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Protein

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1

Gene

SMARCAL1

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

Functioni

ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA). Acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, that unwind DNA. May play an important role in DNA damage response by acting at stalled replication forks.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi458 – 465ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • annealing helicase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • DNA-dependent ATPase activity Source: UniProtKB
  • helicase activity Source: UniProtKB-KW

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • DNA metabolic process Source: UniProtKB
  • DNA repair Source: InterPro
  • regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • replication fork processing Source: UniProtKB
  • t-circle formation Source: BHF-UCL

Keywordsi

Molecular functionHelicase, Hydrolase
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 (EC:3.6.4.-)
Alternative name(s):
HepA-related protein
Short name:
hHARP
Sucrose nonfermenting protein 2-like 1
Gene namesi
Name:SMARCAL1
Synonyms:HARP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138375.12.
HGNCiHGNC:11102. SMARCAL1.

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

Nucleus

Pathology & Biotechi

Involvement in diseasei

Schimke immuno-osseous dysplasia (SIOD)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive pleiotropic disorder characterized by spondyloepiphyseal dysplasia, renal dysfunction and immunodeficiency. Arteriosclerosis may also occur in some case.
See also OMIM:242900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021370468A → P in SIOD. 1 Publication1
Natural variantiVAR_021371548I → N in SIOD. 1 PublicationCorresponds to variant dbSNP:rs119473036Ensembl.1
Natural variantiVAR_021372579S → L in SIOD. 1 Publication1
Natural variantiVAR_021373586R → W in SIOD; impairs without abolishing annealing helicase activity; no effect on specific binding to fork DNA; no effect on recruitment to sites of DNA damage. 3 PublicationsCorresponds to variant dbSNP:rs119473038Ensembl.1
Natural variantiVAR_021374644R → W in SIOD. 1 Publication1
Natural variantiVAR_021375645R → C in SIOD. 1 PublicationCorresponds to variant dbSNP:rs119473037Ensembl.1
Natural variantiVAR_021376647K → Q in SIOD. 1 Publication1
Natural variantiVAR_021377647K → T in SIOD. 1 Publication1
Natural variantiVAR_021379705T → I in SIOD. 1 PublicationCorresponds to variant dbSNP:rs200644381Ensembl.1
Natural variantiVAR_021381764R → Q in SIOD; abolishes annealing helicase activity; no effect on specific binding to fork DNA; no effect on recruitment to sites of DNA damage. 3 PublicationsCorresponds to variant dbSNP:rs267607071Ensembl.1
Natural variantiVAR_021382820R → H in SIOD. 1 PublicationCorresponds to variant dbSNP:rs200666300Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi17 – 19RQK → AAA: Loss of interaction with RPA2 and impaired recruitment by the RPA complex to sites of DNA damage. 1 Publication3

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi50485.
GeneReviewsiSMARCAL1.
MalaCardsiSMARCAL1.
MIMi242900. phenotype.
OpenTargetsiENSG00000138375.
Orphaneti1830. Schimke immuno-osseous dysplasia.
PharmGKBiPA35952.

Polymorphism and mutation databases

BioMutaiSMARCAL1.
DMDMi60390962.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000743482 – 954SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1Add BLAST953

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei112PhosphoserineCombined sources1
Modified residuei123PhosphoserineCombined sources1
Modified residuei129PhosphoserineCombined sources1
Modified residuei151PhosphoserineCombined sources1
Modified residuei198PhosphoserineCombined sources1

Post-translational modificationi

DNA damage-regulated phosphorylation by kinases that may include ATM, ATR and PRKDC.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9NZC9.
MaxQBiQ9NZC9.
PaxDbiQ9NZC9.
PeptideAtlasiQ9NZC9.
PRIDEiQ9NZC9.

PTM databases

iPTMnetiQ9NZC9.
PhosphoSitePlusiQ9NZC9.

Expressioni

Tissue specificityi

Ubiquitously expressed, with high levels in testis.2 Publications

Gene expression databases

BgeeiENSG00000138375.
CleanExiHS_SMARCAL1.
ExpressionAtlasiQ9NZC9. baseline and differential.
GenevisibleiQ9NZC9. HS.

Organism-specific databases

HPAiHPA020337.

Interactioni

Subunit structurei

Interacts with RPA2; the interaction is direct and mediates the recruitment by the RPA complex of SMARCAL1 to sites of DNA damage.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RPA2P1592713EBI-5457961,EBI-621404

Protein-protein interaction databases

BioGridi119072. 10 interactors.
ELMiQ9NZC9.
IntActiQ9NZC9. 7 interactors.
MINTiMINT-8415341.
STRINGi9606.ENSP00000349823.

