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O43374

- RASL2_HUMAN

UniProt

O43374 - RASL2_HUMAN

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Protein

Ras GTPase-activating protein 4

Gene

RASA4

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

Functioni

Ca2+-dependent Ras GTPase-activating protein, that switches off the Ras-MAPK pathway following a stimulus that elevates intracellular calcium. Functions as an adaptor for Cdc42 and Rac1 during FcR-mediated phagocytosis.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri675 – 71137Btk-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. GTPase activator activity Source: UniProtKB
  2. metal ion binding Source: UniProtKB-KW
  3. Ras GTPase activator activity Source: UniProtKB

GO - Biological processi

  1. cellular response to calcium ion Source: UniProtKB
  2. intracellular signal transduction Source: InterPro
  3. negative regulation of Ras protein signal transduction Source: RefGenome
  4. positive regulation of Ras GTPase activity Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Ras GTPase-activating protein 4
Alternative name(s):
Calcium-promoted Ras inactivator
Ras p21 protein activator 4
RasGAP-activating-like protein 2
Gene namesi
Name:RASA4
Synonyms:CAPRI, GAPL, KIAA0538
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:23181. RASA4.

Subcellular locationi

Cytoplasmcytosol 1 Publication. Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: Localized to the cytosol as a result of its lack of phosphoinositide binding activity. Upon agonist-stimulated calcium mobilization, utilizes the C2A and C2B domains to associate with the plasma membrane.

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
  2. cytosol Source: UniProtKB
  3. intrinsic component of the cytoplasmic side of the plasma membrane Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134889495.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 803803Ras GTPase-activating protein 4PRO_0000056647Add
BLAST

Proteomic databases

MaxQBiO43374.
PaxDbiO43374.
PRIDEiO43374.

PTM databases

PhosphoSiteiO43374.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiO43374.
CleanExiHS_RASA4.
ExpressionAtlasiO43374. baseline and differential.
GenevestigatoriO43374.

Organism-specific databases

HPAiHPA043010.

Interactioni

Protein-protein interaction databases

BioGridi115458. 3 interactions.
IntActiO43374. 4 interactions.
MINTiMINT-1370707.
STRINGi9606.ENSP00000262940.

Structurei

3D structure databases

ProteinModelPortaliO43374.
SMRiO43374. Positions 3-562, 573-707.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 8888C2 1PROSITE-ProRule annotationAdd
BLAST
Domaini129 – 21688C2 2PROSITE-ProRule annotationAdd
BLAST
Domaini302 – 512211Ras-GAPPROSITE-ProRule annotationAdd
BLAST
Domaini566 – 673108PHPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi500 – 5034Poly-Leu

Domaini

The PH domain does not bind phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate. This lack of binding activity is due to Leu-592, compared to Arg found in other family members.

Sequence similaritiesi

Contains 1 Btk-type zinc finger.PROSITE-ProRule annotation
Contains 2 C2 domains.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 Ras-GAP domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri675 – 71137Btk-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5038.
GeneTreeiENSGT00760000119092.
HOGENOMiHOG000234324.
HOVERGENiHBG106587.
InParanoidiO43374.
KOiK17630.
OMAiEVKLGTQ.
OrthoDBiEOG7J17Z6.
PhylomeDBiO43374.
TreeFamiTF105302.

