family and domain databases

InterProiIPR028534. HS1.
IPR003134. Hs1_Cortactin.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10829:SF5. PTHR10829:SF5. 2 hits.
PfamiPF02218. HS1_rep. 4 hits.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS51090. CORTACTIN. 4 hits.
PS50002. SH3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P14317-1) [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
MWKSVVGHDV SVSVETQGDD WDTDPDFVND ISEKEQRWGA KTIEGSGRTE
60 70 80 90 100
HINIHQLRNK VSEEHDVLRK KEMESGPKAS HGYGGRFGVE RDRMDKSAVG
110 120 130 140 150
HEYVAEVEKH SSQTDAAKGF GGKYGVERDR ADKSAVGFDY KGEVEKHTSQ
160 170 180 190 200
KDYSRGFGGR YGVEKDKWDK AALGYDYKGE TEKHESQRDY AKGFGGQYGI
210 220 230 240 250
QKDRVDKSAV GFNEMEAPTT AYKKTTPIEA ASSGTRGLKA KFESMAEEKR
260 270 280 290 300
KREEEEKAQQ VARRQQERKA VTKRSPEAPQ PVIAMEEPAV PAPLPKKISS
310 320 330 340 350
EAWPPVGTPP SSESEPVRTS REHPVPLLPI RQTLPEDNEE PPALPPRTLE
360 370 380 390 400
GLQVEEEPVY EAEPEPEPEP EPEPENDYED VEEMDRHEQE DEPEGDYEEV
410 420 430 440 450
LEPEDSSFSS ALAGSSGCPA GAGAGAVALG ISAVAVYDYQ GEGSDELSFD
460 470 480
PDDVITDIEM VDEGWWRGRC HGHFGLFPAN YVKLLE
Length:486
Mass (Da):54,014
Last modified:January 11, 2011 - v3
Checksum:i20AE72A28DA33DFB
GO
Isoform 2 (identifier: P14317-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     134-209: SAVGFDYKGE...IQKDRVDKSA → ITLVALVAGT...RPQLIRRRRP
     210-486: Missing.

Note: No experimental confirmation available.
Show »
Length:209
Mass (Da):24,008
Checksum:i41DA8B0C0178CA56
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti241 – 242KF → FK AA sequence (PubMed:8713105).Curated2
Sequence conflicti486E → D in CAG33075 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055006235T → A.5 PublicationsCorresponds to variant rs2070179dbSNPEnsembl.1
Natural variantiVAR_055007361E → K.Corresponds to variant rs2070180dbSNPEnsembl.1
Natural variantiVAR_056910436V → L.5 PublicationsCorresponds to variant rs9869984dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056429134 – 209SAVGF…VDKSA → ITLVALVAGTGWRRINGTKQ LWDMTTRERRRNTSPREIMP RALVASMESRRTEWIRALSA SMKWRPRPQLIRRRRP in isoform 2. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_056430210 – 486Missing in isoform 2. 1 PublicationAdd BLAST277

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16663 mRNA. Translation: CAA34651.1.
BT006824 mRNA. Translation: AAP35470.1.
AK298663 mRNA. Translation: BAG60831.1.
AK312750 mRNA. Translation: BAG35617.1.
CR456794 mRNA. Translation: CAG33075.1.
AC133750 Genomic DNA. No translation available.
BC016758 mRNA. Translation: AAH16758.1.
CCDSiCCDS3003.1. [P14317-1]
PIRiS07633.
RefSeqiNP_001278970.1. NM_001292041.1.
NP_005326.2. NM_005335.5.
UniGeneiHs.14601.

Genome annotation databases

EnsembliENST00000314583; ENSP00000320176; ENSG00000180353. [P14317-1]
ENST00000495491; ENSP00000418299; ENSG00000180353. [P14317-2]
GeneIDi3059.
KEGGihsa:3059.
UCSCiuc003eeh.5. human. [P14317-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16663 mRNA. Translation: CAA34651.1.
BT006824 mRNA. Translation: AAP35470.1.
AK298663 mRNA. Translation: BAG60831.1.
AK312750 mRNA. Translation: BAG35617.1.
CR456794 mRNA. Translation: CAG33075.1.
AC133750 Genomic DNA. No translation available.
BC016758 mRNA. Translation: AAH16758.1.
CCDSiCCDS3003.1. [P14317-1]
PIRiS07633.
RefSeqiNP_001278970.1. NM_001292041.1.
NP_005326.2. NM_005335.5.
UniGeneiHs.14601.

3D structure databases

ProteinModelPortaliP14317.
SMRiP14317.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109309. 25 interactors.
IntActiP14317. 16 interactors.
MINTiMINT-1343660.
STRINGi9606.ENSP00000320176.

PTM databases

iPTMnetiP14317.
PhosphoSitePlusiP14317.

Polymorphism and mutation databases

BioMutaiHCLS1.
DMDMi317373440.

Proteomic databases

EPDiP14317.
MaxQBiP14317.
PaxDbiP14317.
PeptideAtlasiP14317.
PRIDEiP14317.

Protocols and materials databases

DNASUi3059.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000314583; ENSP00000320176; ENSG00000180353. [P14317-1]
ENST00000495491; ENSP00000418299; ENSG00000180353. [P14317-2]
GeneIDi3059.
KEGGihsa:3059.
UCSCiuc003eeh.5. human. [P14317-1]

Organism-specific databases

CTDi3059.
DisGeNETi3059.
GeneCardsiHCLS1.
HGNCiHGNC:4844. HCLS1.
HPAiHPA019143.
MIMi601306. gene.
neXtProtiNX_P14317.
OpenTargetsiENSG00000180353.
PharmGKBiPA29220.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFV2. Eukaryota.
ENOG410XTAK. LUCA.
GeneTreeiENSGT00530000062953.
HOGENOMiHOG000006523.
HOVERGENiHBG005994.
InParanoidiP14317.
KOiK06106.
OMAiEMDRHEQ.
OrthoDBiEOG091G0CPX.
PhylomeDBiP14317.
TreeFamiTF318935.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180353-MONOMER.
SIGNORiP14317.

Miscellaneous databases

ChiTaRSiHCLS1. human.
GenomeRNAii3059.
PMAP-CutDBP14317.
PROiP14317.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180353.
CleanExiHS_HCLS1.
ExpressionAtlasiP14317. baseline and differential.
GenevisibleiP14317. HS.

Family and domain databases

InterProiIPR028534. HS1.
IPR003134. Hs1_Cortactin.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10829:SF5. PTHR10829:SF5. 2 hits.
PfamiPF02218. HS1_rep. 4 hits.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
SMARTiSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
PROSITEiPS51090. CORTACTIN. 4 hits.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHCLS1_HUMAN
AccessioniPrimary (citable) accession number: P14317
Secondary accession number(s): B4DQ69
, Q53Y93, Q6IBK9, Q9UDK0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 181 of the entry and version 3 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. 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.