Structurei

Secondary structure

1954
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi7 – 29Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4MQVX-ray1.95B/D5-30[»]
ProteinModelPortaliQ9NZC9.
SMRiQ9NZC9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini226 – 303HARP 1PROSITE-ProRule annotationAdd BLAST78
Domaini327 – 398HARP 2PROSITE-ProRule annotationAdd BLAST72
Domaini445 – 600Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST156
Domaini716 – 869Helicase C-terminalPROSITE-ProRule annotationAdd BLAST154

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 30Mediates interaction with RPA2Add BLAST29

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili3 – 34Sequence analysisAdd BLAST32

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi549 – 552DESH box4

Sequence similaritiesi

Belongs to the SNF2/RAD54 helicase family. SMARCAL1 subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG1000. Eukaryota.
COG0553. LUCA.
GeneTreeiENSGT00900000140927.
HOVERGENiHBG054110.
InParanoidiQ9NZC9.
KOiK14440.
OMAiANMGLTF.
OrthoDBiEOG091G0A1B.
PhylomeDBiQ9NZC9.
TreeFamiTF106474.

Family and domain databases

CDDicd00079. HELICc. 1 hit.
InterProiView protein in InterPro
IPR030101. HARP(SMARCAL1).
IPR010003. HARP_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR000330. SNF2_N.
PANTHERiPTHR10799:SF731. PTHR10799:SF731. 2 hits.
PfamiView protein in Pfam
PF07443. HARP. 2 hits.
PF00271. Helicase_C. 1 hit.
PF00176. SNF2_N. 1 hit.
SMARTiView protein in SMART
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SUPFAMiSSF52540. SSF52540. 3 hits.
PROSITEiView protein in PROSITE
PS51467. HARP. 2 hits.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q9NZC9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLPLTEEQR KKIEENRQKA LARRAEKLLA EQHQRTSSGT SIAGNPFQAK
60 70 80 90 100
QGPSQNFPRE SCKPVSHGVI FKQQNLSSSS NADQRPHDSH SFQAKGIWKK
110 120 130 140 150
PEEMPTACPG HSPRSQMALT GISPPLAQSP PEVPKQQLLS YELGQGHAQA
160 170 180 190 200
SPEIRFTPFA NPTHKPLAKP KSSQETPAHS SGQPPRDAKL EAKTAKASPS
210 220 230 240 250
GQNISYIHSS SESVTPRTEG RLQQKSGSSV QKGVNSQKGK CVRNGDRFQV
260 270 280 290 300
LIGYNAELIA VFKTLPSKNY DPDTKTWNFS MNDYSALMKA AQSLPTVNLQ
310 320 330 340 350
PLEWAYGSSE SPSTSSEGQA GLPSAPSLSF VKGRCMLISR AYFEADISYS
360 370 380 390 400
QDLIALFKQM DSRRYDVKTR KWSFLLEEHS KLIAKVRCLP QVQLDPLPTT
410 420 430 440 450
LTLAFASQLK KTSLSLTPDV PEADLSEVDP KLVSNLMPFQ RAGVNFAIAK
460 470 480 490 500
GGRLLLADDM GLGKTIQAIC IAAFYRKEWP LLVVVPSSVR FTWEQAFLRW
510 520 530 540 550
LPSLSPDCIN VVVTGKDRLT AGLINIVSFD LLSKLEKQLK TPFKVVIIDE
560 570 580 590 600
SHFLKNSRTA RCRAAMPVLK VAKRVILLSG TPAMSRPAEL YTQIIAVKPT
610 620 630 640 650
FFPQFHAFGL RYCDAKRMPW GWDYSGSSNL GELKLLLEEA VMLRRLKSDV
660 670 680 690 700
LSQLPAKQRK IVVIAPGRIN ARTRAALDAA AKEMTTKDKT KQQQKDALIL
710 720 730 740 750
FFNRTAEAKI PSVIEYILDL LESGREKFLV FAHHKVVLDA ITQELERKHV
760 770 780 790 800
QHIRIDGSTS SAEREDLCQQ FQLSERHAVA VLSITAANMG LTFSSADLVV
810 820 830 840 850
FAELFWNPGV LIQAEDRVHR IGQTSSVGIH YLVAKGTADD YLWPLIQEKI
860 870 880 890 900
KVLAEAGLSE TNFSEMTEST DYLYKDPKQQ KIYDLFQKSF EKEGSDMELL
910 920 930 940 950
EAAESFDPGS ASGTSGSSSQ NMGDTLDESS LTASPQKKRR FEFFDNWDSF

TSPL
Length:954
Mass (Da):105,938
Last modified:October 1, 2000 - v1
Checksum:iC5C762C24A2FDD3A
GO

