Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 82 (11 Dec 2019)
Sequence version 1 (15 Feb 2005)
Previous versions | rss
Help videoAdd a publicationFeedback
Protein

Signal-induced proliferation-associated 1-like protein 2

Gene

Sipa1l2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionGTPase activation

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Signal-induced proliferation-associated 1-like protein 2
Short name:
SIPA1-like protein 2
Alternative name(s):
Serine-rich synapse-associated protein
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Sipa1l2
Synonyms:Sersap2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiRattus norvegicus (Rat)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10116 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000002494 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Unplaced

Organism-specific databases

Rat genome database

More...
RGDi
1306269 Sipa1l2

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000567511 – 1722Signal-induced proliferation-associated 1-like protein 2Add BLAST1722

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei149PhosphoserineCombined sources1
Modified residuei380PhosphoserineBy similarity1
Modified residuei384PhosphoserineBy similarity1
Modified residuei1030PhosphoserineBy similarity1
Modified residuei1245PhosphoserineCombined sources1
Modified residuei1461PhosphoserineCombined sources1
Modified residuei1472PhosphoserineBy similarity1
Modified residuei1478PhosphoserineCombined sources1
Modified residuei1488PhosphoserineCombined sources1
Modified residuei1549PhosphoserineCombined sources1
Modified residuei1552PhosphoserineBy similarity1
Modified residuei1591PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q5JCS6

PRoteomics IDEntifications database

More...
PRIDEi
Q5JCS6

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q5JCS6

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q5JCS6

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
262684, 1 interactor

STRING: functional protein association networks

More...
STRINGi
10116.ENSRNOP00000026843

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
Q5JCS6

Database of comparative protein structure models

More...
ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini596 – 813Rap-GAPPROSITE-ProRule annotationAdd BLAST218
Domaini951 – 1027PDZPROSITE-ProRule annotationAdd BLAST77

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and domains’ section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili1652 – 1712Sequence analysisAdd BLAST61

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi58 – 64Poly-Gly7
Compositional biasi819 – 822Poly-Thr4
Compositional biasi1126 – 1129Poly-Ser4
Compositional biasi1322 – 1366Ser-richAdd BLAST45

Keywords - Domaini

Coiled coil

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3686 Eukaryota
ENOG410XTIX LUCA

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000154319

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q5JCS6

KEGG Orthology (KO)

More...
KOi
K17702

Database of Orthologous Groups

More...
OrthoDBi
28453at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q5JCS6

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.40.50.11210, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR001478 PDZ
IPR036034 PDZ_sf
IPR035974 Rap/Ran-GAP_sf
IPR000331 Rap_GAP_dom
IPR031203 SIPA1L2
IPR021818 SIPA1L_C