Family and domain databases

Gene3Di1.10.506.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 2 hits.
4.10.1130.10. 1 hit.
InterProiIPR000008. C2_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR001936. RasGAP.
IPR023152. RasGAP_CS.
IPR008936. Rho_GTPase_activation_prot.
IPR001562. Znf_Btk_motif.
[Graphical view]
PfamiPF00779. BTK. 1 hit.
PF00168. C2. 2 hits.
PF00616. RasGAP. 1 hit.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
SMARTiSM00107. BTK. 1 hit.
SM00239. C2. 2 hits.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 2 hits.
PROSITEiPS50004. C2. 2 hits.
PS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
PS51113. ZF_BTK. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O43374) [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
MAKRSSLYIR IVEGKNLPAK DITGSSDPYC IVKVDNEPII RTATVWKTLC
60 70 80 90 100
PFWGEEYQVH LPPTFHAVAF YVMDEDALSR DDVIGKVCLT RDTIASHPKG
110 120 130 140 150
FSGWAHLTEV DPDEEVQGEI HLRLEVWPGA RACRLRCSVL EARDLAPKDR
160 170 180 190 200
NGTSDPFVRV RYKGRTRETS IVKKSCYPRW NETFEFELQE GAMEALCVEA
210 220 230 240 250
WDWDLVSRND FLGKVVIDVQ RLRVVQQEEG WFRLQPDQSK SRRHDEGNLG
260 270 280 290 300
SLQLEVRLRD ETVLPSSYYQ PLVHLLCHEV KLGMQGPGQL IPLIEETTST
310 320 330 340 350
ECRQDVATNL LKLFLGQGLA KDFLDLLFQL ELSRTSETNT LFRSNSLASK
360 370 380 390 400
SMESFLKVAG MQYLHGVLGP IINKVFEEKK YVELDPSKVE VKDVGCSGLH
410 420 430 440 450
RPQTEAEVLE QSAQTLRAHL GALLSALSRS VRACPAVVRA TFRQLFRRVR
460 470 480 490 500
ERFPGAQHEN VPFIAVTSFL CLRFFSPAIM SPKLFHLRER HADARTSRTL
510 520 530 540 550
LLLAKAVQNV GNMDTPASRA KEAWMEPLQP TVRQGVAQLK DFITKLVDIE
560 570 580 590 600
EKDELDLQRT LSLQAPPVKE GPLFIHRTKG KGPLMSSSFK KLYFSLTTEA
610 620 630 640 650
LSFAKTPSSK KSALIKLANI RAAEKVEEKS FGGSHVMQVI YTDDAGRPQT
660 670 680 690 700
AYLQCKCVNE LNQWLSALRK VSINNTGLLG SYHPGVFRGD KWSCCHQKEK
710 720 730 740 750
TGQGCDKTRS RVTLQEWNDP LDHDLEAQLI YRHLLGVEAM LWERHRELSG
760 770 780 790 800
GAEAGTVPTS PGKVPEDSLA RLLRVLQDLR EAHSSSPAGS PPSEPNCLLE

LQT
Length:803
Mass (Da):90,458
Last modified:August 15, 2003 - v2
Checksum:i6E70DBF2F8F5D0E9
GO
Isoform 2 (identifier: O43374-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     611-656: Missing.

Note: No experimental confirmation available.

Show »
Length:757
Mass (Da):85,409
Checksum:iEEBA12E7214670AB
GO

Sequence cautioni

The sequence BAA25464.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
The sequence AAB97935.2 differs from that shown. Reason: Erroneous gene model prediction.
The sequence AAP22345.1 differs from that shown. Reason: Erroneous gene model prediction.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti213 – 2131G → V in AK026441. (PubMed:14702039)Curated
Sequence conflicti260 – 2601D → G in AK026441. (PubMed:14702039)Curated
Sequence conflicti429 – 4291R → L in AK026441. (PubMed:14702039)Curated
Sequence conflicti480 – 4801M → V in AK026441. (PubMed:14702039)Curated
Sequence conflicti606 – 6061T → M in BAA25464. (PubMed:9628581)Curated
Sequence conflicti752 – 7521A → T in BAA25464. (PubMed:9628581)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti352 – 3521M → V.2 Publications
Corresponds to variant rs746316 [ dbSNP | Ensembl ].
VAR_027680
Natural varianti432 – 4321R → P.
Corresponds to variant rs886346 [ dbSNP | Ensembl ].
VAR_027681
Natural varianti731 – 7311Y → C.
Corresponds to variant rs1060228 [ dbSNP | Ensembl ].
VAR_027682

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei611 – 65646Missing in isoform 2. 1 PublicationVSP_039965Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY029206 mRNA. Translation: AAK31582.1.
AB011110 mRNA. Translation: BAA25464.2. Different initiation.
AK026441 mRNA. No translation available.
AC004084 Genomic DNA. Translation: AAB97935.2. Sequence problems.
AC093668 Genomic DNA. No translation available.
AC105052 Genomic DNA. Translation: AAP22345.1. Sequence problems.
BC113663 mRNA. Translation: AAI13664.1.
CCDSiCCDS47674.1. [O43374-2]
CCDS5725.1. [O43374-1]
RefSeqiNP_001073346.2. NM_001079877.2. [O43374-2]
NP_008920.5. NM_006989.5. [O43374-1]
UniGeneiHs.530089.
Hs.656696.

