Q9Y2A7 (NCKP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nck-associated protein 1
Short name=NAP 1

Alternative name(s):
Membrane-associated protein HEM-2
p125Nap1

Gene names

Name:	NCKAP1
Synonyms:	HEM2, KIAA0587, NAP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1128 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1.
Subunit structure	Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterdimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 and WASF2/WAVE2. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Associates preferentially with the first SH3 domain of NCK By similarity. Ref.8
Subcellular location	Cell membrane; Single-pass membrane protein; Cytoplasmic side By similarity. Cell projection › lamellipodium membrane; Single-pass membrane protein; Cytoplasmic side By similarity. Note: At the interface between the lamellipodial actin meshwork and the membrane By similarity.
Tissue specificity	Expressed in all tissues examined except peripheral blood leukocytes, with highest expression in brain, heart, and skeletal muscle.
Sequence similarities	Belongs to the HEM-1/HEM-2 family.
Sequence caution	The sequence BAA25513.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Traceable author statement. Source: ProtInc central nervous system development Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lamellipodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABI1	Q8IZP0	2	EBI-389845,EBI-375446
CYFIP1	Q7L576	3	EBI-389845,EBI-1048143

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y2A7-1)

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.

Isoform 2 (identifier: Q9Y2A7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     36-36: K → KQGQVWK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1128

1128

Nck-associated protein 1

PRO_0000216172

Regions

Transmembrane

995 – 1015

21

Helical; Potential

Natural variations

Alternative sequence

36

1

K → KQGQVWK in isoform 2.

VSP_036558

Secondary structure

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1128

Helix Strand Turn

Details...