The PANTHER Classification System

More...
PANTHERi
PTHR15711:SF7 PTHR15711:SF7, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00595 PDZ, 1 hit
PF02145 Rap_GAP, 1 hit
PF11881 SPAR_C, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00228 PDZ, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF111347 SSF111347, 1 hit
SSF50156 SSF50156, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50106 PDZ, 1 hit
PS50085 RAPGAP, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q5JCS6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSDPRPSQAE KHKLGRAASK FKDPSRAMQS DDYFARKFKA INGSMGPATL
60 70 80 90 100
NTSSLSEGGG GGGGPANGTP AVPKMGVRAR VSEWPPKKDC SKDLACKTLW
110 120 130 140 150
ESRSQSSYES ATSIIQNGQN DQVDRQQEEQ LDLDFVEAKY TIGDIFVHSP
160 170 180 190 200
QRGLHPIRQR SNSDITISDI DTEDVLDQHA VNPNTGAALH REYGSTSSID
210 220 230 240 250
RQGLSGENVF AMLRGYRIES YDPKVTSSFG FPDFFPCDTA ISPSLHAAAQ
260 270 280 290 300
ISRGEFVRIS GLDYMDGGLL MGRDRDKPFK RRLKSESVET SLFRKLRTVK
310 320 330 340 350
SEHETFKFTS DLEEGRLDRG IRPWSCQRCF AHYDVQSILF NINEAMATRA
360 370 380 390 400
SVGKRKNITT GASAASQTPV PVGPAGGCES PLGSKEDLNA KENPDADEGD
410 420 430 440 450
GKSNDLVLSC PYFRNETGGE GDRRIALSRA NSASFSSGES CSFESSLSSH
460 470 480 490 500
CTNAGVSVLE VPRENQPIHR EKVKRYIIEH VDLGAYYYRK FFYGKEHQNY
510 520 530 540 550
FGIDENLGPV AVSIRREKVE DPREKEGSQF NYRVAFRTSE LTTLRGAILE
560 570 580 590 600
DAVPSTARHG TARGLPLKEV LEYVIPELSI PCLRQAANSP KVPEQLLKLD
610 620 630 640 650
EQGLSFQHKI GILYCKAGQS TEEEMYNNET AGPAFEEFLD LLGQRVRLKG
660 670 680 690 700
FSKYRAQLDN KTDSTGTHSL YTTYKDFELM FHVSTLLPYM PNNRQQLLRK
710 720 730 740 750
RHIGNDIVTI VFQEPGALPF TPKNIRSHFQ HVFVIVKVHN PCTENVCYSV
760 770 780 790 800
GVFRSKDVPP FVPPIPKGVT FPRTGVFRDF LLAKGINAEN AAHKSEKFRA
810 820 830 840 850
MATRTRHEYL KDLAENFVTT TTVDTSAKFS FITLGAKKKE RVKPRTDAHL
860 870 880 890 900
FSIGAIMWHV VARYFGQSAD IECLLGISNE FIMLIEKESK NVAFNCSCRD
910 920 930 940 950
VIGWTSGLVS IKIFYERGEC ILLSSVDNSS EDIREIVQRL VIVTRGCETV
960 970 980 990 1000
EMTLRRNGLG QLGFHVNFEG IVADVEPFGF AWKAGLRQGS RLVEICKVAV
1010 1020 1030 1040 1050
ATLTHEQMID LLRTSVTVKV VIIQPHEDGS PRRGCSELCR IPMVEYKLDS
1060 1070 1080 1090 1100
EGTPCEYKTP FRRNTTWHRV PTPALQPVSR ASPVPGTPDR LQCQPLLQQA
1110 1120 1130 1140 1150
QAAIPRSTSF DRKLPDGTRS SPSNQSSSSD PGPGGSGPWR PQVGYDGCPS
1160 1170 1180 1190 1200
PLLLEPQGPG SVECDGSGDH EDLMEVGRLP ETKWHGPPSK VLSSYKERAL
1210 1220 1230 1240 1250
QKDGSCKDSP NKLSHIGDKS CSSHSSSNTL SSNTSSNSDD KHFGSGDLMD
1260 1270 1280 1290 1300
PELLGLTYIK GASTDSGIDT TPCMPATILG PMHLTGSRSL IHSRAEQWAD
1310 1320 1330 1340 1350
AADVSGADED PAKMYTLHGY ASAISSSAAD GSMGDLSEVS SHSSGSHRSG
1360 1370 1380 1390 1400
SPSTHCSKST GSLDSSKVYI VTHSGGQQVP GAVAKPYHRQ GAANKYVIGW
1410 1420 1430 1440 1450
KKSEGSPPPE EPEVTECPRI YGEMDIMSTA SQHPAVVGDS VPEAQHVLSK
1460 1470 1480 1490 1500
DDFLKLMLPD SPLVEEGRRK FSFYGNLSPR RSLYRTLSDE SVCSNRRGSS
1510 1520 1530 1540 1550
FASSRSSILD QALPNDILFS TTPPYHSTLP PRTHPAPSMG SLRNEFWFSD
1560 1570 1580 1590 1600
GSLSDKSKCA DPGLMPLPDT AAGLDWSHLV DAARAFEGLD SDEELGLLCH
1610 1620 1630 1640 1650
HASYLDQRVA SFCTLTDLQH GQELEGAPEL SLCVDPTSGK EFMDTPGERS
1660 1670 1680 1690 1700
PSTLTGKVNQ LELILRQLQT DLRKEKQDKA VLQAEVQHLR QDNMRLQEES
1710 1720
QTATAQLRTF TEWFFSTIDK KV
Length:1,722
Mass (Da):189,653
Last modified:February 15, 2005 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i213DCA7DF7694167
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F1M8G8F1M8G8_RAT
Signal-induced proliferation-associ...
Sipa1l2
1,722Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AY043227 mRNA Translation: AAL02130.1

NCBI Reference Sequences

More...
RefSeqi
NP_001009704.1, NM_001009704.1

Genome annotation databases

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
361442

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
rno:361442

UCSC genome browser

More...
UCSCi
RGD:1306269 rat

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY043227 mRNA Translation: AAL02130.1
RefSeqiNP_001009704.1, NM_001009704.1

3D structure databases

SMRiQ5JCS6
ModBaseiSearch...

Protein-protein interaction databases

BioGridi262684, 1 interactor
STRINGi10116.ENSRNOP00000026843

PTM databases

iPTMnetiQ5JCS6
PhosphoSitePlusiQ5JCS6

Proteomic databases

PaxDbiQ5JCS6
PRIDEiQ5JCS6

Genome annotation databases

GeneIDi361442
KEGGirno:361442
UCSCiRGD:1306269 rat

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
57568
RGDi1306269 Sipa1l2

Phylogenomic databases

eggNOGiKOG3686 Eukaryota
ENOG410XTIX LUCA
HOGENOMiHOG000154319
InParanoidiQ5JCS6
KOiK17702
OrthoDBi28453at2759
PhylomeDBiQ5JCS6

Miscellaneous databases

Protein Ontology

More...
PROi
PR:Q5JCS6

Family and domain databases

Gene3Di3.40.50.11210, 1 hit
InterProiView protein in InterPro
IPR001478 PDZ
IPR036034 PDZ_sf
IPR035974 Rap/Ran-GAP_sf
IPR000331 Rap_GAP_dom
IPR031203 SIPA1L2
IPR021818 SIPA1L_C
PANTHERiPTHR15711:SF7 PTHR15711:SF7, 1 hit
PfamiView protein in Pfam
PF00595 PDZ, 1 hit
PF02145 Rap_GAP, 1 hit
PF11881 SPAR_C, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 1 hit
SUPFAMiSSF111347 SSF111347, 1 hit
SSF50156 SSF50156, 1 hit
PROSITEiView protein in PROSITE
PS50106 PDZ, 1 hit
PS50085 RAPGAP, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSI1L2_RAT
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q5JCS6
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2006
Last sequence update: February 15, 2005
Last modified: December 11, 2019
This is version 82 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again