Genome annotation databases

EnsembliENST00000262940; ENSP00000262940; ENSG00000105808. [O43374-1]
ENST00000449970; ENSP00000412876; ENSG00000105808. [O43374-2]
GeneIDi10156.
KEGGihsa:10156.
UCSCiuc003vae.3. human. [O43374-1]
uc010lih.2. human. [O43374-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY029206 mRNA. Translation: AAK31582.1 .
AB011110 mRNA. Translation: BAA25464.2 . Different initiation.
AK026441 mRNA. No translation available.
AC004084 Genomic DNA. Translation: AAB97935.2 . Sequence problems.
AC093668 Genomic DNA. No translation available.
AC105052 Genomic DNA. Translation: AAP22345.1 . Sequence problems.
BC113663 mRNA. Translation: AAI13664.1 .
CCDSi CCDS47674.1. [O43374-2 ]
CCDS5725.1. [O43374-1 ]
RefSeqi NP_001073346.2. NM_001079877.2. [O43374-2 ]
NP_008920.5. NM_006989.5. [O43374-1 ]
UniGenei Hs.530089.
Hs.656696.

3D structure databases

ProteinModelPortali O43374.
SMRi O43374. Positions 3-562, 573-707.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 115458. 3 interactions.
IntActi O43374. 4 interactions.
MINTi MINT-1370707.
STRINGi 9606.ENSP00000262940.

PTM databases

PhosphoSitei O43374.

Proteomic databases

MaxQBi O43374.
PaxDbi O43374.
PRIDEi O43374.

Protocols and materials databases

DNASUi 10156.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262940 ; ENSP00000262940 ; ENSG00000105808 . [O43374-1 ]
ENST00000449970 ; ENSP00000412876 ; ENSG00000105808 . [O43374-2 ]
GeneIDi 10156.
KEGGi hsa:10156.
UCSCi uc003vae.3. human. [O43374-1 ]
uc010lih.2. human. [O43374-2 ]

Organism-specific databases

CTDi 10156.
GeneCardsi GC07M102220.
H-InvDB HIX0034020.
HIX0201129.
HGNCi HGNC:23181. RASA4.
HPAi HPA043010.
MIMi 607943. gene.
neXtProti NX_O43374.
PharmGKBi PA134889495.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5038.
GeneTreei ENSGT00760000119092.
HOGENOMi HOG000234324.
HOVERGENi HBG106587.
InParanoidi O43374.
KOi K17630.
OMAi EVKLGTQ.
OrthoDBi EOG7J17Z6.
PhylomeDBi O43374.
TreeFami TF105302.

Miscellaneous databases

ChiTaRSi RASA4. human.
GeneWikii RASA4.
GenomeRNAii 10156.
NextBioi 38444.
PROi O43374.
SOURCEi Search...

Gene expression databases

Bgeei O43374.
CleanExi HS_RASA4.
ExpressionAtlasi O43374. baseline and differential.
Genevestigatori O43374.

Family and domain databases

Gene3Di 1.10.506.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 2 hits.
4.10.1130.10. 1 hit.
InterProi IPR000008. C2_dom.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR001936. RasGAP.
IPR023152. RasGAP_CS.
IPR008936. Rho_GTPase_activation_prot.
IPR001562. Znf_Btk_motif.
[Graphical view ]
Pfami PF00779. BTK. 1 hit.
PF00168. C2. 2 hits.
PF00616. RasGAP. 1 hit.
[Graphical view ]
PRINTSi PR00360. C2DOMAIN.
SMARTi SM00107. BTK. 1 hit.
SM00239. C2. 2 hits.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view ]
SUPFAMi SSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 2 hits.
PROSITEi PS50004. C2. 2 hits.
PS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
PS51113. ZF_BTK. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "CAPRI regulates Ca(2+)-dependent inactivation of the Ras-MAPK pathway."
    Lockyer P.J., Kupzig S., Cullen P.J.
    Curr. Biol. 11:981-986(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-352, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Blood.
  2. "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
    Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  4. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-352.
    Tissue: Liver.

Entry informationi

Entry nameiRASL2_HUMAN
AccessioniPrimary (citable) accession number: O43374
Secondary accession number(s): O60286
, Q14CQ4, Q86UW3, Q96QU0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: August 15, 2003
Last modified: October 29, 2014
This is version 131 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 7
    Human chromosome 7: 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

External Data

Dasty 3