Helix

8 – 10

3

Helix

13 – 22

10

Helix

28 – 37

10

Turn

41 – 43

3

Helix

46 – 48

3

Turn

51 – 53

3

Helix

54 – 63

10

Helix

77 – 81

5

Helix

83 – 117

35

Turn

123 – 125

3

Helix

127 – 148

22

Helix

153 – 156

4

Helix

160 – 165

6

Turn

173 – 177

5

Helix

181 – 184

4

Helix

188 – 195

8

Turn

196 – 200

5

Helix

201 – 208

8

Helix

209 – 212

4

Helix

214 – 217

4

Helix

221 – 226

6

Turn

227 – 230

4

Beta strand

232 – 235

4

Helix

236 – 238

3

Helix

248 – 252

5

Helix

255 – 263

9

Turn

273 – 275

3

Helix

277 – 287

11

Beta strand

291 – 296

6

Beta strand

299 – 302

4

Helix

303 – 311

9

Helix

320 – 334

15

Helix

338 – 359

22

Helix

368 – 391

24

Turn

397 – 400

4

Helix

405 – 421

17

Helix

425 – 434

10

Helix

438 – 446

9

Helix

454 – 468

15

Helix

472 – 476

5

Helix

487 – 498

12

Helix

515 – 527

13

Helix

529 – 537

9

Helix

540 – 544

5

Helix

546 – 558

13

Helix

560 – 563

4

Helix

564 – 567

4

Helix

568 – 572

5

Helix

573 – 579

7

Helix

585 – 587

3

Turn

588 – 590

3

Helix

594 – 626

33

Helix

630 – 633

4

Helix

634 – 640

7

Helix

674 – 689

16

Beta strand

695 – 697

3

Beta strand

700 – 702

3

Helix

704 – 720

17

Turn

728 – 731

4

Helix

736 – 752

17

Helix

753 – 755

3

Helix

761 – 771

11

Beta strand

774 – 776

3

Helix

784 – 794

11

Helix

796 – 801

6

Beta strand

805 – 808

4

Turn

809 – 812

4

Beta strand

813 – 816

4

Beta strand

818 – 820

3

Helix

828 – 831

4

Helix

833 – 842

10

Helix

849 – 871

23

Helix

874 – 882

9

Helix

887 – 894

8

Helix

900 – 909

10

Helix

913 – 931

19

Helix

933 – 944

12

Helix

955 – 964

10

Helix

973 – 979

7

Helix

989 – 1006

18

Helix

1007 – 1012

6

Helix

1014 – 1016

3

Turn

1020 – 1022

3

Helix

1029 – 1031

3

Helix

1032 – 1046

15

Helix

1051 – 1068

18

Turn

1075 – 1080

6

Helix

1081 – 1094

14

Helix

1100 – 1106

7

Helix

1109 – 1120

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 12D32BAC7080CB5A	FASTA	1,128	128,790
	10 20 30 40 50 60 MSRSVLQPSQ QKLAEKLTIL NDRGVGMLTR LYNIKKACGD PKAKPSYLID KNLESAVKFI 70 80 90 100 110 120 VRKFPAVETR NNNQQLAQLQ KEKSEILKNL ALYYFTFVDV MEFKDHVCEL LNTIDVCQVF 130 140 150 160 170 180 FDITVNFDLT KNYLDLIITY TTLMILLSRI EERKAIIGLY NYAHEMTHGA SDREYPRLGQ 190 200 210 220 230 240 MIVDYENPLK KMMEEFVPHS KSLSDALISL QMVYPRRNLS ADQWRNAQLL SLISAPSTML 250 260 270 280 290 300 NPAQSDTMPC EYLSLDAMEK WIIFGFILCH GILNTDATAL NLWKLALQSS SCLSLFRDEV 310 320 330 340 350 360 FHIHKAAEDL FVNIRGYNKR INDIRECKEA AVSHAGSMHR ERRKFLRSAL KELATVLSDQ 370 380 390 400 410 420 PGLLGPKALF VFMALSFARD EIIWLLRHAD NMPKKSADDF IDKHIAELIF YMEELRAHVR 430 440 450 460 470 480 KYGPVMQRYY VQYLSGFDAV VLNELVQNLS VCPEDESIIM SSFVNTMTSL SVKQVEDGEV 490 500 510 520 530 540 FDFRGMRLDW FRLQAYTSVS KASLGLADHR ELGKMMNTII FHTKMVDSLV EMLVETSDLS 550 560 570 580 590 600 IFCFYSRAFE KMFQQCLELP SQSRYSIAFP LLCTHFMSCT HELCPEERHH IGDRSLSLCN 610 620 630 640 650 660 MFLDEMAKQA RNLITDICTE QCTLSDQLLP KHCAKTISQA VNKKSKKQTG KKGEPEREKP 670 680 690 700 710 720 GVESMRKNRL VVTNLDKLHT ALSELCFSIN YVPNMVVWEH TFTPREYLTS HLEIRFTKSI 730 740 750 760 770 780 VGMTMYNQAT QEIAKPSELL TSVRAYMTVL QSIENYVQID ITRVFNNVLL QQTQHLDSHG 790 800 810 820 830 840 EPTITSLYTN WYLETLLRQV SNGHIAYFPA MKAFVNLPTE NELTFNAEEY SDISEMRSLS 850 860 870 880 890 900 ELLGPYGMKF LSESLMWHIS SQVAELKKLV VENVDVLTQM RTSFDKPDQM AALFKRLSSV 910 920 930 940 950 960 DSVLKRMTII GVILSFRSLA QEALRDVLSY HIPFLVSSIE DFKDHIPRET DMKVAMNVYE 970 980 990 1000 1010 1020 LSSAAGLPCE IDPALVVALS SQKSENISPE EEYKIACLLM VFVAVSLPTL ASNVMSQYSP 1030 1040 1050 1060 1070 1080 AIEGHCNNIH CLAKAINQIA AALFTIHKGS IEDRLKEFLA LASSSLLKIG QETDKTTTRN 1090 1100 1110 1120 RESVYLLLDM IVQESPFLTM DLLESCFPYV LLRNAYHAVY KQSVTSSA
	Isoform 2 [UniParc]. Checksum: 71019B9B0BCA760D	FASTA	1,134	129,517
	10 20 30 40 50 60 MSRSVLQPSQ QKLAEKLTIL NDRGVGMLTR LYNIKKQGQV WKACGDPKAK PSYLIDKNLE 70 80 90 100 110 120 SAVKFIVRKF PAVETRNNNQ QLAQLQKEKS EILKNLALYY FTFVDVMEFK DHVCELLNTI 130 140 150 160 170 180 DVCQVFFDIT VNFDLTKNYL DLIITYTTLM ILLSRIEERK AIIGLYNYAH EMTHGASDRE 190 200 210 220 230 240 YPRLGQMIVD YENPLKKMME EFVPHSKSLS DALISLQMVY PRRNLSADQW RNAQLLSLIS 250 260 270 280 290 300 APSTMLNPAQ SDTMPCEYLS LDAMEKWIIF GFILCHGILN TDATALNLWK LALQSSSCLS 310 320 330 340 350 360 LFRDEVFHIH KAAEDLFVNI RGYNKRINDI RECKEAAVSH AGSMHRERRK FLRSALKELA 370 380 390 400 410 420 TVLSDQPGLL GPKALFVFMA LSFARDEIIW LLRHADNMPK KSADDFIDKH IAELIFYMEE 430 440 450 460 470 480 LRAHVRKYGP VMQRYYVQYL SGFDAVVLNE LVQNLSVCPE DESIIMSSFV NTMTSLSVKQ 490 500 510 520 530 540 VEDGEVFDFR GMRLDWFRLQ AYTSVSKASL GLADHRELGK MMNTIIFHTK MVDSLVEMLV 550 560 570 580 590 600 ETSDLSIFCF YSRAFEKMFQ QCLELPSQSR YSIAFPLLCT HFMSCTHELC PEERHHIGDR 610 620 630 640 650 660 SLSLCNMFLD EMAKQARNLI TDICTEQCTL SDQLLPKHCA KTISQAVNKK SKKQTGKKGE 670 680 690 700 710 720 PEREKPGVES MRKNRLVVTN LDKLHTALSE LCFSINYVPN MVVWEHTFTP REYLTSHLEI 730 740 750 760 770 780 RFTKSIVGMT MYNQATQEIA KPSELLTSVR AYMTVLQSIE NYVQIDITRV FNNVLLQQTQ 790 800 810 820 830 840 HLDSHGEPTI TSLYTNWYLE TLLRQVSNGH IAYFPAMKAF VNLPTENELT FNAEEYSDIS 850 860 870 880 890 900 EMRSLSELLG PYGMKFLSES LMWHISSQVA ELKKLVVENV DVLTQMRTSF DKPDQMAALF 910 920 930 940 950 960 KRLSSVDSVL KRMTIIGVIL SFRSLAQEAL RDVLSYHIPF LVSSIEDFKD HIPRETDMKV 970 980 990 1000 1010 1020 AMNVYELSSA AGLPCEIDPA LVVALSSQKS ENISPEEEYK IACLLMVFVA VSLPTLASNV 1030 1040 1050 1060 1070 1080 MSQYSPAIEG HCNNIHCLAK AINQIAAALF TIHKGSIEDR LKEFLALASS SLLKIGQETD 1090 1100 1110 1120 1130 KTTTRNRESV YLLLDMIVQE SPFLTMDLLE SCFPYVLLRN AYHAVYKQSV TSSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a novel apoptosis-related gene, human Nap1 (NCKAP1), and its possible relation to Alzheimer disease." Suzuki T., Nishiyama K., Yamamoto A., Inazawa J., Iwaki T., Yamada T., Kanazawa I., Sakaki Y. Genomics 63:246-254(2000) [PubMed: 10673335] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[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: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Trachea.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Structure and control of the actin regulatory WAVE complex." Chen Z., Borek D., Padrick S.B., Gomez T.S., Metlagel Z., Ismail A.M., Umetani J., Billadeau D.D., Otwinowski Z., Rosen M.K. Nature 468:533-538(2010) [PubMed: 21107423] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF WAVE1 COMPLEX, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB014509 mRNA. Translation: BAA77295.1.
AB011159 mRNA. Translation: BAA25513.2. Different initiation.
AK292914 mRNA. Translation: BAF85603.1.
BT007033 mRNA. Translation: AAP35681.1.
AC108514 Genomic DNA. Translation: AAX93118.1.
AC064871 Genomic DNA. Translation: AAY24196.1.
BC015025 mRNA. Translation: AAH15025.1.