Sequence cautioni

Q9NZC9: The sequence BAA90955 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti118A → T in AAF24984 (PubMed:10857751).Curated1
Sequence conflicti335C → G in AAF24984 (PubMed:10857751).Curated1
Sequence conflicti344E → K in BAA90955 (PubMed:14702039).Curated1
Sequence conflicti882I → M in AAF24984 (PubMed:10857751).Curated1
Sequence conflicti900L → V in AAF24984 (PubMed:10857751).Curated1
Sequence conflicti911A → G in AAF24984 (PubMed:10857751).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03837022A → G1 PublicationCorresponds to variant dbSNP:rs17851400Ensembl.1
Natural variantiVAR_02136343A → T. Corresponds to variant dbSNP:rs2066524Ensembl.1
Natural variantiVAR_021364114R → H. Corresponds to variant dbSNP:rs11555797Ensembl.1
Natural variantiVAR_021366207I → F. Corresponds to variant dbSNP:rs6734114Ensembl.1
Natural variantiVAR_021367315S → R. Corresponds to variant dbSNP:rs2066522Ensembl.1
Natural variantiVAR_021368377E → Q2 PublicationsCorresponds to variant dbSNP:rs2066518Ensembl.1
Natural variantiVAR_021369424D → V. Corresponds to variant dbSNP:rs2066520Ensembl.1
Natural variantiVAR_036026432L → V in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_021370468A → P in SIOD. 1 Publication1
Natural variantiVAR_021371548I → N in SIOD. 1 PublicationCorresponds to variant dbSNP:rs119473036Ensembl.1
Natural variantiVAR_021372579S → L in SIOD. 1 Publication1
Natural variantiVAR_021373586R → W in SIOD; impairs without abolishing annealing helicase activity; no effect on specific binding to fork DNA; no effect on recruitment to sites of DNA damage. 3 PublicationsCorresponds to variant dbSNP:rs119473038Ensembl.1
Natural variantiVAR_021374644R → W in SIOD. 1 Publication1
Natural variantiVAR_021375645R → C in SIOD. 1 PublicationCorresponds to variant dbSNP:rs119473037Ensembl.1
Natural variantiVAR_021376647K → Q in SIOD. 1 Publication1
Natural variantiVAR_021377647K → T in SIOD. 1 Publication1
Natural variantiVAR_021378649D → N. Corresponds to variant dbSNP:rs2066523Ensembl.1
Natural variantiVAR_021379705T → I in SIOD. 1 PublicationCorresponds to variant dbSNP:rs200644381Ensembl.1
Natural variantiVAR_021380742T → M. Corresponds to variant dbSNP:rs2271336Ensembl.1
Natural variantiVAR_021381764R → Q in SIOD; abolishes annealing helicase activity; no effect on specific binding to fork DNA; no effect on recruitment to sites of DNA damage. 3 PublicationsCorresponds to variant dbSNP:rs267607071Ensembl.1
Natural variantiVAR_021382820R → H in SIOD. 1 PublicationCorresponds to variant dbSNP:rs200666300Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF082179 mRNA. Translation: AAF24984.1.
AF210842
, AF210833, AF210834, AF210835, AF210836, AF210837, AF210838, AF210839, AF210840, AF210841 Genomic DNA. Translation: AAF70454.1.
AF432223 mRNA. Translation: AAL73034.1.
AC098820 Genomic DNA. Translation: AAX93097.1.
CH471063 Genomic DNA. Translation: EAW70567.1.
BC016482 mRNA. Translation: AAH16482.1.
BC043341 mRNA. Translation: AAH43341.1.
AL122076 mRNA. Translation: CAB59251.1.
AK000117 mRNA. Translation: BAA90955.1. Different initiation.
CCDSiCCDS2403.1.
PIRiT34557.
RefSeqiNP_001120679.1. NM_001127207.1.
NP_054859.2. NM_014140.3.
XP_005246688.1. XM_005246631.2.
XP_005246689.1. XM_005246632.1.
UniGeneiHs.516674.

Genome annotation databases

EnsembliENST00000357276; ENSP00000349823; ENSG00000138375.
ENST00000358207; ENSP00000350940; ENSG00000138375.
GeneIDi50485.
KEGGihsa:50485.
UCSCiuc002vgc.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSMAL1_HUMAN
AccessioniPrimary (citable) accession number: Q9NZC9
Secondary accession number(s): A6NEH0
, Q53R00, Q96AY1, Q9NXQ5, Q9UFH3, Q9UI93
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: October 1, 2000
Last modified: October 25, 2017
This is version 146 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 2
    Human chromosome 2: 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
  6. SIMILARITY comments
    Index of protein domains and families