IPI

IPI00031982.
IPI00409684.

RefSeq

NP_038464.1. NM_013436.3.
NP_995314.1. NM_205842.1.

UniGene

Hs.603732.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3P8C	X-ray	2.29	B	1-1128	[»]

ProteinModelPortal

Q9Y2A7.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31119N.

IntAct

Q9Y2A7. 6 interactions.

MINT

MINT-244824.

STRING

Q9Y2A7.

PTM databases

PhosphoSite

Q9Y2A7.

Polymorphism databases

DMDM

12643947.

Proteomic databases

PRIDE

Q9Y2A7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361354; ENSP00000355348; ENSG00000061676.

GeneID

10787.

KEGG

hsa:10787.

UCSC

uc002upc.1. human.

Organism-specific databases

CTD

10787.

GeneCards

GC02M183753.

H-InvDB

HIX0018862.

HGNC

HGNC:7666. NCKAP1.

HPA

HPA020449.

MIM

604891. gene.

neXtProt

NX_Q9Y2A7.

PharmGKB

PA31468.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15970.

GeneTree

ENSGT00390000016619.

HOVERGEN

HBG006344.

OMA

SCFPYAL.

OrthoDB

EOG4M0F0V.

PhylomeDB

Q9Y2A7.

Gene expression databases

ArrayExpress

Q9Y2A7.

Bgee

Q9Y2A7.

CleanEx

HS_NCKAP1.

Genevestigator

Q9Y2A7.

GermOnline

ENSG00000061676. Homo sapiens.

Family and domain databases

InterPro

IPR019137. Nck-associated_protein-1.
[Graphical view]

KO

K05750.

Pfam

PF09735. Nckap1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

40972.

SOURCE

Search...

Entry information

Entry name

NCKP1_HUMAN

Accession

Primary (citable) accession number: Q9Y2A7
Secondary accession number(s): O60329 , Q53QN5, Q53S94, Q53Y35

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	November 1, 1999
Last modified:	January 25, 2012
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.